Download “A Clinician`s Guide to Using Light Therapy” Clinician Resource

“A Clinician’s Guide to Using Light Therapy”
Clinician Resource Package
Raymond W. Lam, MD, FRCPC
Professor and Head, Mood and Anxiety Disorders Program
Department of Psychiatry, University of British Columbia
Medical Director, Mood Disorders Centre
UBC Hospital, Vancouver Coastal Health
Vancouver, BC, Canada V6T 2A1
Tel: 604-822-7325, Fax: 604-822-7922
[email protected] www.UBCmood.ca
Edwin M. Tam, MDCM, FRCPC
Clinical Associate Professor, Mood and Anxiety Disorders Program
Department of Psychiatry, University of British Columbia
Associate Medical Manager, Mood Disorders Centre
UBC Hospital, Vancouver Coastal Health
[email protected]
 Copyright, Drs. Lam and Tam, 2009
INTRODUCTION
Dr. Tam and I recently published “A Clinician’s Guide to Using Light Therapy,” (Cambridge
University Press, 2009, www.cambridge.org) a step-by-step manual for mental health clinicians about
how to incorporate light therapy into their daily practice. This clinician resource package is offered,
free of charge, as a supplement to the book. It includes many useful tools for clinical practice. Please
feel free to use any of these tools; however, we would appreciate an acknowledgment or citation to
us if they are used in presentations or copied for educational events or other clinical settings. And,
please let us know if you have ideas about other resources that we can include in the package.
Raymond W. Lam, MD, FRCPC
Professor and Head, Mood and Anxiety Disorders Program
Department of Psychiatry, University of British Columbia
RESOURCE LIST
1.
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10.
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16.
17.
Frequently Asked Questions about SAD (patient brochure).
Self-care Tips for Winter Blues and SAD (patient handout)
How to Use the 10,000 Lux Light Box (patient handout).
Where to Get a Light Device (patient handout)
Notes on Using the SPAQ and HAM-D
Seasonal Pattern Assessment Questionnaire (screening questionnaire)
Hamilton Depression Rating Scale, SAD version (outcome scale)
PHQ-9 (outcome scale)
QIDS-SR (outcome scale)
Morningness-Eveningness Questionnaire (chronotype questionnaire)
Adverse Event Scale (side effects scale)
Sample Insurance Reimbursement Letter
Audit Form for practice management.
Clinical Update on SAD, by Å.Westrin & R.W. Lam (journal article)
Long term and preventative treatment in SAD, by Å Westrin & R.W. Lam (journal article)
Update on the biology of SAD, by C.H Sohn & R.W. Lam (journal article)
Light therapy vs. antidepressants for SAD, by R.W. Lam & colleagues (journal article)
HELPFUL WEB SITES

SAD Information Page, University of BC, www.UBCsad.ca

Society for Light Treatment and Biological Rhythms, www.sltbr.org

Circadian Lighting Association (light device suppliers), www.cla.org

Center for Environmental Therapeutics, www.cet.org

Canadian Network for Mood and Anxiety Treatments, www.canmat.org
UBC HOSPITAL MOOD DISORDERS CENTRE
TEL: (604) 822-7512 FAX: (604 ) 822-7922
WWW.UBCMOOD.CA
Frequently Asked Questions about
Seasonal Affective Disorder (SAD)
What is SAD? How is it different from the winter blues?
Many people feel mildly “depressed” during the winter, but some people have more severe bouts of
feeling down all the time, low energy, problems with sleep and appetite, loss of interest, and
reduced concentration to the point where they have difficulty functioning at work or in the home.
We say that these people have a clinical depression, to distinguish it from everyday ups and downs.
Seasonal affective disorder (‘affective’ is a psychiatric term for mood), or SAD, describes people
who have these clinical depressions only during the autumn and winter seasons. During the spring
and summer, they feel well and “normal”.
Other common symptoms of SAD include oversleeping, extreme fatigue, increased appetite with
carbohydrate craving, overeating, and weight gain. With more severe episodes, people may have
suicidal thoughts.
How common is SAD?
Researchers believe that SAD results from the shorter daylength in winter. Recent studies estimate
that SAD is more common in northern countries because the winter day gets shorter as you go
farther north. Studies in Ontario suggest that 1% to 3% of the general population have SAD. This
means that up to 1 million in Canada may have difficulties in the winter due to significant clinical
depression. Another 15% of people have the “winter blues” or “winter blahs” – winter symptoms
similar to SAD, but not to the point of having a clinical depression.
What treatments are available for SAD?
Research has shown that many patients with SAD improve with exposure to bright, artificial light,
called light therapy, or phototherapy. As little as 30 minutes per day of sitting under a speciallydesigned light device results in significant improvement in 60% to 70% of patients with SAD.
How do you use light therapy?
A fluorescent light box is the best-studied light therapy treatment. People usually purchase a light
box and use it in their own homes. The usual “dose” of light is 10,000 lux, where lux is a
measurement of light intensity. Indoor light is usually less than 400 lux; a cloudy day about 3,000
lux; and a sunny day is 50,000 lux or more. Using the 10,000 lux light box for about 30 minutes a
day is usually enough for a beneficial response. A light box with a lower lux rating usually requires
more time for a response. For example, 5,000 lux light boxes usually require 45-60 minutes of daily
exposure, while 2,500 lux light boxes require 1-2 hours of exposure.
Other light devices are also commercially available. Some devices use light-emitting diodes (LEDs)
which are longer-lasting and are much smaller and portable than light boxes. Light visors and other
head-mounted units can offer more portability than light boxes. Dawn simulators are devices that
gradually increase the lights in the bedroom to “simulate” a summer dawn in the winter. While
these devices can be beneficial for some people, there is less evidence to show that they are
effective for SAD compared to light boxes.
Most light devices use white light. Currently, narrow-band blue-light devices are NOT recommend
because they have not been extensively tested, there is no indication that blue light is better than
white light for SAD, and there is no information on long term safety (unlike white light devices).
There are some theoretical reasons why blue light may be harmful to the eyes.
What about sun tanning studios?
People are cautioned NOT to use sun tanning studios to treat SAD because there is NO evidence
that they are helpful. The effect of light therapy is through the eyes, not through skin exposure, and
people should not open their eyes in tanning booths because of the harmful effects of ultraviolet
exposure. Fluorescent light boxes have filters to block the harmful ultraviolet rays and LED lights
do not emit ultraviolet wavelengths.
How do I get a light box?
Safe and portable light devices are now commercially available. Ask your doctor, or contact our
clinic for more information (or check our web site at www.UBCsad.ca). The cost of a light box is
usually between $150 and $300 (Cdn). We do not recommend building your own light box, because
of the safety hazards, and the difficulty in getting the correct dose of light.
Are there side effects to light therapy?
Side effects of light therapy are usually mild. Some people may experience mild nausea, headaches,
eyestrain, or feeling “edgy” when they first start using light therapy. These effects usually get better
with time or reducing the light exposure. People who have bipolar disorder (manic-depressive
illness) should consult their doctor before using light therapy.
There are no known long-term harmful effects of light therapy. However, people with certain
medical conditions (such as retinal disease, macular degeneration or diabetes) or taking certain
medications (such as thioridazine, lithium or melatonin) should have special eye examinations
before considering light therapy.
2
Are there other treatments for SAD?
Other treatments for depression, including the newer antidepressant medications (e.g., selective
serotonin reuptake inhibitors, or SSRIs such as fluoxetine [Prozac]; bupropion-XL [Wellbutrin];
moclobemide [Manerix]; and others) are also effective for patients with SAD and can be used to
prevent episodes. Counselling or cognitive-behaviour therapy may also help. People with milder
symptoms of the “winter blahs” may be helped by simply spending more time outdoors and
exercising regularly in the winter (e.g., a daily noon hour walk).
Some people with SAD find that they also feel better by increasing the indoor light in their homes
and/or offices, painting their walls in light colours, and sitting near windows for natural light. There
is no evidence, however, that these activities alone can treat SAD.
What causes SAD and how does light therapy work?
We don’t know, exactly, but research shows that light has a biological effect on brain chemicals
(neurotransmitters) and function. One theory is that people with SAD have a disturbance in the
“biological clock” in the brain that regulates hormones, sleep and mood, so that this clock “runs
slow” in the winter. The bright light may help to “reset the clock” and restore normal function.
Other theories are that neurotransmitter functions, particularly serotonin and dopamine, are
disturbed in SAD, and that these neurotransmitter imbalances are corrected by light therapy and/or
antidepressant medications. Still other scientists believe that patients with SAD have reduced retinal
light sensitivity or immune function in the winter that is corrected by light therapy. There is also
evidence for a genetic contribution to SAD.
What should I do if I think I have SAD?
Everyone who is significantly depressed should be assessed by their family doctor because some
physical problems (e.g., thyroid disease) can show up as depression. People with SAD can be
treated by their family doctor, referred to a psychiatrist who is aware of SAD, or (in Vancouver)
referred to the Seasonal Mood Disorders Clinic at UBC Hospital (telephone: 604-822-7512), for
further assessment. To find a SAD specialist, check with the nearest university medical school
department of Psychiatry. People should not treat themselves with light exposure until after
assessment by a qualified health professional.
Can I read more about SAD?
Check our web site at www.UBCsad.ca , or this book:
Winter Blues: Everything you Need to Know to Beat Seasonal Affective Disorder, by Dr. Norman
Rosenthal (one of the pioneer researchers in SAD and light therapy). Guilford Press, revised 2005,
about $18.00 (Cdn).
3
Self-Care Tips for Winter Blues and Seasonal Affective Disorder (SAD)

Educate your self, family and close friends about SAD to gain their understanding and support.
Here are some helpful web sites for more information and support:
 SAD Information Page at the University of BC. Our site includes many resources available
for free download. www.UBCsad.ca
 Center for Environmental Therapeutics. Includes information on recent research and
treatment, on-line screening and assessment tools for the public. www.cet.org
 The Seasonal Affective Disorder Association. Based in the England, this is the world’s
longest established support organization for those with SAD. The site includes a low cost
information pack available to order. www.sada.org.uk

Share experiences regarding SAD and treatment with others for information, understanding,
validation and support. Here are some helpful books on the topic:
 Winter Blues, Revised Edition. Everything You Need to Know to Beat Seasonal Affective
Disorder. By Norman E. Rosenthal, Guilford Press, 2006, about $28.
 Coping with the Seasons. A Cognitive Behavioral Approach for Seasonal Affective Disorder.
Workbook. By Kelly J. Rohan, Oxford University Press, 2008, about $30.
 Seasonal Affective Disorder for Dummies. By Laura L. Smith and Charles H. Elliott, Wiley
Press, 2007, about $22.

Get as much light as possible and avoid dark environments during daylight hours in winter.

Rearrange workspaces at home and work near a window, or set up bright lights in your work
area. Allow natural light to shine through open windows when temperatures are moderate

Consider going without sunglasses in the winter except in very bright sun/snow or decrease the
amount of time wearing them.

Be aware of cold outdoor temperatures and dress to conserve energy and warmth. Many affected
by seasonal changes report sensitivity to extreme temperatures.

Reduce mild winter depressive symptoms by exercising daily – outdoors when possible to take
advantage of natural light, but inside is okay too.

Stay on a regular sleep/wake schedule. People who get up every morning and go to sleep at the
same time, report being more alert and less fatigued than when they vary their schedules.

Try putting your bedroom lights on a timer set to switch on ½ hour or more before awakening.
Some people report it is easier to wake up when using this technique with lights.

Some find it helpful to record their biological rhythms during fall and winter. They keep a daily
log noting weather conditions and their energy levels, moods, appetite/weight, sleep times and
activities.

Arrange family outings and social occasions for day times and early evening in winter. Avoid
staying up late which disrupts the sleep schedule and biological clock.

Postpone making major life changes until spring or summer when possible.

If you are able, arrange a winter vacation to a warm, sunny climate!
INSTRUCTIONS FOR USING LIGHT THERAPY
Note that this information does not substitute for medical consultation. You should always check out
information with your own doctor. These instructions should only be used in conjunction with supervision by
a qualified health professional.
1.
These instructions are for fluorescent light boxes that emit 10,000 lux light (lux is a measurement of
light intensity). Light boxes with lower lux rating usually require more time for response. For example,
5,000 lux light boxes usually require 45-60 minutes of daily exposure, while 2,500 lux light boxes
require 1-2 hours of exposure.
2.
Other light devices are also commercially available (e.g., LED lights, light visors, dawn simulators).
They may be beneficial for some patients, but there is less evidence to show that they are effective
compared to light boxes. When using these devices, follow the instructions from the manufacturer.
3.
The light boxes we recommend contain cool-white fluorescent lights, but full-spectrum fluorescent
lights are also effective (although more expensive). The light box should have an ultraviolet filter.
Do not use sunlamps, tanning lamps or halogen lamps as these may be harmful to your eyes!
4.
During light therapy, you should keep to a regular sleep schedule (going to sleep and waking up at
regular times, for example, 11:00 p.m. to 7:00 a.m.).
5.
The light box should be placed on a table or counter so that you can sit comfortably. You must be
positioned correctly, so follow the manufacturer’s information about the distance to the light box.
6.
You can read or eat while sitting under the lights, but your eyes must be open for the effect to occur.
You cannot sleep during your light exposure! You should not stare directly at the lights.
7.
Start with 30 minutes of light exposure per day. Start light therapy in the early morning, as soon as
possible after awakening (between 6:00 a.m. and 9:00 a.m.).
8.
Response usually starts in a few days, and by two weeks the symptoms should be definitely improving.
Most people need to continue light therapy throughout the winter until the springtime. When light
therapy is stopped, symptoms do not usually reappear for a few days, so most people can stop the
treatment for one or two days without much problem (e.g., for a weekend trip).
9.
If the symptoms are not improving after 10-14 days, try spending up to 60 minutes per day in front of
lights each morning, or divided between the morning and evening. Do not use the light box too near
bedtime, as the light exposure can disturb sleep. If this still does not help, contact your doctor.
10. When there is a good response to light therapy, some patients like to experiment with the timing and
duration of daily light exposure, e.g., by reducing the daily exposure to 15 minutes, or using the light at
a more convenient time of the day (e.g., 7:00 p.m.). We suggest making one change at a time, for 2
weeks. If symptoms start returning, go back to the original dosing schedule.
11. There are no reported harmful effects on the eyes with light therapy as described, but the long-term
effects have not yet been studied. If you have eye problems (e.g., retinal disease, macular degeneration,
or diabetes), or worries about eye damage, please tell your doctor.
12. Some people experience mild headaches, nausea, dizziness or eye strain when using the lights. These
symptoms usually occur at the beginning of treatment, and get better in a few days. Otherwise, they can
be relieved by reducing the daily exposure time, or by sitting slightly farther away from the lights.
13. Occasionally people report feeling irritable, or euphoric, or being “too high” when treated with light
therapy. If this happens, the treatment should be stopped, and you should contact your doctor. If light
therapy is restarted, use a shorter exposure time (e.g., 15 minutes per day) or sit slightly farther away
from the lights. People with bipolar disorder (manic-depressive illness) should consult with their doctor
before using light therapy.
Mood Disorders Centre, UBC Hospital
Vancouver Coastal Health
Tel: 604-822-7512, www.UBCmood.ca
Director: Dr. Raymond W. Lam
Light Therapy Devices for SAD
Seasonal affective disorder (SAD) is a type of clinical depression that regularly occurs in the winter,
with normal mood in the summer. Light therapy is an effective and safe treatment for SAD. Other treatments
for depression (for example, antidepressant medications) are also effective. Self-diagnosis or self-treatment
of SAD is not recommended because there are other medical causes for depressive symptoms, and because
light therapy may be harmful to people with certain medical conditions (for example, eye disease). See your
doctor first!
Although light therapy is effective for SAD, we still do not fully understand how the light works and
what is the best method for light therapy. There are now many light therapy devices available on the market
making claims about light treatment, but light therapy devices are not well regulated in Canada. Therefore,
we believe it is wise to be cautious about recommending light therapy devices. Our recommendations are
based on the following principles: 1) the light device should be tested and found effective in scientifically
valid studies, 2) the light device should have a filter that blocks harmful ultraviolet rays, 3) the light device
should be CSA approved if used in Canada (UL approved in the US), and 4) the light device company should
have a track record of reliability.
We recommend fluorescent light boxes because they have been extensively tested with the greatest
evidence for effectiveness in scientific studies, and we have experience with these devices. Other light
devices, for example, light emitting diode (LED) devices, light visors and dawn simulators, may be
beneficial for some patients but there is less evidence for effectiveness compared to light boxes.
Most light devices use white light. We do NOT recommend narrow-band blue-light devices because
they have not been extensively tested, there is no indication that blue light is better than white light for SAD,
and there is no information on long term safety (unlike white light devices). There are some theoretical
reasons why blue light may be harmful to the eyes.
We have no direct financial interest in any companies listed below, nor can we take any
responsibility for their products.
British Columbia Suppliers
Canadian Direct-Order Suppliers
Shoppers Drug Mart carries a range of light
devices. www.shoppersdrugmart.ca
Up-Lift Technologies, Halifax, NS
www.day-lights.com
Tel: (902) 422-0804 / 1-800-387-0896
Clinical Sleep Solutions,
www.clinicalsleep.com
Vancouver and other cities
Tel: 1-866-432-9271
VitalAire, www.vitalaire.com
Unit 201-9087B-198th Street
Langley, BC V1M 3B1
Tel: (604) 881-0214
Northern Light Technologies, St. Laurent PQ
www.northernlight-tech.com
Tel: 514-335-1763 / 1-800-263-0066
Litebook Company, Medicine Hat, AB
www.litebook.com
Tel: 1-877-723-5483
Bio-Brite Inc., Bethesda, MD (CSA approved)
www.biobrite.com
Tel: 1-301-961-5943
International Direct-Order Suppliers
Circadian Lighting Association
www.claorg.org
Notes on the SPAQ and Ham-24 (see following pages)
Seasonal Pattern Assessment Questionnaire (SPAQ)
Ø The SPAQ is a widely used screening questionnaire for SAD.
Ø The Global Seasonality Score (GSS) is the total sum of the 6 items on Question 11. This
gives a score from 0 (no seasonality) to 24 (extreme seasonality). The average GSS in
community samples is about 5. The average GSS in patients with SAD is about 16.
Ø The screening criteria for a “diagnosis” of SAD are based on the GSS and the score on
Question 17, the degree of problems associated with seasonal changes.
Ø A GSS of 11 or higher and a score on Q.11 of moderate or greater is indicative of SAD.
Ø As with most screening questionnaires, these criteria tend to overdiagnose SAD. On
clinical interview, some people with these criteria will turn out to have subsyndromal
features. On the other hand, very few people with a true diagnosis of SAD will be missed
using these criteria.
Summary Sheet for the 24- and 29-item Version of the Hamilton Depression Rating Scale
Ø The Hamilton Depression Rating Scale (Ham-D) is the most widely used outcome scale
for depression studies. The Ham-D is based on a clinical interview with the patient and is
rated by the interviewer. The interview asks the patient about symptoms experienced in
the past week, compared to a time when they were well.
Ø There are various versions of the Ham-D, which was originally developed in the 1960’s.
The original version (17 items, Ham-17) and a later version (with an additional 4 items,
Ham-21) did not include items rating atypical symptoms (like oversleeping, overeating,
weight gain, etc). An 8-item atypical symptom addendum was added to rate these
symptoms. The resulting 29-item version (Ham-29) is widely used in SAD studies.
Ø However, the 4 additional items (including the diurnal variation item) on the Ham-21 and
1 item on the Ham-8 are not related to severity of depression. Hence, the Ham-24 (sum of
the Ham-17 and Ham-7) is a better indicator of severity than the Ham-29.
Ø The Ham-24 and Ham-29 scores can be categorized this way:
Category
Ham-24 Score
Ham-29 score
Normal, not depressed
9 or less
11 or less
Mildly depressed
10 to 19
12 to 21
Moderately depressed
20 to 29
22 to 32
30 or more
33 or more
Markedly/severely depressed
SEASONAL PATTERN ASSESSMENT QUESTIONNAIRE
1. Name _____________________________________
2. Age ___________
3. Place of birth - City / Province (State) / Country _________________________________________________
4. Today's date
________
Month
________
Day
________
Year
5. Current weight (in lbs.)
____________
6. Years of education
Less than four years of high school
1
High school only
2
1-3 years post high school
3
4 or more years post high school
4
7. Sex -
Male
1
Female
8. Marital Status -
Single
1
Married
2
INSTRUCTIONS
* Please circle the number
beside your choice.
Example:
Sex Male 1
Female 2
2
Sep./Divorced 3
Widowed
4
9. Occupation ______________________________________
10. How many years have you lived in this climatic area?
________________
The purpose of this form is to find out how your mood and behaviour change over time.
Please fill in all the relevant circles. Note: We are interested in your experience; not others
you may have observed.
11. To what degree do the following change with the seasons?
No
Change
Slight
Change
Moderate Marked
Change Change
Extremely
Marked
Change
A. Sleep length
0
1
2
3
4
B. Social activity
0
1
2
3
4
C. Mood (overall feeling of well being)
0
1
2
3
4
D. Weight
0
1
2
3
4
E. Appetite
0
1
2
3
4
F. Energy level
0
1
2
3
4
12. In the following questions, fill in circles for all applicable months. This may be a single month O,
a cluster of months, e.g. O O O , or any other grouping.
At what time of year do you....
A. Feel best
B. Gain most weight
C. Socialize most
D. Sleep least
E. Eat most
F. Lose most weight
G. Socialize least
H. Feel worst
I. Eat least
J. Sleep most
J
a
n
F
e
b
M
a
r
A
p
r
M
a
y
J
u
n
J
u
l
A
u
g
S
e
p
O
c
t
N
o
v
D
e
c
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
OR
No particular month(s)
stand out as extreme
on a regular basis
OR
O
O
O
O
O
O
O
O
O
O
14. How much does your weight fluctuate during the course of the year?
0-3 lbs
1
12-15 lbs
4
4-7 lbs
2
16-20 lbs
5
8-11 lbs
3
Over 20 lbs
6
15. Approximately how many hours of each 24-hour day do you sleep during each season? (Include naps)
Winter
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Over18
Spring
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Over18
Summer
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Over18
Fall
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Over18
16. Do you notice a change in food preference during the different seasons?
No
1
Yes
2
If yes, please specify :
17. If you experience changes with the seasons, do you feel that these are a problems for you?
No
1
Yes
2
If yes, is this problem - mild
1
moderate
2
marked
3
severe
4
disabling
5
Thank you for completing this questionnaire.
* Raymond W. Lam 1998 (modified from Rosenthal, Bradt and Wehr 1987).
SIGH-SAD (Ham-D) Summary Score Sheet
Date: (dd/mon/yr) ____ / ____ / ____
Patient Name: ___
1. Depressed Mood
0 = Absent.
1 = These feeling states indicated only on questioning.
2 = These feeling states spontaneously reported verbally.
3 = Communicates feeling states non-verbally - i.e., through
facial expression, posture, voice, and tendency to
weep.
4 = Patient reports virtually only these feeling states in his
spontaneous verbal and non-verbal communication.
7. Weight Gain
0 = No weight gain.
1 = Probable weight gain due to current depression.
2 = Definite (according to patient) weight gain due to
depression.
8. Appetite Increase
0 = No increase in appetite.
1 = Wants to eat a little more than usual.
2 = Wants to eat somewhat more than normal.
3 = Wants to eat much more than usual.
2. Work and Activities
0 = No difficulty.
1 = Thoughts and feelings of incapacity, fatigue or
weakness related to activities; work or hobbies.
2 = Loss of interest in activities; hobbies or work - either
directly reported by patient, or indirect in listlessness,
indecision and vacillation (feels he has to push self to
work or activities).
3 = Decrease in actual time spent in activities or decrease
in productivity. In hospital rate 3 if patient does not
spend at least three hours a day in activities (hospital
job or hobbies) exclusive of ward chores.
4 = Stopped working because of present illness. In hospital,
rate 4 if patient engages in no activities except ward
chores, or if patient fails to perform ward chores
unassisted.
9. Increased Eating
0 = Is not eating more than usual.
1 = Is eating a little more than usual.
2 = Is eating somewhat more than usual.
3 = Is eating much more than normal.
10. Carbohydrate Craving
0 = No change in food preference or consumption.
1 = Craving or eating more carbohydrates (starches or
sugars) than before.
2 = Craving or eating much more carbohydrates than
before.
3 = Irresistible craving or eating of sweets or starches.
11. Insomnia  Early
0 = No difficulty falling asleep.
1 = Complains or occasional difficulty falling asleep - i.e.,
more than 1/2 hour.
2 = Complains of nightly difficulty falling asleep.
3. Social Withdrawal
0 = Interacts with other people as usual.
1 = Less interested in socializing with others but continues
to do so.
2 = Interacting less with other people in social (optional)
situations.
3 = Interacting less with other people in work or family
situations (i.e. where this is necessary).
4 = Marked withdrawal from others in family or work
situations.
12. Insomnia  Middle
0 = No difficulty.
1 = Patient complains of being restless and disturbed
during the night.
2 = Waking during the night - any getting out of bed rates 2
(except for purposes of voiding).
4. Genital Symptoms
0 = Absent.
1 = Mild.
2 = Severe.
13. Insomnia  late
0 = No difficulty.
1 = Waking in early hours of the morning but goes back to
sleep.
2 = Unable to fall asleep again if he gets out of bed.
5. Somatic Symptoms  GI
0 = None.
1 = Loss of appetite but eating without staff
encouragement. Heavy feelings in abdomen.
2 = Difficulty eating without staff urging. Requests or
requires laxatives or medication for bowels or
medication for G.I. symptoms.
14. Hypersomnia
0 = No increase in sleep length.
1 = At least 1 hour increase in sleep length.
2 = 2+ hour increase.
3 = 3+ hour increase.
4 = 4+ hour increase.
6. Loss of Weight
0 = No weight loss.
1 = Probable weight loss associated with present illness.
2 = Definite (according to patient) weight loss.
15. Somatic Symptoms  General
0 = None.
1 = Heaviness in limbs, back or head. Backaches,
headache, muscle aches. Loss of energy and
fatigability.
2 = Any clear-cut symptom rates 2.
1
16. Fatigability
0 = Does not feel more fatigued than usual.
1 = Feels more fatigued than usual but this has not
impaired function significantly; less frequent than in
(2).
2 = More fatigued than usual; at least one hour a day; at
least three days a week.
3 = Fatigued much of the time most days.
4 = Fatigued almost all the time.
24. Agitation
0 = None.
1 = Fidgetiness.
2 = Playing with hands, hair, etc.
3 = Moving about can't sit still.
4 = Hand wringing, nail biting, hair pulling, biting of lips.
17. Feelings of Guilt
0 = Absent.
1 = Self reproach, feels he has let people down.
2 = Ideas of guilt or rumination over past errors or sinful
deeds.
3 = Present illness is a punishment. Delusions of guilt.
4 = Hears accusatory or denunciatory voices and/or
experiences threatening visual hallucinations.
17-item Ham-D Total: ______________
(do not include shaded items)
7-item Atypical Total: ______________
(only shaded items)
24-item Ham-D Total: ______________
(all items)
18. Suicide
0 = Absent.
1 = Feels life is not worth living.
2 = Wishes he were dead or any thoughts of possible death
to self.
3 = Suicide ideas or gestures.
4 = Attempts at suicide (any serious attempt rates 4).
25. Diurnal Variation
0 = None.
1 = Mild.
2 = Severe.
19. Anxiety  Psychic
0 = No difficulty.
1 = Subjective tension and irritability.
2 = Worrying about minor matters.
3 = Apprehensive attitude apparent in face or speech.
4 = Fears expressed without questioning.
Worse in:
AM
PM
26. Reverse Diurnal (Afternoon Slump)
0 = No.
1 = yes, of mild intensity.
2 = Yes, of moderate intensity.
3 = yes, of severe intensity.
27. Depersonalization/Derealization
0 = Absent.
1 = Mild.
2 = Moderate.
3 = Severe.
4 = Incapacitating.
20. Anxiety  Somatic
0 = Absent.
1 = Mild.
2 = Moderate.
3 = Severe.
4 = Incapacitating.
28. Paranoid Symptoms
0 = None.
1 = Suspicious.
2 = Ideas of reference.
3 = Delusions of reference and persecution.
21. Hypochondriasis
0 = Not present
1 = Self-absorption (bodily).
2 = Preoccupation with health.
3 = Frequent complaints, requests for help, etc.
4 = Hypochondriacal delusions.
29. Obsessive/Compulsive
0 = Absent.
1 = Mild.
2 = Severe.
22. Insight
0 = Acknowledges being depressed and ill.
1 = Acknowledges illness but attributes cause to bad food,
climate, over work, virus, need for rest, etc.
2 = Denies being ill at all.
29-item Ham-D Total: ______________
23. Motor Retardation
0 = Normal speech and thought.
1 = Slight retardation at interview.
2 = Obvious retardation at interview.
3 = Interview difficult.
4 = Complete stupor.
(all items)
2
Patient Health Questionnaire (PHQ-9)
Patient name: __________________________________ Date: ___________________
1. Over the last 2 weeks, how often have you been bothered by any of the following problems?
Not at all
(0)
Several
days (1)
More than
half the
days (2)
Nearly
every day
(3)
a. Little interest or pleasure in doing things.




b. Feeling down, depressed, or hopeless.




c. Trouble falling/staying asleep, sleeping too much.




d. Feeling tired or having little energy.




e. Poor appetite or overeating.




f. Feeling bad about yourself, or that you are a
failure, or have let yourself or your family down.




g. Trouble concentrating on things, such as reading
the newspaper or watching TV.




h. Moving or speaking so slowly that other people
could have noticed.
Or the opposite; being so fidgety or restless that
you have been moving around more than usual.




i. Thoughts that you would be better off dead or of
hurting yourself in some way.




2. If you checked off any problem on this questionnaire so far, how difficult have these
problems made it for you to do your work, take care of things at home, or get along with
other people?

Not difficult
at all
TOTAL SCORE

Somewhat
difficult

Very
difficult
_________________
PHQ9 Copyright © Pfizer Inc. All rights reserved. Reproduced with permission.
PRIME-MD ® is a trademark of Pfizer Inc.

Extremely
difficult
Instructions – How to Score the PHQ-9
Major depressive disorder is suggested if:
 Of the 9 items, 5 or more are checked as at least ‘more than half the days’
 Either item a. or b. is positive, that is, at least ‘more than half the days’
Other depressive syndrome is suggested if:
 Of the 9 items, a., b. or c. is checked as at least ‘more than half the days’
 Either item a. or b. is positive, that is, at least ‘more than half the days’
Also, PHQ-9 scores can be used to plan and monitor treatment. To score the instrument, tally
each response by the number value under the answer headings, (not at all=0, several days=1,
more than half the days=2, and nearly every day=3). Add the numbers together to total the score
on the bottom of the questionnaire. Interpret the score by using the guide listed below.
Guide for Interpreting PHQ-9 Scores
Score
0-4
5-9
10-14
15-19
20 or
higher
Recommended Actions
Normal range or full remission. The score suggests the patient may not need
depression treatment.
Minimal depressive symptoms. Support, educate, call if worse, return in 1
month.
Major depression, mild severity. Use clinical judgment about treatment, based
on patient’s duration of symptoms and functional impairment. Treat with
antidepressant or psychotherapy.
Major depression, moderate severity. Warrants treatment for depression, using
antidepressant, psychotherapy or a combination of treatment.
Major depression, severe severity. Warrants treatment with antidepressant and
psychotherapy, especially if not improved on monotherapy; follow frequently.
Functional Health Assessment
The instrument also includes a functional health assessment. This asks the patient how emotional
difficulties or problems impact work, things at home, or relationships with other people. Patient
responses can be one of four: Not difficult at all, Somewhat difficult, Very difficult, Extremely
difficult. The last two responses suggest that the patient’s functionality is impaired. After
treatment begins, functional status and number score can be measured to assess patient
improvement.
For more information on using the PHQ-9, visit www.depression-primarycare.org
QUICK INVENTORY OF DEPRESSIVE SYMPTOMATOLOGY (SELF-REPORT)
(QIDS-SR)
NAME: ________________________________________________
TODAY’S DATE _______________
Please circle the one response to each item that best describes you for the past seven days.
1.
Falling Asleep:
0
1
2
3
2.
2
3
3.
0
1
2
3
4.
Most of the time, I awaken no more than
30 minutes before I need to get up.
More than half the time, I awaken more
than 30 minutes before I need to get up.
I almost always awaken at least one hour
or so before I need to, but I go back to
sleep eventually.
I awaken at least one hour before I need
to, and can't go back to sleep.
Sleeping Too Much:
0
1
2
3
2
3
7.
I sleep no longer than 7-8 hours/night,
without napping during the day.
I sleep no longer than 10 hours in a 24hour period including naps.
I sleep no longer than 12 hours in a 24hour period including naps.
I sleep longer than 12 hours in a 24-hour
period including naps.
1
2
3
8.
0
1
2
3
0
2
I do not feel sad
I feel sad less than half the time.
I feel sad more than half the time.
I feel sad nearly all of the time.
I have not had a change in my weight.
I feel as if I've had a slight weight gain.
I have gained 2 pounds or more.
I have gained 5 pounds or more.
10. Concentration/Decision Making:
Feeling Sad:
0
1
2
3
I have not had a change in my weight.
I feel as if I've had a slight weight loss.
I have lost 2 pounds or more.
I have lost 5 pounds or more.
Increased Weight (Within the Last Two
Weeks):
1
5.
There is no change from my usual
appetite.
I feel a need to eat more frequently than
usual.
I regularly eat more often and/or greater
amounts of food than usual.
I feel driven to overeat both at mealtime
and between meals.
Decreased Weight (Within the Last Two
Weeks):
0
1
2
3
9.
There is no change in my usual appetite.
I eat somewhat less often or lesser
amounts of food than usual.
I eat much less than usual and only with
personal effort.
I rarely eat within a 24-hour period, and
only with extreme personal effort or when
others persuade me to eat.
Increased Appetite:
0
I do not wake up at night.
I have a restless, light sleep with a few
brief awakenings each night.
I wake up at least once a night, but I go
back to sleep easily.
I awaken more than once a night and stay
awake for 20 minutes or more, more than
half the time.
Waking Up Too Early:
Decreased Appetite:
0
1
I never take longer than 30 minutes to fall
asleep.
I take at least 30 minutes to fall asleep,
less than half the time.
I take at least 30 minutes to fall asleep,
more than half the time.
I take more than 60 minutes to fall asleep,
more than half the time.
Sleep During the Night:
0
1
6.
3
There is no change in my usual capacity to
concentrate or make decisions.
I occasionally feel indecisive or find that
my attention wanders.
Most of the time, I struggle to focus my
attention or to make decisions.
I cannot concentrate well enough to read
or cannot make even minor decisions.
14. Energy Level:
11. View of Myself:
0
1
2
3
0
I see myself as equally worthwhile and
deserving as other people.
I am more self-blaming than usual.
I largely believe that I cause problems for
others.
I think almost constantly about major and
minor defects in myself.
1
2
3
12. Thoughts of Death or Suicide:
0
1
2
3
I do not think of suicide or death.
I feel that life is empty or wonder if it's
worth living.
I think of suicide or death several times a
week for several minutes.
I think of suicide or death several times a
day in some detail, or I have made specific
plans for suicide or have actually tried to
take my life.
15. Feeling slowed down:
0
1
2
13. General Interest:
0
1
2
3
There is no change in my usual level of
energy.
I get tired more easily than usual.
I have to make a big effort to start or finish
my usual daily activities (for example,
shopping, homework, cooking or going to
work).
I really cannot carry out most of my usual
daily activities because I just don't have
the energy.
3
There is no change from usual in how
interested I am in other people or
activities.
I notice that I am less interested in people
or activities.
I find I have interest in only one or two of
my formerly pursued activities.
I have virtually no interest in formerly
pursued activities.
I think, speak, and move at my usual rate
of speed.
I find that my thinking is slowed down or
my voice sounds dull or flat.
It takes me several seconds to respond to
most questions and I'm sure my thinking is
slowed.
I am often unable to respond to questions
without extreme effort.
16. Feeling restless:
0
1
2
3
I do not feel restless.
I'm often fidgety, wringing my hands, or
need to shift how I am sitting.
I have impulses to move about and am
quite restless.
At times, I am unable to stay seated and
need to pace around.
To Score:
1.
Enter the highest score on any 1 of the
4 sleep items (1-4)
____
2.
Item 5
3.
Enter the highest score on any 1
appetite/weight item (6-9)
4.
Scoring Criteria
0–5
Normal
6–10
Mild
____
11–15
Moderate
Item 10
____
16–20
Severe
5.
Item 11
____
≥21
Very Severe
6.
Item 12
____
7.
Item 13
____
8.
Item 14
____
9.
Enter the highest score on either of
the 2 psychomotor items (15 and 16)
____
TOTAL SCORE (Range 0-27)
©2000, A. John Rush, M.D.
____
____
Revised 5/1/00
MORNINGNESS-EVENINGNESS QUESTIONNAIRE (MEQ)
Instructions:
 Please read each question very carefully before answering.
 Please answer each question as honestly as possible.
 Answer ALL questions.
 Each question should be answered independently of others. Do NOT go back and check your answers.
1. What time would you get up if you were entirely free to plan your day?
5:00 – 6:30 AM
6:30 – 7:45 AM
7:45 – 9:45 AM
9:45 – 11:00 AM
11:00 AM – 12 NOON
12 NOON – 5:00 AM
5
4
3
2
1
0
2. What time would you go to bed if you were entirely free to plan your evening?
8:00 – 9:00 PM
9:00 – 10:15 PM
10:15 PM – 12:30 AM
12:30 – 1:45 AM
1:45 – 3:00 AM
3:00 AM – 8:00 PM
5
4
3
2
1
0
3. If there is a specific time at which you have to get up in the morning, to what extent do you
depend on being woken up by an alarm clock?
Not at all dependent
Slightly dependent
Fairly dependent
Very dependent
4
3
2
1
4. How easy do you find it to get up in the morning (when you are not woken up unexpectedly)?
Not at all easy
Not very easy
Fairly easy
Very easy
1
2
3
4
5. How alert do you feel during the first half hour after you wake up in the morning?
Not at all alert
Slightly alert
Fairly alert
Very alert
1
2
3
4
6. How hungry do you feel during the first half-hour after you wake up in the morning?
Not at all hungry
Slightly hungry
Fairly hungry
Very hungry
1
2
3
4
7. During the first half-hour after you wake up in the morning, how tired do you feel?
Very tired
Fairly tired
Fairly refreshed
Very refreshed
1
2
3
4
8. If you have no commitments the next day, what time would you go to bed compared to your
usual bedtime?
Seldom or never later
Less than one hour later
1-2 hours later
More than two hours later
4
3
2
1
9. You have decided to engage in some physical exercise. A friend suggests that you do this for one
hour twice a week and the best time for him is between 7:00 – 8:00 am. Bearing in mind nothing
but your own internal “clock”, how do you think you would perform?
Would be in good form
Would be in reasonable form
Would find it difficult
Would find it very difficult
4
3
2
1
10. At what time of day do you feel you become tired as a result of need for sleep?
8:00 – 9:00 PM
9:00 – 10:15 PM
10:15 PM – 12:45 AM
12:45 – 2:00 AM
2:00 – 3:00 AM
5
4
3
2
1
11. You want to be at your peak performance for a test that you know is going to be mentally
exhausting and will last for two hours. You are entirely free to plan your day. Considering only
your own internal “clock”, which ONE of the four testing times would you choose?
8:00 AM – 10:00 AM
11:00 AM – 1:00 PM
3:00 PM – 5:00 PM
7:00 PM – 9:00 PM
4
3
2
1
12. If you got into bed at 11:00 PM, how tired would you be?
Not at all tired
A little tired
Fairly tired
Very tired
1
2
3
4
13. For some reason you have gone to bed several hours later than usual, but there is no need to get
up at any particular time the next morning. Which ONE of the following are you most likely to
do?
Will wake up at usual time, but will NOT fall back asleep
Will wake up at usual time and will doze thereafter
Will wake up at usual time but will fall asleep again
Will NOT wake up until later than usual
4
3
2
1
14. One night you have to remain awake between 4:00 – 6:00 AM in order to carry out a night
watch. You have no commitments the next day. Which ONE of the alternatives will suite you
best?
Would NOT go to bed until watch was over
Would take a nap before and sleep after
Would take a good sleep before and nap after
Would sleep only before watch
1
2
3
4
15. You have to do two hours of hard physical work. You are entirely free to plan your day and
considering only your own internal “clock” which ONE of the following time would you choose?
8:00 AM – 10:00 AM
11:00 AM – 1:00 PM
3:00 PM – 5:00 PM
7:00 PM – 9:00 PM
4
3
2
1
16. You have decided to engage in hard physical exercise. A friend suggests that you do this for one
hour twice a week and the best time for him is between 10:00 – 11:00 PM. Bearing in mind
nothing else but your own internal “clock” how well do you think you would perform?
Would be in good form
Would be in reasonable form
Would find it difficult
Would find it very difficult
1
2
3
4
17. Suppose that you can choose your own work hours. Assume that you worked a FIVE hour day
(including breaks) and that your job was interesting and paid by results). Which FIVE
CONSECUTIVE HOURS would you select?
5 hours starting between 4:00 AM and 8:00 AM
5 hours starting between 8:00 AM and 9:00 AM
5 hours starting between 9:00 AM and 2:00 PM
5 hours starting between 2:00 PM and 5:00 PM
5 hours starting between 5:00 PM and 4:00 AM
5
4
3
2
1
18. At what time of the day do you think that you reach your “feeling best” peak?
5:00 – 8:00 AM
8:00 – 10:00 AM
10:00 AM – 5:00 PM
5:00 – 10:00 PM
10:00 PM – 5:00 AM
5
4
3
2
1
19. One hears about “morning” and “evening” types of people. Which ONE of these types do you
consider yourself to be?
Definitely a “morning” type
Rather more a “morning” than an “evening” type
Rather more an “evening” than a “morning” type
Definitely an “evening” type
6
4
2
0
page 1
Adverse Events Scale
Please rate according to these definitions:
 Slight: Awareness of a sign or symptom which is easily tolerated.
 Moderate: Discomfort enough to cause interference with usual activity.
 Severe: Incapacitating with inability to do work or usual activity.
Have you experienced any of the
following within the last week or since
your last visit?
How troubling or disabling is this for you?
Please circle your response.
Do you think
this is related
to treatment?
Not at all
Slight
Moderate
Severe
Yes
No
Anxiety (“feeling wired”)
1
2
3
4
Y
N
Nervousness
1
2
3
4
Y
N
Agitation
1
2
3
4
Y
N
Tremor
1
2
3
4
Y
N
Twitching
1
2
3
4
Y
N
Irritability
1
2
3
4
Y
N
Dizziness
1
2
3
4
Y
N
Feeling faint when suddenly standing up
1
2
3
4
Y
N
Tightness in Chest
1
2
3
4
Y
N
Palpitations
1
2
3
4
Y
N
Dry Mouth
1
2
3
4
Y
N
Abdominal Pain
1
2
3
4
Y
N
Heartburn
1
2
3
4
Y
N
Nausea
1
2
3
4
Y
N
Diarrhea
1
2
3
4
Y
N
Constipation
1
2
3
4
Y
N
Sweating
1
2
3
4
Y
N
Flushing
1
2
3
4
Y
N
Swelling
1
2
3
4
Y
N
Muscle Pain
1
2
3
4
Y
N
page 2
Please rate according to these definitions:
 Slight: Awareness of a sign or symptom which is easily tolerated.
 Moderate: Discomfort enough to cause interference with usual activity.
 Severe: Incapacitating with inability to do work or usual activity.
Have you experienced any of the
following within the last week or since
your last visit?
How troubling or disabling is this for you?
Please circle your response.
Do you think
this is related
to treatment?
Not at all
Slight
Moderate
Severe
Yes
No
Weakness / Fatigue
1
2
3
4
Y
N
Sleepiness
1
2
3
4
Y
N
Decreased Appetite
1
2
3
4
Y
N
Increased Appetite
1
2
3
4
Y
N
Weight Gain
1
2
3
4
Y
N
Weight Loss
1
2
3
4
Y
N
Increased Sleep
1
2
3
4
Y
N
Decreased Sleep
1
2
3
4
Y
N
Sleep Disturbance
1
2
3
4
Y
N
Headache
1
2
3
4
Y
N
Blurred Vision
1
2
3
4
Y
N
Other Eye or Vision Problems
1
2
3
4
Y
N
Rash
1
2
3
4
Y
N
Increased Sex Drive
1
2
3
4
Y
N
Decreased Sex Drive
1
2
3
4
Y
N
Male Erection Problems
1
2
3
4
Y
N
Female Lubrication Problems
1
2
3
4
Y
N
Delayed orgasm
1
2
3
4
Y
N
Spontaneous Orgasm
1
2
3
4
Y
N
Premature Ejaculation
1
2
3
4
Y
N
Delayed Ejaculation
1
2
3
4
Y
N
September 1, 2009
To whom it may concern:
Seasonal affective disorder (SAD), or winter clinical depression, is an accepted psychiatric diagnosis with
standardized diagnostic criteria. In the most recent edition of the Diagnostic and Statistical Manual of Mental
Disorders (DSM-IV-TR), the standard medical classification system published by the American Psychiatric
Association, SAD is listed as a seasonal pattern course specifier for:
CODE NO.
DSM-IV-296.3x
DSM-IV-296.4x
DSM-IV-296.5x
DSM-IV-296.6x
DSM-IV-296.70
DIAGNOSIS
___
Major Depressive Disorder, Recurrent
Bipolar Disorder, Manic
Bipolar Disorder, Depressed
Bipolar Disorder, Mixed
Bipolar Disorder, NOS
The current recommended first-line treatment for SAD or seasonal pattern is light therapy. Light therapy is now
a standard medical treatment and is no longer considered experimental. Light therapy has been included as a
recommended treatment for SAD in the latest clinical practice guidelines of the American Psychiatric
Association, the Canadian Network for Mood and Anxiety Treatments, and the World Federation of Societies of
Biological Psychiatry. Summary references for these clinical guidelines are included below.
In order to administer light therapy, a 10,000 lux fluorescent light box or other light device is required. This
light box and treatment should be regarded as a medical necessity and preferable to other forms of treatment.
Sincerely,
PRACTITIONER NAME
Practitioner Address
References
American Psychiatric Association: Practice Guideline for the Treatment of Patients with Major Depressive
Disorder (Revision, April, 2000). American Journal of Psychiatry, Vol. 157, No.4 (Supplement), p.31, 2000.
www.psych.org
Bauer M, Whybrow PC, Angst J, Versiani M, Moller H-J: World Federation of Societies of Biological
Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, Part 1: Acute and
continuation treatment of major depressive disorder. World Journal of Biological Psychiatry Vol. 3, pp 5-43,
2002.
Lam RW, Levitt AJ, editors: Canadian Consensus Guidelines for the Treatment of Seasonal Affective Disorder.
Vancouver, BC; Clinical & Academic Publishing, 1999, ISBN 0-9685874-0-2. Available at www.UBCsad.ca
Ravindran AV, Filteau MJ, Lam RW, Lesperance F, Kennedy SH, Parikh SV, Patten SB: Canadian Network for
Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder
in adults. V. Complementary and alternative medicine treatments. Journal of Affective Disorders Vol. 117,
Supplement 1, pp S54-S64, 2009. www.canmat.org
Audit Form -- Best Practices Course
Evidence-based Management of SAD: Focus on Light Therapy
Pull the charts of the last 10 patients whom you have seen in the past 12 months for
whom you have made the diagnosis of depressive disorder or seasonal affective disorder.
Note: Bold items refer to follow-up care; all other items refer to initial assessment.
Behaviour
Yes
Diagnosis
1. Checked for atypical features?
2. Checked for recurrent seasonal episodes?
3. Checked for summer remissions?
4. Checked for regular seasonal psychosocial stressors?
5. Checked for eating disorders?
6. Checked for summer hypomania/mania?
7. Checked for winter worsening of depression?
8. Checked relevant laboratory tests, e.g., TSH?
No
For Optimal
Management:
Total:
All 8 items should be
checked YES
Total:
At least 10 items should
be checked YES:
Total:
All 4 items should be
checked YES
Management – Light Therapy
1. Discussed light therapy?
2. Warned against suntan studio use?
3. Checked for retinal and systemic risk factors?
4. Advised light therapy with 10,000 lux light box?
5. Checked specifications of light box used?
6. Discussed reimbursement issues re: light boxes?
7. Advised light therapy for at least 30 minutes per day?
8. Advised light therapy in early morning?
9. Advised light therapy daily for at least 2 weeks?
10. Checked for side effects to light therapy?
11. Checked response to light therapy?
12. Used a rating scale to check response?
13. Advised when to stop light therapy in the spring?
14. Advised when to restart light therapy next season?
Management – Antidepressants (if applicable)
1. Checked whether antidepressant medication needed?
2. Used an SSRI (fluoxetine, sertraline) as first-line medication?
3. Checked side effects/response to antidepressant?
4. Advised when to stop antidepressant?
Management – Combined Light Therapy/Antidepressant (if applicable)
1. Used monotherapy before using combination therapy?
2. Used combined light therapy/antidepressant?
3. Checked side effects/response to light therapy/antidepressant?
Total:
At least 2 items should
be checked YES
Annals of Clinical Psychiatry, 19[4]:239–246, 2007
Copyright © American Academy of Clinical Psychiatrists
ISSN: 1040-1237 print / 1547-3325 online
DOI: 10.1080/10401230701653476
Seasonal Affective Disorder:
A Clinical Update
UACP
ÅSA WESTRIN, MD, PHD
Seasonal Affective Disorder: A Clinical Update
Department of Clinical Sciences, Division of Psychiatry, Lund University Hospital, Lund, Sweden
Downloaded By: [Canadian Research Knowledge Network] At: 20:59 31 October 2008
RAYMOND W. LAM, MD, FRCPC
Division of Clinical Neuroscience, Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
Background. Seasonal affective disorder (SAD) consists of recurrent major depressive episodes in the fall/winter with
remissions in spring/summer.
Method. A Medline search was conducted to identify studies relating to clinical management of SAD using the Medical
Subject Heading, seasonal affective disorder, and key words, depress* and season*, focusing on studies published in the
past 10 years. The Cochrane library of systematic reviews was also searched for relevant studies.
Results. A careful history is important to make the diagnosis and differentiate SAD from other similar conditions such as
subsyndromal SAD and atypical depression. Seasonal patterns with winter worsening are also recognized in “nonseasonal”
depression as well as many other psychiatric conditions, and comorbidity with SAD is common. The pathophysiology of SAD
seems to be heterogeneous as research on circadian, neurotransmitter function and genetic hypotheses have shown discrepant
results. A dual vulnerability model with differential loading on separate seasonal and depression factors has been proposed to
explain these findings. Recent systematic reviews have shown that light therapy is an efficacious and well-tolerated treatment for
SAD. There is also evidence for efficacy of pharmacotherapy to treat and prevent SAD. Clinical studies show equal effectiveness
with light and antidepressants, so patient preference should be considered in the selection of initial treatment. Dawn stimulation,
negative air ions, exercise and cognitve behaviour therapy are under investigation and may also be helpful treatments for SAD.
Conclusions. SAD is a common condition with significant psychosocial impairment. Clinicians should be vigilant in
recognizing seasonal patterns of depressive episodes because there are effective, evidence-based treatments for SAD.
Keywords Seasonal affective disorder, Depression, Light, Seasons, Diagnosis
INTRODUCTION
The identification of seasonal patterns for mood disturbances
dates back to ancient times, with astute medical observers such as
Hippocrates, Pinel, and Kraepelin reporting clear recurrent winter
depressive episodes in some of their patients (1). The first systematic description of seasonal affective disorder (SAD) in 1984
(2) led to the development of bright, artificial light, or light therapy, as a treatment. In the past two decades, the concept of SAD
has captured media and public interest, while at the same time
provoking some skepticism amongst some in the medical community. Recent systematic reviews have demonstrated that light
therapy is a safe, well-tolerated and effective treatment for winter
Address correspondence to Dr. Raymond W. Lam, Department of
Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver,
B.C., Canada V6T 2A1. E-mail: [email protected]
depression, but advances in chronobiology and genetics have
suggested that the pathophysiology of SAD and the mechanism
of light therapy may be more complex than previously thought.
For this review, we identified relevant clinical studies of
SAD by conducting an electronic search on Medline using
the Medical Subject Heading, seasonal affective disorder, and
the key words, depress* and season*. We also searched the
Cochrane library of systematic reviews for relevant studies. In
this article, we focus on recent findings within the past 10
years and their importance to the clinical management of SAD.
DIAGNOSIS
The first criteria for the diagnosis of winter SAD were described
by Rosenthal and colleagues (2). The diagnostic criteria have since
been revised and narrowed but they have basically remained the
239
240
Å. WESTRIN AND R.W. LAM
Table 1 DSM-IV Criteria for Seasonal Pattern of Major Depressive Disorder
(Recurrent Major Depressive Disorder, Bipolar I Disorder or Bipolar II Disorder)
A. There has been a regular temporal relationship between the onset of major
depressive episodes and a particular time of the year.
B. Full remissions (or change from depression to mania or hypomania) also
occur at a characteristic time of the year.
C. In the last two years, two major depressive episodes have occurred that
demonstrate the temporal seasonal relationships defined in criteria A and B,
and no nonseasonal major depressive episodes have occurred during the
same period.
D. Seasonal major depressive episodes (as described above) substantially
outnumber the nonseasonal major depressive episodes that may have
occurred over the individual’s lifetime.
One of the difficulties in making the diagnosis of SAD is
that the diagnosis rests on the patient’s retrospective history.
Despite the presence of physical symptoms, medical examination and laboratory studies are routinely normal in SAD.
A helpful clinical characteristic of SAD is a positive mood
response to increased (usually outdoor) light exposure and to
winter travel to more southerly latitudes. Collateral information from family and/or friends may also help with diagnosis.
A prospective spring/summer evaluation for hypomania is very
informative in supporting a bipolar diagnosis.
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Symptom Profile
same: a regular temporal relationship between the onset of major
depressive episodes during the fall/winter period, and an occurrence of full remission (or change from depression to mania or
hypomania) of symptoms during the spring/summer period.
In DSM-IV, SAD is defined as a specifier of recurrent major
depressive episodes (Table 1). This seasonal pattern specifier
can be applied to recurrent major depressive disorder (MDD) or
to bipolar I or II disorder. Some patients with SAD may experience nonseasonal depressive episodes (e.g., a winter episode
that extends into the summer months) during their lifetime, but
these must be substantially less common than the seasonal
episodes. The DSM-IV criteria also require that the last two
seasonal depressive episodes occur in consecutive winters, but
this criterion is controversial because it is not evidence-based.
Other explanations for seasonal patterns of depressive episodes,
such as regularly recurring psychosocial stressors such as winter unemployment and holidays, must be ruled out.
To diagnose SAD, it is important to carefully determine the
time of onset and offset of previous depressive episodes, and to
ensure that patients have full remission in summer. Many patients
with nonseasonal depressions (including dysthymia and chronic
MDD) may experience winter worsening of their symptoms, but
they can be differentiated from those with SAD because they are
still symptomatic in the summer. Up to 20% of patients with SAD
will have bipolar I or II disorder (3), so it is also important to identify spring or summer hypomania/mania. A follow-up reassessment in summer can help to identify these bipolar patients, as they
may not retrospectively recognize hypomanic symptoms.
SAD versus Seasonality
There is some debate as to whether SAD is a categorical
diagnosis or an extreme form of a dimensional seasonality
trait. Some people have marked symptoms (especially the vegetative symptoms described below) during the winter, but not
to the point where they meet criteria for MDD, or what is
termed “subsyndromal” SAD (4). People with subsyndromal
SAD may still experience significant distress and impairment
of function (5), and they may also respond to the same treatments as SAD (6).
Patients with SAD may suffer from general symptoms of
depression including diminished pleasure or interest, psychomotor agitation or retardation, loss of energy, feelings of
worthlessness or excessive or inappropriate guilt, diminished
ability to think or concentrate, indecisiveness, or recurrent
thoughts of death. A somatic symptom such as pain is often the
presenting complaint at visits to general practice.
The majority of SAD patients report at least one of the
“atypical” depressive symptoms associated with SAD such as
fatigue, hypersomnia, increased appetite and weight gain,
although some patients report reduced appetite, insomnia and
weight loss. The increased appetite is typified by carbohydrate
craving for sugars and starches that is often described as
uncontrollable. Binge type eating can occur, although purging
behaviors are uncommon. The increased eating and reduced
activity usually leads to significant weight gain. With initial
winter episodes patients lose the weight during the summer
months when their appetite returns to normal and they are more
active. However, with increasing age it becomes more difficult
to shed the winter weight gain and there is a gradual year round
increase in weight.
The presence of these atypical features has led some investigators to suggest that SAD may be a form of atypical depression, another episode specifier that is characterized by mood
reactivity, a marked but temporary improvement in mood in
response to favorable external circumstances. However, studies have shown that patients with SAD do not have higher rates
of mood reactivity, leaden paralysis or rejection sensitivity
than do nonseasonal depressed patients (7). Therefore the overlap between the two subtypes appears to be limited to the atypical vegetative symptoms. Of interest is that these atypical
symptoms, particularly the overeating, predict good response
to light therapy (8).
Differential Diagnosis
The differential diagnosis of SAD is similar to that of MDD
in general. Physical illnesses such as hypothyroidism need to
be ruled out, as do other conditions such as phase delayed sleep
disorder and anniversary grief reactions. Mixed conditions and
annals of clinical psychiatry
vol. 19 no. 4 2007
SEASONAL AFFECTIVE DISORDER: A CLINICAL UPDATE
comorbidity should be considered, especially since seasonal
patterns are becoming increasingly recognized in other psychiatric conditions including bulimia nervosa, premenstrual
depressive disorder, panic disorder, obsessive compulsive
disorder, post traumatic stress disorder and attention deficit
hyperactivity disorder (9–11). The lifetime prevalence of anxiety disorder (generalized anxiety disorder, simple phobia,
social phobia) in patients with SAD is also high, though perhaps not different from that seen in nonseasonal MDD (12).
Furthermore, premenstrual depressive disorder has been
reported to be much more common in SAD patients than in
comparison subjects (13).
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EPIDEMIOLOGY
Many epidemiological studies have reported prevalence
rates for SAD as high as 10% (14), but most of these studies
were not conducted in general population samples and were
based on the Seasonal Pattern Assessment Questionnaire
(SPAQ), a retrospective self-report questionnaire that assesses
seasonality rather than the diagnosis of SAD (15). The more
rigorous studies of large community samples using diagnostic
interviews and DSM criteria have found prevalence rates for
SAD of 0.4% in the United States (16) and 1.7% to 2.9% in
Canada (17;18). SAD appears linked to photoperiod (the light/
dark cycle) since the prevalence of SAD is correlated with latitude (i.e., more northerly latitudes have shorter winter days)
(19) but not to other environmental factors such as temperature, sunshine hours, cloud cover, snowfall, etc., especially in
North American studies (for reviews, see (14,20))
ETIOLOGY
The major theories explaining the pathophysiology of SAD
have recently been reviewed (21,22) and include circadian,
neurotransmitter function, and genetic hypotheses. The most
prominent of the circadian rhythm hypotheses is the phase shift
hypothesis (23), which suggests that SAD is associated with an
abnormal phase delay of the internal circadian rhythms relative
to the external clock. In this hypothesis, light therapy timed in
the morning would exert a corrective phase-advance of circadian rhythms. Support for the phase-shift hypothesis includes
recent studies suggesting an optimal circadian timing for light
therapy (24) and beneficial effects of circadian phase-shifting
doses of melatonin in patients with SAD (25). However, studies using rigorous methodologies for examining circadian
rhythms have not found evidence for circadian dysregulation in
patients with SAD (22) and many treatment studies have not
found correlation of therapeutic response with circadian phaseshifts following treatment (e.g., (26)).
Research examining the monoamine hypothesis has focused
on serotonin as there is clear seasonal variation in brain and
peripheral serotonin in healthy people, e.g., serotonin turnover
241
and hypothalamic serotonin transporter sites are lower in winter than in summer (27,28). Several studies show that tryptophan depletion can reverse the antidepressant effect of light
therapy, suggesting that the therapeutic effect of light involves
a serotonergic mechanism (29,30). However, other reports
implicate catecholamines in the pathogeneses of SAD, e.g., retinal light sensitivity (which is dependent on retinal dopamine
function) is lower in SAD patients than in healthy controls (31)
and catecholamine depletion can also reverse the effects of
light therapy (32).
Genetic studies have also focused on monoamine-related
genes in SAD and seasonality. Promising candidate genes
include 5 HT2A (33–35), 5-HT2C (36) and the dopamine-4
receptor (DRD4) (37). G protein (38,39) and clock-related
genes (40) have also been investigated. However, these smallsample association studies are at risk for false-positive results,
and as yet there are few replicated findings in the field.
These discrepant results are likely related to heterogeneity in
the pathophysiology of SAD and may be explained by a dual
vulnerability model that was first proposed by Young et al. (41)
and subsequently expanded upon by Lam et al. (6). According to
this hypothesis, seasonality and SAD may be phenotypically
expressed via differential loading on separate seasonal and
depression factors with different mechanisms. For example, the
seasonal factor may have a circadian mechanism while the
depression factor may be related to monoamine dysregulation.
Alternatively, the depression factor may reflect psychological
vulnerability (41), such as neuroticism. A recent study (42) suggested that vulnerability to distress symptoms in response to seasonal physiological changes is associated with neuroticism, so
that individuals with high levels of seasonality but too high of a
loading on the depression factor (neuroticism) may not show a
pattern of SAD because their higher level of vulnerability to distress may manifest as non-seasonal depressive episodes.
TREATMENT
Light Therapy
Although light treatment for SAD is closely intertwined
with the original description of the syndrome, its efficacy has
been questioned. There have been dozens of positive efficacy
studies of light therapy, but the results are clouded by methodological weaknesses in study designs. For example, there has
been a lack of an accepted standard for adequate dosing of light
treatment and for credible placebo conditions.
However, two recent systematic reviews have rigorously
addressed the efficacy question. The first used Cochrane Collaboration methodology to review 14 randomized controlled trials (RCTs) of light therapy versus control conditions (43). The
second was commissioned by the Council on Research of the
American Psychiatric Association (APA) (44). The authors
identified 50 RCTs, of which eight studies meeting strict methodological criteria were included in the meta-analysis. Both
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242
Å. WESTRIN AND R.W. LAM
meta-analyses found that bright light was superior to credible
control conditions, with an odds ratio of 2.83 (indicating almost
3 times better odds of achieving response with light therapy)
and an effect size of 0.83 (indicating a medium to large treatment effect), respectively. These results show that the therapeutic effects of light therapy are equal to, or larger than, those
found in most antidepressant pharmacotherapy trials.
In clinical practice the preferred device for light therapy is the
fluorescent light box that produces light intensities of greater than
2,500 lux. Lux is a unit of illumination intensity that corrects for
the phototopic spectral sensitivity of the human eye. For comparison, indoor evening room light is usually less than 100 lux while a
brightly lit office is less than 500 lux. In contrast, outdoor light is
much brighter: a cloudy grey winter day is around 4,000 lux and a
sunny day can be 50,000 to 100,000 lux or more. Newer light
devices under investigation use light-emitting diodes (LEDs) that
allow much smaller and more portable fixtures.
Table 2 summarizes a standard protocol for light therapy
that is recommended in clinical practice guidelines (45) and
that in naturalistic clinical use has resulted in response rates of
65% or higher (6). Patients should be instructed to properly
position themselves and maintain a correct distance to the light
source. They have to be awake with their eyes open during
light exposure, but they are not required to look directly at the
light source, i.e., they can read or eat during the light treatment.
The standard “dose” of light is 10,000 lux for 30 minutes per
day. There appears to be a relationship between intensity and
duration of exposure, so that light boxes rated at 2,500 lux
require 2 hours of daily exposure for the same response. Light
therapy is usually administered in the early morning as soon as
possible upon arising, e.g., at 7:00 am or earlier, because most
studies and meta-analyses have found that early morning
exposure is superior to other times of the day (46).
The onset of action of light therapy is usually rapid with significant clinical improvement found in studies of 1 or 2 weeks’
duration. However, individual patients may require 2–3 weeks
to show clear responses to light therapy. When light therapy is
discontinued, most patients will relapse after a similar period
of a couple of weeks. Patients are therefore advised to use light
therapy regularly during their symptomatic winter season until
the time of their usual spring summer remission. Once patients
have remitted they can often experiment with individual dosing
Table 2
Bright Light Therapy: Summary of Method
• 10,000 lux white, fluorescent light; no ultraviolet wavelengths
• 30 minutes/day in the early morning, upon arising
• Stay awake, with eyes open; not necessary to stare at the light, so may eat
and/or read
• Determine response after 2–3 weeks
• After remission, individualize dosing during the rest of the winter season
• Initiate treatment in early autumn in following years to avoid relapses
• In patients with retinal risk factors, obtain baseline eye examinations and
monitor during treatment
• In patients with bipolar I disorder, maintain on a mood stabilizer
required to stay well. Thus, they may be able to maintain their
response while reducing the daily time of exposure to 15 or 20
minutes, or by using the light box on weekdays only. In subsequent years, patients may need to begin light treatments in the
early autumn before the onset of symptoms to avoid any gradual impairment of function (47).
Side effects to light therapy are generally mild and transient
and include headache, nausea, eyestrain, blurred vision and
agitation (Table 3) (46). Bright light exposure in the later
evening may also interrupt onset and maintenance of sleep. As
Table 3 Reported Adverse Effects of Light Therapy (10,000 Lux Fluorescent
Light Box, 30 Minutes/Day) for SAD. Only Side Effects Reported in More
Than 5% of Treated Patients Are Shown
Study:
Length of treatment
Emergent Side Effect
Gastrointestinal
Abdominal discomfort/pain
Nausea/vomiting
Diarrhea
Constipation
Appetite/weight
Decreased appetite
Increased appetite
Weight loss
Weight gain
Central nervous system
Headache
Fatigue/weakness
Increased sleep
Decreased sleep
Overactive/excited/agitated
Anxiety
Sexual dysfunction
Decreased sexual interest
Increased sexual interest
Difficulties with orgasm
Difficulties with erection
Eyes/Ear/Nose/Throat
Eye or vision problem
Mouth sores
Nasal congestion
Dry mouth/throat
Chest
Shortness of breath
Coughing
Breast tenderness
Other
Muscle/bone/joint pain
Fever/chills
Sweating/Flushing
Feeling faint
Kogan &
Guilford,
1998 (62)
Terman &
Terman,
1999*(63)
Lam et al.
2006*(57)
4 to 10 days,
N = 70
%
10 to 14 days,
N = 83
%
8 weeks,
N = 48
%
7
21
6
6
3
10
16
13
2
6
4
4
8
19
15
19
10
15
8
2
8
3
9
7–14
9–10
5
7
18
6
5
19
4–6
8
12
4–8
17
8–17
13
23
13
15
5
19
6
15
6
8
7
13
6
6
*Unlike most clinical trials that depend on spontaneous patient reports, these
studies used systematic questionnaires to detect treatment-emergent adverse
events.
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SEASONAL AFFECTIVE DISORDER: A CLINICAL UPDATE
with any effective antidepressant, light therapy carries a risk
for precipitating hypomanic or manic episodes in susceptible
individuals. Therefore, patients with bipolar I disorder (with
manic episodes) should be on mood-stabilizing medications if
light therapy is used.
There are no absolute contraindications to light therapy
(although retinopathies are a relative contraindication) and no evidence that light therapy is associated with ocular or retinal damage
with current dosing guidelines (48). However, caution should be
applied when treating patients at higher theoretical risk for bright
light-induced eye toxicity (49). This includes patients with pre
existing retinal disease (such as retinitis pigmentosa) or systemic
illnesses that involve the retinal (such as diabetes), and those taking photosensitizing medications (such as lithium, phenothiazine
antipsychotics, melatonin, and St. John’s wort). For these higherrisk patients, an ophthalmologic examination is recommended
before starting light therapy as well as regular follow-up exams.
Some hospitals and outpatient clinics in Europe have designed
light therapy rooms for patient use, but as most clinical studies use
home treatment, which is much more convenient for patients, the
necessity of light therapy rooms is not clear. Many web sites now
offer helpful advice and resource materials for the clinical use of
light (e.g., UBCsad.ca, SLTBR.org, CET.org).
Pharmacotherapy
There have been fewer RCTs on pharmacotherapy for SAD
(Table 4). Selective serotonin reuptake inhibitors (SSRIs),
especially fluoxetine (20 mg/day, (50) and sertraline (50–200
mg/day, (51)), have the best evidence for efficacy, but likely
Table 4
243
other antidepressants are also efficacious for acute treatment.
A large clinical trial also found that citalopram (20–40 mg/day)
was superior to placebo in preventing relapse after one week of
treatment with light therapy (52).
In the only antidepressant prevention trial to date, patients
with a history of SAD (N = 1042) were randomized to bupropion-XL (300 mg/day) or placebo starting early in autumn and
followed throughout the winter (53). Recurrence of winter
depressive episodes was significantly lower in the bupropion
group (15.7% vs. 28%, respectively). However, it should be
noted that the recurrence rate of SAD in this study was low
overall, even in the placebo-treated group.
Open-label studies suggest that other medications may also
be beneficial in SAD. These include antidepressants such as
reboxetine, a selective inhibitor of noradrenaline reuptake (54),
and moclobemide, a reversible inhibitor of monoamine oxidase
A (55). The wake-promoting agent, modafinil, was also reported
to significantly reduce fatigue in patients with SAD (56).
Light versus Antidepressants
One criticism of light therapy research has been the lack of
comparisons with antidepressant medications. A recent study
directly compared the two treatments in a “double-dummy”
design, in which patients with SAD (N = 96) were randomly
assigned to 8 weeks of double-blind treatment with either
10,000 lux (active) light treatment plus a placebo capsule, or
100-lux (placebo) light treatment and fluoxetine, 20 mg/day
(57). Both groups improved during the 8 weeks with no significant differences between the two in reduction of depression
Studies on Pharmacotherapy of SAD. Statistically Significant Differences in Efficacy are Indicated by “ > ”
Antidepressant(s)
Study design (N = number of patients)
Outcome
Authors
Fluoxetine
vs. placebo, RCT, 5 weeks, N = 68
• Fluoxetine = placebo in reducing depression scores
• Fluoxetine > placebo in response rates
• Fluoxetine = moclobemide in reducing depression
scores and in remission rates
• Fluoxetine = light therapy in reducing depression
scores and in response rates
• Fluoxetine = light therapy in reducing depression scores
• Trend to superiority of fluoxetine in response rates
• Sertraline > placebo in reducing depression scores and
in response rates
• Following 1 week of successful light therapy,
citalopram > placebo in preventing relapse
• Bupropion > placebo in preventing seasonal depressive
episode
• Improvement with all antidepressants
Lam et al. (50)
vs. moclobemide, RCT, 6 weeks, N = 32
vs. bright light, RCT, 8 weeks, N = 96
vs. bright light, RCT, 5 weeks, N = 40
Sertraline
vs. placebo, RCT, 8 weeks, N = 187
Citalopram
vs. placebo, RCT, 15 weeks, N = 282
Bupropion
vs. placebo, prevention RCT, N = 1042
Bupropion, desipramine,
tranylcypromine
Reboxetine
Moclobemide
Case series, open-label treatment, N = 47
Case series, open-label treatment, N = 16
vs. placebo, RCT, 3 weeks, N = 34
Hypericum (St. John’s wort)
vs. light therapy, RCT, 4 weeks, N = 20
Modafinil
Case series, open-label treatment, N =13
• Improvement with reboxetine
• Moclobemide = placebo in reducing depression scores,
but > placebo in reducing atypical symptoms
• Hypericum = hypericum+bright light in reducing
depression scores
• Improvement with modafanil
annals of clinical psychiatry
vol. 19 no. 4 2007
Partonen and
Lönnquist (64)
Lam et al. (57)
Ruhrmann et al. (65)
Moscovitch et al. (51)
Martiny et al. (52)
Modell et al (66)
Dilsaver et al. (67)
Hilger et al. (54)
Lingjaerde et al. (55)
Martinez et al. (68)
Lundt (56)
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Å. WESTRIN AND R.W. LAM
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scores, clinical response rates (67% for both groups) or remission rates (50% for light treatment and 54% for fluoxetine).
Light therapy showed earlier onset of response (at 1 week) and
lower rates of some adverse events (agitation, sleep disturbance and palpitations) relative to fluoxetine, but both treatments were well-tolerated overall. In the subgroup of patients
with greater severity of depression at baseline, there were again
no differences in the efficacy or response/remission rates
between light and fluoxetine.
These findings suggest that other factors, including patient
preference, should be used to guide decisions about light or
drugs as first-choice treatment. And, although there are as yet
limited data on the combination, many patients with SAD use
both light and antidepressant medication for optimal benefit.
CONCLUSIONS
The diagnosis of SAD can be made by taking a careful
history of recurrent winter depressive episodes and ruling
out other diagnoses. Although the etiology and pathogenesis
of SAD remain unclear, the high prevalence of SAD (0.4%
to 2.9%) makes it a significant health problem, particularly
in northern countries. Light therapy is an evidence-based,
effective, well-tolerated treatment for SAD, while antidepressant medications also have demonstrated efficacy. For
many patients, the choice of light or drug (or the combination) will depend on personal preference. Research in
progress on newer treatments, including smaller and more
efficient light devices, dawn simulation, negative ions,
exercise, and CBT, may expand the options for people with
winter depression.
Other Treatments
In addition to bright light and pharmacotherapy, other treatments under investigation may be beneficial for SAD. These
include dawn simulation, negative air ionization, exercise and
cognitive behaviour therapy (CBT).
Dawn simulation imitates the natural summer dawn signal
by gradually increasing ambient bedroom illumination while
the patient is sleeping. An electronic dawn simulation device
controls a bedside lamp that turns on about 90 minutes before
the desired wake time and reaches a final illumination of 250
lux, which continues until the patient arises. In the systematic
review by the APA, five dawn simulation studies included in a
meta-analysis showed a medium-to-large effect size of 0.73
favoring dawn simulation over placebo conditions (44). However, the total number of patients in the meta-analysis was
small and the positive results came from one centre, so these
results need further replication.
Negative air ionization is a new treatment and the mechanism of action is still poorly understood. In patients with
SAD (N = 158), the antidepressant effects of high-density
negative ions were not significantly different from those of
bright light (58); therapeutic effects have also been observed
in patients with chronic (nonseasonal) depression (59).
Another study compared the effects of physical exercise and
bright light in age-matched groups of female patients (60).
The women with winter depression (N = 27) responded
equally well to both exercising and light, while exercising
was superior to light in patients with nonseasonal depression
(N = 18).
A 6-week pilot study of 23 patients with SAD compared a
standard light therapy protocol, a novel, SAD-tailored, group
CBT intervention, and the combination (61). All conditions
demonstrated significant but similar reductions in depressive
symptoms and good remission rates. However, during the subsequent winter naturalistic follow-up, patients who had CBT,
particularly in combination with light therapy, had better outcomes as measured by symptom severity, remission rates, and
relapse rates.
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annals of clinical psychiatry
vol. 19 no. 4 2007
CME
3
Review Article
CME
Update on the Biology of
Seasonal Affective Disorder
By Chang-Ho Sohn, MD, and Raymond W. Lam, MD, FRCPC
Accreditation Statement
Mount Sinai School of Medicine is accredited by the Accreditation
Council for Continuing Medical Education to provide Continuing
Medical Education for physicians.
Mount Sinai School of Medicine designates this educational
activity for a maximum of 3.0 Category 1 credit(s) toward the AMA
Physician’s Recognition Award. Each physician should claim only
those credits that he/she actually spent in the educational activity.
Credits will be calculated by the MSSM OCME and provided for the
journal upon completion of agenda.
It is the policy of Mount Sinai School of Medicine to ensure
fair balance, independence, objectivity and scientific rigor in all its
sponsored activities. All faculty participating in sponsored activities
are expected to disclose to the audience any real or apparent discussion of unlabeled or investigational use of any commercial product
or device not yet approved in the United States.
This activity has been peer-reviewed and approved by
Eric Hollander, MD, professor of psychiatry, Mount Sinai School of
Medicine. Review Date: June 10, 2005.
Needs Assessment
A comprehensive review of studies on the pathophysiology of
seasonal affective disorder (SAD) was published in 2000. Since
then, researchers have documented many new findings that clarify
several biological hypotheses in SAD, including studies of circadian rhythms, neurotransmitter function, and molecular genetics.
Clinicians will be better able to diagnose and treat patients with
SAD by understanding these latest theories of the biology of SAD.
Learning Objectives
At the end of this activity, the participant should be able to:
• Compare and contrast the evidence to support circadian
rhythm theories of SAD.
• Describe the data supporting neurotransmitter theories
of SAD.
• Summarize the findings from gene association studies
of SAD.
• Identify methodological and integrative issues in the biological study of SAD.
To Receive Credit for This Activity
Read this article, and the two CME-designated accompanying
articles, reflect on the information presented, and then complete
the CME quiz found on pages 672 and 673. To obtain credits, you
should score 70% or better. Termination date: August 31, 2007.
The estimated time to complete this activity is 3 hours.
Target Audience
Neurologists and psychiatrists
ABSTRACT
The etiology and pathophysiology of seasonal affective disorder (SAD) has been linked to the seasons and
to light since its first conceptualization. Aspects of SAD
that make it particularly amenable to biological investigation include the predictable recurrent episodes, the rapid
response to a nonpharmacologic treatment, the specific
neurovegetative features, and the availability of rich animal models of seasonality. This paper reviews new findings for the major biological hypotheses for SAD, focusing
on circadian rhythms, neurotransmitters, and molecular
genetics. Integrative issues and future directions for the
study of SAD, including the heuristic value of a dual-
vulnerability hypothesis that conceptualizes seasonality as
a dimensional construct and the importance of studying
endophenotypes, will be discussed.
CNS Spectr. 2005;10(8):635-646
INTRODUCTION
All living organisms are influenced by the seasons. The degree of seasonal change in mood and
behavior is termed “seasonality” 1 while seasonal
affective disorder (SAD) is usually considered to be
at the extreme end of the spectrum of seasonality.2
In the Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition,3 winter SAD is concep-
Dr. Sohn is clinical fellow at the Mood Disorders Centre at the University of British Columbia Hospital and Vancouver Coastal Health Research
Institute, both in Vancouver, British Columbia, Canada. Dr. Lam is professor in the Department of Psychiatry, head of the Department of
Psychiatry’s Division of Clinical Neuroscience, and director of the Mood Disorders Centre at the University of British Columbia.
Disclosure: Dr. Sohn does not have an affiliation or financial interest in any organization that might pose a conflict of interest. Dr. Lam is on the advisory boards of Biovail Canada, the Canadian Network for Mood and Anxiety Treatments, Eli Lilly Canada, GlaxoSmithKline Canada, Litebook,
Lundbeck Canada, Shire Canada, and Wyeth Canada; and has received research support from AstraZeneca Canada, the Canadian Institutes
of Health, Eli Lilly Canada, Janssen Canada, Lundbeck Canada, Merck Canada, Roche Canada, Servier Canada, the Vancouver Hospital
Foundation of Health Research, and Wyeth Canada. This article was submitted on January 4, 2005, and accepted on June 17, 2005.
Please direct all correspondence to: Raymond Lam, MD, FRCPC, Division of Clinical Neuroscience, Department of Psychiatry, University of British
Columbia, 2255 Westbrook Mall, Vancouver, BC, Canada V6T 2A1; Tel: 604-822-7325, Fax: 604-822-7922; E-mail: [email protected].
Volume 10 – Number 8
635
CNS Spectrums – August 2005
CME
Review Article
tualized as a seasonal pattern of recurrent major
depressive episodes during the fall/winter in the
absence of seasonal psychosocial stressors, with full
remission of symptoms in spring/summer. This seasonal pattern can be applied to both unipolar major
depressive disorder (MDD) and bipolar disorder.
Based on DSM criteria, the prevalence of SAD
in epidemiological studies has been estimated at
0.8% to 2.8% in North America,4,5 but the prevalence of significant seasonality (or “subsyndromal
SAD”) is likely much higher, with estimates of
15% to 25% in the global population.6 In addition
to seasonality, SAD has two prominent characteristics: so-called atypical depressive symptoms
and responsiveness to light treatment. Most
patients with SAD experience atypical symptoms
including increased need for sleep, carbohydrate
craving with increased appetite and weight, and
extreme fatigue. These symptoms, which are
similar to seasonal changes in behavior shown by
many mammals in response to winter, might be a
human expression of a basic evolutionary process
to achieve maximum conservation of energy during winter.7 The other important characteristic of
SAD is the response to exposure to bright light,
known as light therapy or phototherapy.
There are four specific aspects to SAD that make
it particularly of interest for biological investigation. The first is the seasonality of the condition.
The predictable onset and offset of winter episodes
allow the investigation of biological parameters at
different stages of the disorder, from acute illness
to natural remission and vice versa. The second
aspect is the rapid response to light therapy. This
nonpharmacologic treatment allows comparison of
the treated state to the natural, untreated summer
remission state. The third aspect is the specificity of
the neurovegetative symptoms of SAD (eg, extreme
fatigue, hypersomnia, and increased appetite).
These symptoms contrast to those of other types
of mood disorders (eg, melancholic depression)
and may be especially important when comparing SAD to other psychiatric conditions in which
similar symptoms are prominent, such as atypical
depression and certain sleep and eating disorders.
Finally, there is a rich abundance of animal models
of seasonality to develop and test specific biological
hypotheses about SAD.
In 2000, Lam and Levitan 8 comprehensively
reviewed the pathophysiology of SAD focusing on
evidence for and against the major hypotheses: circadian rhythms, neurotransmitter function, and
genetics. In the current article, we update the review
Volume 10 – Number 8
with new data from the past 5 years of studies of SAD
and its response to light therapy. We also highlight
some important integrative issues and future directions for the study of SAD and seasonality.
CIRCADIAN RHYTHMS
In humans, the central pacemaker that entrains
internal circadian rhythms to synchronize with
external time cues (zeitgebers) is located in the
suprachiasmatic nucleus (SCN) of the hypothalamus. Light, the most powerful zeitgeber, is
conveyed to the SCN through the eyes via the retinohypothalamic tract. A complex neural pathway
links the SCN to the pineal gland, where melatonin is secreted under influence of both the SCN
(a circadian mechanism) and external light exposure (a direct suppression effect). In many animals,
melatonin is a mediating hormone between light
and seasonal behavior.
Melatonin displays a robust circadian rhythm
with high levels secreted at night and low plasma
levels present during the day. The circadian rhythm
phase of melatonin can be described by the usual
time at which the melatonin level begins to rise at
night, usually around 8:00 PM, collected under dim
light conditions to prevent any direct suppressant
effects of light exposure. This is known as the dim
light melatonin onset (DLMO).
Light can predictably shift circadian rhythms,
with the direction and magnitude of phase shift
dependent on when the light exposure occurs
in the circadian cycle. For example, bright light
exposure in the late evening can delay the circadian rhythm of melatonin (ie, the DLMO occurs
at a later time each day, such as 10:00 PM), while
morning light exposure results in phase advance of
the melatonin rhythm (ie, the DLMO occurs at an
earlier time than usual, such as 8:00 PM) (Figure 1).
The phase shift of one circadian rhythm (eg, melatonin) can change the time interval to another
circadian rhythm (eg, sleep-wake cycle), the socalled phase angle. Figure 1 illustrates an example
of phase shift of DLMO causing a change in phase
angle with waking time.
Circadian rhythm theories, 2 including photoperiod and phase-shift hypotheses, initiated the
study of SAD and the use of light treatment in
depression and other psychiatric conditions. These
hypotheses remain prominent in the pathophysiology of SAD and seasonality, but there are also
other recent circadian findings in SAD,9,10 such as
disturbances in thermoregulation and electroencephalographic slow-wave sleep.
636
CNS Spectrums – August 2005
Review Article
Photoperiod Hypothesis
Phase-Shift Hypothesis
In contrast to photoperiod, the phase-shift
hypothesis as first proposed by Lewy and colleagues24 states that SAD results from internal circadian rhythms that are phase delayed relative to
the external clock or to other rhythms, such as the
sleep-wake cycle. According to this hypothesis, light
therapy exerts its effect by correcting the abnormal
phase delay. Morning light exposure that results in
phase advance of circadian rhythms should therefore show superior effectiveness to that of evening
light, which induces a further phase delay.
The phase-delay hypothesis has proven to be
one of the most robust theories of SAD, but also,
because of some conflicting findings, the most
controversial. In part, this is due to the difficulty
in studying circadian rhythms in humans due to
masking effects of external zeitgebers including
light exposure, sleep, and activity. As previously
reviewed,8 no phase differences were observed in
patients with SAD in 24-hour rhythms of melatonin, cortisol, prolactin, thyrotropin, and body
temperature, 25-27 although these rhythms may be
influenced by masking effects. Studies28-31 using the
DLMO, a marker of circadian phase that is relatively
Rosenthal and colleagues2 first suggested that the
shorter winter photoperiod (light/dark cycle) might
induce depression. There have been three lines of
investigation to verify the photoperiod theory.11 The
first involves studies correlating the prevalence of
SAD with increasing latitude, since photoperiod is
directly influenced by latitude (eg, the winter days
are shorter at more northerly latitudes). The results of
numerous epidemiological studies have been inconsistent, in part due to methodological limitations of
the various studies. The most rigorous studies4,11 did
not find correlations of prevalence of SAD with latitude, although the range of latitude studied was small.
Reviews6,12 summarizing the more methodologically
sound studies have shown that there does appear to
be a relationship between SAD and latitude, but this
effect is complex and relatively weak.
Since melatonin is only secreted in the dark, the
duration of melatonin secretion acts as a signal for
photoperiod for many mammalian circadian systems.13
Previous studies8 of melatonin as a hormonal indicator of photoperiod showed conflicting results in SAD.
Recently, Wehr and colleagues14 measured the duration of melatonin secretion in constant dim light in
55 patients with SAD and matched healthy control
subjects. While there were no significant differences in
the duration of melatonin secretion between the two
groups in winter, the patients with SAD had a significant seasonal variation with longer melatonin duration in winter than in summer. This suggests that only
people with SAD respond to photoperiod in a manner similar to other mammals, while healthy people
seem to have lost this seasonal time signal. Potential
mechanisms to explain this finding include seasonal
differences in the experience of natural or artificial
light exposure,15,16 differences in retinal sensitivity to
light,17-19 or differences within the neural pathways of
the circadian system (eg, abnormal clock genes).
The third line of investigation involves the
mechanism of light treatment, specifically whether
photoperiod extension by artificial light is necessary
to treat SAD.2 One meta-analysis20 of light therapy
studies found that morning-plus-evening light (a
photoperiod extension schedule) was superior to
single exposures at other times of the day. Other
meta-analyses,21-23 however, indicate that morning
light exposure is superior to evening light, which
initially seems to refute the photoperiod extension
hypothesis. An alternative interpretation is that
morning light may still act to extend the photoperiod by truncating early morning melatonin secretion and reducing the overall melatonin duration.
Volume 10 – Number 8
Morning
Light
Plasma Melatonin
Evening
Light
a
A
b
B
Wake up
DLMO-A DLMO-B
Sleep
Sleep-Wake
Wake
Cycle
Light-Dark
Cycle
Wake
Day
Night
8 pm
10 pm
Day
7 am
FIGURE 1. Schematic diagram of circadian rhythms
of melatonin and sleep-wake cycles*
* Phase of the melatonin cycle (A) is represented by DLMO-A,
while the phase of the sleep-wake cycle is represented by the
wake-up time. The phase angle between the melatonin and
sleep-wake cycles is represented by the time interval between
DLMO-A and wake-up time (a). Light exposure in evening results
in a phase delay of the melatonin rhythm (B), as measured by
DLMO-B. If wake-up time remains constant, then the phasedelayed melatonin rhythm results in a smaller phase angle
with the sleep-wake cycle (b). A phase-delayed rhythm can be
corrected using morning light exposure, which causes a phaseadvance of circadian rhythms.
DLMO-A=dim light melatonin onset for melatonin rhythm A;
DLMO-B=dim light melatonin onset for melatonin rhythm B.
Sohn C-H, Lam RW. CNS Spectr. Vol 10, No 8. 2005.
637
CNS Spectrums – August 2005
Review Article
free from masking effects,28 have more consistently
found evidence for phase delays in SAD.29-31
Other studies using specific techniques to study
endogenous circadian rhythms in SAD have had
mostly negative results. 30-35 In studies using constant routine protocols that rigorously control for
masking effects, one study32 found phase delays in
body temperature, DLMO, and cortisol rhythms in
6 female patients with hypersomnic SAD studied in
winter, while the other did not find any significant
phase differences.33 Forced desynchrony studies,34,35
in which 20-hour sleep-wake cycles are imposed on
subjects thereby unmasking the endogenous circadian rhythm, also found no differences in 7 patients
with SAD compared with controls studied in winter
and summer. However, one patient did show significant phase-delayed circadian rhythms,36 suggesting that there may be inter-individual variation in
SAD. Given that examining endogenous circadian
rhythms requires technically demanding and/or
resource-intensive methods, only small numbers of
patients are usually studied. Hence, patient selection
is particularly important in these small-sample studies and may explain some of the negative findings.
Similarly, there have been conflicting results in
the effects of light therapy on phase changes in SAD.
The phase-shift theory rests on two necessary components of treatment—that a corrective phase advance
of circadian rhythms should occur and that the phase
advance should be correlated with the antidepressant
effect. In support of the first component, most studies and meta-analyses21-23 have shown that morning
light exposure results in the phase advance of circadian rhythms and is more effective than light at other
times of the day. However, there are conflicting results
for the second component: a correlation between the
phase advance and antidepressant effect. 31,32,37,38 For
example, some previous studies31 have found that clinical improvement was correlated with degree of phase
advance while others have not.32,37,38
Recent light therapy studies,39 however, have
provided more evidence to support the phase-shift
hypothesis. Terman and colleagues39 sampled the
DLMO in 42 patients with SAD before and after light
therapy. They found that the magnitude of phase shifts
depended on the phase angle from the DLMO to the
time of light exposure, with responses to morning light
increasing with the size of the phase advance. An
optimal time for administration of morning light was
found to be 8.5 hours after the DLMO or 2.5 hours
from the midpoint of sleep duration.
Another study40 involved 26 patients with SAD
who had rectal core body temperature monitoring
Volume 10 – Number 8
during a light therapy protocol. In this study, the
degree of phase advance in core body temperature was
only weakly correlated with antidepressant response,
although there appeared to be an optimal phase angle
for response occurring when the wake time was ~3
hours from the nocturnal temperature minima.
Melatonin, administered at an appropriate
time in the evening to achieve a circadian phaseadvance, can also be used to examine the phase-shift
hypothesis. A pilot study 41 showed that low-dose
melatonin administered in the evening was effective in SAD, but a subsequent larger study (N=100
patients with SAD)42 found no overall treatment
differences between morning and evening dosing of
melatonin and a placebo pill condition. However,
a post hoc analysis42 showed that the patients who
were most phase delayed at baseline responded to a
corrective phase advance by melatonin and that the
best responses occurred when patients achieved an
optimal phase angle in which the DLMO occurred
~14 hours from wake time.42
In summary, there is substantial evidence to support
that some, but not all, patients with SAD have phasedelayed circadian rhythms that can be corrected by
appropriately timed circadian interventions (melatonin or bright light exposure) with resultant improvement in depressive symptoms. However, there is also
evidence indicating that other people with SAD have
beneficial effects of light therapy independent of circadian phase-shifting effect.
NEUROTRANSMITTERS
Since SAD is a subtype of major depression, there
has been much interest in studying the major neurotransmitters of interest in depression, namely serotonin (5-HT), noradrenaline, and dopamine. There
has been special interest in 5-HT, given the abundant
evidence that seasonal variation of brain and peripheral 5-HT occurs in healthy people. For example,
recent studies found that both 5-HT turnover43 and
availability of hypothalamic 5-HT transporter sites,
as measured by single photon emission computed
tomography,44 are lower in winter than in summer.
In SAD, past studies 8 of metabolites of 5-HT
and catecholamines in peripheral blood and cerebrospinal fluid were inconclusive. More consistent
results were found in neuroendocrine challenge
studies, in which blood levels of hormones are measured after administering a drug that acts on specific
receptors that control secretion of that hormone.
Studies using primarily serotonergic drugs acting
on various 5-HT receptors consistently showed
evidence for serotonergic receptor dysfunction in
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SAD.45 However, there are problems with interpreting the results of neuroendocrine challenge studies. For example, they are only indirect measures of
brain function since they involve the pituitary gland
which is outside the blood-brain-barrier. Also, they
only provide correlative measures, since there is no
way to determine whether any receptor dysfunction
is directly related to SAD symptoms, or whether
they are merely epiphenomena of the illness.
More recent investigations focus on monoamine
depletion protocols in which brain monoamines can
be experimentally manipulated to determine whether
changes lead to depressive symptoms, thereby giving a
more direct means of linking neurotransmitter function
to behavior.46 For example, tryptophan depletion studies are conducted on the understanding that tryptophan is the dietary amino acid precursor for conversion
to 5-HT in the brain. When a mixture containing large
amounts of amino acids without tryptophan is ingested,
the ensuing increase in liver enzyme metabolism can
temporarily reduce the blood levels of free tryptophan
by >80% within 5 hours. Animal studies and neuroimaging studies in humans show that brain 5-HT is
reduced by a similar magnitude using this procedure.47,48
This technique has been widely used in studies investigating mechanisms of antidepressant action and the
neurobiology of nonseasonal depression.49,50
In the study of untreated, symptomatic patients
with SAD,51 tryptophan depletion did not exacerbate
the depressive symptoms in winter, similar to findings in nonseasonal depression. However, in patients
with SAD in short-term clinical remission with light
therapy, Lam and colleagues52 first reported that tryptophan depletion induced relapse of depressive symptoms, thereby reversing the effect of light therapy, a
finding subsequently replicated by two independent
groups.53,54 Interestingly, atypical symptoms like carbohydrate craving were most sensitive to the tryptophan
depletion protocol, implicating the role of 5-HT in the
development of these symptoms. During the natural
summer remitted state, tryptophan depletion studies
produced mixed findings; two studies55,56 reported significant relapse of symptoms while another57 did not.
A preliminary report58 also found that patients with
SAD who showed relapse with tryptophan depletion
in summer were more likely to experience a depressive
episode in the following winter, suggesting that tryptophan depletion may predict risk for SAD.
Similarly, depletion of brain catecholamines
can be accomplished using α-methyl-para-tyrosine
(AMPT), an inhibitor of tyrosine hydroxylase that
decreases synthesis of dopamine and noradrenaline.46,59,60 In a study by Neumeister and colleagues,54
Volume 10 – Number 8
tryptophan depletion and catecholamine depletion each induced relapse of symptoms in patients
with SAD in remission with light treatment, indicating that light therapy may act through several
neurotransmitters. Patients in summer remission
also showed robust relapses with catecholamine
depletion, suggesting that dopamine and/or noradrenaline dysfunction is directly involved in the
pathogenesis of winter depression.61 Of note in this
regard is that reboxetine (a selective inhibitor of
noradrenaline reuptake) and bupropion (an inhibitor of noradrenaline and possibly dopamine reuptake) may be beneficial treatments for SAD.62,63
Other studies 1 9 , 6 4 , 6 5 also support dopamine
involvement in SAD. Electroretinography (ERG)
is a method to assess retinal function in light- and
dark-adapted states that involves dopamine as the
mediating neurotransmitter. ERG studies19 found
evidence of reduced b-wave amplitude consistent
with decreased retinal dopaminergic activity in
SAD. A neuroimaging study64 using [123]β-carbomethoxy-3beta-(4-iodophenyl) tropane single-photon
emission computed tomography showed decreased
availability of striatal dopamine transporter binding sites in symptomatic patients, although another
similar study also found evidence of reduced brain
5-HT transporter sites in patients with SAD.65
GENETICS
Much of the recent activity in the biological
investigation of SAD has involved the pursuit of
genetic mechanisms through different approaches
including family studies, twin studies, and candidate gene association studies.66-74 provided evidence
for hereditary factors in both SAD and seasonality (Table 1). In family history studies,66-70 25% to
67% of patients with SAD had a positive family
history of affective illness while 13% to 17% had
first-degree relatives with SAD. These rates are
significantly higher than expected from population
prevalence studies.71 However, no significant differences in psychiatric disorders among first-degree
relatives were found in patients with SAD compared with those with nonseasonal depression.66,72
Although there are no twin studies involving
SAD, per se, there have been two studies of seasonality (Table 1).73,74 In Australia, Madden and colleagues73 conducted volunteer-based twin studies with
4,639 adult twins and reported that genetic effects
accounted for 29% of variance in seasonality scores.
A similar twin study in Canada74,75 found greater heritability for seasonality scores, accounting for 45% to
69% of the total variance, perhaps because the phe639
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notypic expression of seasonality is greater at higher
latitudes. These and the family history findings indicate that SAD and seasonality has robust heritability. Of course, signals from family history and twin
studies must be further investigated using molecular
genetic analyses, which has been the most active area
for SAD research in the past 5 years. Formal genetic
linkage studies for complex conditions, such as SAD,
are limited by low power and poor feasibility, therefore, the focus has been on case-control association
studies of candidate genes (Table 2).
Obvious candidate genes include genes involved
in the 5-HT system. Several studies77-81 examined the
5-HT transporter promoter repeat length polymorphism (5-HTTLPR) after Rosenthal and colleagues77
and Sher and colleagues78 first reported that the short
variant allele of the 5-HTTLPR was associated with
SAD and seasonality. Unfortunately, other studies79,80
could not replicate this finding. Johansson and colleagues81 subsequently conducted a pooled analysis
of all three studies (including the original sample)
that also failed to find an association between 5HTTLPR and SAD. However, that report did show
a difference in 5-HTTLPR genotypes between high
and low seasonality groups in a separate populationbased sample.81
There are several reports of positive findings with the
5-HT2A gene, including increases in the frequency of
the 102C allele82 and the -1438A allele of the 5-HT2A
gene,83 and an association of the 102T/C genotype with
childhood attention deficit disorder.84 However, there
are also negative studies involving 5-HT2A genes79,85
and other 5-HT-related genes (Table 2).73
It may be more worthwhile to investigate the
TABLE 1. FAMILY HISTORY AND TWIN STUDIES IN SAD
Author(s) (Year)
Type of Study
Sample
Results
Rosenthal et al (1986)
Family history
7 children with SAD
5 of 7 children with SAD had a parent
with SAD.
Thompson et al70 (1988)
Family history
51 patients with SAD
25% and 14% of SAD patients had a
positive history in first-degree relatives of
affective illness and SAD, respectively.
Lam68 (1989)
Family history
46 patients with SAD
64% and 13% of SAD patients had a
positive history in first-degree relatives of
affective illness and SAD, respectively.
White et al69 (1990)
Family history
61 patients with SAD
66% of SAD patients had family members with nonseasonal depression, SAD
or alcohol abuse.
Allen et al66 (1993)
Family history
34 patients with SAD;
34 matched nonseasonal
depressed patients
27% of SAD patients had first-degree relatives with mood disorders. No differences
were found in family histories between
SAD and nonseasonal depression.
Sasaki et al76 (1998)
Family history
129 small families from
the general population
in Japan
No association between children and
biological parents in seasonal changes
of sleep and eating behaviour.
Stamenkovic et al72 (2001)
Family history
36 patients with SAD;
36 matched nonseasonal
depressed patients
No differences in the lifetime prevalence for psychiatric disorders among
the first-degree relatives in both groups
(SAD=16.5% and nonseasonal depression=19%).
Madden et al73 (1996)
Twin
4,639 adult twins from
a volunteer-based registry in Australia
Genetic effects accounted for at least 29%
of the variance in seasonality scores.
Jang et al74 (1997)
Twin
339 adult twins from a
volunteer-based registry in Canada
Genetic effects in men and women
accounted for 69% and 45% of the variance in seasonality scores, respectively.
75
SAD=seasonal affective disorder.
Sohn C-H, Lam RW. CNS Spectr. Vol 10, No 8. 2005.
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genetics of specific endophenotypes of SAD.86 For
example, differences in 5-HTTLPR have been associated with comorbid premenstrual depressive disorder87 and self-directedness scores on personality
testing88 in some patients with SAD. Furthermore,
Levitan and colleagues89 studied a putative endophenotype of SAD, women with carbohydrate
craving and hyperphagia or binge-eating, and its
relationship with the 7R allele of the D4 dopamine receptor gene (DRD4). The 7R allele was not
associated with the diagnosis of SAD, per se, but
instead was associated with a history of childhood
attention-deficit disorder and higher body mass
index;89 moreover, this association appeared to be
mediated through binge eating behavior.90
Another candidate gene comes from the guanine nucleotide-binding (G-protein) system that
is involved in postsynaptic signal transduction and
which has been of significant interest in nonseasonal
depression. 91 There is some evidence for G-protein dysfunction in SAD, as one study92 found that
patients with SAD had decreased levels of Gβ-subunit in peripheral leukocytes. A single nucleotide
polymorphism (C825T) in the Gβ3-subunit gene
has been shown to influence intracellular response to
G-protein-coupled stimuli93 and an association of the
T allele with nonseasonal affective disorder has been
reported.94 In SAD, one study95 found that patients
were more likely than control subjects to carry the
T allele of the Gβ3-subunit gene polymorphism, but
there was no association of the polymorphism with
seasonality scores. Unfortunately, another study96 did
not replicate these findings.
Circadian clock genes are also of significant
interest given the prominence of circadian rhythm
hypotheses for SAD. In animal studies, mutations
in clock and period genes result in altered circadian
rhythms.97-99 Johansson and colleagues81 conducted
a study for potential association between polymorphisms in clock-related genes (clock, period2,
period3, and NPAS2 and SAD, seasonality and diurnal preference. They found a significant difference
between patients with SAD and control subjects in
NPAS2 471 Leu/Ser, indicating a recessive effect of
the leucine allele on disease susceptibility.100 Period3
647 Val/Gly was also associated with scores on selfreported morningness-eveningness (a measure of diurnal preference) with higher scores found in individuals
with at least one glycine allele. However, none of the
polymorphisms in this study were associated with seasonality in the SAD case-control material.
In summary, there are a number of positive findings in gene association studies involving seroVolume 10 – Number 8
tonin-, dopamine-, G-protein- and clock-related
genes. Association studies are susceptible to false
positive results, so replication of these results will
be important. For example, initial enthusiasm for
an abnormality in 5-HTTLPR was not confirmed
in subsequent pooled analyses.
INTEGRATIVE ISSUES
AND FUTURE DIRECTIONS
There has been considerable progress in studying
the biology of SAD, but many findings require replication and there continue to be conflicting results
that need to be explained. It is now widely recognized that there must be heterogeneity in SAD
similar to that seen in nonseasonal depression. One
possibility is that the clinical presentation of SAD
represents a final common pathway with multiple
etiologies that contribute to heterogeneity when
examining groups of patients. This may be especially true for circadian hypotheses, since there is
great interindividual variability in circadian phase
position and phase shifts produced by circadian
interventions. Hence, averaging group data, especially in small-sample studies, may not reflect the
endogenous circadian rhythms in a subset of subjects. Similarly, circadian treatments given at the
same clock time may produce very different phasechanges between individuals, depending on their
starting circadian phase at baseline.
Another explanation for this heterogeneity may be
related to the inadequacies of the current definition of
SAD as a subtype of depression. Considering seasonality as a dimensional construct instead of a categorical
diagnosis may be more informative in understanding biological mechanisms. In this regard, a dual-vulnerability hypothesis, first proposed by Young and
colleagues101 and subsequently extended by Lam and
colleagues,102 posits distinct factors associated with
seasonality and depression. Differential loading of
each factor within an individual may explain some of
the different presentations of seasonality. For example,
a person with high loadings on a seasonality factor
coupled with moderate loadings on a depression factor may present as having SAD, whereas someone
with low seasonality and high depression may present
with a nonseasonal depressive episode.102 Other differences in loading on the two factors may result in
different clinical presentations such as subsyndromal
SAD (high seasonality, low depression) and “seasonal”
MDD (ie, winter worsening of nonseasonal MDD
[high seasonality, high depression]).
There may be separate biological mechanisms
involved with each factor so that, for example, the
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seasonality factor may be due to an underlying circadian disturbance while the depression factor may
be caused by serotonergic or dopaminergic dysfunc-
tion (or, as proposed by Young and colleagues,101
by cognitive distortions). Since patients with SAD
may have different loadings of the two factors, some
TABLE 2. GENETIC ASSOCIATION STUDIES IN SAD
Author(s) (Year)
Gene Studied
(Polymorphism)
Sample
Results
Ozaki et al
(1996)
5-HT2A (T102C,
Ala447Val, C516T)
50 patients with SAD;
62 control subjects
No associations found.
Enoch et al82
(1999)
5-HT2A (-1438G/A)
67 patients with SAD;
69 control subjects
Increase in frequency of the -1438A allele
in patients with SAD; No association
between -1438G/A and seasonality scores.
Arias et al81
(2001)
5-HT2A (T102C)
159 patients with SAD
and nonseasonal depression; 164 control subjects
Genotype distributions were different
between SAD and nonseasonal depressed
patients; 102C-allele carriers were more
frequent in the patients with SAD.
Levitan et al83
(2002)
5-HT2A (T102C)
66 women with SAD
T102C genotypes associated with childhood attention-deficit disorder.
Sher et al71
(1999)
5-HT1A (Gly22Ser,
Ile28Val),
5-HT1D (T1350C),
5-HT1B (C861G),
5-HT1E (C531T),
5-HT2C (Cys23Ser)
74 patients with SAD;
80 control subjects
No associations found.
Han et al103
(1999)
TPH (T1095C)
72 patients with SAD; other
patients with psychiatric
disorders
No associations found.
Lenzinger et al104
(1999)
5-HTT gene
18 patients with SAD;
matched control subjects
No differences genotypes in patients
with SAD; no correlation with depression scores after tryptophan depletion.
Rosenthal et al77
(1998)
5-HTTLPR
(long/short)
97 patients with SAD;
71 control subjects with low
seasonality scores.
5-HTTLPR short allele was more prevalent among patients with SAD.
Sher et al78
(1999)
5-HTTLPR
(long/short)
209 healthy subjects
5-HTTLPR short allele associated with
higher seasonality scores.
Johansson et al79
(2001)
5-HTTLPR
(long/short),
5-HT2A (-1438G/A,
45His/Tyr),
5-HT2C
(23Cys/Ser),
TRH (218A/C),
White (2457G/A)
82 patients with SAD;
82 matched control subjects
No associations with SAD or seasonality and the genotypes of these genes.
Praschak-Reider
et al87 (2002)
5-HTTLPR
(long/short)
44 women with SAD and
PMDD; 43 women with
SAD without PMDD
Long/short allele-heterozygosity was
associated with presence of PMDD in
patients with SAD.
Willeit et al80
(2003)
5-HTTLPR
(long/short)
138 patients with SAD;
146 control subjects with
low seasonality
No difference in genotype distribution
and short allele frequency in patients
with SAD. Melancholic depression was
associated with the long allele and atypical depression with the short allele
84
continued on page 643
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circadian and neurotransmitter studies may show
positive results while others may not. Studying the
phenomena of seasonality and subsyndromal variants may thus be informative for SAD. For example,
some investigators105 have shown that seasonality
(ie, lowering of mood in winter) is associated with
circadian phase delay and that subsyndromal SAD is
associated with changes in retinal light sensitivity on
ERG,106 similar to findings in patients with SAD.
A major advantage of studying seasonality is
in the multitude of animal models available to
study seasonal changes in behavior. An example
of capitalizing on an animal model is the study of
neuroimmune function. There is substantial evidence from animal studies107 showing that melatonin mediates seasonal changes in the immune
system and seasonal variations in immune function
have also been reported in humans.108,109 Other
studies110 indicate that (nonseasonal) depression
and immune function can influence each other
bi-directionally via inflammatory cytokines. Thus,
it is possible that the symptoms of SAD result from
TABLE 2. GENETIC ASSOCIATION STUDIES IN SAD (continued from page 642)
Author(s) (Year)
Gene Studied
(Polymorphism)
Johansson et al
(2003)
Sample
Results
5-HTTLPR
(long/short)
Pooled analysis: 464 patients
with SAD; 414 control subjects; 226 individuals from
a population-based registry;
46 patients with nonseasonal depression.
Pooled data from previous 3 case-control studies74,77,76 includes new sample
of 147 patients with SAD and 115 control subjects. No association between
5-HTTLPR and SAD was found in the
new case-control material or in the
pooled analysis of all samples. A difference in 5-HTTLPR was detected
between the population-based high and
low seasonality groups, when assuming
a recessive effect of the short allele.
Thierry et al88
(2004)
5-HTTLPR
(long/short)
56 female patients with
SAD; 76 age-matched
control subjects
Patients with SAD carrying the short
allele had lower Self-Directedness scores
on personality testing.
Levitan et al89
(2004)
DRD4 (7R allele)
108 female patients with
SAD with increased eating
behavior
7R allele was associated with childhood
attention deficit disorder symptomatology and higher maximal lifetime body
mass index in patients with SAD.
Levitan et al88
(2004)
DRD4 (7R allele)
131 female patients with
SAD with increased eating behavior
7R allele was associated with greater
frequency of binge-eaters in patients
with SAD.
Willeit et al95
(2003)
Gβ3 (C825T)
172 patients with SAD;
143 control subjects
Increase in frequency of the C825Tallele in patients with SAD. The polymorphism was not associated with
seasonality.
Johansson et al96
(2004)
Gβ3 (C825T)
159 patients with SAD;
159 matched control subjects
No association between C825T and
SAD or seasonality. Some evidence for
an effect on diurnal preference but only
in a subset (N=92) of the control group.
Johansson et al81
(2003)
Clock,
period 2,
period 3
(647 Val/Gly),
NPAS2
(471 Leu/Ser)
159 patients with SAD;
matched control subjects
NPAS2 471 Leu/Ser was associated with
SAD and Period3 647 Val/Gly was associated with diurnal preference.
81
SAD=seasonal affective disorder; 5-HT=serotonin; Ala=alanine; Val=valine; Gly=glycine; Ser=serine; Ile=isoleucine; Cys=cysteine;
TPH=tryptophan hydroxylase; 5-HTT=serotonin transporter; 5-HTTLPR=serotonin transporter promoter polymorphism; His=histidine;
Tyr=tyrosine; TRH=thyroid releasing hormone; PMDD=premenstrual dysphoric disorder; DRD4=D4 dopamine receptor; Gβ3=G-protein β3
subunit; NPAS2=neuronal PAS domain protein 2; Leu=Leucine;
Sohn C-H, Lam RW. CNS Spectr. Vol 10, No 8. 2005.
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REFERENCES
the seasonal activation of cytokines in anticipation of winter stress.111 Preliminary studies112 have
shown that people with SAD had significantly
higher plasma levels of cytokine interleukin (IL)
-6 and a trend to higher soluble IL-2 receptor levels than control subjects. Tryptophan and catecholamine depletion of patients in remission with
light therapy also found that changes in cytokine
soluble IL-4 correlated with increase in depressive
symptoms.113 Further investigation of the role of
cytokines and neuroimmune function in SAD and
seasonality will be of interest.
Another method to reduce heterogeneity is to
study more specific endophenotypes of SAD, such
as patients with distinct neurovegetative features
or comorbidity. It may also be possible to link
some of these endophenotypes to other psychiatric
conditions via common neurophysiological mechanisms, such as modeling differences in 5-HT2A
and DRD4 gene polymorphisms to the appetite and
attention disturbances found in women with SAD
and bulimia nervosa.85
Progress in research on mechanisms of circadian regulation will also likely provide clues for
research in SAD and seasonality. For example,
several studies19,106,114 have found evidence for electrophysiological changes in retinal light sensitivity
in SAD, but most of these changes reflect rod and
cone photoreceptor function. Recent research115117
has shown that photic input to the circadian
system is mediated through a separate pathway
from that of the visual system, and that traditional
visual photoreceptors (eg, rods and cones) are not
involved in the transduction of circadian light
signals. Instead, novel photopigments, such as
melanopsin115,117 and cryptochrome,116 have been
implicated as circadian photoreceptors. Based on
these new findings, research on melanopsin and
other circadian photopigments will be of great
interest in SAD.
Finally, it is also recognized that the different
hypotheses proposed for SAD may not be mutually exclusive. For example, 5-HT can modulate
photic response to the SCN and sleep disturbances
due to abnormal circadian rhythms may be mediated through serotonergic pathways that depend
on postsynaptic G-protein signal transduction. An
integrative approach involving circadian rhythms,
neurotransmitters and genetics will be more likely
to explain the biology of SAD than a single, reductionist approach CNS
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Article
The Can-SAD Study: A Randomized Controlled Trial of the
Effectiveness of Light Therapy and Fluoxetine in Patients
With Winter Seasonal Affective Disorder
Raymond W. Lam, M.D.,
F.R.C.P.C.
Anthony J. Levitt, M.B.B.S.,
F.R.C.P.C.
Robert D. Levitan, M.D.,
F.R.C.P.C.
Murray W. Enns, M.D., F.R.C.P.C.
Rachel Morehouse, M.D.,
F.R.C.P.C.
Erin E. Michalak, Ph.D.
Edwin M. Tam, M.D.C.M.,
F.R.C.P.C.
Objective: Light therapy and antidepressants have shown comparable efficacy in
separate studies of seasonal affective disorder treatment, but few studies have directly compared the two treatments. This
study compared the effectiveness of light
therapy and an antidepressant within a
single trial.
Method: This double-blind, randomized,
controlled trial was conducted in four Canadian centers over three winter seasons.
Patients met DSM–IV criteria for major depressive disorder with a seasonal (winter)
pattern and had scores ≥23 on the 24item Hamilton Depression Rating Scale.
After a baseline observation week, eligible patients were randomly assigned to 8
weeks of double-blind treatment with either 1) 10,000-lux light treatment and a
placebo capsule, or 2) 100-lux light treatment (placebo light) and fluoxetine, 20
mg/day. Light treatment was applied for
30 minutes/day in the morning with a fluorescent white-light box; placebo light
boxes used neutral density filters.
Results: A total of 96 patients were randomly assigned to a treatment condition.
Intent-to-treat analysis showed overall
improvement with time, with no differences between treatments. There were
also no differences between the light and
fluoxetine treatment groups in clinical response rates (67% for each group) or remission rates (50% and 54%, respectively).
Post hoc testing found that light-treated
patients had greater improvement at 1
week but not at other time points. Fluoxetine was associated with greater treatment-emergent adverse events (agitation,
sleep disturbance, palpitations), but both
treatments were generally well-tolerated
with no differences in overall number of
adverse effects.
Conclusions: Light treatment showed
earlier response onset and lower rate of
some adverse events relative to fluoxetine, but there were no other significant
differences in outcome between light
therapy and antidepressant medication.
Although limited by lack of a double-placebo condition, this study supports the effectiveness and tolerability of both treatments for seasonal affective disorder and
suggests that other clinical factors, including patient preference, should guide selection of first-line treatment.
(Am J Psychiatry 2006; 163:805–812)
S
easonal affective disorder is the term applied to a clinical subtype of mood disorder that consists of recurrent episodes of major depression occurring with a seasonal pattern (1). The most common type of seasonal affective
disorder is winter depression in which patients experience
symptoms of clinical depression during the fall and winter,
with full remission to normal mood (or a switch into mania
or hypomania) during the spring and summer seasons.
Symptoms of seasonal affective disorder include depressed
mood, profound lack of energy, hypersomnia, hyperphagia
with carbohydrate craving, and weight gain (2). Seasonal
affective disorder is also associated with significant impairment in occupational and social functioning (3, 4). Epidemiological studies from Canada and the United States, using diagnostic interviews conducted among random
community samples, have reported winter seasonal affective disorder rates of between 0.4% and 2.7% in the general
population (5–7). There is considerable evidence that seaAm J Psychiatry 163:5, May 2006
sonal affective disorder is effectively treated by daily exposure to bright artificial light, known as light therapy or phototherapy, and by antidepressant medication.
More than 70 controlled studies of light therapy for seasonal affective disorder have been conducted. An early
pooled analysis of over two dozen studies found that
bright light treatment was superior to control conditions
(usually dim light) but primarily in less severely ill patients
(8). However, these findings were criticized for methodological limitations, including small sample sizes and
short treatment durations (1–2 weeks) of the included
studies. Subsequently, two randomized controlled trials
with larger sample sizes and longer durations found that
bright light therapy using fluorescent light boxes was superior to plausible placebo control conditions (9, 10). Terman et al. (9) studied 144 patients with seasonal affective
disorder randomly assigned to one of four treatments for
2–4 weeks: 1) morning or 2) evening bright light (exposure
ajp.psychiatryonline.org
805
LIGHT THERAPY VERSUS FLUOXETINE
FIGURE 1. Patient Progression Through Study
Eligible subjects
screened and entered in
baseline week (N=117)
Withdrew consent (N=16)
Taking ineligible medications (N=2)
Spontaneously improved (N=3)
Subjects randomly assigned
to a treatment condition
(intent-to-treat group [N=96])
Received light treatment
plus placebo pill (N=48)
Dropped out (N=8):
Moved away (N=1)
Lost to follow-up (N=1)
Withdrew consent (N=3)
Lack of efficacy (N=2)
Adverse events (N=1)
Completed study (N=40)
Received placebo light
plus fluoxetine (N=48)
Dropped out (N=7):
Moved away (N=2)
Lost to follow-up (N=3)
Adverse events (N=2)
Completed study (N=41)
to 10,000-lux fluorescent light for 30 minutes) or 3) highdensity or 4) low-density negative ions emitted from a
negative ion generator (the placebo condition). Eastman
and colleagues (10) studied 96 patients randomly assigned
to 5 weeks of treatment with morning or evening bright
light (consisting of a 6,000-lux fluorescent light box for 1.5
hours), or morning use of a deactivated negative ion generator (the placebo condition). In both studies, bright light
was superior to the placebo condition in producing clinical remissions, and morning light exposure was superior
to evening on some measures. In addition, three systematic reviews incorporating meta-analyses have also supported the efficacy of light therapy, although it was noted
that the treatment duration of included studies remained
relatively short (5 weeks or less) (11–13). This evidence resulted in the recommendation of light therapy as a firstline treatment for seasonal affective disorder in expert and
consensus clinical guidelines (14–17).
Antidepressant medications have not been studied as
extensively as light therapy in the treatment of seasonal affective disorder. Selective serotonin reuptake inhibitors
(SSRIs) have the best-demonstrated evidence for medication efficacy. In one study, patients with seasonal affective
disorder (N=68) were randomly assigned to treatment
with fluoxetine, 20 mg/day, or placebo for 5 weeks (18).
The improvement in overall depression scores was not significantly different, but the effect size of 0.5 for fluoxetine
was similar to that found in other antidepressant trials for
nonseasonal depression. In addition, the clinical response
806
ajp.psychiatryonline.org
rate (greater than 50% improvement in depression scores)
for fluoxetine was significantly higher than placebo (59%
versus 34%, respectively). In the subset of patients who
were more severely ill at baseline, fluoxetine did show statistical superiority in improving the overall depression
scores. In a larger study (N=187), sertraline in a flexible
dose (50–200 mg/day) for 8 weeks was superior to placebo
both in improving depression scores and in the clinical response rate (63% versus 46%, respectively) (19). In both
studies, the SSRI drugs were well tolerated, with few dropouts in any condition (between 3.1% and 7.5%).
Smaller controlled studies have shown that other medications, including moclobemide, L-tryptophan, and hypericum (St. John’s wort), may be effective treatments for
seasonal affective disorder. There have also been case series suggesting that bupropion, citalopram, reboxetine,
and tranylcypromine are beneficial (reviewed by Lam and
Levitt [15]).
In summary, both light therapy and antidepressants
have evidence showing efficacy in seasonal affective disorder treatment and are considered first-line therapies. An
important clinical question remains: How does light therapy compare with antidepressant treatment? There are
few systematic comparisons of light therapy versus antidepressant drugs in seasonal affective disorder. A singlecase study suggested that citalopram, an SSRI antidepressant, was as effective as light therapy (20). A small randomized controlled trial (N=35) compared bright light
therapy (3,000 lux, 2 hours/day) combined with placebo
capsules versus fluoxetine (20 mg/day) combined with
placebo light (100 lux, 2 hours/day) for 5 weeks in patients
with seasonal affective disorder (21). Both conditions produced significant response, with no difference in final depression scores and no difference in clinical response
rates (>50% reduction in depression scores: light therapy,
70%; fluoxetine, 65%). However, when strict criteria for
clinical remission were used (>50% reduction in depression scores and a posttreatment score within the normal
range), light therapy showed a superiority over fluoxetine
(50% versus 25%) that approached significance (p=0.10).
In addition, post hoc testing showed that light therapy resulted in significantly lower depression scores after 1 week
of treatment. There were no differences between treatments at other time points. The limitations of this study
were its small size (hence low power to detect differences)
and that the timing of exposure to light (morning, evening,
or morning and evening) was chosen by the patient. In
fact, there was some suggestion that morning light was
more effective, since 10 of 12 patients responded to morning light, compared with two of five for evening light, and
two of three for morning and evening light. Using the
more optimal morning timing of light exposure for all patients may have further added to the superior response
rate of light therapy over fluoxetine.
Important questions that remain to be answered for the
clinical treatment of seasonal affective disorder are 1)
Am J Psychiatry 163:5, May 2006
LAM, LEVITT, LEVITAN, ET AL.
TABLE 1. Demographic and Clinical Characteristics of Patients With Seasonal Affective Disorder Randomly Assigned to 8
Weeks of Double-Blind Treatment With Light Therapy Plus Placebo Capsules or Fluoxetine Plus Placebo Light
Active Treatment
Characteristic
Female
Married
Atypical features specifier included in diagnosis
Bipolar II disorder diagnosis
Previous psychiatric contact
Previous hospitalization
Family history of mood disorder
Previous antidepressant treatment
Previous psychotherapy
Age (years)
Number of previous winter episodes
Number of previous total episodes
CGI severity rating
Global Assessment of Functioning score
Expectation scoresa
Light therapy
Fluoxetine
a
Light Therapy (N=48)
N
%
31
64.6
24
50.0
15
31.3
2
4.2
13
27.1
2
4.2
20
41.7
22
45.8
11
22.9
Fluoxetine (N=48)
N
%
33
68.8
20
41.7
17
35.4
3
6.3
14
29.2
2
4.2
21
43.8
16
33.3
13
27.1
Mean
SD
Mean
SD
42.3
11.0
11.8
4.2
57.2
9.2
8.1
8.6
0.6
6.3
44.6
10.5
11.8
4.1
58.5
11.3
8.0
8.6
0.6
5.7
12.3
9.6
2.6
3.1
12.5
9.4
2.2
3.3
From the Expectation of Response questionnaire (24).
whether light therapy is effective over longer treatment
periods, since controlled treatment studies have only
been 1–5 weeks in duration, and 2) how light therapy compares with antidepressant drugs, especially for more severely ill patients. To help answer these questions, we conducted a multicenter randomized controlled trial that
compared the effectiveness of light therapy to the SSRI antidepressant fluoxetine. We randomly assigned depressed
patients with seasonal affective disorder recruited from
four Canadian cities to 8 weeks of treatment during the
winter. To balance potential expectation effects, each patient received both a light box and a pill, but only one
treatment was active in each condition.
Method
Protocol
This randomized, double-blind study was approved by a clinical research ethics board at each center. After giving written informed consent, eligible subjects entered a 1-week baseline
phase without treatment to regularize their sleep-wake schedule
(patients were instructed to sleep only between the hours of 10:00
p.m. and 8:00 a.m.) and to identify spontaneous responders. Patients who were significantly improved after the baseline week
(defined as 25% or greater improvement in depression scores)
were dropped from the study. Otherwise, they were randomly allocated to one of two treatment conditions for 8 weeks: active
light therapy plus placebo capsules, or placebo light therapy plus
active drug. Randomization codes were centrally computer generated and stratified by site in random blocks of 3–5. Allocation
concealment used opaque envelopes at each site that could only
be opened after the unique subject number was entered in a master log. Patients returned to the clinic for outcome assessments at
weeks 1, 2, 4, and 8 or at unexpected termination.
Subjects
Subjects were recruited by referral and advertisements at mood
disorders clinics in 1) Vancouver, 2) Winnipeg, 3) Toronto, and 4)
Am J Psychiatry 163:5, May 2006
Saint John, New Brunswick. The inclusion criteria for the study
were male and female outpatients 18–65 years of age who had
major depressive episodes with a seasonal (winter) pattern as determined by the Structured Clinical Interview for DSM-IV (SCID)
modified to include criteria for seasonal pattern (5). In addition,
subjects were required to have a score of 20 or higher on the 17item Hamilton Depression Rating Scale or a score of 14 or higher
on the 17-item version if the score on a 24-item version (subsequently described) was 23 or higher. Patients had to meet these
criteria, which indicate moderate to severe depression, both at
initial assessment and at the end of the baseline week.
Subjects were excluded from the study if they 1) were pregnant
or lactating (or were sexually active women of childbearing potential not using medically accepted means of contraception); 2)
were at serious suicidal risk in the judgment of the investigator; 3)
met DSM-IV criteria for organic mental disorders, substance use
disorders (including alcohol) within the last year, schizophrenia,
paranoid or delusional disorders, other psychotic disorders, bipolar I disorder, panic disorder, or generalized anxiety disorder not
concurrent with major depressive episodes; 4) had a serious unstable medical illness; 5) had retinal disease that precluded the
use of bright light; 6) had a history of severe allergies or multiple
drug adverse reactions; 7) were currently using other psychotropic drugs including lithium, L-tryptophan, St. John’s wort, or melatonin; 8) were currently using beta blocking drugs; 9) had used
antidepressants or mood-altering medications within 7 days of
baseline; 10) had been treated previously with fluoxetine or light
therapy; 11) had undergone formal psychotherapy (e.g., cognitive
behavior or interpersonal psychotherapy) in the 3 months preceding the study or initiated it during the study itself; or 12) performed shift work or traveled south during the protocol.
Subjects were entered into the study during the autumn and
winter months starting from Sept. 15. Enrollment was stopped by
Feb. 15 in order to reduce the possibility of spontaneous spring
remission. The study was conducted over three winter seasons
(2000/2001–2002/2003).
Light Treatment
The active light treatment consisted of daily exposure to a
white fluorescent light box (Uplift Technologies Inc. [Dartmouth,
N.S.], Model Daylight 10000, fitted with an ultraviolet filter and
rated at 10,000 lux at a distance of 14 in from screen to cornea) for
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LIGHT THERAPY VERSUS FLUOXETINE
TABLE 2. Clinician- and Patient-Rated Outcome in Patients With Seasonal Affective Disorder Randomly Assigned to 8
Weeks of Double-Blind Treatment With Light Therapy Plus Placebo Capsules or Fluoxetine Plus Placebo Light
Treatment Week
Baseline
Measure and Active Treatment Condition
Hamilton Depression Rating Scale scoreb
Total (24 items)
Light therapy
Fluoxetine
Typical symptoms (17 items)
Light therapy
Fluoxetine
Atypical symptoms (7 items)
Light therapy
Fluoxetine
Beck Depression Inventory II
Light therapy
Fluoxetine
Week 1
Week 2
SD
Mean
Week 4
SD
Mean
Week 8
Mean
SD
Mean
SD
Mean
SD
30.2
29.6
5.5
5.3
20.7
22.2
9.0
8.3
19.0
19.4
9.2
8.4
14.5
14.3
9.4
7.5
11.6
11.6
9.9
9.5
17.3
17.9
3.7
3.4
12.1
13.7
5.4
5.1
11.0
11.9
5.5
5.2
8.4
8.9
5.7
5.1
6.4
6.5
5.3
5.9
13.0
11.7
3.6
4.3
8.6
8.5
4.4
4.3
8.0
7.5
4.5
4.6
6.1
5.4
4.5
3.2
5.2
5.1
5.1
4.2
24.5
22.9
8.5
9.3
17.9
18.1
9.8
11.0
15.9
15.7
10.2
10.9
11.7
12.9
9.2
10.7
10.3
11.9
9.1
11.2
a
Repeated measures ANOVA examining within-subject factor of time and between-subject factors of treatment condition and site. Significant
effects were seen only for time; no main effects of treatment or site or interaction effects were found.
b The 17-item version of the Hamilton depression scale is the most widely used measure of depression severity in clinical trials. The Hamilton
total score comprises the score from the 17-item “typical symptom” version plus seven items that assess severity of atypical symptoms that
predominate in seasonal affective disorder.
30 minutes as soon as possible after awakening, between 7:00
a.m. and 8:00 a.m. A suitable placebo condition for bright light is
problematic and controversial (23). In this study, the placebo light
treatment was an identical light box fitted with a neutral density
gel filter to reduce light exposure to 100 lux. Deception was used
to enhance the plausibility of the light control condition by explaining to patients (using a structured script) that the objective
of the study was to examine different wavelengths of light and
light boxes, without mentioning the different intensities. After being shown the assigned light box, pretreatment ratings of expectations for light therapy (and separately for medication) were measured with a modified Expectation of Response questionnaire
(24) used in other seasonal affective disorder studies (25). On
study completion, the patients were debriefed and allowed to
continue receiving active light treatment if they wished.
Patients were given verbal and written instructions on the use
of the light box and a measurement tape was used to ensure
proper positioning. Illumination intensities were confirmed by
digital photometer. Adherence was measured by using daily logs
of treatment times that were completed by subjects and reviewed
at each visit. Patients were also instructed to avoid spending an
excessive or unusual amount of time outdoors during the entire
study period.
Medication Treatment
The active medication treatment was a daily, fixed dose of fluoxetine, 20 mg/day, taken between 7:00 a.m. and 8:00 a.m. while the
placebo was an identical capsule containing inert filler. Adherence
was measured by pill counts at each visit. In addition, blood samples were taken at the completion of the study, and a random subset of samples were assayed for serum fluoxetine levels.
Outcome Measures
The primary outcome measure was the 24-item Hamilton depression scale score obtained by board-certified psychiatrists
blind to treatment assignment (the blind was maintained by having a separate research assistant managing the light device treatment and asking patients not to discuss side effects or specifics of
treatment with the rater). A semistructured interview, the Structured Interview Guide for the Hamilton Depression Rating Scale,
Seasonal Affective Disorders Version (SIGH-SAD) (22) was used to
increase reliability. The SIGH-SAD generates scores for several
versions of the Hamilton depression scale, including the 17-item
version, the 21-item version, and an eight-item atypical symptom
808
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addendum. This atypical addendum was included because the
original Hamilton scale does not rate symptoms such as hypersomnia, increased appetite, and weight gain, which predominate
in seasonal affective disorder. Some seasonal affective disorder
studies report the total 29-item SIGH-SAD score, which consists
of the 21-item Hamilton scale plus the eight-item atypical symptom addendum. However, the 17-item Hamilton scale is the most
widely used measure of depression severity in clinical trials because the 21-item measure includes four items (diurnal variation
of mood, paranoid thoughts, obsessive-compulsive symptoms,
depersonalization) originally added to subtype the depressive episode, not to measure severity. Similarly, the eight-item atypical
symptom addendum includes one comparable subtyping item
reflecting diurnal mood variation (afternoon slump). Therefore,
like other seasonal affective disorder studies (10), we used the
Hamilton measure that best reflects severity of depression in seasonal affective disorder, namely the 24-item Hamilton depression
scale (comprising 17 “typical symptom” items plus seven “atypical symptom” items). Interrater reliability of the SIGH-SAD was
assessed using videotaped interviews with an intraclass correlation of 0.95 for the 24-item Hamilton scale.
Clinical response was defined as 50% or greater reduction from
baseline in 24-item Hamilton depression scale scores at the last
visit, while clinical remission was defined as clinical response
plus a score of 8 or less. Other outcome measures included Clinical Global Impression rating and score on the patient-rated Beck
Depression Inventory II, which includes items for atypical symptoms. Adverse effects were monitored using the Adverse Events
Scale (unpublished scale from the Canadian Network for Mood
and Anxiety Treatments available on request). This self-rated
scale assesses both frequency and severity (rated as none, mild,
moderate or severe) of 32 adverse events (including a category for
“other”) and provides a more comprehensive and systematic
evaluation of adverse events than is usually conducted in antidepressant clinical trials. A treatment-emergent adverse event was
defined as any increase in rating during treatment to a score of
moderate or severe.
Statistical Analysis
All patients randomly assigned to a treatment condition were
included in the intent-to-treat analysis, with missing data handled using the last observation carried forward method. Sample
size was estimated on the basis of a power analysis using endpoint change scores on the main outcome variable. Assuming a
Am J Psychiatry 163:5, May 2006
LAM, LEVITT, LEVITAN, ET AL.
FIGURE 2. Change in 24-Item Hamilton Depression Rating
Scale Scores in Patients With Seasonal Affective Disorder
Randomly Assigned to 8 Weeks of Double-Blind Treatment
With Light Therapy Plus Placebo Capsules or Fluoxetine
Plus Placebo Light
Analysisa
0
Time effect: F=81.6, df=3.3, 85, p<0.0005
Time effect: F=41.4, df=2.9, 85, p<0.0005
Time effect: F=48.5, df=3.0, 85, p<0.0005
standard deviation of 6 points, a study with 45 patients per condition would allow 80% power to detect a mean difference of at least
3.6 points or an effect size of 0.6, regarded as a medium-sized
treatment effect in behavioral studies.
All treatment variables remained coded, and the analysts and
investigators were blind to variable identity during the primary
analysis and interpretation. The continuous outcome scores were
analyzed by using repeated measures analysis of variance
(ANOVA), with one within-subject factor (time) and two betweensubject factors (treatment condition and site). A Greenhouse-Geisser correction was conducted to adjust for degrees of freedom if
the Mauchly Test of Sphericity was significant. In this analysis,
differences between treatment conditions would show as significant condition-by-time or condition-by-time-by-site interaction
effects. This analysis also assumes compound symmetry, which,
if violated, may lead to type I errors greater than the nominal values. Post hoc t tests were done to examine differences between
conditions on change scores at each visit. Dichotomous variables
were tested by using chi square tests with Fisher’s exact tests as
appropriate. All analyses were done by using SPSS v.11.
Results
Figure 1 shows the patient numbers through the phases
of the study. A total of 96 patients were randomly assigned
to a treatment condition. Table 1 shows clinical information on the patients in the two groups. There were no significant differences noted for any of the clinical variables.
The analysis of expectation ratings showed a main effect
for modality, in that higher expectations were recorded for
the light treatment compared with fluoxetine (F=9.8, df=1,
75, p=0.003), but there were no main or interaction effects
with treatment condition, so that there were no differences in expectations for light or drug between patients
assigned to either treatment.
Table 2 shows the results of the repeated measures
ANOVA for the primary outcome variable, the 24-item
Hamilton scale, and for the “typical” and “atypical” symptoms as represented by the 17-item Hamilton scale and
the seven-item atypical symptom addendum. Significant
main effects of time were found for all comparisons, but
Am J Psychiatry 163:5, May 2006
Mean Change in Score on
24-Item Hamilton Depression Rating Scale
Time effect: F=77.0, df=2.7, 85, p<0.0005
Fluoxetine (N=48)
Light treatment (N=48)
–4
–8
a
–12
–16
–20
0
1
2
4
8
Week of Treatment
a
Significantly greater improvement in the first week of treatment for
those receiving light therapy relative to those receiving fluoxetine
(t=2.1, df=94, p<0.05).
no main effects were seen for treatment condition or site.
There were no significant interaction effects for conditionby-time or condition-by-time-by-site. The same findings
held for the patient-rated measure, the Beck Depression
Inventory II. These analyses show that both groups improved on all measures over time but that there were no
differences in the responses to the two conditions or between the four sites. Another analysis showed no differences in outcome measures with month of entry into the
study (data not shown).
There were no significant differences between light
treatment and fluoxetine in the clinical response rate (67%
for both conditions) (χ2=0, df=1, p=1.00) or the clinical remission rate (50% versus 54%, respectively) (χ2=0.04, df=1,
p=0.84). Similarly, there were no significant differences between conditions in the CGI improvement rating at last
visit (mean=1.90 [SD=1.15] versus 1.92 [SD=1.09], respectively) (t=0.09, df=94, p=0.93). Another measure of clinical
response is the percentage of patients with “much improved” or “very much improved” CGI ratings; again, there
were no differences between conditions on this measure
(73% for both groups) (χ2=0, df=1, p=1.00).
Figure 2 shows the changes in 24-item Hamilton depression scale scores from baseline for each week of treatment.
Post hoc t tests showed that patients in the bright light
condition improved more in the first week of treatment
relative to those in the fluoxetine condition. However, the
subsequent treatment weeks showed no differences between the two conditions. The effect size found in this
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LIGHT THERAPY VERSUS FLUOXETINE
TABLE 3. Treatment Emergent Adverse Events Occurring in
>5% of Patients With Seasonal Affective Disorder Randomly Assigned to 8 Weeks of Double-Blind Treatment
With Light Therapy Plus Placebo Capsules or Fluoxetine
Plus Placebo Light
Subjects Reporting an
Increase From Baseline to at
Least Moderate Severity (%)
Treatment Emergent Adverse Event
Gastrointestinal
Abdominal pain
Nausea
Diarrhea
Constipation
Decreased appetite
Increased appetite
Weight loss
Central nervous system
Anxiety
Nervousness
Agitation
Tremor
Irritability
Sleepiness
Increased sleep
Decreased sleep
Sleep disturbance
Headache
Sexual dysfunction
Decreased sex drive
Male erection problems
Female delayed orgasm
Other
Feeling faint
Palpitations
Sweating
Muscle pain
Weakness/fatigue
Rash
Dry mouth
Flushing
Light Therapy
(N=48)
Fluoxetine
(N=48)
6.3
4.2
4.2
8.3
14.6
8.3
2.1
8.3
10.4
10.4
6.3
14.6
14.6
6.3
12.5
12.5
0
2.1
4.2
8.3
12.5
22.9
2.1
16.7
25.0
10.4
12.5*
6.3
8.3
12.5
18.8
20.8
29.2**
10.4
14.6
4.7
0
16.7
6.3
6.3
6.3
0
6.3
12.5
16.7
0
18.8
6.3
0
10.4*
10.4
12.5
16.7
6.3
14.6
4.2
*p<0.05.**p<0.01.
study for the 24-item Hamilton change score between
treatments at the final visit was 0.03 in favor of light treatment, indicating a trivial difference between conditions.
A subset of patients (N=49) was identified as being more
severely depressed at baseline (24-item Hamilton depression scale scores ≥30). In this more severely ill subgroup,
there were no significant differences in the 24-item Hamilton depression scale scores between the light-treated patients (N=27) and the fluoxetine-treated patients (N=22).
The results again showed a significant main effect for time
(F=49.2, df=2.9, 39, p<0.0005), but no other significant
main effects or interaction effects were found. Similarly, in
these more severely ill patients, there were no significant
differences between light treatment and fluoxetine in the
clinical response rates (70% versus 73%, respectively) (χ2=
0, df=1, p=1.00) or the remission rates (48% versus 50%, respectively) (χ2=0, df=1, p=1.00).
The percentage of patients experiencing at least one
treatment-emergent adverse event was 77% for light treatment and 75% for fluoxetine. Table 3 shows the treatmentemergent adverse events reported in more than 5% of pa-
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tients for either condition. Significant differences in treatment-emergent adverse events, all higher in the fluoxetinetreated patients, were found for agitation, sleep disturbance, and palpitations. There were no switches to hypomania with either treatment. The percentage of patients reporting at least one treatment-emergent adverse events
self-rated as “severe” at least once during treatment was
33.3% for bright light and 35.4% for fluoxetine (χ2=0, df=1,
p=1.00). Similarly, there were no significant differences between light and fluoxetine treatment in overall dropout
rates in the study (8 versus 7, respectively; χ2=0, df=1, p=
1.00) or in dropouts due to treatment-emergent adverse
events (N=1 and 2, respectively; χ2=0, df=1, p=1.00).
Discussion
The main results of this study showed that there were no
differences in the primary or secondary outcomes for patients with seasonal affective disorder who received active
light therapy versus those who received fluoxetine. The
clinical response and remission rates for light therapy and
fluoxetine were very similar throughout the study. The benefits of treatment were apparent in both interviewer-rated
and patient-rated outcome scales and in the typical and
atypical symptom subscales. The light-treated patients had
a greater improvement after 1 week of treatment (a finding
which, given the post hoc nature of the analysis, needs to be
regarded with caution), but thereafter there were no differences between conditions. Another caveat is that the study
was only powered to detect medium-sized or larger effects.
However, the actual differences between treatments in this
study were so small that a huge sample (numbering in the
thousands of patients) would be required to detect these effect sizes. Even if statistically significant, these small effect
sizes would not be clinically meaningful.
This trial is the longest controlled study of light therapy.
At 8 weeks, it is the only one of similar duration to the standard antidepressant clinical trial. Given the natural course
of seasonal affective disorder with spontaneous clinical
remission in the spring/summer, it is important for a
longer-duration study to start treatment well before the
time of spontaneous remission (18). In this study, there
were no differences in outcome with month of entry, indicating that spontaneous remissions were avoided with patients entered in the later months. We also used a higher
entry score on the 24-item Hamilton depression scale
than other seasonal affective disorder studies, ensuring
that patients were at least moderately depressed before
treatment assignment.
Comparing light therapy and antidepressant medication is difficult because of differences in procedure and expectations with the two treatments. Light therapy has a
behavioral component in that patients must wake up and
spend 30 minutes in quiet activity while receiving light.
The finding that expectation ratings were higher for light
therapy than for medication confirms that it was also imAm J Psychiatry 163:5, May 2006
LAM, LEVITT, LEVITAN, ET AL.
portant to control for positive expectation effects of light
treatment. We chose to use the “double dummy treatment” method to control for these nonspecific effects by
having patients use both a light device and a pill. “Dim”
light of 100 lux is still plausible to patients but is no
brighter than ordinary kitchen lighting that patients might
experience in their own homes. The deception was effective because there were no differences in pretreatment expectations for light between the groups even after patients
were shown their assigned light box. Regardless, because
100-lux light may have some biological activity under certain conditions (26), we cannot exclude the possibility that
the dim light may have some active antidepressant effect.
Another limitation of this study is that a “double placebo” was not used, so we cannot rule out placebo effects
(or the effects of waking up early) in the overall responses
to both treatments. Given that both light therapy and fluoxetine have evidence for efficacy versus placebo, we believed that an effectiveness study (comparing two active
treatments) would be adequate to answer the clinical
questions. Reassuringly, the response and remission rates
for light and fluoxetine in this study were similar in magnitude to those reported in placebo-controlled trials.
Of interest is that the response to light therapy in this
study was not as rapid as reported in other shorter-term
light studies. Patients showed steady improvement during
the course of the 8 weeks, a pattern more similar to a medication effect. A possible explanation is that different expectation effects for a shorter-term study may contribute
to the rapid response (27).
This study was a comparison of fixed-dose strategies. It
is possible that the response rates would be higher if
higher dosing was used. However, fluoxetine has a flat
dose-response curve so that studies comparing higher fluoxetine doses do not show greater response (28–30). As for
light therapy, there have been few studies of optimal “dosing” of light (31). The morning timing of light therapy followed standard practice based on results from randomized controlled trials and meta-analyses. However, one
meta-analysis found that morning plus evening light exposure was more effective than exposure at a single time
of day (32). Another study suggested that light therapy is
most effective if applied at an optimal time in the circadian phase of the patient (33), which may be at different
external clock times for individual patients. Although this
latter finding has yet to be replicated, if true, then the
morning timing of light in this study may not have been
optimal for every patient.
Some previous studies have suggested that fluoxetine is
more effective than placebo in more severely ill patients
(18), while light therapy is more effective in less severely ill
patients (8). In our study, just over half of the patients were
considered to be more severely depressed, i.e., with a baseline score ≥30 on the 24-item Hamilton depression scale. In
Am J Psychiatry 163:5, May 2006
the post hoc analysis for this subset of patients, there was a
good response to both treatments, but no differences were
seen between treatments in improvement in depression
scores or in clinical response or remission rates. Therefore,
both light therapy and fluoxetine are comparably effective,
even in more severely ill outpatients.
Fluoxetine was associated with a greater frequency of
some treatment-emergent adverse events (agitation, sleep
disturbance, palpitations) than light therapy, but both
treatments were generally well tolerated, and there were
no differences in severe treatment-emergent adverse
events or dropouts due to adverse events. The higher rate
of treatment-emergent adverse events reported in this
study is likely related to the use of a self-rated adverse
events scale instead of relying on unsystematic and spontaneous reports of adverse events as per usual in clinical
trials. Despite this more intensive approach, the rates of
many treatment-emergent adverse events, such as sexual
dysfunction, were low (less than 5%) for both light therapy
and fluoxetine. Adherence to treatment was also good in
this study, as evidenced by patient logs and pill counts.
However, studies have suggested that objective measures
of adherence with light therapy usually show lower adherence rates than subjective patient reports (34).
In summary, light therapy and fluoxetine are comparably effective treatments for patients with seasonal affective disorder, although light treatment may have a slightly
faster onset of effect and slightly fewer treatment-emergent adverse events. The choice of treatment always depends on individual assessment of risks and benefits (15),
but in the absence of clear superiority for either treatment,
patient preference should be a major factor in treatment
selection. Predictive factors (symptoms, personality traits,
circadian measures) of response to light or medication,
and differences in quality of life and cost-benefit of treatments, also should be of interest; analyses of other data
from this study addressing these issues are in progress. Future seasonal affective disorder studies should also examine the combination of light therapy and antidepressants
for nonresponders to monotherapy.
Received Nov. 9, 2004; revision received March 18, 2005; accepted
April 8, 2005. From the Division of Clinical Neuroscience, Department of Psychiatry, University of British Columbia, Vancouver; the
Mood Disorders Centre, UBC Hospital, Vancouver; the University of
Toronto Department of Psychiatry, Toronto; the Mood Disorders Program, Sunnybrook and Women’s College Health Sciences Centre, Toronto; the Mood and Anxiety Disorders Program, Centre for Addiction
and Mental Health, Toronto; the Department of Psychiatry, University of Manitoba, Winnipeg; the Mood Disorders Program, Health Sciences Centre, Winnipeg; and the Department of Psychiatry, Dalhousie University, Saint John, N.B. Address correspondence and reprint
requests to Dr. Lam, Director, Mood Disorders Centre, UBC Hospital,
2255 Wesbrook Mall, Vancouver, BC V6T 2A1; [email protected] (e-mail).
This study was funded by a grant (CT62962) from the Canadian Institutes of Health Research (CIHR) and a CIHR/Wyeth Postdoctoral Fellowship Award to Dr. Michalak. Light boxes were supplied by Uplift
Technologies.
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LIGHT THERAPY VERSUS FLUOXETINE
CME Disclosure
Anthony J. Levitt, M.B.B.S., F.R.C.P.C.: Consultant for Lilly Solutions
for Wellness; Raymond W. Lam, M.D., F.R.C.P.C.: Speaker/Advisory
Boards for AstraZeneca, Biovail, Canadian Network for Mood and
Anxiety Treatments, Eli Lilly, GlaxoSmithKline, Janssen, Litebook
Company, Inc., Lundbeck, Servier, Shire, and Wyeth. He has received
research funds from: AstraZeneca, Canadian Institutes of Health Research, Eli LIlly, GlaxoSmithKline, Janssen, Lundbock, Merck, Roche,
Servier, Vancouver Hospital Foundation, and Wyeth. Dr. Lam will discuss unapproved uses of products discussed in CME programs. Robert D. Levitan, M.D., F.R.C.P.C., Murray W. Enns, M.D., F.R.C.P.C., Rachel
Morehouse, M.D., F.R.C.P.C., Erin E. Michalak, Ph.D., and Edwin M.
Tam, M.D.C.M., F.R.C.P.C. have no conflict of interest to report.
APA policy requires disclosure by CME authors of unapproved or investigational use of products discussed in CME programs. Off-label
use of medications by individual physicians is permitted and common. Decisions about off-label use can be guided by scientific literature and clinical experience.
17. American Psychiatric Association: Practice guideline for the
treatment of patients with major depressive disorder (revision). Am J Psychiatry 2000; 157:1–45
18. Lam RW, Gorman CP, Michalon M, Steiner M, Levitt AJ, Corral
MR, Watson GD, Morehouse RL, Tam W, Joffe RT: Multicenter,
placebo-controlled study of fluoxetine in seasonal affective disorder. Am J Psychiatry 1995; 152:1765–1770
19. Moscovitch A, Blashko CA, Eagles JM, Darcourt G, Thompson C,
Kasper S, Lane RM: A placebo-controlled study of sertraline in
the treatment of outpatients with seasonal affective disorder.
Psychopharmacology 2004; 171:390–397
20. Wirz-Justice A, van der Velde P, Bucher A, Nil R: Comparison of
light treatment with citalopram in winter depression: a longitudinal single case study. Int Clin Psychopharmacol 1992; 7:
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Am J Psychiatry 163:5, May 2006