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UNDERSTANDING ALL THAT IS
DEPRESSION
RICHARD J. METZNER, M.D.
ARS
Pre-Test Questions
ARS
Which of the following is a false statement
concerning depression?
1. Up to half of all patients with major depressive
disorder are not recognized and treated.
2. This percentage is even higher for culturally diverse
patients.
3. Complicated presentation particularly focused on
somatic complaints is one of the barriers to early
recognition and treatment.
4. Most patients with major depressive disorder are
treated by mental health professionals.
5. All of the above.
ARS
Elizabeth is a 40 year old woman who sees you for the
first time complaining of chronic abdominal discomfort,
constant neck and back pain, headache, and recurring
insomnia. She reports frequent anxiety, sometimes which
seems unwarranted. She seems very sad, and notes that
her marriage is in difficulty because she always “just
feels bad.” All of these symptoms have been present for
the past 7 months. Your initial evaluation should focus on
which of the following?
1. Family history, including family history of depressive
disorder
2. Physical examination
3. CT scan of brain
4. MRI of spine
5. All of the above
6. 1 and 2
ARS
After your initial evaluation you identify major depressive
disorder. You decide to initiate antidepressant medication.
Which of the following pieces of information is important
for her understanding and care?
1. Most antidepressant medications have no side effects.
2. She may continue to drink alcohol with whichever
medication you should choose.
3. It is important that she commit to regular follow-up visits
with you.
4. Her medication regimen should be limited to a single
medication.
ARS
You start Elizabeth on an SSRI, and see her back after
one month. She is having side effects including
decreased energy that is causing problems. Her neck
and back pain have improved.
Which of the following have the best likelihood for
success in her care?
1. Combine her SSRI with a catecholaminergic
antidepressant.
2. Change to a dual-mechanism antidepressant.
3. Discontinue her medication and refer for cognitive and
behavioral therapy.
4. 1 or 2
5. All of the above
ARS
Elizabeth comes back after not being seen for 8
months. She notes that she improved after her last
visit, but continued to have problems with abdominal
pain and anxiety. After 3 months she discontinued all
medicine. Which of the following are reasonable
options?
1. Tell her that she will feel better over time without any
treatment.
2. Tell her that the goal of treatment is for her to feel normal
again, and not to have pain or anxiety.
3. Suggest to her that not all medications have the same side
effects, and that there are others that might work better.
4. None of the above.
5. 1 & 2
6. 2 & 3
From recurrence to remission
EXAMPLE
ARS
The primary diagnosis for this patient is most likely:
1. Psychotic depression
2. Bipolar depression
3. Atypical depression
4. Major depression
5. Tay-Sachs disease
6. None of the above
The Most Disabling, Treatable and
Mismanaged Disorder
•
Depression has surpassed all other medical
disorders as the number one cause of
disability in the world
•
Nine out of ten depressed patients will
respond to treatment with antidepressant
medication
•
Only one out of five depressed patients
receives appropriate treatment
Clinical Practice Recommendation
•
Practice Recommendation:
Appropriate diagnosis and treatment of depression by primary care
physicians can prevent unnecessary hospitalizations.
•
Evidence-Based Source:
AHRQ
•
Web Site of Supporting Evidence:
http://www.ahrq.gov/research/jun00/0600RA10.htm#head1
•
Strength of Evidence:
Systematic review of claims database of a large managed care
organization to correlate diagnosis of depression among adults assigned
to a PCP (457 family physicians and internists) with avoidable
hospitalizations for a variety of conditions during 1995.
A common occurrence in medicine
EXAMPLE
ARS
The workup of this patient’s body ache
should include:
1.
2.
3.
4.
5.
a toxicology screen
a PET scan
a lumbar puncture
a bone marrow biopsy
a history of recent
stresses
6. none of the above
STRESS AND MOOD
Stress
Mood
Normal
Adjustment Disorder with
Depression
Minor Depression
Dysthymia
Major Depression/Bipolar
Background history
EXAMPLE
ARS
Genetic factors probably:
1. account for 90% of all susceptibility to depression
2. involve only one or two loci
3. do not involve polymorphisms
4. do not interact with environmental factors
5. all of the above
6. none of the above
GENETICS AND DEPRESSION
• Genetic factors may account for as much as 30% of
the variance in susceptibility to depression
• Functional polymorphisms in promoter regions for
the serotonin transporter may be among these
factors
• It is likely that there are numerous separate loci
combining to form each depressive genotype
• Environmental and internal triggers such as
emotional stress and physical illness act upon these
diatheses to bring about clinical depression
RISK FACTORS FOR DEPRESSION
GENETIC
FAMILY HISTORY
SOMATIC
e.g.,SYSTEMIC ILLNESS
CHRONIC PAIN,
ENDOCRINE DISORDER
PSYCHOLOGICAL
e.g., LOW SELF-ESTEEM,
POOR COPING SKILLS
ENVIRONMENTAL
e.g., UNEMPLOYMENT,
DIVORCE, ABUSE,
BEREAVEMENT
Neurotransmitters offer a well-studied
biochemical bridge between the mind
and the brain.
SEROTONIN SYNTHESIS & METABOLISM
SYNTHESIS
DIETARY PROTEIN
TRYPTOPHAN
5- OH-TRYPTOPHAN
(5-HTP)
SEROTONIN
(5- OH-TRYPTAMINE
or 5-HT)
METABOLISM
MAO
5-HIAA
SYNTHESIS
CATECHOLAMINE SYNTHESIS
& METABOLISM
DIETARY PROTEIN
TYROSINE
NOREPINEPHRINE
L-DOPA
DOPAMINE
MAO
MAO
HVA
METABOLISM
MHPG
Neurotransmitters and normal behavior
SEROTONIN
NOREPINEPHRINE
MODULATION
ACTIVATION
DOPAMINE
•
ADAPTED FROM HEALY AND MCMONAGLE (1997)
Impaired neurotransmission
and reduced neural adaptability
SEROTONIN
SEROTONIN
NOREPINEPHRINE
NOREPINEPHRINE
IMPAIRED
MODULATION
Anxiety
Irritability
Hostility
Impulsivity
Agitation
Hypochondriasis
Suicidality
IMPAIRED
ACTIVATION
DEPRESSION
DOPAMINE
DOPAMINE
Fatigue
Apathy
Anhedonia
Hypersomnia
Lack of initiative
Inability to concentrate
Decreased productivity
THE CYCLE OF STRESS AND DEPRESSION
INCREASED
STRESS
CORTICOSTEROIDS
H
H
PP
A
A
FEEDBACK
FEEDBACK
BDNF
BDNF
DEPRESSION
NEUROTRANSMITTER
DYSFUNCTION
DSM-IV criteria for major depression
•
•
•
•
•
•
•
•
Persistent depressed mood (+)(-)
Anhedonia (+)
Weight loss (+) or gain (-)
Insomnia (+) or hypersomnia (-)
Agitation (+) or retardation (-)
Excessive worthlessness or guilt (+)
Diminished cognitive function (-)
Suicidal ideation (+)
(+)=DEMODULATED
(-)=DEACTIVATED
Clinical Practice Recommendation
•
Practice Recommendation:
Adults should be screened for depression in clinical practices that have
systems in place to assure accurate diagnosis, effective treatment, and
follow-up.
•
Evidence-Based Source:
AHRQ
•
Web Site of Supporting Evidence:
http://www.ahrq.gov/clinic/uspstf/uspsdepr.htm
•
Strength of Evidence:
"B" recommendation
Clinical Practice Recommendation
•
Practice Recommendation:
Depression often coexists with other long-term health problems,
presenting additional complexities. Therefore, patients with
chronic other chronic diseases should be screened for depression.
•
Evidence-Based Source:
AHRQ
•
Web Site of Supporting Evidence:
http://www.ahrq.gov/research/deprqoc.htm
•
Strength of Evidence:
Consensus statement
DEPRESSION ASSESSMENT TOOLS
http://www.neurotransmitter.net/depressionscales.html
•
•
PROFESSIONALLY- RATED
–
HAMILTON DEPRESSION RATING SCALE (HDRS) -17 item, 21 item &
other versions
–
MONTGOMERY ASBERG DEPRESSION RATING SCALE (MADRS)
SELF-RATING SCALES
–
BECK DEPRESSION INVENTORY (BDI)
–
ZUNG SELF RATED DEPRESSION SCALE (ZUNG SRS)
–
HOSPITAL ANXIETY AND DEPRESSION SCALE (HADS)
–
MAJOR DEPRESSION INVENTORY (MDI)
–
HARVARD NATIONAL DEPRESSION SCREENING SCALE
–
GOLDBERG DEPRESSION & MANIA SCALES
–
DEPRESSION ANXIETY STRESS SCALES (DASS)
–
CLINICALLY USEFUL DEPRESSION OUTCOME SCALE (CUDOS)
–
TARGETED TREATMENT DEPRESSION INVENTORY
Deactivation, demodulation & distress items in 13
mood measuring scales (larger areas = more items)
DEACTIVATION
DEMODULATION
RATIO = 4:6:3
DISTRESS
Ratio of demodulation to deactivation items in
same scales(red bars are approximately 1:1)
The TTDI
is the first depression test designed to guide AD treatment
•
•
The Targeted Treatment of
Depression Inventory is a free
self-administered, computerscored 17-item questionnaire
which has been tested for over
5 years in primary care and
psychiatric offices throughout
the U.S.
Preliminary studies on more
than a thousand patients
indicate that it rapidly provides a
quantified measure of
demodulation and deactivation
that can help guide
antidepressant selection.
TTDI test: distinguishing features
•
•
www.ttdi.info
•
High reliability bivalent scales
(minus and plus values) designed
to measure severity of
depression, mania and emotional
blunting
Two independent subscales modulation (M) and activation (A)
for diagnosing subtypes and
guiding choice of antidepressants
Single depression score (D=
M+A) to measure overall severity
REMISSION RATES AND SCORE CHANGES USING TTDI
IN PRIMARY CARE AND PSYCHIATRIC SETTINGS
∆ SCORE = -13.8*
N=61
∆ SCORE = -12.1*
N=36
∆ SCORE = -4.9†
N=20
* p<.001
† n.s.
t=5.7 weeks
t=5.1 weeks
t=6.9 weeks
TARGETED
TREATMENT
PARTIALLY
TARGETED
UNTREATED
Metzner and Ho, unpublished data, August, 2008
SSRI more effective in anxious depression;
Catecholaminergic better in retarded depression
IMPROVEMENT
P<.01
P<.01
ANXIOUS
RETARDED
CITALOPRAM
REBOXETINE
A 16 week double-blind study of post-stroke depressed patients; improvement was
measured using a 26-symptom subtyping scale
Rampello, et al, 2004
Depressive symptoms correlate with
different neuroanatomic structures
HAM-D vs. PET scan
n=298
HYPERLIMBIC
HYPOCORTICAL
DEMODULATED items, e.g.,
insomnia, suicidality
DEACTIVATED items, e.g.,
apathy, low libido
Milak MS, et al, Arch Gen Psych, 62:2005.
Three functional subtypes
SUBTYPE
DEMODULATED
TRADITIONAL
TERMS
anxious, agitated,
hostile, hypochondriacal
OPTIMAL TREATMENT
serotonergic
DEACTIVATED
psychomotor-retarded,
blunted, apathetic
catecholaminergic
MIXED
melancholic, atypical,
resistant
dual-mechanism
Metzner R, APA Annual Meeting, 2000
Three functional subtypes (cont.)
SUBTYPE
DEMODULATED
ENERGY
same or
increased
REACTIVITY
increased
SLEEP
decreased
DEACTIVATED
decreased
decreased
increased
MIXED
variable
variable
variable
Metzner R, APA Annual Meeting, 2000
ARS
Which of the following statements is
false:
1. Demodulated patients are often anxious and/or hostile
and may respond better to SSRI’s
2. Deactivated patients are frequently fatigued and/or
apathetic and may do best with catecholaminergic AD’s
3. Mixed patients are a combination of the above and may
improve most on dual-mechanism regimens
4. There is no test for identifying these subtypes and
determining appropriate treatment
CASE EXAMPLE 1: DEMODULATED
30 yo male software expert who became severely anxious
and depressed over financial and personal problems.
M=17
M=0
4 WEEKS LATER
Treatment with an SSRI brought full recovery. He continues
to take it and has improved his life in many ways.
CASE EXAMPLE 2: DEACTIVATED
75 yo former nurse with bipolar disorder whose MD was afraid
to treat her depression and possibly induce manic switching.
Bupropion plus a mood stabilizer relieved her depression.
A=20
M=-11
A=2
M=3
5 WEEKS LATER
CASE EXAMPLE 3: MIXED
31 yo married working mother with low energy, crying spells,
and high irritability.
DEACTIVATION
DEMODULATION
A=13
M=13
25
20
15
10
5
0
2 WEEKS LATER
BUPROPION
A=0
M=14
4 WEEKS LATER
BUPROPION
ESCITALOPRAM
A=0
M=0
She continues to do well on her combined regimen.
ANTIDEPRESSANTS
DEMODULATED
SSRI:
CITALOPRAM (CELEXA), ESCITALOPRAM
(LEXAPRO), FLUOXETINE (PROZAC),
PAROXETINE (PAXIL) or SERTRALINE
(ZOLOFT)
DEACTIVATED
BUPROPION (WELLBUTRIN) SR or XL
MIXED (PRIMARY OR
SECONDARY)
SSRI + BUPROPION SR or XL; or
DULOXETINE (CYMBALTA), MIRTAZEPINE
(REMERON), or VENLAFAXINE (EFFEXOR)
XR
Avoiding oversedation
EXAMPLE
ARS
Treating depression with
benzodiazepines/sedatives
1.
2.
3.
4.
5.
6.
7.
can result in iatrogenic addictive disorders
is preferable to using sedating antidepressants
is the same as using atypical neuroleptics
may be useful on a short-term basis
1 and 4
3 and 4
none of the above
TREATMENT SUMMARY (continued)
ATYPICAL
NEUROLEPTICS
ARIPIPRAZOLE (ABILIFY)
OLANZAPINE (ZYPREXA)
PALIPERIDONE (INVEGA)
QUETIAPINE (SEROQUEL)
RISPERIDONE (RISPERDAL)
ZIPRASIDONE (GEODON)
MOOD STABILIZERS
CARBAMAZEPINE (TEGRETOL)
LAMOTRIGINE (LAMICTAL)
LITHIUM (LITHOBID)
VALPROIC ACID (DEPAKOTE)
Adjunctive treatment
EXAMPLE
ARS
Treating depression adjunctively with
atypical neuroleptics:
1.
2.
3.
4.
5.
6.
can improve results in resistant patients
has advantages over benzodiazepines
may be associated with weight gain
should be carefully monitored in geriatric patients
all of the above
none of the above
KEY QUESTIONS IN EVALUATING
DEPRESSION
1. Is the patient suicidal? YES? Start SSRI
2. Is the patient bipolar? YES? Start atypical
neuroleptic or mood stabilizer before
antidepressant
3. Can the patient identify the source of sadness
or worry, (e.g., my marriage, job, health, etc.)?
YES? Consider psychotherapy referral in
addition to medication
PSYCHOTHERAPY IN A NUTSHELL
•
•
•
COGNITIVE-BEHAVIORAL
– IDENTIFY DEPRESSIVE THOUGHTS
– DEVELOP ALTERNATIVES
– PRACTICE THEM OUTSIDE OF THERAPY
PSYCHODYNAMIC
– IDENTIFY OLD PATTERNS
– LINK THEM TO PRESENT PROBLEMS
– WORK THEM OUT IN THERAPY
INTERPERSONAL
– IDENTIFY SOCIAL DEFICITS AND
DYSFUNCTIONS
– CORRECT THEM
One out of five patients with diagnosed
depression* meets the SPAQ criteria for
SAD
Lifetime History
of Diagnosed
Depression*
SPAQ-Classified SAD
20.2%*
are SPAQclassified
SAD
N = 13,358
*Self-reported, physician-diagnosed depression
SPAQ = Seasonal Pattern Assessment Questionnaire
Rosenthal NE et al. Poster presented at the 158th Annual Meeting of the American Psychiatric Association;
Atlanta, Ga: May 21–26, 2005.
Light therapies1
•
Equipment typically costs from $200 to $500
•
Can be ordered online without a prescription
•
May not be covered by insurance
•
Light should come from above line of sight
•
Patient should avoid looking directly at light
source
•
Reduced UV light is preferable
•
Contraindicated in patients with skin or eye
photosensitivities
•
May induce manic episode
1http://www.mayoclinic.com/health/seasonal-affective-disorder/MH00023
OTHER TARGETS
WHEN TO REFER A PATIENT TO A
MENTAL HEALTH PROFESSIONAL
•
•
•
•
•
ARE YOU WITHIN YOUR COMFORT LEVEL?
IS THE PATIENT TAKING TOO MUCH OF YOUR
TIME?
ARE THE PSYCHOTROPIC DOSAGES YOUR
USED TO USING INSUFFICIENT?
IS SUICIDALITY OR SOME OTHER DEVIANT
BEHAVIOR A CONCERN?
IS PSYCHIATRIC HOSPITALIZATION A
POSSIBILITY?
Probability of
remaining symptomfree (%)
Incomplete Remission Predicts Greater
Relapse*
100
80
(Remission)
60
(Response)
40
20
0
0
2
4
6
8
Months of follow-up
10
12
*After termination of cognitive behavior therapy for depressed patients.
Thase ME et al. Am J Psychiatry. 1992;149:1046-1052.
Consequences of Failing to
Achieve Remission
•
•
•
•
•
•
Greater risk of relapse
Continued psychosocial limitations
Continued impairments at work
Worsened prognosis of Axis III disorders
Increased utilization of medical services
Sustained elevation of suicide and
substance abuse risks
Thase M. Defining Remission in Patients Treated with Antidepressants. J Clin Psychiatry. 1999;60(suppl 22)3-6.
Hirschfeld RMA, Keller MB, Panico S et al. The National Depressive and Manic Depressive Association
Consensus Statement on the Undertreatment of Depression. JAMA. 1997;277:333-340.
Treating depression to remission is
rewarding for all concerned
EXAMPLE
Information on the TTDI test is available at
www.ttdi.info
ARS
Post-Test Questions
ARS
Which of the following is a false statement
concerning depression?
1. Up to half of all patients with major depressive
disorder are not recognized and treated.
2. This percentage is even higher for culturally diverse
patients.
3. Complicated presentation particularly focused on
somatic complaints is one of the barriers to early
recognition and treatment.
4. Most patients with major depressive disorder are
treated by mental health professionals.
5. All of the above.
ARS
Elizabeth is a 40 year old woman who sees you for the
first time complaining of chronic abdominal discomfort,
constant neck and back pain, headache, and recurring
insomnia. She reports frequent anxiety, sometimes which
seems unwarranted. She seems very sad, and notes that
her marriage is in difficulty because she always “just
feels bad.” All of these symptoms have been present for
the past 7 months. Your initial evaluation should focus on
which of the following?
1. Family history, including family history of depressive
disorder
2. Physical examination
3. CT scan of brain
4. MRI of spine
5. All of the above
6. 1 and 2
ARS
After your initial evaluation you identify major depressive
disorder. You decide to initiate antidepressant medication.
Which of the following pieces of information is important
for her understanding and care?
1. Most antidepressant medications have no side effects.
2. She may continue to drink alcohol with whichever
medication you should choose.
3. It is important that she commit to regular follow-up visits
with you.
4. Her medication regimen should be limited to a single
medication.
ARS
You start Elizabeth on an SSRI, and see her back after
one month. She is having side effects including
decreased energy that is causing problems. Her neck
and back pain have improved.
Which of the following have the best likelihood for
success in her care?
1. Combine her SSRI with a catecholaminergic
antidepressant.
2. Change to a dual-mechanism antidepressant.
3. Discontinue her medication and refer for cognitive and
behavioral therapy.
4. 1 or 2
5. All of the above
ARS
Elizabeth comes back after not being seen for 8
months. She notes that she improved after her last
visit, but continued to have problems with abdominal
pain and anxiety. After 3 months she discontinued all
medicine. Which of the following are reasonable
options?
1. Tell her that she will feel better over time without any
treatment.
2. Tell her that the goal of treatment is for her to feel normal
again, and not to have pain or anxiety.
3. Suggest to her that not all medications have the same side
effects, and that there are others that might work better.
4. None of the above.
5. 1 & 2
6. 2 & 3