Download Depression

Anxiety And Depression
Dennis Mungall , Pharm.D.
Director,Virtual Education, Non traditional Doctor of Pharmacy Program
Associate Professor , Pharmacy Practice
Ohio State University/ College of Pharmacy
Learning Objectives
1. Understand the various anxiety disorders ,
Depression and how each disorder presents
2. Understand the treatment strategies for each
disorder
3. Understand the signs and symptoms of each
disorder
4. Understand the consequences to the health care
system of anxiety and depression
History of Depression
It is thought that ancient man saw
mental illness as possession by
supernatural forces. Ancient human
skulls have been found with large holes in
them, a process that has become known
as trepanning. The accepted theory is that
it was an attempt to let evil spirits out. We
cannot be certain of this, but we do know
that again and again human kind has
returned to the idea of mental illness
being caused by “evil forces”.
History of Depression
And yet in certain of these cases there is mere anger
and grief and sad dejection of mind………those
affected with melancholy are not every one of them
affected according to one particular form but they are
suspicious of poisoning or flee to the desert from
misanthropy or turn superstitious or contract a hatred
of life. Or if at any time a relaxation takes place, in
most cases hilarity supervenes. The patients are dull
or stern, dejected or unreasonably torpid……they also
become peevish, dispirited and start up from a
disturbed sleep.”
Arateus (AD 150)
History of Depression
Hippocrates (460-377 BC) lived at the time of
Hellenic enlightenment, when great advances were
made in all areas of knowledge. He applied Empedocles’
theory to mental illness and was insistent that all illness
or mental disorder must be explained on the basis of
natural causes. Unpleasant dreams and anxiety were
seen as being caused by a sudden flow of bile to the
brain, melancholia was thought to be brought on by an
excess of black bile4, and exaltation by a predominance
of warmth and dampness in the brain. Temperament
was thought to be choleric, phlegmatic, sanguine or
melancholic depending on the dominating humor
History of Depression
By the end of the fifteenth century psychological
problems were greatly entwined with legal and religious
issues and were not seen alone. The devil was seen as
the cause of all ills .Mental disorder was equated with
sin. They also stated that where doctors could find no
cause for a disease and where the disease did not
respond to traditional treatment it was caused by the
devil. A witch was stripped and her pubic hair was
shaved before presentation to judges, so that the devil
would have nowhere to hide. On being found guilty a
witch would be burnt at the stake. Literally hundreds of
thousands of women and children suffered this fate and
probably many of the mentally ill.
History of Depression
• Robert Burton’s anatomy of melancholy appeared for
the first time in 1621.2 He described in detail the
psychological and social causes (such as poverty, fear
and solitude) that were associated with melancholia
and seemed to cause it
• In Early nineteenth century Heinroth believed that sin
was the causal factor in mental illness. Not sin in the
theological sense, but the offending of an individual’s
morals by their own thoughts. He was referring to an
internal conflict
• The man who exemplified the hard-nosed scientific feel
of this era was the German psychiatrist Wilhelm
Griesinger (1817-1868). For him mental diseases were
somatic diseases6, and the cause of mental illness was
always to be found in the brain. He firmly believed that
psychiatry and neuropathology were one
History of Depression
• Freud successfully realised was that
neurophysiological and psychological
knowledge need not be contradictory.
• Psychoanalysis predominated until the
1970s, which was followed by renewed
interest in genetic, biochemical and
neuropathological causes of mental
disorder which came to be known as
biological psychiatry
Introduction
Lifetime Prevalence of Depression and Anxiety
Disorders
Comparision with Other
Medical Conditions
Sx Overlap of Anxiety and
Depression
Sx Overlap ( cont.)
Physical Symptoms
Risk Of Psychiatric Disorder
Percent
Physical Symptoms (#)
Kroenke et al. Arch Fam Med. 1994;3:774.
Somatic Symptoms In Mood And Anxiety Disorders
Fatigue
Headache
Abdominal Pain
Chest Pain
Insomnia
Fainting
0
10
20
Mood Disorder
Kroenke et al. Arch Fam Med. 1994;3:774.
30
40
50
Anxiety Disorder
60
70
Lifetime Rates Of Anxiety Disorders In
Alcohol-Dependence
**
10
9
8
7
Rates 6
5
4
3
2
1
0
*
**
Panic
Agoraphobia
Control
Social
Anxiety
Disorder
OCD
Any Anxiety
Disorder
Alcohol-Dependent
Mood/Anxiety Disorder
Occurring Prior To Substance Dependence
100
80
Percent
60
40
20
0
Mood Disorder
Alcohol Dependence
Merikangas et al. Psychologic Med. 1998;28:773.
Anxiety Disorder
Drug Dependence
Primary Care Presentation
Anxiety and Depression in
Primary Care
Depression and Gender
Days Lost from Work
Costs of Depression in the United
States
Costs of Depression in the United States
Cost Center
Amount ($ billion)
Direct costs
Inpatient care
Outpatient care
Partial care
Pharmaceuticals
8.3
2.8
0.1
1.2
Total direct costs
12.4
Indirect costs
Absenteeism
Decreased
productivity
Suicide
Total indirect costs
11.7
2.1
7.5
31.3
Recovery Rates
Relapse Rates
Utilizers of Medical Care
Depression
Case Study
Depression Prevalence
Morbidity and Mortality
Morbidity and Mortality
Suicide
Depression : DSM IV
Major Depressive
Episode:Criteria
Criteria (cont.)
Hamilton Rating Score for
Depression
Interview Techniques
• Depressed or
Down
• Restless
• Fatigued
• Guilty
• Inability to
Concentrate
Associated Features
Associated Features (cont.)
Depression Risk Factors
• Prior episodes
• Recent childbirth
• Family history
• Medical comorbidity
• Prior suicide attempts
• Alcohol or substance
abuse
• Female gender
• Recent separation or
bereavement
Depression Guideline Panel. Depression in Primary Care: Volume 1. Detection and Diagnosis.
Clinical Practice Guideline, Number 5. Rockville, MD. U.S. Department of Health and Human Service,
Public Health Service, Agency for Health Care Policy and Research. AHCPR Publication No. 93-0550. April 1993.
Recurrent Depression Risk Factors
• Inadequate treatment
• Poor medication compliance
• Frequent +/- multiple episodes
• Preexisting dysthymia
• Onset after age 60
• Long duration or severe index episode
• Seasonal pattern
• Familial mood disorders
• Comorbid anxiety or substance abuse disorder
Factors Complicating Diagnosis Of
Late Life Depression
• Comorbid general medical/neurologic illness
• Cognitive decline
• Multiple losses/bereavement
Disease Management
Depression Treatment Outcome
The Five Rs
Remission
Recovery
Relapse
Response
Recurrence
x
x
Symptoms
x
Syndrome
Treatment Phases
Acute 6-12
Weeks
Kupfer. J Clin Psychiatry. 1991;52(Suppl 5):28.
Continuation
4-9 Months
Maintenance
 1 Year
Response to Therapy
Relapse
Compliance
Guidelines
Criteria For An Adequate Trial Of Antidepressant
Treatment
• Accurate diagnosis
• Appropriate antidepressant
• Adequate dose/duration
Initial Approach to RX
Initial Approach to RX
Initial Approach to RX
Choosing an Antidepressant
Long Term Treatment Strategies
Rules of Dosing
Serotonin Side Effects
Pharmacokinetics of
Antidepressants
Drug Interactions
Treatment Choices
Treatment Choices ( cont.)
Treatment Choices ( cont.)
Treatment Summary
Strategies In Treatment Resistant Depression
• Maximize dose
• Augmentation:
– Thyroid hormone (T3 > T4)
– Lithium (levels  0.7 mEq/mL)
• Combination therapy: eg, SSRI/TCA
• Other:
– MAOIs
– ECT
- venlafaxine
SSRIs And Sexual Dysfunction
• Common, class effect
• Affects men and women
• Reduced libido
• Dysfunctional orgasm
– delayed ejaculation
– inability to ejaculate
– anorgasmia
Keller-Ashton et al. J Sex Marital Ther. 1997;23:165.
Segraves. J Clin Psychiatry. 1998;59(Suppl 4):48.
SSRI - Related Sexual Dysfunction
Potential Management Strategies
• Tolerate sexual dysfunction in favor of optimal therapeutic
response
•  Dose (or consider drug holiday), but monitor for relapse
• Beneficial in case reports: bupropion, buspirone, amantadine,
bromocriptine, methylphenidate, yohimbine, gingko biloba
• Consider alternate antidepressant
Keller-Ashton et al. J Sex Marital Ther. 1997;23:165.
Segraves. J Clin Psychiatry. 1998;59(Suppl 4):48.
Rothschild. Am J Psychiatry. 1995;152:1514.
Antidepressants And Weight Gain
• Weight gain associated with TCAs, MAOIs, SSRIs, and
newer antidepressants
•  Appetite, weight loss associated with depression;
therapeutic response may increase weight to normal
• Weight gain during SSRI therapy has not been systematically
studied
TCAs: Enhanced Side Effects In The Elderly
• Sedation
• Anticholinergic effects
• Orthostatic hypotension
• Cardiac toxicity
Anticancer Drugs Associated With Depression
• Corticosteroids
• Vinblastine
• Interferon
• Vincristine
• Asparaginase
• Procarbazine
• Cyproterone
• Tamoxifen
Massie et al. J Pain Symptom Manage. 1994;9:325.
Risk Factors For Suicide In Cancer Patients
• Current or prior suicidality
• Depression
• Psychosis/irrational
thinking
• Substance abuse
• Recent loss
• Poor social support
• Older male
Massie et al. J Pain Symptom Manage. 1994;9:325.
•
•
•
•
Uncontrolled pain
Advanced disease
Poor prognosis
Cancer site (head/neck,
lung, GI, urogenital,
breast)
• Exhaustion/fatigue
Dysthymia: Criteria
Treatment of Dysthymia
Generalized Anxiety
Disorder: Excessive Chronic
Anxiety and Worry
DSM IV Classification
Case Studies : GAD
Acute Anxiety
Chronic Anxiety
Uncontrolled Anxiety
Symptom Overlap In GAD And Depression
Depression
GAD
•
•
•
•
Interest
Appetite
Esteem
Suicide
•
•
•
•
•
•
Agitation
Dysphoria •
•
Sleep
•
Fatigue
Concentration
Roy-Byrne et al. J Clin Psychiatry. 1997;58(Suppl 3):34.
Restlessness
Tension
Irritability
Worry
Criteria
GABA
Benzodiazepines
Rx of GAD
Treatment
Rx of GAD
Social Phobia/Social Anxiety
Disorder : Fear of Scrutiny
Case Study: Social Anxiety
DSM-IV Social Anxiety Disorder
• Fear/avoidance of social situations
• Feared situations avoided or endured with
intense anxiety or distress
• Fear recognized as excessive or unreasonable
• Fear/avoidance interferes with work, social,
family activities
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC,
American Psychiatric Association, 1994.
Prevalence Of Social Anxiety Disorder
20
15
14.4
13.3
Prevalence
(%) 10
5
4.5
4.9
0
General Population*
Lifetime Prevalance
* Magee et al. Arch Gen Psychiatry. 1996;53:159.
**Weiller et al. Br J Psychiatry. 1996;168:169.
Primary Care**
One-month Prevalence
Common Somatic Complaints
Palpitations
“Butterflies”
Sweating
Beidel. J Clin Psychiatry. 1998;59(Suppl 17):27.
Trembling/
Shaking
Blushing
Differential Diagnosis
Social Anxiety Disorder And Agoraphobia
Disorder
Common Fear
Key Concerns
Social
Anxiety
Disorder
Fear of negative
Public scrutiny
evaluation or
humiliation in social or
performance situations
Avoids speaking,
eating, drinking,
writing, or using
restrooms
only in public
Agoraphobia
Fear that help won’t
be available or
escape won’t be
possible
Avoids being alone
or away from
home; being in a
crowd; traveling in
a car, bus or
airplane; or being
on a bridge or in an
elevator
Being caught in
situation where
escape may be
difficult
Example
Differential Diagnosis
Social Anxiety Disorder And Panic Disorder
Disorder
Common Fear
Key Concerns
Social
Anxiety
Disorder
Fear of negative
Public scrutiny
evaluation or
humiliation in social or
performance situations
Avoids speaking,
eating, drinking,
writing, or using
restrooms
only in public
Panic
Disorder
Fear of having a
heart attack, dying,
or “going crazy”
Discrete attacks
about 10 minutes,
including chest
pain, fear of dying,
or smothering
sensations/avoids
places where
attacks have
occurred
Sudden,
unexpected
panic attacks
alone or in
public; not
exclusively
limited to social
situations
Example
Differential Diagnosis
Social Anxiety Disorder And GAD
Disorder
Common Fear
Social
Anxiety
Disorder
Fear of negative
Public scrutiny
evaluation or
humiliation in social or
performance situations
Generalized Fear of everyday
Anxiety
routine, life
Disorder
circumstances, e.g.
job, finances, health,
or minor matters
Key Concerns
Anxiety/worry
shifting from
one concern to
another - no
fear of social
situations
Example
Avoids speaking,
eating, drinking,
writing, or using
restrooms
only in public
Worries almost
constantly about
routine, everyday
matters
Screening Questions For Social Anxiety Disorder In
Primary Care
• Are you afraid of being scrutinized in public?
• Do you fear speaking to others?
• Do you avoid social situations or events?
Social Anxiety Disorder
Common Fears
• Participating in small groups
• Eating, drinking, writing in public
• Talking to authority figures
• Performing or giving a talk
• Attending social events
• Working while being observed
• Meeting strangers or dating
• Using public bathroom
• Being center of attention
Social Anxiety Disorder
• Distinguishable from other anxiety disorders
• Very common, but undiagnosed, undertreated,
costly
• Effectively treated with SSRIs +/- psychotherapy
• Easily screened with patient self-rated
questionnaire
Social Anxiety Disorder Treatment Goals
• Reduce anxiety/phobic avoidance
• Reduce disability
• Treat depression/other comorbidities
• Choose therapy that is tolerable over long-term
Davidson. J Clin Psychiatry. 1998;59(Suppl 17):47.
Treatment
Benzodiazepine Treatment Of Social Anxiety Disorder
• Can be effective
• Potential problems in patients with
alcohol/substance abuse
• Not effective for comorbid depression
• Side effects
– disruption of cognitive function/sedation
– tolerance/dependence/withdrawal
Fluvoxamine Treatment Of Social Anxiety Disorder
60
50
50
Responders 40
(%)
30
20
7
10
0
Fluvoxamine
Placebo
Treatment Group (N = 30)
van Vliet et al. Psychopharmacology. 1994;115:128.
Sertraline Treatment Of Social Anxiety Disorder
60
50
50
Responders 40
(%)
30
20
9
10
0
Sertraline
Placebo
Treatment Group (N = 12)
Katzelnick et al. Am J Psychiatry. 1995;152:1368.
Paroxetine Treatment Of Social Anxiety Disorder
45
40
35
%
Improvement 30
25
Over
Baseline
20
15
10
5
0
*
*
*
†
Avoidance
Fear/
Anxiety
Paroxetine (N=90)
* P<.001 † P=.03 ‡ P=.17
Stein et al. JAMA. 1998;280:708.
Social Life
Work
‡
Family Life
Placebo (N=92)
Monoamine Oxidase Inhibitor Treatment Of
Social Anxiety Disorder
• Irreversible, nonselective
– effective
– poorly tolerated
– hazardous
• Reversible, selective
– moderate effectiveness
– well tolerated
– not available in US
MAOI: Diet
-Blocker Treatment Of Social Anxiety Disorder
• Effective for mild, occasional performance anxiety
• Not effective in generalized social anxiety disorder
• Will not treat comorbid conditions
• Very limited role
Tricyclic Antidepressant Treatment Of
Social Anxiety Disorder
• Doubtful efficacy
• Poor side effect profile
–
–
–
–
–
sedation, tremor, dry mouth
effects on cognitive function
sexual dysfunction
weight gain
constipation
Conclusions: Social Anxiety Disorder
• Frequently undiagnosed and untreated
• Presents as marked and persistent fear of social or
performance situations or with physiologic
symptoms
• Treatment options: psychosocial and pharmacologic
– SSRIs show most promise
Panic Disorder: Spontaneous
panic attacks
Case Study : Panic
Criteria For Panic Attacks
Other Causes of Panic Sx
Other Causes of Panic Sx
Rx: Panic Disorder
Benzodiazepines
Clonazepam
Benzodiazepines (cont.)
Antidepressants
Antidepressants (cont.)
Post Traumatic Stress
Disorder
PTSD : Case Study
Prevalence Of PTSD
12
10
8
6
4
2
0
15 - 24
25 - 34
35 - 44
Males
45 - 54
Total
Females
Core Features Of PTSD
Trauma
•
•
•
•
Intrusive symptoms
Avoidance behavior
Numbing
Hyperarousal
symptoms
Criteria
Non-Combat Related Trauma Associated With PTSD
30
25
Incidence
20
(%)
15
10
5
0
Rape
Molestation
Males
Kessler et al. Arch Gen Psychiatry.
1995;52:1048.
Physical
Attack
Accident
Females
Physical
Abuse
Diagnosis Of PTSD In Primary Care
• Must specifically ask about trauma
• Assess presence of core symptoms
• Patient self-rated scales (eg Impact of Event Scale,
MINI)
• Assess comorbidity (depression, substance use
disorders, anxiety disorders)
Treatment Of PTSD
• Education
• Support
• Anxiety management
– pharmacotherapy
– psychotherapy
• Lifestyle modification
SSRI Treatment Studies
Non-Combat Related PTSD
:
Author
N
Regimen
Outcome
Van Der Kolk
et al. 1994
64*
Flu vs. Pbo;
5 weeks
Significant  symptoms
with Flu
Davidson
et al. 1991
5
Flu;
8 - 32 weeks
 Intrusive and
avoidant symptoms
Rothbaum
et al. 1996
7
Ser;
12 weeks
 Symptoms in 4/5
responders
Marshall
et al. 1998
19
Par;
12 weeks
Significant  all core
symptoms
* Including 31 cases of combat related PTSD
Davidson et al. J Trauma Stress. 1991;4:419.
Marshall et al. J Clin Psychopharmacol. 1998;18:10.
Rothbaum et al. J Trauma Stress. 1996;9:865.
Van Der Kolk et al. J Clin Psychiatry. 1994;55:517.
Treatment