Transcript Introduction to Working with the Asian Patient in Primary Care

Current Issues in Depression and
Bipolar Disorder
Descartes Li, M.D.
Associate Professor of Clinical Psychiatry
University of California, San Francisco
[email protected]
7/21/2015
By the end of the seminar, a participant
should:
Describe efficacy of using first line antidepressants for Major
Depression in primary care.
Understand the STAR*D results regarding augmentation and
switch strategies in antidepressant treatment.
Identify the key diagnostic signs and symptoms of Bipolar
Disorder.
Be aware of high rates of bipolar disorder in primary care
settings and in the general population.
Major Depressive Episode:
SIG E CAPS criteria
Depressed mood (or anhedonia), plus:
 S –Sleep symptoms
 I—lack of Interest.
 G—feelings of Guilt

E—lack of Energy.

C--lack of Concentration.
A--lack of Appetite.
P--Psychomotor changes
S--thoughts of Suicide
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Major Depressive Episode: DSM IV Criteria
Five (or more) of the following symptoms have been
present during the same 2-week period and represent a
change from previous functioning; at least one of the
symptoms is either (1) depressed mood or (2) loss of
interest or pleasure.
1. depressed mood most of the day, nearly every day, as
indicated by either subjective report (e.g., feels sad or
empty) or observation made by others (e.g., appears
tearful). (In children and adolescents, this may be
characterized as an irritable mood.)
2. markedly diminished interest or pleasure in all, or
almost all, activities most of the day, nearly every day
3. significant weight loss when not dieting or weight gain
(e.g., a change of more than 5% of body weight in a
month), or decrease or increase in appetite nearly
every day.
4. insomnia or hypersomnia nearly every day
Major Depressive Episode: DSM IV Criteria
(continued)
5. psychomotor agitation or retardation nearly every day
6. fatigue or loss of energy nearly every day
7. feelings of worthlessness or excessive or inappropriate
guilt nearly every day
8. diminished ability to think or concentrate, or
indecisiveness, nearly every day
9. recurrent thoughts of death (not just fear of dying),
recurrent suicidal ideation without a specific plan, or a
suicide attempt or a specific plan for committing
suicide.
Major Depressive Disorder
Treatments
Psychopharmacological:
SSRI’s, TCA’s, MAOI’s, psychostimulants
 Psychosocial (may also be used first-line):
Cognitive-behavioral therapy, interpersonal therapy
 Somatic:
Electroconvulsive therapy, transcranial magnetic
stimulation, vagal nerve stimulation (efficacy remains
unclear)

N.B. All treatments for major depression about equally
efficacious (ECT may be a bit better)
What percentage of patients have
a successful outcome with an
initial trial of antidepressant?
(How does pharma make their drugs look good?)
Current Issues in Depression
Sequenced treatment alternatives to relieve
depression (STAR*D)
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2,876 outpatients started on citalopram
“real world” practices: mixed psychiatric and primary care
settings
Only exclusions: schizophrenia, bipolar disorder, eating
disorders, OCD
Advocated usage of standardized depression measure
each visit (Quick Inventory of Depressive Symptoms)
available free at http://www.ids-qids.org/
Not placebo-controlled, therefore unblinded
Evaluation of Outcomes with Citalopram for Depression Using Measurement-Based Care in
STAR*D: Implications for Clinical Practice. Trivedi et al. Am J Psychiatry 2006; 163:28-40.
Current Issues in Depression
Sequenced treatment alternatives to relieve
depression (STAR*D)
The average STAR*D patient:
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Six prior episodes of depression
Continuously depressed for two years
Recurrent episodes over the past 15 years
Three or more medical conditions
Education below college level
Evaluation of Outcomes with Citalopram for Depression Using Measurement-Based Care in
STAR*D: Implications for Clinical Practice. Trivedi et al. Am J Psychiatry 2006; 163:28-40.
Current Issues in Depression
Sequenced treatment alternatives to relieve
depression (STAR*D) – Steps one and two
Step One: citalopram (Celexa) up to 60mg/d
Step Two:
switch to venlafaxine (Effexor) XR, bupropion
(Wellbutrin) SR, sertraline (Zoloft) or cognitive therapy
OR
augment with buspirone (Buspar), bupropion SR or
cognitive therapy
Evaluation of Outcomes with Citalopram for Depression Using Measurement-Based Care in
STAR*D: Implications for Clinical Practice. Trivedi et al. Am J Psychiatry 2006; 163:28-40.
Current Issues in Depression
STAR*D study
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Remission rates were 32.9%, response rate was 47%
(QIDS-SR)
No difference in response rates between primary care
and psychiatric settings
Mean exit dosage = 41.8mg/d
(started at 20mg/d; inc. to 40mg/d by week 4, 60mg/d by week 6)

Most subjects responded by week 8
Evaluation of Outcomes with Citalopram for Depression Using Measurement-Based Care in
STAR*D: Implications for Clinical Practice. Trivedi et al. Am J Psychiatry 2006; 163:28-40.
Figure 3: Percent
of patients who
achieved
response or
remission
Current Issues in Depression
STAR*D study
Baseline features associated with response/remission:
Caucasian (24% non-Caucasian subjects)
Female, better educated, better paid
Having private insurance, fewer concurrent
medical/psychiatric conditions, greater life satisfaction,
shorter current episode
Being married or living with someone
Evaluation of Outcomes with Citalopram for Depression Using Measurement-Based Care in
STAR*D: Implications for Clinical Practice. Trivedi et al. Am J Psychiatry 2006; 163:28-40.
What percentage of patients
respond to a switch in therapy?
Switching Antidepressants:
STAR*D
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Unblinded, no placebo
Patients had a choice: switch or augment
 Therefore, the patients who switched who those
who tended to have more side effects and less
initial benefit
 Patients randomly (equipoise) switched to
bupropion, sertraline, or venlafaxine XR.
Bupropion-SR, Sertraline, or Venlafaxine XR After Failure of SSRI’s for Depression. AJ Rush et
al. NEJM 2006, 354:1231-42.
Switching Antidepressants
56% could not tolerate CIT
250 VEN XR
62 (25.0%) remit
194mg/d avg dose
Bupropion-SR, Sertraline, or Venlafaxine XR After Failure of SSRI’s for Depression. AJ Rush et
al. NEJM 2006, 354:1231-42.
What percentage of patients
respond to an augmentation to
their original SSRI?
Augmenting Antidepressants
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Random (equipoise) design between bupropion and
buspirone
Unblinded, no placebo
Recall: patients had a choice: switch or augment
 Many of these patients had a partial response to
citalopram
Medication Augmentation after the Failure of SSRIs for Depression. Trivedi MH et al. NEJM
2006, 354:1243-52.
Augmentation of SSRI
Medication Augmentation after the Failure of SSRIs for Depression. Trivedi MH et al. NEJM
2006, 354:1243-52.
QIDS = Quick Inventory of Depressive Symptoms
Conclusions from STAR*D
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Citalopram treatment requires relatively high dose
(40-60mg/d) and at least 8 weeks
Switching to Bupropion-SR, Sertraline, or Venlafaxine
XR equally efficacious (remit rate for all: about 25%)
Augmentation with Bupropion (39% remission rate)
slightly better than buspirone (33%)
Overall, remission rates rather disappointing but the
study demonstrates up to date methodology that can
be applied to “real world” practices
Current Issues in Depression
Sequenced treatment alternatives to relieve
depression (STAR*D) – Still to come
Step Three: One of the following options:
switch to mirtazapine (Remeron) or nortriptyline OR
Augment with lithium or Cytomel (T3)
Step Four: Switch to tranylcypromine (Parnate)
or venlafaxine (Effexor) XR + mirtazapine (Remeron)
Evaluation of Outcomes with Citalopram for Depression Using Measurement-Based Care in
STAR*D: Implications for Clinical Practice. Trivedi et al. Am J Psychiatry 2006; 163:28-40.
Major Depressive Disorder
Overview: Other Antidepressants
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Mirtazapine (Remeron): sedation and weight gain
Venlafaxine (Effexor): Mixed NE and 5HT activity, increases
BP, similar side effect profile to ssri’s
Duloxetine (Cymbalta): Also mixed NE and 5HT activity
Buproprion (Wellbutrin): low rate of sexual side effects or
weight gain, associated with increase rate of seizures, not for
use in patients with eating disorders, prior seizure d/o
Nefazodone (Serzone)5-HT2 blocker, often recommended for
anxious depression, black box warning for liver failure, low
rate of sexual se’s
Trazodone (Desyrel) – usually prescribed as a hypnotic (ie,
sleep aid)
Major Depressive Disorder
Overview: Tricyclic Antidepressants and MAOI’s
TCA’s (tricyclic antidepressants):
anticholinergic side effects, tremor, weight gain, sexual side
effects, cardiac conduction delay (quinidine like effect), NE
reuptake inhibitors
Examples [not a complete list]: amitriptyline (Elavil), doxepin
(Sinequan), imipramine (Tofranil), desipramine (Norpramin),
nortriptyline (Pamelor, Aventyl), maprotiline (Ludiomil)
MAOI’s (monoamine oxidase inhibitors): important: dietary
restrictions! (b/o hypertensive crisis), new patch*
side effects: sedation, sexual side effects, weight gain
phenelzine (Nardil), trancylopramine (Parnate), [selegiline
(Eldepryl) for Parkinson’s]
Current Issues in Bipolar Disorder
EPIDEMIOLOGY OF BIPOLAR DISORDER
Prevalence: 1.8 to 3.6 million Americans
 Morbidity (untreated): 14 year cumulative loss of
productivity
 Suicide rate: 10-20%
 9.2-year reduction in life expectancy
 1-3% prevalence in general population
(recent estimates suggest higher prevalence)

Altemus. In: Schulkin. Hormonally Induced Changes in Mind and Brain. 1993
McEachron. In: Schulkin. Hormonally Induced Changes in Mind and Brain. 1993
EPIDEMIOLOGY OF BIPOLAR DISORDER
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Genetic: Bipolar disorder tends to run in families.
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80-90% of individuals with bipolar disorder have a relative
with either depression or bipolar disorder (which is 10-20
times higher than that found in the general population).
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Triggers: trauma, social stress, sleep deprivation,
antidepressants (without accompanying mood stabilizers)
Altemus. In: Schulkin. Hormonally Induced Changes in Mind and Brain. 1993
McEachron. In: Schulkin. Hormonally Induced Changes in Mind and Brain. 1993
Misdiagnosis of Bipolar Disorder in 1994
 Years
to diagnosis: 8
 Number
of clinicians before diagnosis: 3.3
 48%
not diagnosed with BP until seeing more
than 3 mental health professionals
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Lish JD et al. J Affect Disord 1994; 31: 281-294. The DMDA survey of bipolar
members.
Altemus. In: Schulkin. Hormonally Induced Changes in Mind and Brain. 1993
McEachron. In: Schulkin. Hormonally Induced Changes in Mind and Brain. 1993
Misdiagnosis of Bipolar Disorder in 2000
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Mean number of clinicians seen before diagnosis: 4
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Mean number of diagnoses received before bipolar
diagnosis made: 3.5
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Percentage of respondents misdiagnosed: 69%
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More than one-third reported a lapse of 10 years or
more between first seeking treatment and then
receiving appropriate treatment.
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Hirschfeld RM et al. Perceptions and impact of bipolar disorder: how far have we really come?
Results of the National Depressive and Manic-Depressive Association 2000 survey of
individuals with bipolar disorder. J Clin Psychiatry 2003;64:45-59.
Bipolar Disorder in Primary Care
 Of
108 consecutive anxious and depressed
patients in primary care clinic,
 Using
DSM-IV criteria in a semi-structured
interview by family physician,
 25%
were diagnosed with bipolar disorder: BP I
(2.8%), BP II (18.5%), BP III (3.7%)
Manning JS et al. Compr Psychiatry 1997; 38: 102-108. On the Nature of Depressive
and Anxious States in a Family Practice Setting: The High Prevalence of Bipolar II
and Related Disorders in a Cohort Followed Longitudinally.
Bipolar Disorder in Primary Care
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Of 1146 patients who were screened from a waiting
room of a primary care clinic,
Using the Mood Disorders Questionnaire, PRIME-MD,
and medical record review
112 (9.8%) screened positive for bipolar disorder
In these 112, primary care providers recognized:
some mental disorder/psychiatric symptoms in 67.7%
depression or depressive symptoms in 49.0%
bipolar disorder in 0%
Das AK et al. JAMA 2005; 293:956-963. Screening for Bipolar Disorder in a
Primary Care Practice.
Subtypes of Bipolar Disorder
Bipolar I:
Depression with Classic Mania
Bipolar II: Depression with Hypomania
Bipolar III: Antidepressant Associated
Hypomania
-?A less penetrant type of bipolar
disorder?
-Not in DSM-IV
Major Depressive
Disorder
Dysthymic Disorder
Cyclothymic
Disorder
Bipolar I Disorder
Bipolar II Disorder
Diagnostic Criteria
[Depressive episodes]
Hypomanic episodes
Manic episodes
Mixed episodes
Rapid cycling specifier
Bipolar Disorder:
DIG FAST Mnemonic
D – Distractibility
I – Insomnia
G – Grandiosity (or inflated self esteem)
F – Flight of Ideas (or racing/crowded thoughts)
A – Activities (increased goal directed activities)
S- Speech (pressured)
T- Thoughtlessness (impulsivity, ie, increased
pleasurable activities with potential for negative
consequences: sex, money, traveling, driving)
DSM-IV Diagnostic Criteria
Hypomanic Episode:
A. A distinct period of abnormally and
persistently elevated, expansive, or irritable
mood, lasting at least 4 days.
B. During the period of the mood disturbance,
three or more of the following symptoms (four
if the mood is only irritable):
APA Diagnostic and Statistical Manual. 1994
DSM-IV Diagnostic Criteria
Hypomanic Episode:
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1) inflated self-esteem or grandiosity
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2) decreased need for sleep (eg, feels rested
after only 3 hours of sleep)
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3) more talkative than usual or pressure to
keep talking
APA Diagnostic and Statistical Manual. 1994
DSM-IV Diagnostic Criteria
Hypomanic Episode: (continued)
 4)
flight of ideas or subjective experience that
thoughts are racing
 5)
distractibility (ie, attention too easily drawn to
unimportant or irrelevant external stimuli)
 6)
increase in goal-directed activity (either
socially, at work or school, or sexually) or
psychomotor agitation
APA Diagnostic and Statistical Manual. 1994
DSM-IV Diagnostic Criteria
Hypomanic Episode: (continued)
 7)
excessive involvement in pleasurable
activities that have a high potential for painful
consequences (eg, engaging in unrestrained
buying sprees, sexual indiscretions, or foolish
business investments)
APA Diagnostic and Statistical Manual. 1994
DSM-IV Diagnostic Criteria
Hypomanic Episode: (continued)
C. The episode is associated with an
unequivocal change in functioning that is
uncharacteristic of the person when not
symptomatic.
D. The disturbance in mood and the change in
functioning are observable by others.
APA Diagnostic and Statistical Manual. 1994
DSM-IV Diagnostic Criteria
Hypomanic Episode: (continued)
E. The episode is not severe enough to cause marked
impairment in social or occupational functioning, or
to necessitate hospitalization, and there are no
psychotic features.
F. The symptoms are not due to the direct physiological
effects of a substance (e.g., a drug of abuse, a
medication, or other treatment) or a general medical
condition (e.g., hyperthyroidism) [video]
APA Diagnostic and Statistical Manual. 1994
DSM-IV Diagnostic Criteria
Manic Episode:
A. A distinct period of abnormally and
persistently elevated, expansive, or irritable
mood, lasting at least 1 week (or any
duration if hospitalization is necessary).
B. Same as for hypomanic episode
DSM-IV Diagnostic Criteria
Manic Episode: (continued)
C. The symptoms do not meet criteria for a Mixed
Episode.
D. The mood disturbance is sufficiently severe to
cause marked impairment in occupational
functioning or in usual social activities or
relationships with others, or to necessitate
hospitalization to prevent harm to self or others,
or there are psychotic features.
DSM-IV Diagnostic Criteria
Manic Episode: (continued)
E. The symptoms are not due to the direct
physiological effects of a substance (eg, a
drug of abuse, a medication, or other
treatment) or a general medical condition
(eg, hyperthyroidism).
[video]
DSM-IV Diagnostic Criteria
Mixed Episode:
Rapidly alternating moods (sadness, irritability,
euphoria) accompanied by criteria for both a Manic
Episode and a Major Depressive Episode.
 Duration of 1 week.
 Frequently includes agitation, insomnia, appetite
dysregulation, psychotic features, and suicidal
thinking.
 Symptoms are not due to the direct effects of a
substance, or a general medical condition. [video]

DSM-IV Diagnostic Criteria
Rapid Cycling specifier
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Four or mood episodes per year.
Considered more treatment-refractory.
Probably not a separate illness but a phase in the
evolution of bipolar disorder that may last years.
Often associated with clinical or subclinical
hypothyroidism (up to 60%).
Associated with antidepressant monotherapy.
Responds better to valproate or carbamazepine than
to lithium.
DIAGNOSTIC CONSIDERATIONS
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Rarely see patients in manic or hypomanic episode.
When ill, majority of time is spent depressed (30/1).
Patients usually do not view hypomanic episodes as
pathologic (nor are they).
Patients frequently do not have classic presentations.
High levels of psychiatric co-morbidity: anxiety
disorders, substance abuse disorders, ADHD,
personality disorders.
Collateral information from family or friends can be
critical.
Treatment Implications
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The course of bipolar disorder may be worsened with
antidepressants, especially TCA’s.
Patients frequently benefit from treatment with mood
stabilizers and/or low-dose atypical neuroleptics.
Patients should be educated about common triggers
of manic or depressive episodes: sleep deprivation,
street drugs (particularly amphetamines, cocaine,
hallucinogenics), psychosocial stress.
Summary
1) While the STAR*D study demonstrates the efficacy of
ssri monotherapy (citalopram),
the dosage should be high (40-60mg/d) and of sufficient
duration (eight weeks)
2) Switching to Bupropion-SR up to 400mg/d,
 Or Sertraline up to 200mg/d
 Or Venlafaxine XR up to 375mg/d
Was equally efficacious (remit rate for all: about 25%)
Summary (continued)
3) Augmentation with Bupropion up to 400mg/d
(39% remission rate)
Was slightly better than buspirone up to 60mg/d
(33% remission rate)
4) Be alert for further results of the STAR*D study
Summary (continued)
5) Bipolar disorder in the primary care population is
more common than previously thought.
6) Correct diagnosis requires a high index of
suspicion and familiarity with various
presentations of hypomanic or manic or mixed
episodes.
7) Antidepressant monotherapy can lead to
induction of mania or rapid cycling.
The End: Questions and Comments