Transcript Bipolar Disorder - Roger Peele: Introduction

Bipolar Disorder
All questions, unless otherwise indicated, are from “Practice
Guideline for the Treatment of Patients with Bipolar Disorder,
Second Edition, AJP, April 2003 Supplement. Or from
Goodwin and Jamison’s MANIC-DEPRESSIVE ILLNESS,
2ND Edition, 2007
As of 30Mar2007. Next update of this PowerPoint is due on
May 31, 2007.
Bipolar - DSM
• Q. What are the four major DSM-IV-TR
types of bipolar disorders? [Don’t spend
time on this one, it is just to get us started.]
Bipolar disorder, types
• Ans.
• -- Bipolar I disorder [with subtypes of most
recent episode: hypomanic, manic, mixed,
depressed, or unspecified]
• -- Bipolar II disorder [with subtypes of most
recent episode hypomanic or depressed]
• -- Cyclothymic disorder
• -- Bipolar, NOS
• DSM-IV-TR, p 20.
Bipolar – DSM criteria for
manic episode
• Q. What are the symptoms of a manic
episode? List the required one, then list
the seven of which 3 or 4 are required.
Manic episode criteria
• Criteria:
• A. At least one week of abnormally
elevated, expansive, or irritable mood.
• B. In addition to “A” during that week or
more: 3 of the those listed on the next
slide [4 if “irritability” is all of “A”]
• C. Not part of another disorder or illness.
• Continued on next slide
Manic episode criteria - 2
•
•
•
•
•
•
•
Elements of “B”:
-- grandiose
-- decrease need for sleep
-- talkative
-- flight of ideas
-- distractibility
-- increase in goal-directed activity or psychomotor
agitation
• -- excessive involvement in activity is likely to have
untoward results [e.g., buying sprees]
DSM-IV-TR, 362
Criteria for depressive episode
• Q. What are nine symptoms that form the
criteria for depressive episode?
Depressive episode
criteria - 1
• Criteria, two weeks or more of five or more
of the following -- and not part of another
disorder:
• 1. sad [irritable counts in children]
• 2. diminished interest in activities.
• 3. weight loss or gain
• 4. insomnia or hypersomnia
• continued
Depressive episode
criteria - 2
•
•
•
•
•
5. psychomotor agitation or retardation.
6. anergy
7. feelings of worthlessness or guilt
8. difficulty concentration
9. recurrent thoughts of death or suicidal
DSM-IV-TR, P 356
Dx criteria for
hypomania
• Q. What is the criteria for hypomania?
Criteria for hypomania
• Ans.
• Same as manic episode except
– Only has to be for 4 days
– Is not severe enough to cause social or
occupational/educational impairment.
– Others have observed the symptoms, i.e.,
can’t be based on pt’s word alone [often a
forgotten point by Board candidates].
DSM-IV-TR, P 368
Criteria for
mixed episode
• Q. What is criteria for mixed episode?
Criteria for
mixed episode
• Ans. At least one week of meeting both
the signs of depressive episode and manic
episode.
DSM-IV-TR, 365
Criteria for
cyclothymic disorder
• Q. What is the criteria for cyclothymic
disorder?
Criteria for
cyclothymia
• Ans.
• 1. At least two years of numerous
hypomanic episodes and numerous
depressive episodes not severe enough to
meet criteria of depressive episode [one
year for kids].
• 2. Not part of another disorder.
DSM-IV-TR, 400
Criteria for
catatonic specifier
• Q. What are the criteria for the catatonic
specifier?
Criteria for catatonic
specifier
• At least two of the following:
• 1. motoric immobility
• 2. excessive motor activity
• 3. negativism
• 4. stereotyped behaviors
• 5. echolalia or echopraxia
[same as when “catatonia” is applied to
schizophrenia]
DSM-IV-TR, 418
Criteria for
Melancholia
• Q. What are criteria for melancholia?
Criteria for melancholia - 1
• Ans. Two sets of signs:
• 1. Either loss of please in almost all
activities or does not feel pleasure even
when something good happens
• 2. Three or more of the six signs on the
next slide
Criteria for melancholia - 2
• Continued, 3 or more of 6:
• 1. Sadness is distinctly different than sadness
associated with tragic events of the past.
• 2. Sadness worse in the morning
• 3. Early morning awaking
• 4. Psychomotor retardation or agitation
• 5. Anorexia or weight loss
• 6. Excessive guilt
DSM-IV-TR, 420
Criteria for
Atypical
• Q. What is the criteria for the Atypical
specifier?
Criteria for atypical
• Ans.
• 1. Mood brightens with positive events.
• 2. At least two of the following:
– Weight gain
– Hypersomnia
– Laden paralysis
– Hyper rejection sensitivity
DSM-IV-TR, 422
Criteria for
postpartum specifier
• Q. What is the criteria for the postpartum
specifier?
Criteria for postpartum
specifier
• Ans. Onset of episode within 4 weeks of
delivery.
DSM-IV-TR, 423
Criteria for seasonal
pattern
• Q. What is criteria for seasonal pattern
specifier?
Criteria for seasonal pattern
specifier
• Ans. For at least two years:
• 1. onset of mood episode has a temporal
relationship, e.g., each October.
• 2. no episodes other than those with a
temporal episode.
DSN-IV-TR, 427
“Chronic”
• Q. With mood disorders, “chronic” means?
“Chronic”
• Ans. Criteria have been met continuously for at least two
years.
• [Two years is also the way “chronic” is used in
schizophrenia, although not part of DSM-IV-TR, “chronic”
is part of the current ICD-9-CM for schizophrenia. For
adjustment disorders, “chronic” is for 6 months. For
PTSD, “chronic” is for 3 months.}
DSM-IV-TR, 417
Prevalence
• Q. Prevalence of Bipolar I and II in the
general population?
Prevalence
• Ans. 3.8%
• [DSM-IV-TR: Bipolar I: 1%, Bipolar II:
0.5%]
Ref: Hirschfield RMA: Guideline Watch:
Practice Guideline for the Treatment of
Patients with Bipolar Disorder. Arlington,
VA: American Psychiatric Association.
Hereafter: “Watch.”
Co-morbidity
Q. Most common co-morbid psychiatric
disorder?
Co-morbidity
Ans. Alcohol abuse.
G&R [=Goodwin and Jamison], p 225
gender
• Q. Gender breakdown of bipolar disorder?
• Give general breakdown, then which
episode do men tend to have first? Which
do women? Which has more rapid
cycling?
Gender
• Ans.
-- about equal generally, but some
differences.
-- men more likely to have a first episode of
mania.
-- women more likely have a first episode be
depression.
-- women more likely to rapid cycle.
DSM-IV-TR, p 385
Quality of life
• Q. Does manic episodes or depressive
episodes have the greatest impact on
quality of life and duration of symptoms?
Quality of life
• Ans. Depressive episodes have the
greatest negative impact on quality of life
and have the longer duration.
• Source: APA Watch on bipolar.
Suicide
• Q. Suicide rate among bipolar I
disordered?
Suicide
• Ans. 10-15%
Suicide
• Q. What two phases of bipolar disorder
have the high suicide rates -- manic,
depressed or mixed?
Suicide
• Ans.
• 1] depressive episodes
• 2] mixed episodes
Suicide risk factors
• Q. List symptoms/signs that are
associated with increased risk of suicide in
bipolar I pts?
Suicide risks
•
•
•
•
•
Ans. Practice Guideline lists:
-- agitation
-- pervasive insomnia
-- impulsiveness
-- psychosis [especially command
hallucinations]*
[Despite research that questions the lethality
of command hallucinations, this wording is
in the Guideline.]
Suicide risks
• Q. What co-morbid psychiatric disorders
increase the risk of suicide in bipolars?
Suicide risks
• Ans. Practice Guideline lists:
• -- Substance-related disorders
• -- Personality disorders
Med associated with
suicide reduction
• Q. What med has the clearest evidence of
reducing suicides?
Med associated with
suicide reduction
• Ans. Li.
Secondary mania
neurological disorders
• Q. What neurological disorders are
associated with secondary mania?
Secondary mania
neurological disorders
• Ans. Practice guidelines mentions:
• -- MS
• -- lesions involving right-side subcortical
areas.
• -- lesions close to limbic system,
Secondary mania
substances
• Q. What meds are associated with
secondary mania [not asking about
antidepressants]?
Secondary mania
substances
• Ans. Practice guideline lists:
• -- L-Dopa
• -- corticosteroids
Hospitalization
• Q. Under what conditions should a person
with bipolar disorder be hospitalized?
Hospitalization
•
•
•
•
Ans.
1. A threat to harm self or others
2. Severely ill and lack social support
3. Severely ill and significantly impaired
judgment.
• 4. Has another complicating medical
[including psychiatric] illness.
• 5. Has not responded to outpt treatment.
Daily activities
• Q. As to daily activities, what should be
advised to pt and family?
Daily activities
• Ans. Regular patterns for eating, physical
activities, social stimulation, and sleep are
important.
Meds for severe mania
or mixed type
• Q. What meds are recommended for first
episode of severe mania or mixed
episode?
Meds
• Ans. Two correct answers
• Li and an antipsychotic
• Valproate and an antipsychotic
Meds
• Q. First break mania, mild or moderately
ill, list medication options. List FDA
approved.
Meds
• Ans. Practice guidelines uses a lot of “may” as to
mild or moderate manic episodes:
• -- Li
• -- valproate
• -- atypical antipsychotic
• -- carbamazepine or oxcarbazepine
[FDA’s list: aripiprazole, chlorpromazine, Li,
olanzapine, quetiapine, risperidone, valproate,
and ziprasidone]
Li and antipsychotic
Q. You’ve placed your pt with mania on Li
and she is no better, after two week. You
add ziprasidone and still not better five
days later. What to do?
Li and antipsychotic
Ans. Add an anticonvulsant mood stabilizer.
G & J, p 729
Benzodiazepines
• Q. Role of benzodiazepines in manic or
mixed episodes?
Benzodiazepines
• Ans. As an adjunct and for only a short
time. G & J use for insomnia to get the pt’s
sleep pattern normal.
Antidepressants
• Q. What should be the approach to a pt on
antidepressants and treating that pt’s firstbreak manic episode?
Antidepressants
• Ans. The antidepressant should be
tapered and discontinued if practical.
“breakthrough”
• Q. How to manage breakthrough manic or
mixed episode? By “breakthrough,” we
mean that the pt was on a maintenance
med or meds and now has a manic
episode.
breakthrough
• Ans.
• 1. Check serum levels to see if the pt is in
therapeutic levels and consider higher levels
that are still with acceptable levels, e.g.
valproate at 90, consider pushing to 120..
• 2. Consider adding an antipsychotic
• 3. Consider short-term use of a benzodiazepine,
especially if very agitated.
Inadequate Response
• Q. If first choice med fails to develop an
adequate in a manic or mixed pt in two
weeks, what to do? [Ans. has five general
categories.]
Inadequate response
• Ans. Consider:
– Another first line med
– Adding an antipsychotic if not already using.
If using, consider switching to another
antipsychotic.
– Adding carbamazepine/oxcarbazepine
– Clozapine [Practice Guideline wording not
clear, but apparently as an addition]
– ECT
ECT
• Q. When is ECT an especially attractive
option in the manic or mixed pt?
ECT
• A. Attractive when:
• 1] Mania very severe and not responding
to meds.
• 2] Pt prefers ECT
• 3] Pregnant
• 4] Psychotic signs prominent.
• [not listed, but catatonic or suicidal are
probably correct answers too]
Acute depression
• Q. First line management of acute
depression in bipolar?
Acute depression
• Ans. Three: Li, lamotrigine or olanzapinefluoxetine combination.
[Ref: Watch]
SSRIs
• Q. What about SSRIs for depressive
episode?
SSRIs
• Ans. Not recommended as monotherapy.
May be useful as an adjunct to a mood
stabilizer, but mood stabilizers are first
choice.
• [Tertiary centers for bipolar disorders find
they have to use an antidepressant with
about a fifth of their pts.]
Acute depression
• Q. What about ECT?
Acute depression
•
•
•
•
•
Ans. ECT is useful for:
1] life-threatening inanition
2] suicidal
3] psychotic
4] pregnant
Acute depression
• Q. What about psychotherapy?
Acute depression
• Ans.
• In addition to meds – not as solo,
interpersonal or CBT has empirical basis.
• Psychodynamic is frequently used but
lacks controlled studies.
Breakthrough depression
• Q. Bipolar pt on maintenance meds and
has breakthrough depression. What to
do?
Breakthrough depression
• Ans. First, ensure serum levels of meds
are at high therapeutic range.
Breakthrough depression
• Q. If serum levels of the mood stabilizers
are at a high therapeutic level and still
depressed? [“Breakthrough depression” =
bipolar pt who was on maintenance mood
stabilizer as adequate levels. List three
general choices.]
breakthrough depression
• Ans. Three general choices.
• 1] Add antidepressant:
SSRI/venlafaxine/bupropion or MAOI or
• 2] If psychotic, add antipsychotic [probably
an acceptable choice even if not
psychotic], or
• 3] ECT
Still depressed
• Q. When to consider ECT?
Still depressed, ECT
•
•
•
•
Ans. ECT when:
-- medication resistant
-- psychotic signs
-- catatonic features
Rapid cycling
• Q. What is definition of rapid cycling?
Rapid cycling
• Ans. 4 or more episodes/year and there
has been two months of remission or
partial between episodes. Hypomanic
episodes count. Rapid cycling also can
mean switching from one polarity to the
opposite without the two months of
remission or partial remission.
Rapid cycling
• Q. Identify two conditions that can lead to
rapid cycling.
Rapid cycling
• Ans. There are lots, and the Practice
Guideline lists two that may be among the
examination’s choices
• -- substances, including alcohol
• -- hypothyroidism
Rapid cycling
• Q. Meds for rapid cycling?
Rapid cycling - meds
Meds for rapid cycling:
• Li
• Valproate or
• Lamotrigine
Rapid cycling
• Q. Rapid cycling pt doesn’t respond to
your initial med selection, so what next?
Rapid cycling
•
•
•
•
•
Ans. Two choices?
-- Add another mood stabilizer
Or
-- Add an antipsychotic
[While not mentioned by Guideline, ECT is
also an acceptable answer]
Catatonic signs
• Q. Which phase has catatonic signs and of
what signs do they commonly consist?
Catatonic signs
• Ans. More common in manic episodes and
consist of motor excitement, mutism, and
stereotypic movements.
Catatonic
• Q. Treatment choice for bipolar with
catatonia?
Catatonia
• Ans. While ECT is most efficacious,
Practice Guideline seems to imply trying a
benzodiazepine first.
Maintenance
• Q. Preferred meds for the maintenance
[stable] phase?
Maintenance
• Ans.
• Treatments with the most empirical
support are Li and valproate.
• Possible alternatives are lamotrigine,
olanzapine, carbamazepine of
oxcarbazepine.
Watch provides additional support for
lamotrigine and olanzapine.
Maintenance - ECT
• Q. ECT?
Maintenance - ECT
• Ans. Maintenance ECT should be consider
for those pts whose stabilization was
achieved with ECT. [In discussing this,
keep in mind that outpt ECT, like meds,
has high non-compliance.]
Maintenance - Antipsychotics
• Q. Role of antipsychotics for
maintenance?
Maintenance - antipsychotics
• Ans. Not easy to answer. Practice Guidelines
says they should be discontinued unless they
have been shown with a pt to be needed to
prevent relapse or to prevent psychotic features.
• APA Watch on bipolar suggests that olanzapine
is OK for maintenance, and is clear in saying
that typical antipsychotics are not desirable.
Other atypicals are listed for maintenance [e.g.,
Stephen Stahl’s Prescription Guide].
Maintenance - psychotherapies
• Q. Role of psychotherapies. If a role,
which are used?
Maintenance - psychotherapies
• A. Supportive and psychodynamic
therapies are commonly used in addition
to the meds. CBT has been shown to
reduce number of exacerbations.
Maintenance – group therapies
• Q. During maintenance, is group therapies
used and, if so, for what purpose?
Maintenance – group therapy
• Ans. Supportive groups are used to
educate as to:
– Information about the illness
– Adherence strategies
– Address enhancing self-esteem
– Adaptation to having a chronic illness
– Management of psychosocial issues, e.g. job
related issues
Maintenance – family therapy
• Q. Family therapy in the maintenance
phase is used to?
Maintenance – family therapy
• A. Same as the issues listed for group
psychotherapy supra.
Maintenance - problems
• A. If the pt is still having subthreshold
symptoms or breakthrough manic or
depression, what to do?
Maintenance - problems
•
•
•
•
A. Consider:
-- adding another mood stabilizer
-- adding an atypical antipsychotic
-- adding an antidepressant if the mood
breakthrough is depressive signs.
• -- adding maintenance ECT
Li - workup
• Q. What is the workup for Li?
Li - workup
•
•
•
•
•
•
A.
1] general medical hx and physical exam.
2] BUN and creatinine level
3] Thyroid function
4] > 40 years old, EKG
5] Women in child bearing age, pregnancy
test
Li - dosing
• Q. What is typical Li dosing?
Li - dosing
• A. Usually start at 300 mg tid or even
lower and gradually increase until control
of signs is reached of blood level gets to
about 1.0
Li – blood levels
• Q. When to check blood levels?
Li – blood levels
• A. Check with each increase in dosing, but
keep in mind that it takes 5 days before
the new level plateaus.
• B. After desired level is reached, check
every 6 months.
• C. Check when there is a significant
change in signs or symptoms.
Li – renal function
• Q. How often to check renal function?
Li – renal function
• A. Every 6 to 12 months.
Li – thyroid function
• Q. How often should one check thyroid
function?
Li – thyroid function
• Ans. Every 6 to 12 months.
Alcohol and Li
• Q. Alcohol dehydration does what to the Li
blood level?
Alcohol and Li
• Ans. Alcohol dehydration can raise Li to
toxic levels
Valproate – work up
• Q. Work up for valproate?
Valproate – work up
• Ans.
• 1. general medical hx with attention to
hepatic, hematological and bleeding
abnormalities
• 2. Obtain liver function tests
• 3. Obtain hematological measures
Valproate - dosing
• Q. What is typical dosing?
Valproate - dosing
• Ans.
• For hospitalized inpts in manic phase, 2030 mg/kilo, aiming for blood level of 50 125.
• B. For outpts, 250 mg tid and go up slowly
aiming for blood level of 50 – 125.
Valproate - ER
• Q. How does Extended Release valproate
compare to immediate release in terms of
blood level of the med?
Valproate - ER
• A. ER tends to achieve blood level about
15% lower than immediate release.
Valproate – lab tests
• Q. If pt is stable on valproate, what lab
tests are still indicated and how often?
Valproate – lab tests
• Ans. Test hematology and hepatic
functions every 6 months.
Valproate & lamotrigine
• Q. Pt on valproate and you want to add
lamotrigine. What dose of lamotrigine is
advised?
Valproate & lamotrigine
• A. Since valproate inhibits lamotrigine
metabolism, begin lamotrigine at half the
usual doses.
Lamotrigine – Stevens-Johnson
• Q. Frequency of Stevens-Johnson, in
children? In adults?
Lamotrigine – Stevens-Johnson
• Q. 1% in children. 0.3% in adults in the
use in pts with epilepsy. Rate has been
less in psychiatry with bipolar adults when
used as monotherapy: 0.08%. When used
as an adjunctive med: 0.13%.
Lamotrigine – worrisome rash
• Q. Signs that make the rash worrisome
include?
rash - worrisome
• A. Worrisome if:
– Fever
– Sore throat
– Rash is diffuse and wide-spread
– Prominent facial and mucosal involvement
Rash - worrisome
• Q. What to do if worrisome? What if the pt
is on both lamotrigine and valproate?
Rash - worrisome
• A. Discontinue lamotrigine. If on both,
discontinue both.
Lamotrigine dosing
• Q. What is typical lamotrigine dosing?
Lamotrigine dosing
• A. 25 mg/d for 2 weeks, then increase 25
mg every two weeks until desired clinical
results or reach 200 mg/d. [With
valproate, would be ½ that.]
Lamotrigine & carbamazepine
• Q. Lamotrigine doses when combined with
carbamazepine?
Lamotrigine & carbamazepine
• A. Carbamazepine increases metabolism
of lamotrigine, so will need to use
increased doses of lamotrigine.
Carbamazepine – work up
• Q. What is the expected work up for
carbamazepine?
Carbamazepine – work up
• Ans.
– Hematological
– Liver function
– Renal function
– Electrolytes
Electrolytes
Q. What is the worry as to electrolytes?
Carbamazepine - electrolytes
• Ans. hyponatremia
Oral contraceptives
• Q. What does carbamazepine,
oxcarbazepine and topiramate do the
metabolism of oral contraceptives?
Oral contraceptives
• Ans. Increases the metabolism and
reduces their effectiveness.
Pregnancy - Li
• Q. Your pt on Li becomes pregnant. Your
advice should include?
Pregnancy - Li
• Ans. While wording, obviously varies from
pt to pt, the facts are that Ebstein’s
anomaly is 10-20 times more common if
on Li during first trimester. Discontinuing
Li, especially rapidly, however, increases
chance of return of bipolar episodes.
Ebstein’s anomaly
• Q. What is Ebstein’s anomaly?
Ebstein’s anomaly
• Ans. Congenital downward displacement
of the tricuspid valve into the right
ventricle.
[PDR Medical Dictionary, 1995, p 94]
Pregnancy - valproate
• Q. What abnormalities are associated with
valproate during first trimester?
Pregnancy - valproate
• Ans.
• neural tube defects*
• craniofacial abnormalities
• limb abnormalities
• cardiac defects
* Probable the focus of an examiner’s
question.
Pregnancy - carbamazepine
• Q. Associated with carbamazepine
exposure?
Pregnancy - carbamazepine
• Ans.
• -- neural tube defects, first trimester
• -- craniofacial abnormalities
Antidepressant meds –
teratogenic
• Q. Which antidepressant meds have been
shown to be teratogenic?
Antidepressant meds –
teratogenic
• Ans. None, including tricyclics, have been
shown to be teratogenic.
Pregnancy – antipsychotics
• Q. What, if any, antipsychotics are
recommended during pregnancy?
Pregnancy - antipsychotics
• Ans. If an antipsychotic is needed, a
typical high potency one is recommended,
e.g., haloperidol. Neonates may show
EPS after birth, but usually short-lived.
Prenatal monitoring
• Q. Your pt has decided to remain on Li, on
valproate or on carbamazepine during first
trimester. What test do you want to
perform before 20th week?
Prenatal monitoring
• Ans.
• Amniocentesis checking for elevated
alpha-fetoprotein.
• Ultrasound examination to detect cardiac
abnormalities.
Alpha-fetoprotein
Q. What is the significance of alphafetoprotein?
Alpha-fetoprotein
Ans. If found in amniocentesis, an indicator
of neural tube defect.
Postpartum issues
• Q. Your bipolar pt is pregnant and
psychiatrically stable. Will the postpartum
period be problematic?
Postpartum issues
• Ans. Marked increase chance of manic,
depressed or mixed episodes.
Breast feeding
• Q. Which meds, routinely used in treating
bipolar pts, are secreted in breast milk?
Breast feeding
• Ans. All are secreted.
Breast feeding –
med especially not recommended
• Q. Of the meds routinely used in bipolar
disorder, which does the practice guideline
specially suggest not be used if
breastfeeding?
Breast feeding –
med specifically not recommended
• Ans. Li
Dosing Chinese pts
• Q. When dosing Chinese pts, what
cytochrome fact needs to be kept in mind
as to dosing?
Dosing Chinese pts.
• Ans. Lower cytochrome P-450 isoenzyme
levels mean using lower does of meds
metabolized by that enzyme.