Transcript BIPOLAR DISORDER - New York State Academy of Family

BIPOLAR
DISORDER
Indra Singh MD
Burden of the disease
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Bipolar Disorder (BD)is an episodic, potentially
life-long, disabling disorder
Characterized by Mood elevation
Associated with significant Morbidity and
Mortality if untreated
Often underdiagnosed.
Epidemiology
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Lifetime prevalence
BD I : 1.0%
 BD II : 1.1 %
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Gender:
BPD I : Affects men and women equally
 BPD II : is more common in women
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Age of Onset : 15-30 years
Genetics
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Lifetime risk in relatives of BD probands is
40-70% for MZ twins
 5-10% for a first degree relative
 0.5-1.5 % for an unrelated person
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Linkage studies implicate TPH2 gene
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No candidate gene identified
Diagnostic criteria
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BD I
Episodes of Mania
 Often have depression
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BD II
One or more depressive episodes
 At least one episode of hypomania
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Manic episode
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Persistently elevated or irritable mood, lasting at least
1 week
3 additional sx in the same period affecting
• self-esteem
• sleep
• Speech
• Thoughts
• Attention
• PMA
• Functioning
Hypomania
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Unlike Mania
shorter duration of manic symptoms (at least four
days),
 less severe level of symptoms.
 Absence of Psychoses
 mild functional impairment
 Often does not often lead to hospitalization;
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Depression
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Dx requires 5/9 sx during the same period
with one must be either depressed mood or loss
of interest.
Symptoms should be present daily or for most
of the day for at least two weeks.
The symptoms must cause clinically significant
distress or impairment in functioning,
Unipolar v Bipolar depression
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Patients with Bipolar depression more likely to
have
Family hx of BD
 Early age of Onset
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Pts. Presenting with depression should be asked
about past Mania or Hypomania
Mixed
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Presence of both depressive and mood elevated sx
simultaneously.
May thus occur with bipolar I or bipolar II disorder.
The frequency is estimated between 20 and 70 %
The most common symptoms were
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irritability,
racing or crowded thoughts,
psychomotor agitation,
or increased talkativeness
concurrent with symptoms of depression.
BD
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3 SUBTYPES
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BD I
At least 1 manic episode
 Major depression frequent, but not required for dx
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BD II
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One hypomanic + at least 1 episode of major dep
BD NOS
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Features do not meet criteria of BD I or II
Course of BD
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90% of pt.'s with BD have at least one psych
hospitalization
Course influenced by high rates of comorbid
alcohol or substance abuse.
Comorbid anxiety disorder is also common
Suicide rates are high
Rapid Cycling if four or more mood episodes
occurred during the previous 12 months
Course of BD
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BD I
marked by relapses and remissions,
 often alternating manic with depressive episodes.
 Ninety percent of individuals have a second manic
episode within five years
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Depressive sx frequent over the course of
bipolar disorder than manic sx
3 x more frequently than mania in BD I
 37 x more frequently than hypomania in BD II
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BD
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Assessment and Rx for
Mania
 Hypomania
 MIxed
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Clinical Assessment
 Medical
comorbidity
 Psychiatric comorbidity
 Psychosocial Stressors
 Medications current and past
 Suicide risk
 Substance Use
Assessment
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Stop Anti Depressants
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Beware of discontinuation syndromes symptoms
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Dizziness
Headache
Paresthesias
Nausea
Diarrhea
Insomnia
Irritability
Reasons for Hospitalization
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Delirium
Marked psychotic symptoms
Severe mania
Suicidality or homicidality
Potential for violence
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ideas / intent to harm others;
hx of violent behavior;
severe agitation or hostility;
active psychosis
Substance withdrawal or intoxication
GOALS FOR Rx
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Acute Phase
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Continuation phase
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Focus on managing Sx and pt. safety
Hospitalization often necessary
remission of symptoms is preserved
The goal is to prevent relapse of the mood episode.
maintenance phase
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and aims to prevent recurrence of a new mood episode.
Long-term or lifetime maintenance is recommended for
patients who have suffered one manic episode
Rx Principles for Mood Elevated
Syndromes
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Assess for risk of suicide, aggressiveness, and
violence to others.
Discontinue ADs
Reduce their use of alcohol, caffeine, and
nicotine.
In breakthrough episode assess for adherence
to Rx
Treatment of mood elevated syndromes is based
upon studies in BD I
Acute Phase
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Drugs used to induce remission
Lithium
 Anticonvulsants
 Antipsychotics
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allow up to two weeks before determining the
drug’s clinical effectiveness.
Acute Phase
Efficacy mostly similar across first line medications
 With or without Psychoses
 Mania or mixed
 With or without rapid cycling
•Response independent of
Lifetime number of episodes
Hx of lifetime comorbid SUD
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Acute Phase
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If no remission within 2 weeks
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Switch
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Add
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If no response
If partial response
Goal of Rx is full remission
Choice of Drug
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Overall First line drugs have better response than placebo
Efficacy similar across first line medications
Lithium associated with reduced risk of suicide attempts
Monotherapy maybe sufficient for less severely ill
patients
Combination therapy frequently for pts with manic or
mixed episodes
Combination therapy is
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Li + Antipsychotic
Valproate + Antipsychotic
Choice of Drug
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Past response to medications
Side-effect profiles
Comorbid medical illness
Pregnancy
Concurrent medications
Cost
Lithium
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More controlled trials demonstrating the efficacy of
lithium monotherapy than any other medication
The starting dose of lithium is usually 300 mg BID
increased by 300 to 600 mg every 3-5 days
Serum level
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target 0.8 and 1.2 meq/L
measured five to seven days after each dose increase.
levels should be drawn 12 hours after the last dose
Check s Cr, Cr Cl, TFTs, CBC D annually
Lithium
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Acute side effects include
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nausea,
tremor,
polyuria and thirst,
weight gain,
loose stools, and
cognitive impairment
Severe or a sudden worsening of side effects may be a sign of lithium
toxicity.
long term adverse effects of lithium involve
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the kidneys and
thyroid gland.
cardiac rhythm disturbances almost always occur in patients with
preexisting cardiac disease.
LITHIUM TOXICITY
Lithium conc.
s/s of toxicity
Management
1.2 -1.5 mEq/L
Worsening tremor, n/v,
diarrhea, drowsiness
Hold lithium till serum conc.
Returns to normal
1.6 .2.5 meq/L
Coarse tremors, apathy,
drowsiness, slurred speech,
ataxia, increase in
s.creatinine
Hold lithium, repeat levels,
assess electrolytes and renal
fx, may require admission
> 2.5 mEq/L
Medical emergency
n/v, diarrhea, involuntary
movements, dysarthria,
coarse tremors, delirium, sz,
coma
Admit inpt.
Lithium drug interactions
Increase Li conc
Decrease Li conc
Neurotoxicity
Thiazides
Lasix
Caffeine
Desmopressin
ACEIs
ARBs
NSAID
Reduced Na intake
Theophylline
Verapamil
Osmotic diuretics
Na bicarb antacids
Increased Na intake
Antipsychotics
Carbamazepine
Methyldopa
SSRIs
MAOIs
Verapamil
VALPROATE
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starting dose of 250 mg 2-3 times per day.
Increased by 250 mg - 500 mg every 1-3 days to reach a
therapeutic serum level,
Oral loading and rapid titration to a full dose within one to
two days by prescribing 20 mg/kg/day
Target serum level between 50 and 125 mcg/mL.
 Levels should be drawn 12 hours after the last dose
 efficacy increased as serum levels increased
 Levels should be checked at 6 to 12 month intervals.
Annual CBC D, LFTs, BMP
Valproate
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Common side effects include
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weight gain,
nausea, vomiting,
hair loss, easy bruising, and
tremor.
Divalproex is generally used rather than valproate to
minimize gastrointestinal distress.
Hepatic failure and thrombocytopenia have rarely been
associated with valproate use;
liver function tests and platelets should be monitored at
6 to 12 month intervals in all patients taking the drug
Carbamazepine
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Starting Dose 100 mg to 200 mg 1-2 times per
day,
Increase dose by 200 mg every 1-4 days, to a
final dose of about 800 to 1000 mg per day,
effective dose range 200 and 1800 mg per day.
Therapeutic serum levels have not been
established for BD.
However, many clinicians use levels established
for treatment of epilepsy: 4 to 12 mcg/mL.
Atypical APs
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Olanzapine
Start 10-15mg /day
 Max 20 mg daily
 Side effects include
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Somnolence
 dry mouth
 Dizziness
 Weight gain
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Monotherapy or combination with Li/Depakote
Risperidone
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Start 1mg BID
Increase to 6mg/day
Onset of action between 1-6 days
Mono or combination therapy
Side effects
Somnolence
 EPSE
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Ziprasidone
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Start 40mg BID
Max 80mg BID
Onset of action at day 2
Monotherapy
Side effects:
Nausea
 Akathisia
 tremors
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Aripiprazole
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Start 15mg/day
Max 30mg /day
Mono or combination therapy
Separates form placebo by day 4
Side effects
N/V
 insomnia
 akathisia
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Quetiapine
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100mg day 1
Up to 800mg daily
Superior to placebo at day 21
Side effects
Dry mouth
 Dizziness
 Weight gain
 somnolence
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Metabolic effects of Atypicals
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Weight gain
Clozapine and olanzapine : most wt. gain
 Risperidone and Quetiapine : moderate
 Aripiprazole and Ziprasidone : minimal
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Hyperlipidemia
DM
Monitoring parameters
Weight and BMI
Baseline, 2, 8 and 12 weeks then
@ 3 months, annually
Waist circumference
Baseline, annually
BP
Baseline,12 weeks,anually
Fasting Plasma Glucose
Baseline,12 weeks then annually
Fasting Lipid Profile
Baseline,12 weeks, every 5 years
Pregnancy test
Baseline
Effective Meds in Bipolar
Mania/Hypomania or Mixed
Episodes
Likely Beneficial
Unlikely to be Beneficial
or Maybe Harmful
Mania
Lithium, valproate,
carbamazepine,
Atypical APs
Combining (lithium or
valproate) with Atypical APs
Gabapentin
Lamotrigine
Topiramate
AD Monotherapy
Mixed Episode
Valproate, carbamazepine,
aripiprazole, olanzapine,
risperidone, or ziprasidone
Gabapentin
Lamotrigine
Topiramate
Acute Phase
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Reassess every 1-2 weeks for 6 weeks
Monitor treatment response at 4 to 8 weeks after
initiation of treatment, after each change in
treatment, and periodically until full remission is
achieved.
Remission
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In Mania : if free from significant symptoms for two
months
In Mixed episode : if free from significant symptoms of
mania or depression for 2 months
Continuation Phase
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Check for Compliance.
Assessment of ADR.
Monitoring of serum concentration
Monitor for metabolic syndrome for those on
Atypical APs
Assess for improvement or change of the core
symptoms of mania and mixed
Careful risk assessment for those with s/i.
BD
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Rx for Bipolar depression
Acute Phase Rx for BD Depression
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Monotherapy
Lithium
 Lamotrigine
 Quetiapine
 Olanzapine +/- fluoxetine
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Combination Strategies
Li+ Lamictal
 Augmentation with ADs for short term
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Effective meds in BD depression
Likely Beneficial
Lithium
Quetiapine
Lithium with lamotrigine
Unlikely to be beneficial
Abilify
Neurontin
AD Monotherapy
Goal of Maintenance Therapy
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reduce residual symptoms,
delay and prevent recurrence of new mood
episodes,
reduce the risk of suicide, and
enhance psychosocial functioning.
Indications of Maintenance
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BD I
BD II
BD NOS
Medications for Maintenance
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Lithium
Lamotrigine
Risperidal Consta
2nd line
Depakote
 Aripiprazole
 Olanzapine
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