bipolar disorder indra singh md. burden of the disease bipolar disorder (bd)is an episodic,...
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BIPOLAR DISORDER
Indra Singh MD
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Burden of the disease
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.
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Epidemiology
Lifetime prevalence BD I : 1.0% BD II : 1.1 %
Gender: BPD I : Affects men and women equally BPD II : is more common in women
Age of Onset : 15-30 years
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Genetics
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
Linkage studies implicate TPH2 gene
No candidate gene identified
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Diagnostic criteria
BD I Episodes of Mania Often have depression
BD II One or more depressive episodes At least one episode of hypomania
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Manic episode
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
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Hypomania
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
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,
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Unipolar v Bipolar depression
Patients with Bipolar depression more likely to have Family hx of BD Early age of Onset
Pts. Presenting with depression should be asked about past Mania or Hypomania
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Mixed 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
irritability, racing or crowded thoughts, psychomotor agitation, or increased talkativeness concurrent with symptoms of depression.
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BD
3 SUBTYPES BD I
At least 1 manic episode Major depression frequent, but not required
for dx BD II
One hypomanic + at least 1 episode of major dep
BD NOS Features do not meet criteria of BD I or II
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Course of BD
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
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Course of BD
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 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
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
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Assessment Stop Anti Depressants
Beware of discontinuation syndromes symptoms
Dizziness Headache Paresthesias Nausea Diarrhea Insomnia Irritability
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Reasons for Hospitalization
Delirium Marked psychotic symptoms Severe mania Suicidality or homicidality Potential for violence
ideas / intent to harm others; hx of violent behavior; severe agitation or hostility; active psychosis
Substance withdrawal or intoxication
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GOALS FOR Rx
Acute Phase Focus on managing Sx and pt. safety Hospitalization often necessary
Continuation phase remission of symptoms is preserved The goal is to prevent relapse of the mood
episode. maintenance phase
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
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Rx Principles for Mood Elevated Syndromes
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
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Acute Phase
Drugs used to induce remission Lithium Anticonvulsants Antipsychotics
allow up to two weeks before determining the drug’s clinical effectiveness.
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Acute Phase
• Efficacy mostly similar across first line medications
With or without Psychoses Mania or mixed With or without rapid cycling
•Response independent ofLifetime number of episodesHx of lifetime comorbid SUD
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Acute Phase
If no remission within 2 weeks Switch
If no response
Add If partial response
Goal of Rx is full remission
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Choice of Drug 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
Li + Antipsychotic Valproate + Antipsychotic
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Choice of Drug
Past response to medications Side-effect profiles Comorbid medical illness Pregnancy Concurrent medications Cost
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Lithium 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
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
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Lithium Acute side effects include
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
the kidneys and thyroid gland. cardiac rhythm disturbances almost always occur in patients
with preexisting cardiac disease.
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LITHIUM TOXICITYLithium 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 emergencyn/v, diarrhea, involuntary movements, dysarthria, coarse tremors, delirium, sz, coma
Admit inpt.
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Lithium drug interactions
Increase Li conc Decrease Li conc Neurotoxicity
ThiazidesLasixCaffeineDesmopressinACEIsARBsNSAIDReduced Na intake
TheophyllineVerapamilOsmotic diureticsNa bicarb antacidsIncreased Na intake
AntipsychoticsCarbamazepineMethyldopaSSRIsMAOIsVerapamil
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VALPROATE 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
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Valproate
Common side effects include 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
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Carbamazepine
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.
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Atypical APs
Olanzapine Start 10-15mg /day Max 20 mg daily Side effects include
Somnolence dry mouth Dizziness Weight gain
Monotherapy or combination with Li/Depakote
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Risperidone
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
Start 40mg BID Max 80mg BID Onset of action at day 2 Monotherapy Side effects:
Nausea Akathisia tremors
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Aripiprazole
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
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
Weight gain Clozapine and olanzapine : most wt.
gain Risperidone and Quetiapine : moderate Aripiprazole and Ziprasidone : minimal
Hyperlipidemia DM
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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
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Effective Meds in Bipolar Mania/Hypomania or Mixed Episodes
Likely Beneficial Unlikely to be Beneficial or Maybe Harmful
Mania Lithium, valproate,carbamazepine,Atypical APsCombining (lithium orvalproate) with Atypical APs
GabapentinLamotrigineTopiramateAD Monotherapy
Mixed Episode Valproate, carbamazepine,aripiprazole, olanzapine,risperidone, or ziprasidone
Gabapentin Lamotrigine Topiramate
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Acute Phase
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 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
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Continuation Phase
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.
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BD
Rx for Bipolar depression
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Acute Phase Rx for BD Depression
Monotherapy Lithium Lamotrigine Quetiapine Olanzapine +/- fluoxetine
Combination Strategies Li+ Lamictal Augmentation with ADs for short term
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Effective meds in BD depression
Likely Beneficial Unlikely to be beneficial
LithiumQuetiapineLithium with lamotrigine
AbilifyNeurontinAD Monotherapy
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Goal of Maintenance Therapy
reduce residual symptoms, delay and prevent recurrence of new
mood episodes, reduce the risk of suicide, and enhance psychosocial functioning.
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Indications of Maintenance
BD I BD II BD NOS
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Medications for Maintenance
Lithium Lamotrigine Risperidal Consta 2nd line
Depakote Aripiprazole Olanzapine