BIPOLAR DISORDER

1. BIPOLAR DISORDER Indra Singh MD

2. 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.

3. 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

4. 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

5. Diagnostic criteria • BD I • Episodes of Mania • Often have depression • BD II • One or more depressive episodes • At least one episode of hypomania

6. 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

7. 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;

8. 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,

9. 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

10. 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.

11. 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

12. 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

13. 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

14. BD • Assessment and Rx for • Mania • Hypomania • MIxed

15. Clinical Assessment Medical comorbidity Psychiatric comorbidity Psychosocial Stressors Medications current and past Suicide risk Substance Use

16. Assessment • Stop Anti Depressants • Beware of discontinuation syndromes symptoms • Dizziness • Headache • Paresthesias • Nausea • Diarrhea • Insomnia • Irritability

17. 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

18. 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

19. 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

20. Acute Phase • Drugs used to induce remission • Lithium  • Anticonvulsants • Antipsychotics • allow up to two weeks before determining the drug’s clinical effectiveness.

21. 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

22. Acute Phase • If no remission within 2 weeks • Switch • If no response • Add • If partial response • Goal of Rx is full remission

23. 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

24. Choice of Drug Past response to medications Side-effect profiles Comorbid medical illness Pregnancy Concurrent medications Cost

25. 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

26. 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.

27. LITHIUM TOXICITY

28. Lithium drug interactions

29. 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

30. 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

31. 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.

32. 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

33. Risperidone • Start 1mg BID • Increase to 6mg/day • Onset of action between 1-6 days • Mono or combination therapy • Side effects • Somnolence • EPSE

34. Ziprasidone • Start 40mg BID • Max 80mg BID • Onset of action at day 2 • Monotherapy • Side effects: • Nausea • Akathisia • tremors

35. Aripiprazole • Start 15mg/day • Max 30mg /day • Mono or combination therapy • Separates form placebo by day 4 • Side effects • N/V • insomnia • akathisia

36. Quetiapine • 100mg day 1 • Up to 800mg daily • Superior to placebo at day 21 • Side effects • Dry mouth • Dizziness • Weight gain • somnolence

37. Metabolic effects of Atypicals • Weight gain • Clozapine and olanzapine : most wt. gain • Risperidone and Quetiapine : moderate • Aripiprazole and Ziprasidone : minimal • Hyperlipidemia • DM

38. Monitoring parameters

39. Effective Meds in Bipolar Mania/Hypomania or Mixed Episodes

40. 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

41. 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.

42. BD Rx for Bipolar depression

43. Acute Phase Rx for BD Depression • Monotherapy • Lithium • Lamotrigine • Quetiapine • Olanzapine +/- fluoxetine • Combination Strategies • Li+ Lamictal • Augmentation with ADs for short term

44. Effective meds in BD depression

45. Goal of Maintenance Therapy reduce residual symptoms, delay and prevent recurrence of new mood episodes, reduce the risk of suicide, and enhance psychosocial functioning.

46. Indications of Maintenance BD I BD II BD NOS

47. Medications for Maintenance • Lithium • Lamotrigine • Risperidal Consta • 2nd line • Depakote • Aripiprazole • Olanzapine