1. Bipolar Disorders (Manic Depressive Illness) Larry Labbate, M.D.

2. Mania sometimes brings Euphoria

3. All Things Possible

4. What is bipolar disorder? Cyclic mood disorder Extremes of euphoria and depression during episodes Mania and depression May include psychosis, paranoia, hallucinations Suicide common (>10%) Alcohol and drug addiction common (50%)

5. Mania Descriptions “When you’re high it’s tremendous” “The ideas and feelings are fast and frequent like shooting stars.” “Sensuality is pervasive. Shyness goes” “I bounce checks, think I can do anything, get wild ideas.” “When will it happen again?”

6. Mania Descriptions “Too much of everything is just enough” “Rock music played far too loud is what satisfies” “Emotions tear me apart. I can laugh and cry at the same time”

7. Mania Descriptions “A feeling of intimate personal relationship with God is perhaps its paramount feature” “I was God!” “I could find the cure for cancer.”

8. Language Changes in Mania Puns and Rhymes common: “God is a Herbivore/ Thyme passes/ Mixed with long grasses of herbs in the field/ Rosemary weeps into meadow sweeps”

9. Depression in Bipolar “My life is in ruins. Look what I did when I was manic” “I just want to be in bed all the time” “I can’t do anything” “I just want to be by myself and cry” “What is the use of this life”

10. Recurrent Illness Long lived illness that often starts in 20s May start any time in life span.5% - 1% population; milder forms more common? Most have depression and mania, 10% pure mania (one manic episode buys the diagnosis) Episodes come more frequently over time

11. Kindling Seizure model: low level electrical impulses start with no effect, then seizures in response to same impulse. Eventually spontaneous seizures follow without impulse. Bipolar first related to environmental changes, loss, stress, drugs, sleep deprivation Ultimately: autonomous cycling

12. What is Mania? Intense change in behavior, feelings, beliefs Lasts weeks Often feel euphoric, smarter, sexier Often become paranoid or delusional Cook up schemes: inventions, money spending Don’t sleep Talk fast

13. Manic Symptoms - DSM IV Inflated self esteem Decreased need for sleep Distractibility Pressured/rapid speech Flight of ideas or racing thoughts Increased goal directed behavior Excessive involvement in pleasurable activities (sex, cars, money) that may have painful results.

14. Soft signs of mania Large hats on men Multiple rings on men Excessive visible cleavage on women or exposed chest on men Public nudity Public masturbation

15. Thought disorder: mania vs schizophrenia May appear to have schizophrenia because of prominent delusions or hallucinations and thought disorder Thoughts often disorganized, abundant, elaborate, and sometimes playful Schizophrenia thoughts more bland, fragmented, bizarre with affect less intense

16. Illness Affects Many Family and friends Work disrupted Legal system involved

17. Bipolar Disorder Types Bipolar I - Manic episode, with or without an episode of major depression. Bipolar II - Major depression & hypomania (hypo means below)

18. Bipolar diagnosis One episode of mania gets the diagnosis of Bipolar 1 because 90% go on to have depression Only called Bipolar II if you have hypomania and another episode of major depression Some have “mixed episodes” with depression and mania at the same time

19. Bipolar Spectrum

20. Bipolar Epidemiology Lifetime prevalence (adults) –Bipolar I1 % –Bipolar II1 % –(May be underestimates) Age of onset –Mean age21 years –Peak age15-19 years Gender –Bipolar Imale = female –Bipolar IIfemale > male

21. Model of Evolution of Bipolar Course Modified from: Post RM, Rubinow DR, Ballenger JC. Conditioning and sensitization in the longitudinal course of affective illness. Br J Psychiatry. 1986;149:191-201

22. Range of Illness Some patients may do very well between episodes: true cycles Mild mania (hypomania) may be helpful in work Many have residual signs/symptoms of illness Psychotic mania predicts poor outcome

23. Range of Illness Depression is commonly chronic Sometimes looks like schizophrenia (e.g. with prominent psychotic signs) in acute mania Substance abuse worsens course Suicide in 15%

24. Secondary Mania Mania due to… or substance induce mood disorder Early onset mania is usually idiopathic bipolar Onset of mania after 40 is often related to some medical cause – drugs (dopamine agonists – cocaine, antidepresants, amphetamine; steroids – anabolic or glucocorticoids; brain trauma, HIV, stroke, multiple sclerosis, epilepsy, brain tumor)

25. Mania precipitants Post-partum state Sleep deprivation Dopamine agonist drugs (amphet/L-Dopa) Antidepressants Stroke or brain injury Jet lag; especially West to East Severe life stress

26. Hypomania vs. Mania Hypo (below) Less intense form of mania – not hospitalized Paranoia, delusions, hallucinations, need for hospitalization = mania Hypomania may be effective (in business) Hypomanic patients diagnosed Bipolar II

27. Insight Patients are often unaware in mania Feels too good to be an illness Family, friends, legal system, bring them to attention False positives on retrospective questions (“yeah I had periods of feeling good, didn’t sleep”)

28. Course of Bipolar Most people who experience mania will have a recurrence and have depressive episodes Up to 40% may experience a mixed state or dysphoric mania (both mania and major depression simultaneously). 10-15% develop Rapid Cycling, defined as 4 or more mood episodes/year.

29. Course of Bipolar Mania or depression may last for 4-8 months and remit spontaneously May go from mania directly into depression or vice-versa May go for years without episodes Depressions usually more common than manias Depression may be chronic, last years

30. Bipolar Disorder Symptoms Are Chronic and Predominantly Depressive 53% 32% 9% 6% Asymptomatic Depressed Manic/hypomanic Cycling/mixed % of Weeks 146 bipolar I patients followed 12.8 years 86 bipolar II patients followed 13.4 years 46%* 50% 1% 2% Judd LL, et al. Arch Gen Psychiatry. 2002;59:530-537. Judd LL, et al. Arch Gen Psychiatry. 2003;60:261-269. *%s do not add to 100 due to rounding

31. Bipolar Depression Often have “atypical depression” Excessive sleeping Increased eating Suicide risk Teen atypical depression may be first sign of bipolar disorder

32. Long-Term Prophylaxis in Bipolar I Disorder After 2 manic episodesAlways After 1 manic episode if:Usually –Very severe or –Strong family history After 1 manic episodeSometimes

33. Treatment of Mania Lithium Anticonvulsants Divalproex (valproic acid) Carbamazepine Lamotrigine Mechanism of action unknown; inositol system and second messenger affects are implicated though unproven

34. Treatment of Mania Li and Valproic acid (an anticonvulsant) established for acute mania and recurrence of mood disorder Li and Lamotrigine (anticonvulsant) treat acute depression in bipolar disorder Carbamazepine (anticonvulsant) less well established, though useful

35. Treatment of Mania Antipsychotics treat mania and psychosis related to mania - haloperidol - risperidone, olanzapine, clozapine, ziprasidone, quetiapine *Risk for Tardive Dyskinesia from antipsychotics greater in mood disorder patients

36. Treatment of Mania Benzodiazepines (diazepam, lorazepam) used for sleep and acute agitation Electroconvulsive therapy (ECT) used for mania and depression Long term supportive relationship with MD is critical to success

37. Treatment of Mania Patients need long term care Psychotherapy important because of devastating effects on people’s lives Help patients with insight and compliance Help track phases of illness and risks for new episodes

38. Bipolar Depression Early teen onset depression may mark start of bipolar disorder Often “atypical” features (increased sleeping, increased eating) May be seasonal (winter depressions) May have psychosis (hearing voices, delusions)

39. Bipolar Depression Suicide happens in this phase Hypothyroidism may result from Li+ use Hypothyroid symptoms similar to depression Alcohol use may start during depressed phase

40. Bipolar Depression Most patients have more depression than mania Depression often more debilitating Treatment more difficult for depression Antidepressant treatment tightrope

41. Cyclothymia For at least 2 years, the presence of hypomania and numerous periods of depressive symptoms that do not meet criteria for major depression. Results in distress or functional impairment. A chronic, smoldering form of bipolar illness.

42. Addiction and Bipolar Drug or alcohol addiction are common (>50%) Ethanol or benzodiazepines may slow the high. ?brain structures underlying addiction and mania linked? Cocaine or amphetamine intoxication may mimic mania; patients may seek the intoxicating manic rush Crash from stimulants looks like depression

43. Addiction and Bipolar Some patients not diagnosed until they “dry out” Need to treat addiction and mood disorder Patients often harder to treat because the drug “payoff” is greater in those with bipolar

44. Living with Bipolar When is the next episode coming? Is what I’m feeling normal or part of my illness?

45. Le Joie de Vivre