Bipolar Disorders - 2007

1. Bipolar Disorders - 2007 Ronald A. Remick, MD, FRCP(C) Consultant Psychiatrist Member, Board of Directors, MDA Phone : 604-682-2344 ext 62121 Email : rremick@shaw.ca

2. Epidemiology 1. Lifetime prevalence : bipolar I : 0.8% bipolar II : 0.6% (Murphy, 2000) 2. Bipolar disorder is the 6th leading cause of disability, ages 15-44, worldwide… depression is 2nd! 3. At any given point in time, 60% of bipolars are not in treatment

3. Mood Disorders and the Workplace (new data) 30% of disability claims in Canada ($15-30 billion annually) due to mood disorders (second only to cardiovascular disease)…and increasing!

4. Mood Disorders and the Workplace (new data) Absenteeism vs Presenteeism Presenteeism (lost productivity while at work) – likely a more significant problem with mood disorders than previously recognized in Canada Productivity loss from presenteeism due to depression is 4 hours/week while loss from absenteeism is but 1 hour/week (between $6-60 billion loss per annum)!

5. Epidemiology 1. Course of bipolar I is 9-10 cycles during a lifetime – often stabilizing after 4-5 cycles 2. Without treatment – average depressive episode is 10 weeks, average manic episode is 5 weeks 3. Sixty percent of patients have an increase in episode intensity/duration with age

6. What about the role of ‘stress’ in bipolar illness? 1. Disruption in sleep, but not ‘stress’ per se can lead to a bipolar relapse. 2. Early childhood ‘trauma’ is NOT causative in bipolar illness. However, a. sexual abuse – may increase risk of suicide attempts b. physical abuse – may increase risk of manic relapses c. sexual/physical abuse – may lead to earlier illness onset

7. Genetics of Bipolar Illness 1. Polygenic inheritance. Fifty percent of bipolar patients have a family history of bipolar illness. 2. Linkage studies (in several studies) have identified markers on chromosome 18 &22. 3. Near future is identifying individuals at risk; long term future – superior treatments.

8. Evolving genetic concepts(new data) 1. endophenotypes are gene intermediaries that turn on or turn off a specific gene 2. “Stress/adversity’ can influence endophenotypes. That is, stress or adversity can turn on or turn off certain genes that can either trigger depression (vulnerability) or protect from depression (resiliency)

9. STRESS and the BRAIN(new data) CRF ACTH adrenaline cAMP BDNF brain cell growth

10. STRESS and the BRAIN (new data)CRF ACTH adrenalineSTRESS cAMP BDNF brain cell growth

11. Limbic System Hypothalamus STRESS CRF Mood dysregulation HippocampalShrinkage Memory impairment Pituitary Apoptosis/neuron death ACTH Adrenal Cortex Cortisol + Adrenaline

12. DIAGNOSING BIPOLAR DISORDERS

13. Diagnosis of depression 1.A distinct mood change (depressed, irritable, anxious, etc) for at least two weeks 2. Four or more SIGECAPS : S leep C oncentration I nterest A ppetite G uilt P sychomotor activity E nergy S uicide

14. Diagnosis of mania/hypomania 1. A distinct mood change (elated, irritable, expansive, etc) for > one week (four days for hypomania) 2. Three or more GST RAID : G randiosity R apid thoughts S leep(decreased) A gitation T alkative I mpaired judgement D istractible

15. Diagnosing bipolar illness 1. Distinguish bipolar I (mania) from bipolar II (hypomania) 2. ***Bipolar II is among the most frequently missed diagnoses in psychiatry*** 3. The diagnosis of bipolar II disorder is risky, at best, without collateral information.

18. Diagnosis of hypomania Doctors often fail to ask key questions (*of afamily member and the patient) that assist in the diagnosis of bipolar II disorder : “ Has there been a period of time when you were feeling so good or hyper that other people thought you were not your normal self, or were so hyper you got into trouble?” “ What about a period of time when you were so irritable that you would shout at people or start fights or arguments?”

19. Treatment of Bipolar Disorders

20. Treatment of Bipolar Disorders 1. Bipolar disorder is a chronic illness: a) Expect exacerbations and remissions b) Long term chemotherapy is the rule not the exception 2. It is risky, at best, to treat bipolar patients in a vacuum i.e. without the involvement of family/significant others

21. Treatment of bipolar illness 1. PSYCHOLOGICAL INTERVENTIONS 2. BIOLOGICAL INTERVENTIONS

22. Treatment of bipolar illness PSYCHOLOGICAL TREATMENTS 1. Psycho education : a. Mood Disorders Assoc of British Columbia b. internet/ readings, etc 2. Psychotherapy : a. Cognitive Behavioral Therapy (CBT) for the depressive phase of illness b. Cognitive Behavioral Therapy (CBT) to prevent manic relapses

23. Cognitive Behavioral Therapy (CBT) 1. The evidence based psychotherapies (CBT – cognitive behavioral therapy) are AS EFFECTIVE as antidepressants in mild/moderate MDD. 2. Cognitive therapy (CBT) is accessible in British Columbia.

24. Cognitive Behavioral Therapy CBT response rate(8-12 weekly sessions) – 65% Core features: a. identify automatic maladaptive thoughts and distorted beliefs that lead to depressive moods b. learn strategies to modify these beliefs and practice adaptive thinking patterns c. use a systematic approach to reinforce positive coping behaviors

25. Cognitive Behavioral Therapy CBT is accessible: a. private psychologist (not covered by medical insurance) b. Changeways (www.changeways.com) - a group based CBT program offered at many hospitals/mental health centers throughout BC (free – covered by medical insurance) c. www.carmha.ca/publications - ‘anti- depressant skills workbook’ (free download)- an outstanding self directed CBT workbook

26. Biological Treatments for bipolar disorders 1. LITHIUM 2. VALPROIC ACID 3. CARBAMAZEPINE 4. LAMOTROGINE 5. ATYPICAL ANTIPSYCHOTICS 6. ANTIDEPRESSANTS 7. OTHER ANTICONVULSANTS

27. Lithium* – wherefore art thou?*old, old data!

28. Lithium 1. Expect “two thirds” response to lithium: 33% - complete response 33% - significant mood attenuation 33% - no response/intolerance 2. “anti-suicide” effect of lithium 3. lithium remains the ‘gold standard’ in treating bipolar illness and is among the most effective and underutilized treatments in all of psychiatry!

29. Suicide attempts before, during, one year, and two years post lithium treatment

30. Valproic Acid 1. Valproic acid (divalproex; Depokoate; Epival) is an effective antimanic agent 2. The evidence for the prophylactic efficacy of valproic is still not clear (one short RCT, pharmaceutical company sponsored) 3. Valproic is far superior as an anti manic rather than an antidepressant preventative agent 4. Serum levels appropriate (versus no defined therapeutic range with carbamazepine)

31. Carbamazepine 1. Carbamazepine (Tegretol) is an effective antimanic agent (19 studies) 2. Carbamazepine is an effective prophylactic agent (10 RCTs), but likely less effective than lithium (Davis et al, 1999) 3. Carbamazepine appears to be a forgotten (yet very effective) treatment in bipolar illness 4. Oxcarbazepine (Trileptil) is being touted as a ‘similar’ but ‘superior’ medication to carbamazepine, but recent studies shed some doubt

32. Lamotrogine (Lamictal) 1. There is increasing evidence that lamotrogine is an effective agent in treating both bipolar I and II depression. 2. There is very limited (but some) evidence that lamotrogine is an effective anti-manic or prophylactic agent. 3. Lamotrogine has a relatively benign (e.g. non sedative, weight neutral) side effect profile. Dose range not determined but likely 100-300mg/day

33. Other anticonvulsants in bipolar disorder There is NO evidence that gabapentin (Neurontin) or topiramate (Topramax) has any benefit at all in the treatment of bipolar depression, bipolar mania, and/or the preventative/prophylactic treatment of bipolar illness

34. Typical/Atypical Antipsychotics 1. All are effective in mania. Limited evidence for effectiveness in prophylaxis or in depressive episodes. 2. All atypical antipsychotic research is pharmaceutical industry sponsored . 3. Significant concerns about weight gain, dyslipidemia, & diabetes with atypicals; especially olanzapine(Zyprexa) and clozapine(Clozaril) but alsorisperidone(Risperdol) and quetiapine (Seroquel)

35. Medical Co-Morbidity and Life Expectancy 1.Individuals with schizophrenia and affective disorders have increased risk of death from medical causes and a shorter lifespan 2.Comparing mortality in public mental health clinics in the USA with the general population (1997-2000), patients lost decades of potential years of life (average 25 years)

36. Medical Co-Morbidity and Life Expectancy(cont) 3. As in the general population the main cause of death is coronary heart disease (CHD), but to an even greater extent 4. Cardiovascular standardized mortality rate in schizophrenia is approximately 2X the general population (2.3 in males and 2.1 in females) Patients with both unipolar and bipolar disorder also have increased mortality from CHD

37. Medication Weight gain Diabetes/lipids Metabolic syndrome Cardiac effects Patient Factors Failure to recognize illness Refusal of treatment Non-adherence with treatment Cardiac/Metabolic Co-morbidityHealth Determinants Lifestyle Smoking Substance abuse Diet, exercise Poverty Systemic Factors Limited attention to medical care Separation of psychiatric and mental health care “Falling between the cracks”

38. Lifestyle The diet of individuals with SMI(Serious Mental Illness) has been characterized as high fat,high in calories and high in simple carbohydrates Patients with SMI are less active then those in the general population and are more likely to walk as their sole form of physical activity Smoking rates are elevated in the SMI and range between 32% and 92% in schizophrenia samples

39. Metabolic Abnormalities with Atypical Antipsychotics

40. Typical/Atypical Antipsychotics 1. All are effective in mania. Limited evidence for effectiveness in prophylaxis or in depressive episodes. 2. All atypical antipsychotic research is pharmaceutical industry sponsored . 3. Significant concerns about weight gain, dyslipidemia, & diabetes with atypicals; especially olanzapine(Zyprexa) and clozapine(Clozaril) but alsorisperidone(Risperdol) and quetiapine (Seroquel)

41. Do not rashly use every new product of which the peripatetic siren sings. Consider what surprising reactions may occur in the laboratory from the careless mixing of unknown substances. Be as considerate of your patient and yourself as you are of the test tube. - Sir William Osler

42. Managing depressive and manic relapses

43. Managing depressive and manic relapses “don’t throw out the baby with the bathwater”

45. Managing Depressive Relapse 1. Don’t throw out the baby with the bathwater! 2. The risk of an antidepressant induced manic switch in both bipolar I/II is < 10% 3. Treatment options: a. second mood stabilizer (I), especially lamotrogine b. antidepressant (II,I)/lamotrogine c. CBT(I,II) d. ECT(I,II)

48. Managing Manic/Hypomanic Relapse 1. Don’t throw out the baby with the bath water. 2. Other treatment options : a. hospital care (I) b. no treatment intervention (II) c. second mood stabilizer (I/II) d. atypical /typical antipsychotic (I/II) e. benzodiazepine (II) f. ECT (I)

49. Prevention of future manic relapses – Ulysses Agreement 1. Set it up BEFORE manic relapse with doctors, family, employers, etc. 2. Put it in writing…outline the type of treatment e.g. hospitalization, antipsychotic medication, etc.

50. “Grey zones” in bipolar illness…or topics for future presentations 1.“Stressful life problems” versus mild depressive relapse 2. The role of psychological “adversity” in bipolar illness 3.. To treat or not treat hypomania 4. Social/family/vocational stigma 5. “ Doctor should we have children?” 6. Bipolar illness and creativity