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Ronald A. Remick, MD, FRCP(C) Medical Director, Mood Disorder Association of British Columbia Sophia I. Zisman,

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Presentation on theme: "Ronald A. Remick, MD, FRCP(C) Medical Director, Mood Disorder Association of British Columbia Sophia I. Zisman,"— Presentation transcript:

1 Ronald A. Remick, MD, FRCP(C) Medical Director, Mood Disorder Association of British Columbia Sophia I. Zisman, Bsc Hons. St. George’s University of London Bipolar Disorders 2013

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

3 Work related economic losses due to depression are estimated to cost 6 billion dollars per year in Canada Mood Disorders and the Workplace Health Report, Statistics Canada, 2006

4 Absenteeism vs. Presenteeism Presenteeism (lost productivity while at work) – likely a more significant problem with mood disorders than previously recognized in Canada 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)! 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)! Mood Disorders and the Workplace

5 ① The course of bipolar I is 9-10 cycles during a lifetime – often stabilizing after 4-5 cycles ② Without treatment the average depressive episode is 10 weeks and average manic episode is 5 weeks ③ 60% of patients have an increase in episode intensity/duration with age Epidemiology

6 What about the role of ‘stress’ in bipolar illness? Disruption in sleep, but not ‘stress’ can lead to a bipolar relapse. Early childhood ‘trauma’ is NOT causative in bipolar illness, however; ① sexual abuse – may increase risk of suicide attempts ② physical abuse – may increase risk of manic relapses ③ sexual/physical abuse – may lead to earlier illness onset

7 Polygenic inheritance – fifty percent of bipolar patients have a family history of bipolar illness. Polygenic inheritance – fifty percent of bipolar patients have a family history of bipolar illness. Linkage studies (in several studies) have identified markers on chromosome 18 & 22. Linkage studies (in several studies) have identified markers on chromosome 18 & 22. New research is working to identify individuals at risk which will possibly lead to superior treatments in the future. New research is working to identify individuals at risk which will possibly lead to superior treatments in the future. Genetics of Bipolar Illness

8 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) Evolving genetic concepts

9 CRFACTHAdrenalinecAMPBDNFBrain Cell Growth STRESS and the BRAIN

10 CRF ACTH AdrenalinecAMPBDNF Brain Cell Growth STRESS and the BRAIN

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

12 Diagnosing Bipolar Disorders

13 ① A distinct mood change (depressed, irritable, anxious, etc) for at least two weeks ② Four or more SIGECAPS Diagnosis of depression Sleep Interest Guilt Energy Concentration Appetite Psychomotor Activity Suicide

14 ① A distinct mood change (elated, irritable, expansive, etc) for > one week (four days for hypomania) ② Three or more GST RAID : S leep(decreased) A gitation S leep(decreased) A gitation T alkative I mpaired judgement T alkative I mpaired judgement D istractible D istractible Diagnosis of Mania/Hypomania Grandiosity Sleep Talkative Rapid thoughts Agitation Impaired judgment Distractible

15 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. Diagnosing bipolar illness

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18 “ 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?” Diagnosis of Hypomania “ What about a period of time when you were so irritable that you would shout at people or start fights or arguments?” Doctors often fail to ask key questions (of a family member and the patient) that assist in the diagnosis of bipolar II disorder …

19 Treatment of Bipolar Disorders

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

21 Treatment of Bipolar Illness Psychological Interventions Biological Interventions 1 2

22 Psychological Interventions Mood Disorders Association of British Columbia http - Internet/ readings - Psycho education Cognitive behavioural therapy(CBT) for the depressive phase of the illness CBT to prevent manic relapse Psychotherapy

23 The evidence based psychotherapies are AS EFFECTIVE as antidepressants in mild/moderate MDD. The evidence based psychotherapies are AS EFFECTIVE as antidepressants in mild/moderate MDD. CBT is accessible in British Columbia. CBT is accessible in British Columbia. CBT response rate(8-12 weekly sessions) = 65%. CBT response rate(8-12 weekly sessions) = 65%. Cognitive Behavioral Therapy (CBT)

24 Identify automatic maladaptive thoughts and distorted beliefs that lead to depressive moods Learn strategies to modify these beliefs and practice adaptive thinking patterns Use a systematic approach to reinforce positive coping behaviors Cognitive Behavioral Therapy

25 Not covered by medical insurance Private Psychologist The majority of outpatient psychiatry departments in hospitals offer group based CBT which is covered by MSP funding. Enquire at your local hospital or with your doctor! Public Resources - ‘anti- depressant skills workbook (free download)-an outstanding self directed CBT workbookwww.carmha.ca/publications Online Accessibility

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

27 Lithium

28 Lithium Expect “two thirds” response to lithium: - 33% complete response - 33% significant mood attenuation - 33% no response/intolerance “anti-suicide” effect of lithium Lithium remains the ‘GOLD STANDARD’ in treating bipolar illness and is among the most effective and underutilized treatments in all of psychiatry! No response/intolerance Significant mood attenuation Complete response

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

30 Valproic acid (divalproex; Depokoate; Epival) is an effective antimanic agent Valproic acid (divalproex; Depokoate; Epival) is an effective antimanic agent The evidence for the prophylactic efficacy of valproic is still not clear (one short RCT, pharmaceutical company sponsored)  Recommended as first line maintenance therapy (Dr. Remick) The evidence for the prophylactic efficacy of valproic is still not clear (one short RCT, pharmaceutical company sponsored)  Recommended as first line maintenance therapy (Dr. Remick) Valproic is far superior as an anti manic rather than an antidepressant preventative agent Valproic is far superior as an anti manic rather than an antidepressant preventative agent Recommended to be used as a 1 st line combination therapy medication for the treatment of acute BD-1 depression Recommended to be used as a 1 st line combination therapy medication for the treatment of acute BD-1 depression Serum levels appropriate (versus no defined therapeutic range with carbamazepine) Serum levels appropriate (versus no defined therapeutic range with carbamazepine) Valproic Acid

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

32 ① There is increasing evidence that lamotrogine is an effective agent in treating both bipolar I and II depression  currently recommended as a first line agent in the treatment of 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 mg/day Lamotrogine (Lamictal)

33 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. They are not recommended in the treatment of 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. They are not recommended in the treatment of bipolar disorder. Other anticonvulsants in bipolar disorder

34 ① Quetiapine and Olanzepine show evidence of mood stabilizing properties – both antidepressant and antimanic. ② Current guidelines suggest Quetiapine is preferable to other antipsychotic agents due to its side effect profile. ③ Olanzapine is a 3 rd line treatment due to its side effect profile. ④ Side effects can included: weight gain, dyslipidemia, & diabetes with atypicals; especially olanzapine(Zyprexa) and clozapine(Clozaril) but also risperidone(Risperdol) and quetiapine (Seroquel) Typical/Atypical Antipsychotics

35 The diet of individuals with SMI(Serious Mental Illness) has been characterized as high fat, high in calories and high in simple carbohydrates. 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. 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. Smoking rates are elevated in the SMI and range between 32% and 92% in schizophrenia samples. Lifestyle

36 “ 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.” “ 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

37 Bipolar Medications and Pregnancy ① Lithium – ensure careful monitoring during pregnancy ② Valproic Acid – proven to be harmful for fetuses, it is recommended that new mothers switch to another treatment ③ Carbamazepine – should only be used if it is the only option Always contact your physician if you are being treated for bipolar disorder and are planning to fall pregnant.

38 Managing depressive and manic relapses

39 “don’t throw out the baby with the bathwater” If the treatment has muted or attenuated the illness consider adding a second treatment rather than eliminating the treatment that is offering partial efficacy.

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41 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% (SSRI’s & bupropion < TCA and SNRI) Managing Depressive Relapse

42 Treatment options: Treatment options: a. second mood stabilizer (I) (lamotrogine) a. second mood stabilizer (I) (lamotrogine) b. antidepressant (II,I)/ lamotrogine b. antidepressant (II,I)/ lamotrogine c. CBT(I,II) c. CBT(I,II) d. ECT(I,II) d. ECT(I,II)

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

44 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. Prevention of future manic relapses – Ulysses Agreement Prevention of future manic relapses – Ulysses Agreement

45 medication adherence (70% to 30%) medication adherence (70% to 30%) presence of subsyndromal symptoms presence of subsyndromal symptoms baseline psychosocial stress baseline psychosocial stress higher number of prior episode higher number of prior episode BD-11 versus BD-I BD-11 versus BD-I female gender female gender substance abuse substance abuse Rapid cycling (>4 episodes per year) Rapid cycling (>4 episodes per year) Factors associated with relapse

46 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 “Grey zones” in bipolar illness…(topics for future presentations)

47 ① The onset in bipolar illness can be in late adolescence, particularly in children of bipolar parents. ② The diagnosis of childhood bipolar illness (i.e. ages 5-15)is very different in USA compared to Canada, where childhood bipolar illness is virtually nonexistent. ③ In Canada, the onset of bipolar illness typically begins with a lengthy depressive episode. ④ In the USA, children with mood lability/irritability, anxiety and insomnia are often given a diagnosis of childhood bipolar illness. ⑤ The USA position is not consistent with decades of age of onset research, genetic studies, or current diagnostic criteria for bipolar disorders. What’s the deal with childhood bipolar illness?

48 The risks are real, but small (2% versus 15%). The risks are real, but small (2% versus 15%). Illness severity is not related to the severity of the illness in the family. Illness severity is not related to the severity of the illness in the family. Illness onset is at least twenty years in the future with extensive new developments and treatments on the way. Illness onset is at least twenty years in the future with extensive new developments and treatments on the way. Bipolar illness, without any other risk factors, in a parent is certainly not an exclusion to having and effectively parenting children. Bipolar illness, without any other risk factors, in a parent is certainly not an exclusion to having and effectively parenting children. “Doctor, should we have children?”

49 ① Many studies have shown that between 20 and 35% of artists (musicians, painters, writers, poets, etc ) develop bipolar illness where the rate of bipolar illness in the population is about 2%. ② The higher rate of bipolar illness cannot be explained by ‘stressful’ life style, poverty, etc. ③ Severe manic and depressive episodes impair creative output. ④ Creativity and bipolar illness have a familial (i.e. genetic) link. ⑤ Touched with Fire : Manic Depressive Illness and the Artistic Temperment. by Kay Redfield Jamieson (1993) The relationship between creativity and bipolar illness


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