BIPOLAR DISORDERS “AFTER ALL, THERE IS NOTHING AS INTERESTING AS PEOPLE, AND ONE CAN NEVER STUDY THEM ENOUGH” VINCENT VAN GOGH Brought to you by BIPOLAR DISORDERS Closely Kept Secrets New Treatments B.
“AFTER ALL, THERE IS NOTHING AS INTERESTING AS PEOPLE, AND ONE CAN NEVER STUDY THEM ENOUGH” VINCENT VAN GOGH Brought to you by BIPOLAR DISORDERS • Closely Kept Secrets • New Treatments Brought to you by EPIDEMIOLOGY OF BIPOLAR DISORDER • Prevalence is underestimated at 1% • Prevalence is probably 2% • Calgary est 2%x890000=17,800 citizens Brought to you by COMORBID DISORDERS • Substance Abuse – At least 61% • Alcohol, Cocaine, THC • Effect – More mixed and rapid cycling, poorer response to Lithium, slower time to recovery, and more lifetime hospitalizations • Narcissistic PD • Borderline PD • 20-30% OCD, Panic Disorder Brought to you by DIFFERENTIAL DIAGNOSIS • • • • • • Schizophrenia, Schizoaffective disorder Substance Abuse – Stimulants Pseudo-Unipolar Disorder Steroids, Ginseng, Valerian root Syphilis, Hyperparathyroidism Borderline, Narcissistic and Histrionic Personality disorder Brought to you by ADOLESCENCE • Much more likely to be delusional and co morbid for substance abuse • More likely to be irritable and misdiagnosed as conduct disorder Brought to you by PRECIPITANTS • 60% of first episodes precipitated by psychosocial, physical, or drug causes 30% of second episodes • None of fourth episodes • Illness starts as exogenous and becomes more endogenous • Concept of kindling Brought to you by SCREENING QUESTIONS • Have you ever had a period of a week or so when you felt so happy and energetic that your friends told you that you were talking too fast or that you were behaving differently and strangely? • Has there been a period when you were so hyper and irritable that you got into arguments with people? Brought to you by SCREENING QUESTIONS • Has anyone ever called you manic before? Brought to you by DIGFAST • • • • • • • Distractibility Indiscretion (pleasurable activities) Grandiosity Flight of ideas Activity increase Sleep deficit (decreased need) Talkativeness (pressured speech) Brought to you by Similar Y-MRS Improvement in Non-Psychotic and Psychotic Subjects Baseline :0 Study I three weeks 29.58 27.56 Study II four weeks 30.8 25.5 -5 Mean Change -10 (LOCF) -15 -20 -9.9 * Psychotic Non-psychotic -10.7 -13.0 -15.9 ** *p=0.88; **p=0.41 No difference in mania improvement among olanzapine-treated subjects with and without psychotic features Brought to you by Brought to you by Y-MRS Total: Manic vs Mixed Episodes Study II four weeks 29.19 Baseline: 28.17 Manic episode n=31 -5 Mean Change -10 -15 Mixed episode n=23 -15.39 -13.96 -20 There was no difference in antimanic response (Y-MRS Total beginning to endpoint improvement, four-week study II) between olanzapine-treated patients in manic or mixed episodes (p=.681) Brought to you by Baseline: Depressive Symptoms‡ HAMD Improved During Olanzapine Treatment 26.57 25.62 n=21 n=21 Mean -5 Change in HAMD21 Total -6.81 -10 -12.29 * Olanzapine Placebo -15 In patients with depressive symptoms, olanzapine-treated patients had a statistically significantly greater mean improvement in HAMD21 total scores compared to placebo-treated patients in this four-week study II acute mania trial *p=0.046 ‡HAMD21 total score 20 at baseline Y-MRS Total: Lithium Responders vs Non-Responders Brought to you by Study II four weeks 27.67 Baseline: 29.38 Most Recent -3 Lithium Response: Responder n=18 -6 Mean Change -9 Non-responder n=24 -12 -15 -18 -14.00 -15.88 There was no difference in antimanic response (Y-MRS Total beginning to endpoint improvement, four-week study II) between olanzapine-treated patients with history of good vs poor response to lithium treatment for mania (p=.641) Baker RW et al Bipolar Disorders Conference Phoenix, Arizona, January 2000 Y-MRS Total: Valproic Acid Brought to you by Responders vs Non-Responders Study II four weeks 30.45 Baseline:0 29.48 Most Recent Valproic Acid Response: -5 Responder n=11 Mean Change -10 -15 Non-responder n=21 -11.73 -14.67 -20 There was no difference in antimanic response (Y-MRS Total beginning to endpoint improvement, four-week study II) between olanzapine-treated patients with history of good vs poor response to valproate treatment for mania (p=.546) Baker RW et al Bipolar Disorders Conference Phoenix, Arizona, January 2000 Treatment-Emergent Adverse Effects During Acute Mania Trials Event Somnolence Dry mouth Dizziness Asthenia % Reporting Olanzapine (n=125) Placebo (n=129) 35% 22% 18% 15% 13% 7% 6% 6% These four events were the only ones significantly more common (p