双相情感障碍的脑机制及治疗注意事项概要课件

Bipolar Disorders: Brain Mechanisms and Treatment Considerations Jair C. Soares, MD, PhD Pat Rutherford Jr. Professor and Chair UT Center of Excellence on Mood Disorders Department of Psychiatry and Behavioral Sciences UTHealth Medical School Houston, TX Disclosure I have relationships with one or more pharmaceutical companies that could be perceived as a possible conflict of interest. The relationships are summarised below: Relevant Consultancy / Speaker / Research Support - Merck - Elan - Forest - BMS - Pfizer, Abbott UTHealth Psychiatry and Behavioral Sciences A Corridor in the Asylum, late May or early June 1889 Vincent van Gogh (Dutch, 18531890) Bipolar Spectrum - Prevalence Akiskal et al, 2003 From APA Practice Guidelines, 2002 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 Structural Changes Seen With Successive Bipolar Manic Episodes* Strakowski SM et al. Am J Psychiatry. 2002;159:1841-1847. Increased Ventricular Volume 3.0 Combined Lateral Ventricular Volume (% of Total Cerebral Volume) Healthy Comparison Subjects (n = 32) First Manic Episode (n = 18) Multiple Manic Episodes (n = 17) 2.0 1.0 0.0 *90% had psychotic symptoms Is bipolar disorder neurodevelopmental? Genetics Heritability: 0.8-0.9 for Bipolar disorder 0.45 for Depression Concordance Rate for Bipolar: 58-70% for identical twins 16-24% for fraternal twins Treatment Goals Stabilize mood and facilitate sleep Promote adherence to treatment Abstain from substances Maintain cognition Prevent life-threatening events Suicide Etoh withdrawal or dangerous intoxication Identify and reduce social stressors FDA-approved Treatments for Bipolar Disorder AgentsManicMixedMaintenance Depression MOOD STABILIZER Lithium+ Divalproex+ Divalproex ER+ Carbamazepine ER+ ANTIPSYCHOTICS Chlorpromazine+ Risperidone+ Olanzapine+ Quetiapine+ + Ziprasidone+ Aripiprazole+ OTHER Lamotrigine+ Olanzapine/fluoxetine + Drugs listed in order of approval for a bipolar disorder indication. This chart does not imply comparable efficacy or safety profiles. Physicians Desk Reference. 60th ed. Montvale, NJ: Medical Economics Co; 2006. AgentsManicMixedMaintenance MOOD STABILIZER Lithium+ Divalproex+ Divalproex ER+ Carbamazepine ER+ ANTIPSYCHOTICS Chlorpromazine+ Risperidone+ Olanzapine+ Quetiapine+ Ziprasidone+ Aripiprazole+ OTHER Lamotrigine+ Olanzapine/fluoxetine Monotherapy19% 2 medications28% 3 medications28% 4 or more medications25% Percent of total samplePercent of total sample Medication Use in Bipolar I Disorder (n=457) From the Stanley Center Bipolar Disorder Registry, 1995-1999. Levine, et al. 2000. lFunctional outcome predicted by age at intake family history of mood illicit drug use functional recovery at 6 months Syndromal 90% Functional 39% Recovery at 12 months Conus et al 2006 Symptomatic 59% Symptomatic and functional recovery after first-episode psychotic mania Functional recovery is considered a return to the premorbid level of functioning ie recovering the whole patient Monitor the patients psychiatric status: Monitoring is especially important during manic episodes - insight is often limited or absent. Small changes in mood or behavior may herald the onset of an episode. Consider limiting access to cars, credit card, bank accounts or telephones and cellular phones during the manic phase - risk of reckless behavior. Educate the patient and his or her family: Patients will, over time, vary their ability to understand and retain information and accept long-term treatment. Education - ongoing process - facts about the illness and its treatment. Enhance treatment adherence: Ambivalence about treatment is often expressed as poor adherence. Causes of ambivalence include: - denial, lack of insight about having a serious illness - reluctance to give up the experience of hypomania or mania. - medication side-effects, cost, and other demands of long-term treatment. - Family and patient education Novel treatments possibilities in the horizon Conclusions Possibly etiologically heterogeneous and polygenic Regional abnormalities in fronto-limbic regions involved in mood regulation abnormalities in neuronal resilience? Biological vulnerability interacting w