1、Bipolar Disorders: Brain Mechanisms and Treatment ConsiderationsJair C. Soares, MD, PhDPat Rutherford Jr. Professor and ChairUT Center of Excellence on Mood DisordersDepartment of Psychiatry and Behavioral SciencesUTHealth Medical School Houston, TXDisclosureI have relationships with one or more pha
2、rmaceutical 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, AbbottUTHealth Psychiatry and Behavioral SciencesA Corridor in the Asylum, late May or early
3、June 1889Vincent van Gogh (Dutch, 18531890)Bipolar Spectrum - PrevalenceAkiskal et al, 2003From APA Practice Guidelines, 2002Bipolar Disorder Symptoms AreChronic and Predominantly Depressive53%32%9%6%AsymptomaticDepressedManic/hypomanicCycling/mixed% of Weeks 146 bipolar I patientsfollowed 12.8 year
4、s86 bipolar II patientsfollowed 13.4 years46%*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 roundingStructural Changes Seen With Successive Bipolar Manic Episodes*Strakowski SM et al. Am J Psychiatry. 20
5、02;159:1841-1847. Increased Ventricular Volume3.0Combined Lateral Ventricular Volume(% of Total Cerebral Volume)HealthyComparisonSubjects(n = 32)First Manic Episode(n = 18)Multiple ManicEpisodes(n = 17)2.01.00.0*90% had psychotic symptomsIs bipolar disorder neurodevelopmental?Genetics Heritability:
6、0.8-0.9 for Bipolar disorder0.45 for Depression Concordance Rate for Bipolar:58-70% for identical twins16-24% for fraternal twinsTreatment Goals Stabilize mood and facilitate sleep Promote adherence to treatment Abstain from substances Maintain cognition Prevent life-threatening events Suicide Etoh
7、withdrawal or dangerous intoxication Identify and reduce social stressorsFDA-approved Treatments for Bipolar DisorderAgents Manic Mixed Maintenance DepressionMOOD STABILIZERLithium + + Divalproex + Divalproex ER + + Carbamazepine ER + + ANTIPSYCHOTICS Chlorpromazine + Risperidone + + Olanzapine + +
8、+ Quetiapine + +Ziprasidone + + Aripiprazole + + + OTHERLamotrigine + 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.Monotherapy 19%2 medications 28%3 medications 28%4 or more medications 25% Percent of total sampleMedication Use in Bipolar I Disorder (n=457) From the Stanley Center Bipolar Disorder Registry, 1995-1999.Levine, et al. 2000.
