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Atypical or Second Generation Neuroleptics

Atypical or Second Generation Neuroleptics. Period 4: BPRS Total Score During Double-Blind Period. Which Term Should We Use?. Atypical (implies an unusual mechanism of action—e.g., minimal dopamine blockade or combined dopamine serotonin blockade) Novel (implies new, tho Clozapine is “old”)

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Atypical or Second Generation Neuroleptics

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  1. Atypical or Second Generation Neuroleptics

  2. Period 4: BPRSTotal Score During Double-Blind Period

  3. Which Term Should We Use? • Atypical (implies an unusual mechanism of action—e.g., minimal dopamine blockade or combined dopamine serotonin blockade) • Novel (implies new, tho Clozapine is “old”) • Second generation (perhaps the most neutral term…but too many syllables)

  4. Combined Dopamine and Serotonin Antagonists • Clozapine (weak D2) • Risperidone • Olanzapine • Quetiapine (weak D2) • Ziprasidone • Sertindole • Zodepin

  5. The Atypical Era:Total Antipsychotic Prescriptions in US Older generation Totalprescriptions(000’s) Atypical * *projected linear trending from 1996, 1997, 1998 Levin 1999

  6. European Psychiatrists’ Preferred Treatment for a Member of Their Family 0 20 40 60 80 100 Smith-Laittan and Grundy, 1999

  7. Advantages of Atypical Neuroleptics • Broader therapeutic spectrum • therapeutic efficacy on • positive symptoms • refractory — residual • reduction, prevention: • negative (deficit) syndrome • depressive symptoms • cognitive deficits • No (fewer) side effects • objective: acute EPS, TD • subjective: dysphoric response

  8. More Advantages of Atypical Neuroleptics • Earlier treatment for first episode (prevention?) • More acceptable to take, less stigma • Earlier and better participation in psychosocial rehabilitation programs • Higher compliance, less relapse/rehospitalization • Higher level of reintegration, better quality of life

  9. Reasons to Switch From Classical to Second Generation Neuroleptics • Inadequate response of positive symptoms • Residual negative symptoms • Associated mood symptoms (e.g. depression) • Residual or unresponsive cognitive symptoms • Relapse, despite compliance • Non-compliance due to adverse events • Patient/family request

  10. Switching From Classical to Second Generation Neuroleptics Reduction in use of anticholinergic drugs for EPS 100 75 50 25 0 *p<0.01 Patients using anticholinergicdrugs for EPS (%) (n=31) * Switch Conventional neuroleptics (t=41.1 months) Risperidone (t=20.1 months) Malla A et al. Clin Ther 1999;21(5):806–17

  11. Incidence of TD in Elderly Subjects Treated With Conventional Neuroleptics or Risperidone *Includes elderly patients with dementia

  12. Weight Changes With Atypical Neuroleptics 5 t=10 weeks 4 3 Mean change in body weight (kg) 2 1 Control Risperidone Olanzapine Clozapine *For marketed drugs After Allison DB et al. Am J Psychiatry 1999;156(11):1686–96

  13. Possible Consequences of Weight Gain in Schizophrenia • Cardiovascular morbidity and mortality • Psychosocial distress • Non-compliance with treatment • Further increased risk of diabetes

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