WPA Atypical or Second Generation Neuroleptics

WPA Period 4: BPRS Total Score During Double-Blind Period

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

WPA Combined Dopamine and Serotonin Antagonists Clozapine (weak D2)Clozapine (weak D2) RisperidoneRisperidone OlanzapineOlanzapine Quetiapine (weak D2)Quetiapine (weak D2) ZiprasidoneZiprasidone SertindoleSertindole ZodepinZodepin

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

WPA European Psychiatrists’ Preferred Treatment for a Member of Their Family Smith-Laittan and Grundy,

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

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

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

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

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

WPA t=10 weeks Weight Changes With Atypical Neuroleptics *For marketed drugs After Allison DB et al. Am J Psychiatry 1999;156(11):1686–96 Mean change in body weight (kg) ControlRisperidoneOlanzapineClozapine

WPA Possible Consequences of Weight Gain in Schizophrenia Cardiovascular morbidity and mortalityCardiovascular morbidity and mortality Psychosocial distressPsychosocial distress Non-compliance with treatmentNon-compliance with treatment Further increased risk of diabetesFurther increased risk of diabetes