Atypical antipsychotics: Part II - Adverse effects, drug interactions, andcosts

OBJECTIVE: To compare the adverse effects, drug interactions, and costs of conventional and atypical agents, and to provide a summary of therapeutic g uidelines. Part I compared the pharmacology, pharmacokinetics, and efficacy of atypical and conventional agents. DATA SOURCES: Information was retrieved from a MEDLINE English-language lit erature search from June 1986 to June 1998 and by review of references. Ind exing terms included atypical antipsychotics, neuroleptics, clozapine, risp eridone, olanzapine, sertindole, quetiapine, and ziprasidone. STUDY SELECTION: Comparative studies were selected when possible; placebo-c ontrolled studies were included when data were limited on newer atypical an tipsychotics. DATA EXTRACTION: Emphasis was placed on properly designed clinical trials t hat assessed dosage, expanded efficacy, enhanced adverse effect profile, an d cost. DATA SYNTHESIS : Significant adverse effects are agranulocytosis with cloza pine, dose-dependent extrapyramidal side effects (EPS) with risperidone, an d neuroleptic malignant syndrome with clozapine and risperidone. Clinically relevant drug interactions may occur with clozapine-lorazepam, clozapine-f luvoxamine, and sertindole-quinidine. Newer atypical agents have high acqui sition costs but may reduce noncompliance and rehospitalization rates. CONCLUSIONS: Risperidone or olanzapine an recommended as first-line agents for schizophrenia due to accumulating controlled trials and clinical experi ence. Quetiapine should be considered with partial response or if EPS devel op, and clozapine is an option with treatment-refractory patients. Atypical agents may contribute to a better quality of life, but conventional neurol eptics are the first choice for strictly cost considerations.