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Atypical antipsychotics: Part II: Adverse effects, drug interactions, and costs
C S Brown1, J S Markowitz, T R Moore
1Department of Pharmacy Practice and Pharmacoeconomics, University of Tennessee, Memphis 38163, USA.
Objective:
To compare the adverse effects, drug interactions, and costs of conventional and atypical agents, and to provide a summary of therapeutic guidelines. Part I compared the pharmacology, pharmacokinetics, and efficacy of atypical and conventional agents.
Data Sources:
Information was retrieved from a MEDLINE English-language literature search from June 1986 to June 1998 and by review of references. Indexing terms included atypical antipsychotics, neuroleptics, clozapine, risperidone, olanzapine, sertindole, quetiapine, and ziprasidone.
Study Selection:
Comparative studies were selected when possible; placebo-controlled studies were included when data were limited on newer atypical antipsychotics.
Data Extraction:
Emphasis was placed on properly designed clinical trials that assessed dosage, expanded efficacy, enhanced adverse effect profile, and cost.
Data Synthesis:
Significant adverse effects are agranulocytosis with clozapine, dose-dependent extrapyramidal side effects (EPS) with risperidone, and neuroleptic malignant syndrome with clozapine and risperidone. Clinically relevant drug interactions may occur with clozapine-lorazepam, clozapine-fluvoxamine, and sertindole-quinidine. Newer atypical agents have high acquisition costs but may reduce noncompliance and rehospitalization rates.
Conclusions:
Risperidone or olanzapine are recommended as first-line agents for schizophrenia due to accumulating controlled trials and clinical experience. Quetiapine should be considered with partial response or if EPS develop, and clozapine is an option with treatment-refractory patients. Atypical agents may contribute to a better quality of life, but conventional neuroleptics are the first choice for strictly cost considerations.