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Atypical antipsychotics. Part I: Pharmacology, pharmacokinetics, and efficacy
J S Markowitz1, C S Brown, T R Moore
1Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, USA.
Objective:
To compare the pharmacology, pharmacokinetics, and efficacy of the newer atypical antipsychotics with those of conventional agents and existing atypical agents.
Data Sources:
Information was retrieved from a MEDLINE English-literature search from July 1986 to June 1998 and by review of references. Indexing terms included neuroleptics, atypical antipsychotics, 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:
Like other atypical antipsychotics, the newer agents have an enhanced 5-hydroxytryptophan/dopaminergic receptors (5-HT2/D2) affinity ratio and undergo extensive biotransformation. Risperidone and olanzapine demonstrate more favorable efficacy/adverse effect ratios than clozapine, sertindole, and conventional antipsychotics in nonrefractory and refractory schizophrenics. Future studies will more clearly define the role of quetiapine and ziprasidone in antipsychotic therapy.
Conclusions:
Data from controlled trials on efficacy and extrapyramidal side effects support risperidone or olanzapine as first-line agents for the treatment of schizophrenia. Pharmacologic and pharmacokinetic factors do not distinguish between agents sufficiently for drug selection.