Atypical antipsychotics - Part I: Pharmacology, pharmacokinetics, and efficacy

OBJECTIVE: To compare the pharmacology, pharmacokinetics, and efficacy of t he newer atypical antipsychotics with those of conventional agents and exis ting atypical agents. DATA SOURCES: Information was retrieved from a MEDLINE English-literature s earch from July 1986 to June 1998 and by review of references. Indexing ter ms included neuroleptics, atypical antipsychotics, clozapine, risperidone, 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 vials th at assessed dosage, expanded efficacy, enhanced adverse effect profile, and cost. DATA SYNTHESIS: Like other atypical antipsychotics, the newer agents have a n enhanced 5-hydroxytryptophan/dopaminergic receptors (5-HT2/D-2) affinity ratio and undergo extensive biotransformation. Risperidone and olanzapine d emonstrate more favorable efficacy/adverse effect ratios than clozapine, se rtindole, and conventional antipsychotics in nonrefractory and refractory s chizophrenics. Future studies will more clearly define the role of quetiapi ne and ziprasidone in antipsychotic therapy. CONCLUSIONS: Data from controlled trials on efficacy and extrapyramidal sid e effects support risperidone or olanzapine as first-line agents for the tr eatment of schizophrenia. Pharmacologic and pharmacokinetic factors do not distinguish between agents sufficiently for drug selection.