CLINICAL HANDBOOK OF SCHIZOPHRENIA

CHAPTER 17SIDE EFFECTSOF ANTIPSYCHOTICSCHRISTIAN R. DOLDERThe modern era of antipsychotic pharmacotherapy began in the 1950s with the introductionof chlorpromazine. This agent, along with other conventional antipsychoticssuch as haloperidol, fluphenazine, and thioridazine, enabled health care providers to improvesignificantly the positive symptoms of schizophrenia (e.g., delusions, hallucinations).Unfortunately, the gains in symptom improvement seen with conventionalantipsychotics were often offset by substantial toxicity, especially neurological side effects.The limitations associated with these agents spurred the development of atypicalantipsychotics such as clozapine, risperidone, and olanzapine. As a class, the atypicalantipsychotics were developed to be at least as efficacious as conventional agents, butwith significantly reduced neurological side effects. The ability of the atypical antipsychoticsto do just this have propelled them as the antipsychotics of choice for the treatmentof schizophrenia and related psychotic disorders. Despite the advantages of atypicalantipsychotics over conventional agents, atypical antipsychotics are not without sideeffects. This chapter reviews the most common side effects of antipsychotics (see Table17.1), focusing on atypical agents, and discusses options to treat and to minimizeantipsychotic-induced side effects.Recent results from the Clinical Antipsychotic Trials of Intervention Effectiveness(CATIE) schizophrenia study highlight the negative impact side effects have on antipsychotictherapy. Findings from this National Institute of Mental Health–sponsored trialthat involved nearly 1,500 patients also questions whether the efficacy and safety benefitsassociated with the atypical antipsychotics are really as large as some investigators andclinicians have thought. Over the course of the trial, 74% of participants discontinuedthe study before 18 months. The time to the treatment discontinuation for any causeamong risperidone, olanzapine, quetiapine, ziprasidone, and perphenazine groups wasfound to be significantly longer only in the olanzapine-treated group when compared tothe quetiapine or risperidone groups. The rates of medication discontinuation due to intolerableside effects ranged from 10 to 19% of patients, but the times to discontinuationwere similar among groups. Olanzapine was associated with higher rates of discontinua-168