"Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia" The New England Journal of Medicine. 2005. 353(12):1209-23. PubMed
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Contents 1 Clinical Question 2 Bottom Line 3 Major Points 4 Guidelines 5 Design 6 Population 6.1 Inclusion Criteria 6.2 Exclusion Criteria 6.3 Baseline Characteristics 7 Interventions 8 Outcomes 8.1 Primary Outcome 8.2 Secondary Outcomes 9 Criticisms 10 Funding 11 Further Reading
How do first-generation antipsychotic drugs compare to second-generation, or "atypical", antipsychotic drugs concerning effectiveness in the treatment of schizophrenia over an 18-month period?
When dealing with chronic schizophrenia, olanzapine appeared the most effective concerning rates of treatment discontinuation, with efficacy of the first-generation antipsychotic perphenazine found similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with significant weight gain and metabolic changes, which have implications for the long-term health of patients, such as development of metabolic syndrome.
The CATIE trial found high rates of treatment discontinuation in chronic schizophrenia, highlighting the substantial limitations in the effectiveness of antipsychotic drugs. Olanzapine showed slightly superior efficacy compared to other drugs, with no significant differences in effectiveness between perphenazine and other second-generation drugs. However, olanzapine had higher discontinuation rates due to weight gain and metabolic effects.
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- Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial - N=1,498 patients with recent MI and increased ventricular ectopy - Interventions: Olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day), ziprasidone (40 to 160 mg per day) after FDA approval - Mean follow-up: 18 months
Inclusion Criteria: Patients aged 18 to 65 years diagnosed with schizophrenia were eligible, providing they could take oral antipsychotic medication. They had previous treatment experience but not exclusively treatment-resistant or responsive only to clozapine. Exclusion Criteria: Diagnosis of schizoaffective disorder, mental retardation, severe adverse reactions to treatments, pregnancy or breastfeeding, serious medical conditions. Baseline Characteristics: Patients were predominantly male (74%) with an average age of 40.6 years and a median illness duration of 14.8 years.
Patients were assigned to olanzapine, perphenazine, quetiapine, risperidone, or (after FDA approval) ziprasidone. Dosing was based on clinician judgment with flexibility, but mean modal doses were reported. Concomitant medications were permitted, excluding other antipsychotics.
Primary Outcome: Time to discontinuation of treatment for any cause. Secondary Outcomes: Specific reasons for discontinuation (e.g., inefficacy, intolerable side effects), PANSS scores, CGI Scale scores, incidence of serious adverse events, weight and metabolic changes.
Dosing of second-generation antipsychotics may not have been optimal, and the most common comparator haloperidol was not included, perphenazine was selected in its place. The trial used broad inclusion criteria possibly accounting for differences from previous studies.
Supported by the NIMH and the Foundation of Hope of Raleigh, N.C. Dr. Lieberman and other authors disclosed potential conflicts of interest, including financial ties to pharmaceutical companies involved in antipsychotic drug production.
Complete study available at NEJM.org.