Effectiveness of antipsychotic drugs in patients with chronic schizophrenia

Antipsychotic drugs have been used in patients with chronic schizophrenia for a very long time, but the relative effectiveness has not been explored even with widespread use. Particularly, there exists very little literature describing the relative effectiveness of atypical antipsychotic drugs as compared to older agents. The study aimed at bridging the existing knowledge gap by comparing first-generation antipsychotic-perphenazine, with several newer drugs in a study that encompassed a total of 1493 schizophrenic patients recruited randomly across 53 sites in the U.S.

The study design entailed assigning the participants to receive 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) for up to 18 months. This was meant to identify the salient differences in the overall effectiveness of the treatments used in the study.

The study findings indicated that a 74 percent of patients discontinued the study medication before 18 months, albeit at different rates for all the medicines (olanzapine-75%, perphenazine-82%, risperidone-74%, and ziprasidone-74%).  In all the treatments, the time of discontinuation due to intolerable side effects was similar in all the groups. The findings had a direct correlation with the study hypothesis, although there were remarkable differences in terms of time of discontinuation of treatment and onset of adverse events such as neurologic side effects and weight gain as well as metabolic changes. Generally, only a minority of patients in each group took their assigned drugs for the entire study phase. This outcome indicates that antipsychotic drugs, although considered to be effective, have substantial limitations especially in the management of chronic schizophrenia.

This is evidenced by the fewer number of patients in the olanzapine group as compared to other groups who were hospitalized for exacerbation of schizophrenia, with related side effects such as metabolic effects in the olanzapine, while patients discontinued the use of perphenazine due to extrapyramidal effects. On the other hand, patients in olanzapine and quetiapine groups had low rates of insomnia as compared to other groups, with quetiapine being associated with a higher rate of anticholinergic effects than were other drugs. However, the groups did not express any significant differences in the incidence of extrapyramidal side effects, akathisia, or movement disorders.

Although it can be argued that the rates of discontinuation may have been increased by the blinded, controlled trial design, the findings are to a larger extent consistent with those from previous studies. Notably, there were no significant differences in effectiveness of the conventional drug perphenazine and other atypical drugs until the discontinuation owing to intolerable side effects. However, olanzapine was associated with greater weightgain as well as increased glycosylated hemoglobin, cholesterol and triglycerides-changes that are associated with high susceptibility of comorbidity conditions.

The study concluded that the high rate of discontinuation among the participants is indicative of substantial limitations in the effectiveness of the drugs. As such, within the limited range of schizophrenic treatments, olanzapine appeared to be more effective as compared to the other drugs explored in the study.

Research Paper: Lieberman, Jeffrey A., et al. “Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.” New England Journal of Medicine 353.12 (2005): 1209-1223.

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