Personalized courses of treatment are imperative to improving the condition of patients with mental disorders, as indicated by two studies from the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) published in the March American Journal of Psychiatry. For one subgroup of patients who experienced failure with older medications, a pattern emerged in the efficacy of ­­second-­generation antipsychotics. The second study showed that the greatest gains in social, interpersonal, and community living skills occurred in those who stayed with their initial treatment regimen.

NEWER ANTIPSYCHOTICS MEDICATIONS ARE EFFECTIVE AFTER OLDER ONES FAIL

The first study, led by T. Scott Stroup, MD, MPH, Associate Professor of Psychiatry at the University of North Carolina at Chapel Hill, compared the effectiveness of olanzapine, quetiapine, and risperidone. The study group included 114 participants with chronic schizophrenia, all of whom had been included in an earlier CATIE study where they were randomized to receive, and subsequently discontinued use of, the older antipsychotic perphenazine.

The patients were placed into three treatment groups. Median time to discontinuation was significantly longer for patients treated with quetiapine (9.9 months) or olanzapine (7.1 months) than with risperidone (3.6 months). There were no significant differences in the reasons for treatment discontinuation between the three groups, although some substantial differences in adverse effects were observed: Patients treated with olanzapine gained more weight than those taking risperidone or quetiapine (mean 1.6 pounds per month), and increases in total cholesterol and triglyceride levels were substantial with olanzapine, compared to “more modest” increases with risperidone and quetiapine.

However, among the 55 patients who had discontinued use of perphenazine because of inefficacy, only 25% of the participants in the subgroup receiving olanzapine discontinued treatment, compared with 47% of those receiving quetiapine and 50% of those receiving risperidone. Of the 37 participants who discontinued perphen­azine treatment due to intolerability, 64% of those who were randomized to olanzapine and 69% of those who were randomized to risperidone had to stop treatment again due to intolerability.

Dr. Stroup and colleagues suggested that patient characteristics likely contributed to individual differences in antipsychotic treatment response. “They may have represented a group of patients who are relatively unresponsive to or intolerant of the higher affinity for the dopamine D2 receptor that is characteristic of older antipsychotic drugs,” they suggested. In this context, quetiapine was the least like perphenazine while risperidone was the most like it, with olanzapine being the intermediate. This may be a useful theory with regard to an ultimate goal of CATIE, described by the authors as the “determination of the effectiveness of a specific sequence of antipsychotic treatments … that may help individual patients and physicians find an effective medication sooner than might otherwise be possible.”

ACCURATE INITIAL TREATMENT AND MAINTENANCE ARE IMPORTANT

The second study, led by Marvin S. Swartz, MD, and colleagues, indicated that a high percentage of patients do not stick with their original treatment regimen for one year, which prevented them from gaining the improved social function observed with every medication the researchers tested.

Only 455 patients, about one third of the CATIE participants, made it to the primary end point of 12 months postbaseline. Compared with baseline Quality of Life Scale scores, patients in the olanzapine and risperidone treatment groups experienced small but significant improvements (mean changes in total score, 0.19 and 0.26, respectively), while comparable yet statistically insignificant improvements were observed in the perphenazine and the ziprasidone treatment groups. Improvement with quetiapine was not comparable. However, there were no overall significant differences between the treatment groups at 12 months, and similar results were observed in Quality of Life Scale total and subscale scores at six and 18 months postbaseline.

Lower baseline Quality of Life Scale score was the strongest predictor of improvement, though the authors noted that the participants in this group were also more likely to discontinue treatment early, thus making potential gains from sustained treatment unlikely. Patients who made the fewest gains were those with higher-level psychosocial skills. The researchers believe that the participants in this group may have experienced a “ceiling effect” and that improvement could not be made without additional rehabilitative treatment.

“Over the long run, patients are more likely to function better in the community if they are able to stay on their initial treatment, especially those who are the most impaired,” said Dr. Swartz, who heads the Division of Social and Community Psychiatry at Duke University in Durham, North Carolina. “More intensive rehabilitative interventions and outreach may help patients stick with their treatment and make greater gains.”            

—Jessica Dziedzic

Suggested Reading
Stroup TS, Lieberman JA, McEvoy JP, et al. Effectiveness of olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia after discontinuing perphenazine: a CATIE study. Am J Psychiatry. 2007;164:415-427.
Swartz MS, Perkins DO, Stroup TS, et al. Effects of antipsychotic medications on psychosocial functioning in patients with chronic schizophrenia: findings from the NIMH CATIE study. Am J Psychiatry. 2007;164:428-436.

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