Maintenance of response with atypical antipsychotics in the treatment of schizophrenia: a post-hoc analysis of 5 double-blind, randomized clinical trials

Abstract

Background: How long an antipsychotic is effective in maintaining response is important in choosing the correct treatment for people with schizophrenia. This post-hoc analysis describes maintenance of response over 24 or 28 weeks in people treated for schizophrenia with olanzapine, risperidone, quetiapine, ziprasidone, or aripiprazole.

Methods: This was a post-hoc analysis using data from 5 double-blind, randomized, comparative trials of 24 or 28 weeks duration in which olanzapine was compared to risperidone (1 study; N = 339), quetiapine (1 study; N = 346), ziprasidone (2 studies; N = 548 and 394) or aripiprazole (1 study; N = 566) for treatment of schizophrenia. For each study, time to loss of response in patients who met criteria for response at Week 8 and the proportion of patients who lost response following Week 8 were compared by treatment group. The number needed to treat (NNT) with olanzapine rather than comparator to avoid loss of one additional responder over 24 or 28 weeks of treatment was calculated for each study.

Results: Time maintained in response was significantly longer (p < .05) for olanzapine compared to risperidone, quetiapine, and ziprasidone. Olanzapine did not significantly differ from aripiprazole. The proportion of patients who lost response was significantly lower for olanzapine versus risperidone, quetiapine, and ziprasidone (p < .05). NNTs to avoid one additional patient with loss of response with olanzapine versus risperidone, quetiapine and ziprasidone were favourable, ranging from 5 to 9.

Conclusion: During 24 and 28 weeks of treatment, the antipsychotics studied differed in the time that treated patients with schizophrenia remained in response and the proportion of patients who lost response. Olanzapine treatment resulted in a consistent and statistically significant advantage in maintenance of response compared to treatment with risperidone, quetiapine and ziprasidone; but not compared to treatment with aripiprazole.

Figure 1

Kaplan Meier (KM) Analysis of olanzapine versus risperidone for days to loss of response, where loss of response was defined as a ≥ 20% worsening of PANSS_1–7 Total score and a CGI-S score ≥ 3 in patients who had a ≥ 20% improvement over baseline PANSS_1–7 Total score at Week 8. Olanzapine-treated patients remained in response for significantly longer than patients treated with risperidonse (p < .001).

Figure 2

Kaplan Meier (KM) Analysis of olanzapine versus quetiapine for days to loss of response, where loss of response was defined as a ≥ 20% worsening of PANSS_1–7 Total score and a CGI-S score ≥ 3 in patients who had a ≥ 20% improvement over baseline PANSS_1–7 Total score at Week 8. Olanzapine-treated patients remained in response for significantly longer than patients treated with quetiapine (p = .003).

Figure 3

Kaplan Meier (KM) Analysis of olanzapine versus ziprasidone for days to loss of response, where loss of response was defined as a ≥ 20% worsening of PANSS_1–7 Total score and a CGI-S score ≥ 3 in patients who had a ≥ 20% improvement over baseline PANSS_1–7 Total score at Week 8. Olanzapine-treated patients remained in response for significantly longer than patients treated with ziprasidone (p < .008).

Figure 4

Kaplan Meier (KM) Analysis of olanzapine versus ziprasidone for days to loss of response, where loss of response was defined as a ≥ 20% worsening of PANSS_1–7 Total score and a CGI-S score ≥ 3 in patients who had a ≥ 20% improvement over baseline PANSS_1–7 Total score at Week 8. Olanzapine-treated patients remained in response for significantly longer than patients treated with ziprasidone (p = .08).

Figure 5

Kaplan Meier (KM) Analysis of olanzapine versus aripiprazole for days to loss of response, where loss of response was defined as a ≥ 20% worsening of PANSS_1–7 Total score and a CGI-S score ≥ 3 in patients who had a ≥ 20% improvement over baseline PANSS_1–7 Total score at Week 8. There was no significant difference between treatment groups for time remaining in aripiprazole (p = .97).