Impact of Second-Generation Antipsychotics and Perphenazine on Depressive Symptoms in a Randomized Trial of Treatment for Chronic Schizophrenia

Abstract

Background According to the American Psychiatric Association Clinical Practice Guidelines for schizophrenia, second-generation antipsychotics may be specifically indicated for the treatment of depression in schizophrenia. We examined the impact of these medications on symptoms of depression using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), conducted between January 2001 and December 2004. Method Patients with DSM-IV–defined schizophrenia (N = 1,460) were assigned to treatment with a first-generation antipsychotic (perphenazine) or one of 4 second-generation drugs (olanzapine, quetiapine, risperidone, or ziprasidone) and followed for up to 18 months (phase 1). Patients with tardive dyskinesia were excluded from the randomization that included perphenazine. Depression was assessed with the Calgary Depression Scale for Schizophrenia (CDSS). Mixed models were used to evaluate group differences during treatment with the initially assigned drug. An interaction analysis evaluated differences in drug response by whether patients had a baseline score on the CDSS of ≥ 6, indicative of a current major depressive episode (MDE). Results There were no significant differences between treatment groups on phase 1 analysis, although there was a significant improvement in depression across all treatments. A significant interaction was found between treatment and experiencing an MDE at baseline (P = .05), and further paired comparisons suggested that quetiapine was superior to risperidone among patients who were in an MDE at baseline (P = .0056). Conclusions We found no differences between any second-generation antipsychotic and the first-generation antipsychotic perphenazine and no support for clinical practice recommendations, but we did detect a signal indicating a small potential difference favoring quetiapine over risperidone only in patients with an MDE at baseline.

Comparative efficacy between clozapine and other atypical antipsychotics on depressive symptoms in patients with schizophrenia: Analysis of the CATIE phase 2E data

“…CDSS for depression). Furthermore, this study adopted CDSS score of ≥ 6 as a criterion indicative of MDE consistent with previous work examining the effect of antipsychotics on depressive symptoms in the CATIE sample (Addington et al, 2010). However, since this criterion did not include the number and duration of depressive symptoms, it does not necessarily align with MDE criteria as outlined in the DSM-5 (American Psychiatric Association, 2013).…”

“…Exploratory analyses suggested that risperidone may be more effective than olanzapine in improving depressive symptoms in chronic schizophrenia with MDE. However, two randomized, double-blind, RCTs comparing olanzapine and risperidone in chronic schizophrenia with concomitant MDE (Addington et al, 2010) and post-psychotic depression (Dollfus et al, 2005), respectively, reported no differences in antidepressant effects between these agents. The small sample size associated with our exploratory findings suggests caution in any interpretation of these results.…”

“…The CDSS is a measure of depression specifically designed to assess depressive symptoms separately from negative symptoms in patients with schizophrenia (Addington et al, 1994). It has been validated in independent studies and recommended as the gold standard for assessing depression in schizophrenia for clinical trials (Addington et al, 2010; Collins et al, 1996; Kontaxakis et al, 2000). The Positive and Negative Syndrome Scale (PANSS) were used to assess severity of schizophrenia symptoms (Kay et al, 1987).…”

“…If the overall test was significant at a two-tailed p-value for treatment-by-month interaction of < .05, clozapine was compared with the other three atypical antipsychotics using a Hochberg adjustment for multiple comparisons in which the smallest p-value was compared to .05/3 = .017 and the largest to p-value = .05. The same analyses were conducted for patients with a baseline score of ≥ 6 on the CDSS, which was operationalized as meeting CDSS criteria indicative of a major depressive episode (MDE) (Addington et al, 2010). This level of depression has been previously identified as an appropriate cut-off for the prediction of a major depressive disorder, with a specificity of 77% and sensitivity of 92% (Addington et al, 1993).…”

462 – Quetiapine monotherapy in acute phase for major depressive disorder: a metaanalysis of randomized, placebo-controlled trials

“…Some clinical trials found that quetiapine reduced depressive symptoms considerably in schizophrenic patients [25] and bipolar depression [26,27]. Although some experts view that its antidepressant effect may not be superior to other antidepressants [28], this is the only agent approved for the treatment of acute bipolar depression [29].…”