Anti-depressive effectiveness of olanzapine, quetiapine, risperidone and ziprasidone: a pragmatic, randomized trial

Abstract

Background: Efficacy studies indicate anti-depressive effects of at least some second generation antipsychotics (SGAs). The Bergen Psychosis Project (BPP) is a 24-month, pragmatic, industry-independent, randomized, head-to-head comparison of olanzapine, quetiapine, risperidone and ziprasidone in patients acutely admitted with psychosis. The aim of the study is to investigate whether differential anti-depressive effectiveness exists among SGAs in a clinically relevant sample of patients acutely admitted with psychosis.

Methods: Adult patients acutely admitted to an emergency ward for psychosis were randomized to olanzapine, quetiapine, risperidone or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale-Depression factor (PANSS-D) and the Calgary Depression Scale for Schizophrenia (CDSS).

Results: A total of 226 patients were included. A significant time-effect showing a steady decline in depressive symptoms in all medication groups was demonstrated. There were no substantial differences among the SGAs in reducing the PANSS-D score or the CDSS sum score. Separate analyses of groups with CDSS sum scores > 6 or ≤6, respectively, reflecting degree of depressive morbidity, revealed essentially identical results to the primary analyses. There was a high correlation between the PANSS-D and the CDSS sum score (r = 0.77; p < 0.01).

Conclusions: There was no substantial difference in anti-depressive effectiveness among olanzapine, quetiapine, risperidone or ziprasidone in this clinically relevant sample of patients acutely admitted to hospital for symptoms of psychosis. Based on our findings we can make no recommendations concerning choice of any particular SGA for targeting symptoms of depression in a patient acutely admitted with psychosis.

Trial registration: ClinicalTrials.gov ID; URL: http://www.clinicaltrials.gov/: NCT00932529.

Figure 1

Flow of patients through the study. Not meeting inclusion criteria = score below 4 on all the items: delusions, hallucinatory behaviour, grandiosity, suspiciousness/persecution or unusual thought content in the Positive and Negative Syndrome Scale (PANSS); Uncoop. = the patient was not able or willing to cooperate with testing and assessments; Organic braindis. = Organic brain disorder, principally dementia; Randomization not acceptable = patient or treating clinician not willing to change existing antipsychotic medication; Administrative causes = principally patient discharged before assessments could be made. ¹ Enrolment started March 2003 until 2008, week 26. Full details on enrolment were only registered from 2006, week 31 until 2008, week 26. Consequently only percentages are displayed for patients assessed for eligibility and excluded patients. ² Before discharge/6 weeks. ³ One patient in the risperidone and olanzapine groups missed the first follow-up visit, but was retested on later visits.

Figure 2

Correlation between CDSS sum score and PANSS-D-score at baseline. CDSS = the Calgary Depression Scale for Schizophrenia; PANSS = the Positive and Negative Syndrome Scale; PANSS-D score = PANSS Depression factor = sum score of items G1-G3 and G6 in the general psychopathology subscale of the PANSS.

Figure 3

Change of CDSS sum score. Linear mixed effects model curves. Linear slopes for the randomization groups generated based on linear mixed effects models, CDSS sum score output, as displayed in Table 1 for olanzapine, quetiapine, risperidone and ziprasidone, respectively. The curves are confined to the first 300 days because the major bulk of data is obtained before 300 days. CDSS = the Calgary Depression Scale for Schizophrenia.

Figure 4

Change of PANSS-D score. Linear mixed effects model curves. Linear slopes for the randomization groups generated based on linear mixed effects models, PANSS-D score output, as displayed in Table 1 for olanzapine, quetiapine, risperidone and ziprasidone, respectively. The curves are confined to the first 300 days because the major bulk of data is obtained before 300 days. PANSS = The Positive and Negative Syndrome Scale; PANSS-D = PANSS Depression Factor = sum score of items G1-G3 and G6 in the general psychopathology subscale of the PANSS.