The International Journal of Neuropsychopharmacology

Review Article

A meta-analysis of profile and time-course of symptom change in acute schizophrenia treated with atypical antipsychotics

Megan Sherwood a1a2, Allen E. Thornton a3 and William G. Honer a1c1
a1 Centre for Complex Disorders, Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
a2 Department of Psychiatry, St. Paul's Hospital, Vancouver, BC, Canada
a3 Department of Psychology, Simon Fraser University, Burnaby, BC, Canada

Article author query
sherwood m   [PubMed][Google Scholar] 
thornton ae   [PubMed][Google Scholar] 
honer wg   [PubMed][Google Scholar] 


The profile and time-course of symptom response in acute schizophrenia is unclear. For the present study, we hypothesized that the time-course would be nonlinear. A meta-analysis was performed using randomized, controlled clinical trials of five atypical antipsychotics reported in nine electronic databases. Studies were of subjects experiencing an acute exacerbation of illness, with multiple BPRS or PANSS data-points as outcome measures. A mixed factorial repeated-measures ANOVA was used. Twenty-one published clinical trials were identified. Reduction in total symptoms from baseline to 4 wk was associated with a linear decline in symptomatology (F=23.4, d.f.=1, 7, p=0.002) without attenuation of effect. In contrast, from baseline to 6 wk the linear symptom reduction (F=76.5, d.f.=1, 12, p<0.001) eventually flattened at the end of the trial (F=87.2, d.f.=1, 12, p<0.001). Secondary analyses showed a similar pattern for typical antipsychotics, and the same profile for risperidone and olanzapine as for atypical agents as a whole. Inclusion of LOCF data altered the results at 4 wk, but not 6 wk; completion rates had no effect on results. In conclusion, this meta-analysis confirms our hypothesis for 6-wk data. The profile of symptom change is one of linear symptom reduction until 4 wk, with a flattening of treatment effects by 6 wk. A curvilinear profile of schizophrenia symptom reduction has possible implications with respect to trial design and clinical decision-making.

(Received January 8 2005)
(Reviewed March 17 2005)
(Revised June 12 2005)
(Accepted June 16 2005)
(Published Online September 5 2005)

Key Words: Adult; antipsychotic agents; clinical trials; mental disorders; meta-analysis; psychiatric status rating scales; psychotic disorders; randomized controlled trials; schizophrenia.

c1 Centre for Complex Disorders, Vancouver Coastal Health Research Institute, #203-828 West 10th Ave., Vancouver, BC, Canada, V5Z 1L8. Tel.: 604-875-4827 Fax: 604-875-4376 E-mail: