Sherwood M, Thornton AE, Honer WG. A meta-analysis of profile and time-course symptom change in acute schizophrenia treated with atypical antipsychotics. Int J Neuropsychopharmacol 9: 357-366

Centre for Complex Disorders, Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
The International Journal of Neuropsychopharmacology (Impact Factor: 4.01). 06/2006; 9(3):357-66. DOI: 10.1017/S1461145705005961
Source: PubMed


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.

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    • "To accomplish this, only patients with symptoms of acute psychosis admitted to a psychiatric in-patient emergency department were included, and the patients were followed while hospitalized to minimize use of illicit drugs. By 4–6 weeks most of the long-term effects of illicit drug use should be minimized, and most psychosis symptoms responding to treatment (Sherwood et al., 2006; Szoke et al., 2008). Follow-up was therefore set to time of discharge from the acute ward or after 6 weeks at the latest, if not discharged earlier. "
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    • "This is feasible because delusions change in their severity over time in response to treatment, or spontaneously (Eaton et al., 1995; Gunduz- Bruce et al., 2005; Lieberman et al., 1993; Sherwood et al., 2006). A computational model of JTC behavior (Moore and Sellen, 2006), for which a gain parameter was employed to model increases and decreases in dopamine levels in delusional individuals, predicted that changes in delusions should correspond with changes in JTC behavior. "
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    • "However, from days 14–84 there was virtually no change in response to 10 more weeks of treatment. This is highly unusual for antipsychotic trials in schizophrenia (Sherwood et al, 2006). Furthermore, the drop-off in serum valproate levels seen after day 14 (Figure 2) is consistent with decreased compliance as subjects left the inpatient "
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