A meta-analysis of profile and time-course of symptom change in acute schizophrenia treated with atypical antipsychotics
ABSTRACT 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.
- SourceAvailable from: Rolf Gjestad
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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. "
ABSTRACT: Illicit drug use may influence cognition in non-affective psychosis. Previous studies have shown better cognition in psychosis with illicit drug use as compared to psychosis only. Possibly, illicit drug using patients have more transient drug-related cognitive deficits. Thus, the aim of the present study was to examine cognitive change the first weeks after admission to a psychiatric emergency ward, expecting more cognitive improvement at follow-up in the illicit drug group as compared to psychosis only. Patients with acute non-affective psychosis with (26%) and without illicit drug use were examined at baseline (n=123) and follow-up (n=67), with alternative forms of the Repeatable Battery for the Assessment of Neuropsychological Status. Latent Growth Curve models, controlling for cognition at baseline and age differences between the groups, were used to analyze cognitive change. The illicit drug using patients showed the largest improvement in cognition, especially among the youngest patients. Younger patients with non-affective psychosis and illicit drug use showed more cognitive improvement the first weeks after acute psychosis as compared to psychosis only. This suggests that the illicit drug users constitute a sub-group with less stable cognitive deficits and less cognitive vulnerability.Psychiatry Research 09/2014; 220(3). DOI:10.1016/j.psychres.2014.08.062 · 2.68 Impact Factor
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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. "
ABSTRACT: Evidence has been put forward that premature termination of data collection and jumping to conclusions behavior (JTC) is associated with delusions. However, few investigations have attempted to track associations between changes in delusions and changes in JTC measures. In the current study individuals with schizophrenia spectrum disorders completed a version of the JTC task (involving fishing from lakes as opposed to drawing beads from a jar) at two timepoints 12 weeks apart. The results revealed significant negative correlations between change in task performance (number of requested pieces of information) and change in delusion scores over time. This evidence is consistent with the contention that the JTC task is sensitive to the cognitive systems underlying delusions in schizophrenia spectrum disorders.Psychiatry Research 11/2009; 170(2-3):124-7. DOI:10.1016/j.psychres.2008.10.020 · 2.68 Impact Factor
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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 "
ABSTRACT: The objective of this study was to evaluate the efficacy and safety of divalproex sodium extended release (divalproex ER) vs placebo in combination with olanzapine or risperidone for the treatment of acute exacerbations of schizophrenia. In this 12-week, randomized, double-blind, parallel-group, multi-center trial, a total of 402 patients were randomized and treated; 103 received olanzapine/placebo, 99 received olanzapine/divalproex ER, 101 received risperidone/placebo, and 99 received risperidone/divalproex ER. Divalproex ER was initiated on day 1 at 20 mg/kg per day q AM and was titrated to clinical effect on days 3, 7, and 10, not to exceed a maximum dosage of 35 mg/kg per day. Olanzapine and risperidone were initiated at 5 and 2 mg/day q PM, respectively, increased to 10 and 4 mg/day on day 3, and increased to fixed target doses of 15 and 6 mg/day on day 6. No significant treatment difference was demonstrated between the combination therapy and antipsychotic monotherapy groups on the primary efficacy variable of the mean change from baseline to day 14 last observation carried forward on the Positive and Negative Syndrome Scale (PANSS) total score, although antipsychotic monotherapy did demonstrate superiority to combination therapy on the PANSS Negative subscale at several time points. Combination therapy also failed to show an advantage over antipsychotic monotherapy at day 84 on the PANSS total score. Most adverse events observed in the study were mild to moderate in severity, and the overall number of adverse events did not differ significantly between the combination therapy groups and their corresponding antipsychotic monotherapy group.Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 01/2009; 34(5):1330-8. DOI:10.1038/npp.2008.209 · 7.83 Impact Factor