Smulevich AB, Khanna S, Eerdekens M, Karcher K, Kramer M, Grossman F. Acute and continuation risperidone monotherapy in bipolar mania: a 3-week placebo-controlled trial followed by a 9-week double-blind trial of risperidone and haloperidol. Eur Neuropsychopharmacol 15: 75-84

National Mental Health Research Center, Moscow, Russia.
European Neuropsychopharmacology (Impact Factor: 4.37). 02/2005; 15(1):75-84. DOI: 10.1016/j.euroneuro.2004.06.003
Source: PubMed


In a randomized, double-blind trial, patients with acute bipolar mania received 1-6 mg/day of risperidone, 2-12 mg/day of haloperidol, or placebo for 3 weeks, followed by double-blind risperidone or haloperidol for 9 weeks. Of 438 patients, 154 were randomized to risperidone, 144 to haloperidol, and 140 to placebo. The mean+/-S.D. modal doses were 4.2+/-1.7 mg/day of risperidone and 8.0+/-3.6 mg/day of haloperidol during the initial 3-week phase and 4.1+/-1.8 and 7.4+/-3.7 mg/day during the 12-week period. At week 3, mean Young Mania Rating Scale (YMRS) score reductions from baseline were significantly greater in patients receiving risperidone than placebo (p<0.001). Differences between risperidone and haloperidol on this efficacy measure were not significant. Further reductions in YMRS scores were seen in patients receiving risperidone or haloperidol during the subsequent 9 weeks. No unexpected adverse events were reported. Extrapyramidal disorder and hyperkinesias, the most commonly reported adverse events with antipsychotic use, occurred less frequently with risperidone than haloperidol. We conclude that risperidone monotherapy was an effective and well-tolerated treatment for bipolar mania and that efficacy was maintained over the long term.

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    • "Yet, treatment did not more adversely impact BDP patients. One reason for this discrepancy may be that well-controlled studies that show risperidone is associated with worse motor system effects in BDP than in schizophrenia administer higher doses (4–6 mg [Chouinard et al., 1993; Hirschfeld et al., 2004; Smulevich et al., 2005]) than those in the present study (1–3 mg/day). Furthermore, our patients had lower cumulative exposure to antipsychotic medications than those prior studies, as our patients started on lower doses for the first week or so, consistent with clinical practice in treating first episode patients. "
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    ABSTRACT: Neurocognitive deficits are associated with most psychotic disorders, but may differ across diagnosis and by treatment status. This ambiguity is partly addressed in longitudinal pre/post treatment studies with first episode patients. Antipsychotic-naïve first-episode schizophrenia patients have shown intact performance on a predictive saccade task that assesses simple motor learning, spatial abilities, and response planning. After antipsychotic treatment, however, schizophrenia patients performing this task show a selective impairment in the accuracy of anticipatory responses, generated from learned internal representations of the task stimulus. This finding is in line with other observations of antipsychotic medication effects on frontostriatal systems, particularly dorsolateral prefrontal cortex. We sought to replicate this provocative finding with an independent sample of antipsychotic-naïve first-episode schizophrenia patients and extend it by including a group of patients with first episode bipolar disorder with psychosis (BDP). Matched healthy controls were also studied in parallel. Schizophrenia patients demonstrated intact performance pretreatment followed by impairment post-treatment for accuracy of anticipatory responses, and worse accuracy was associated with higher antipsychotic dose. BDP patients displayed saccade accuracy deficits before and after treatment and had no correlation of performance and antipsychotic dose. The findings suggest different neural alterations early in the course of each psychotic disorder, and different vulnerabilities to antipsychotic treatment effects between schizophrenia and BDP.
    Schizophrenia Research 08/2014; 159(1). DOI:10.1016/j.schres.2014.07.028 · 3.92 Impact Factor
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    • "RCTs with haloperidol were included (McElroy et al. 1996 ; McIntyre et al. 2005 ; Smulevich et al. 2005 ; Tohen et al. 2003a ; Vieta et al. 2005, 2008 ; Young et al. 2009 "

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    • "There were not big differences in inclusion and exclusion criteria, except for the inclusion of mixed episodes or rapid-cyclers. The quetiapine trial (McIntyre et al., 2005) and the risperidone monotherapy trial (Smulevich et al., 2005) did not include mixed patients. The seven included trials showed good quality and low risk of bias overall (Appendix 1). "
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    ABSTRACT: Background: there is a lack of scientific data regarding speed of action of antimanic treatments, a relevant issue in clinical practice. Objective: to assess differences in the speed of onset of antimanic efficacy between haloperidol (as most studied first-generation antipsychotic) and second-generation antipsychotics. Experimental procedures: meta-analysis of double-blind randomized clinical trials in acute mania, comparing treatment with haloperidol and with second-generation antipsychotics. Search was conducted in MEDLINE and CENTRAL databases (last search: September 2011). Differences in mania scale score reduction at week 1 were assessed. Results: 8 randomized clinical trials fulfilled inclusion criteria and 1 of them was excluded due to low methodological quality. 2037 Manic patients had been treated with antipsychotics in the 7 trials. Haloperidol was found to be significantly more efficacious in the reduction of the mania scale score at week 1. The effect size was small, the Standardized Mean Difference (SMD) being 0.17, with a 95% Confidence Interval ranging from 0.01 to 0.32. Haloperidol was significantly more efficacious than olanzapine (SMD: 0.40 [0.21, 0.59]) and ziprasidone (0.39 [0.18, 0.61]). A non-significant trend towards superiority of haloperidol was found over aripiprazole (SMD: 0.13 [-0.02, 0.19]). There were no significant differences between haloperidol and quetiapine (0.17 [-0.11, 0.44]), and haloperidol and risperidone (SMD: -0.10 [0.30, 0.09]). Conclusions: haloperidol shows a faster onset of antimanic action than second-generation antipsychotics. This difference may be related to D2 affinity. Haloperidol may be considered a treatment option in severely ill manic patients who require urgent relief of symptoms.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 07/2012; 23(4). DOI:10.1016/j.euroneuro.2012.05.017 · 4.37 Impact Factor
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