Risperidone in the treatment of acute mania - Double-blind, placebo-controlled study

University of Barcelona, Barcino, Catalonia, Spain
The British Journal of Psychiatry (Impact Factor: 7.99). 10/2005; 187(3):229-34. DOI: 10.1192/bjp.187.3.229
Source: PubMed


Severe mania is life-threatening, carries an increased risk of suicide and has a serious impact on patients and their families. Efficient and rapid control of episodes of acute mania is needed.
To evaluate the safety and efficacy of risperidone monotherapy for acute mania.
In a 3-week, randomised, double-blind trial, 290 in-patients with bipolar I disorder with current manic or mixed episode and a baseline Young Mania Rating Scale (YMRS) score of 20 or more received flexible doses of risperidone (1-6 mg per day) or placebo.
Risperidone was received by 146 patients and placebo by144. Their mean baseline YMRS score was 37.2 (s.e.=0.5). Significantly greater improvements were observed with risperidone than with placebo at weeks 1 and 2 and at end-point (total YMRS: P <0.01). Extrapyramidal symptoms were the most frequently reported adverse events in the risperidone group.
In patients with severe manic symptoms, risperidone produced significant improvements in YMRS scores as early as week 1 and substantial changes at end-point. Treatment was well tolerated.

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    • "In order to ascertain if SGA have similar efficacy in treating manic symptoms in mixed episodes as in pure mania, we computed SMD for SGA separately for these two conditions. For this analysis, we compared the effect sizes of seven of the nine included RCTs (Suppes et al., 2008; Khanna et al., 2005; McIntyre et al., 2009; Sachs et al., 2002; Tohen et al., 2002; Keck et al., 2003a, 2003b; Berwaerts et al., 2012) that reported data for pure manic and mixed episodes separately (Fig. 4 a and b). The SMD for SGA to placebo was comparable in both pure mania [−0.56, 95% CI −0.69, −0.42; total n¼ 1522] and mixed episodes [−0.44, 95% CI −0.59, −0.29; total n¼ 727]. "
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    ABSTRACT: BACKGROUND: The literature on the treatment mixed episodes in Bipolar Disorder [BD] is sparse. Second generation antipsychotics [SGA] have documented efficacy in mania, but not mixed episodes. The objective of this meta-analysis was to ascertain the efficacy of SGA, either as mono- and/or adjunctive therapy, in the treatment of acute mixed episodes of BD, compared to placebo. METHODS: A MEDLINE search for English language publications of randomized controlled trials [RCTs] comparing SGA with placebo in the treatment of an acute manic/mixed episode of BD, during the period 1990-2012, was performed using the terms 'atypical antipsychotics', 'SGA', 'mixed episodes', 'dysphoric mania' and each SGA independently. 9 RCTs reporting data on 1289 mixed episode patients treated with aripiprazole, asenapine, olanzapine, paliperidone-ER, risperidone, and ziprasidone, either as monotherapy or as adjunctive therapy, versus placebo, for 3-6 weeks, were included in the meta-analysis. We extracted data on the number of patients, SGA, duration of study and mean change in mania and depression scores from baseline to endpoint. Standardized mean difference between SGA and placebo for the mean baseline-to-endpoint change in mania and depression rating scores was calculated, with a 95% confidence limit. RESULTS: SGA, either alone or in combination with mood stabilizers, had superior efficacy in treating manic symptoms of mixed episodes compared to placebo (-0.41, 95% CI -0.53, -0.30; overall effect p<0.00001). SGA were equally effective for manic symptoms in mixed episodes and pure mania (p=0.99). SGA had superior efficacy in treating depressive symptoms of mixed episodes (-0.30, 95% CI -0.47, -0.13; p<0.001) compared to placebo in two trials reporting this information. LIMITATIONS: Thirteen relevant studies could not be included as data for mixed-episodes were not presented separately. CONCLUSIONS: SGA are effective in treating acute mixed episodes of BD, with predominant manic symptoms. Their efficacy in treating depressed mixed episodes remains unclear.
    Journal of Affective Disorders 06/2013; 150(2). DOI:10.1016/j.jad.2013.04.032 · 3.38 Impact Factor
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    • "Risperidone is well tolerated at low doses but at 6mgs/day, nearly 50% patients may develop extra pyramidal side-effects (Khanna et al. 2005). "

    Mental Illnesses - Evaluation, Treatments and Implications, 01/2012; , ISBN: 978-953-307-645-4
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    • "Lithium BPRS Significant reduction in elevated mood, excitement, grandiosity and hostility Prien et al., 1972 IMPS SADS Half of lithium-treated subjects demonstrated a 50% reduction in mania scale ratings Bowden et al., 1994 Valproate BPRS Reduction in conceptual disorganization, tension, hostility, excitement and motor activity; Pope et al., 1991 YMRS SADS Half of valproate-treated subjects demonstrated a 50% reduction in YMRS score Bowden et al., 1994 Carbamazepine BPRS Pooled data from randomized controlled trials indicate that approximately 52% of mania patients show reduction in manic symptoms McElroy and Keck, 2000 YMRS BRMS Aripiprazole YMRS Significant reduction in YMRS scores compared with placebo Keck et al. (2003) Asenapine YMRS Significant reduction in YMRS scores compared with placebo McIntyre et al., 2009 Olanzapine YMRS Significant reduction in YMRS scores compared with placebo Tohen et al., 1999 Quetiapine YMRS Significant reduction in YMRS scores compared with placebo; similar efficacy to haloperidol McIntyre et al., 2007 Resperidone YMRS Significant reduction of manic symptoms and diminished excitement/hostility on the PANSS compared with placebo Khanna et al. (2005) CGI PANSS Ziprasidone YMRS Significant reduction of manic and psychotic symptoms compared with placebo on multiple rating scales Keck et al. (2003) CGI PANSS SADS "
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    ABSTRACT: Mania has long been recognized as aberrant behaviour indicative of mental illness. Manic states include a variety of complex and multifaceted symptoms that challenge clear clinical distinctions. Symptoms include over-activity, hypersexuality, irritability and reduced need for sleep, with cognitive deficits recently linked to functional outcome. Current treatments have arisen through serendipity or from other disorders. Hence, treatments are not efficacious for all patients, and there is an urgent need to develop targeted therapeutics. Part of the drug discovery process is the assessment of therapeutics in animal models. Here we review pharmacological, environmental and genetic manipulations developed to test the efficacy of therapeutics in animal models of mania. The merits of these models are discussed in terms of the manipulation used and the facet of mania measured. Moreover, the predictive validity of these models is discussed in the context of differentiating drugs that succeed or fail to meet criteria as approved mania treatments. The multifaceted symptomatology of mania has not been reflected in the majority of animal models, where locomotor activity remains the primary measure. This approach has resulted in numerous false positives for putative treatments. Recent work highlights the need to utilize multivariate strategies to enable comprehensive assessment of affective and cognitive dysfunction. Advances in therapeutic treatment may depend on novel models developed with an integrated approach that includes: (i) a comprehensive battery of tests for different aspects of mania, (ii) utilization of genetic information to establish aetiological validity and (iii) objective quantification of patient behaviour with translational cross-species paradigms.
    British Journal of Pharmacology 03/2011; 164(4):1263-84. DOI:10.1111/j.1476-5381.2011.01318.x · 4.84 Impact Factor
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