Olanzapine Versus Risperidone in the Treatment of Manic or Mixed States in Bipolar I Disorder

Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 12/2006; 67(11):1747-53. DOI: 10.4088/JCP.v67n1112
Source: PubMed


To compare olanzapine and risperidone in the treatment of nonpsychotic acute manic or mixed episodes.
This 3-week, randomized, controlled, double-blind, parallel multicenter study compared olanzapine (5-20 mg/day; N = 165) and risperidone (1-6 mg/day; N = 164) among hospital inpatients who met DSM-IV criteria for bipolar I disorder, manic or mixed episode, without psychotic features. The study was conducted at 30 sites in the United States between July 2001 and June 2002. The primary outcome measure was the mean change in the Young Mania Rating Scale (YMRS) total score. Secondary measures included the 21-item Hamilton Rating Scale for Depression (HAM-D-21), the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impressions-Bipolar Version (CGI-BP) severity of illness scale, and the Cognitive Test for Delirium (CTD). Quality of life (Short Form Health Survey [SF-12]), psychological well-being (Psychological General Well-Being [PGWB] inventory), and sexual functioning were also compared.
Mean modal doses for olanzapine and risperidone were 14.7 mg/day and 3.9 mg/day, respectively. Between treatments, there was no difference in mean change in the YMRS, MADRS, CTD, PGWB, or SF-12 measures or in remission or response rates. Significantly more olanzapine-treated patients completed the study compared with risperidone patients (78.7% vs. 67.0%; p = .019). Olanzapine-treated patients had greater HAM-D-21 (p = .040) and CGI-BP (p = .026) score improvement across the study. Olanzapine-treated patients experienced greater elevations in liver function enzymes (p < .05) and increase in weight (2.5 kg vs. 1.6 kg; p = .004), while risperidone-treated patients were more likely to experience prolactin elevation (51.73 ng/mL vs. 8.23 ng/mL; p < .001) and sexual dysfunction (total score increase of 1.75 vs. 0.64; p = .049).
Both olanzapine and risperidone treatment yielded similar improvements in mania. The olanzapine group had significantly greater improvements in secondary measures of severity and depressive symptoms and better study completion rates but experienced more weight gain.

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    • "Risperidone belongs to the benzisoxazole group and has been used in the treatment of acute mania both as monotherapy and in combinations. Risperidone is significantly better than placebo (Hirschfeld et al. 2004 & Khanna et al. 2005) and has equal efficacy to Lithium, Haloperidol (Segal et al. 1998) and Olanzapine (Perlis et al. 2006). There is significant reduction in symptoms of mania as assessed by Young Mania Rating scale (YMRS). "

    Mental Illnesses - Evaluation, Treatments and Implications, 01/2012; , ISBN: 978-953-307-645-4
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    • "Authors Population Treatment Duration Mean weight gain (kg) p value Bowden et al. 2005 (52) Phase bipolar mania (n = 302) patients randomized; QUE (n = 107); PBO (n = 97); Li (n = 98) QUE vs Li vs PBO 12 weeks QUE: +2.6 (LOCF) and +3.3 (observed cases); PBO: )0.0008 (LOCF) and +0.3 (observed cases); Li: +0.7 (LOCF) and +1 (observed cases) <0.001 in the Li group; NS from PBO Tohen et al. 2003 (43) VPA (n = 126); OLZ (n = 125) OLZ vs VPA 47 weeks OLZ: +2.7; VPA: +1.2 <0.001 DelBello et al. 2006 (82) Pediatric BP-I patients (n = 50) with a manic or mixed episode QUE vs VPA 4 weeks QUE: 4.4 ± 5.0; VPA: 3.6 ± 6.0 0.2 Tohen et al. 2000 (41) Manic or mixed were OLZ (n = 55) or PBO (n = 60) OLZ vs PBO 4 weeks OLZ: +2.1 ± 2.8; PBO: 0.45 ± 2.3 0.002 Tohen et al. 2003 (83) Bipolar depression PBO (n = 377); OLZ (n = 370); OLZ + FLUOX (n = 86) OLZ vs FLUOX vs PBO 8 weeks NR OLZ versus PBO <0.001; OFC versus PBO >0.99 Tohen et al. 2002 (47) Patients achieving remission after treatment with OLZ + Li or VPA received Li or VPA plus either OLZ or PBO (n = 99) OLZ + Li ⁄ VPA vs Li or VPA 18 months Combination: +2; Monotherapy: )1.8 NA Tohen et al. 2003 (19) Comparison flexible dosing of OLZ (n = 234) and HAL (n = 219) OLZ vs HAL 18 months OLZ: +2.82; HAL: +0.02 <0.001 Biederman et al. 2005 (84) Preschool-age children with bipolar disorder (n = 31) RIS vs OLZ 8 weeks RIS: 2.2 ± 0.4; OLZ: 3.2 ± 0.7 NS Brown et al. 2006 (85) BP-I patients, depressed (n = 410) OLZ + FLUOX vs LMG 7 weeks NR 0.001 Perlis et al. 2006 (65) "
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    ABSTRACT: Antipsychotics have been widely used in the treatment of bipolar mania. The purpose of this manuscript was to briefly review the evidence of typical and atypical antipsychotics for the treatment of bipolar mania. A detailed literature review was conducted on the use of typical and atypical antipsychotics in the treatment of bipolar mania using standard search engines. A summary of the published literature on each agent is described followed by a discussion on the overall comparison of the different agents. For typical antipsychotics, up until recently, there was a paucity of published evidence on their strengths and limitations in the treatment of bipolar mania. Recent studies have demonstrated clear evidence on the efficacy of haloperidol on the treatment of acute mania. The literature suggests a faster onset of action of haloperidol as compared to either lithium or atypical antipsychotics. A limitation of typical antipsychotics however, is the risk of tardive dyskinesia, extrapyramidal side effects and a possible increased risk of non-adherence. Evidence on the efficacy for atypical antipsychotics has been demonstrated for aripiprazole, clozapine, olanzapine, quetiapine, risperidone and ziprasidone. Limitations as regards the use of atypical antipsychotics include the risk of weight gain and dyslipidemia. Comparison among different atypical antipsychotics agents are difficult to determine as there are no conclusive head to head studies. There is also a paucity of studies comparing atypical antipsychotics with lithium. Evidence exists on the efficacy of both typical and atypical antipsychotics on the treatment of acute mania such that they are now clearly first-line along with lithium. An important limitation of the published literature is that most of the studies were designed to obtain regulatory approval for the different agents therefore the generalizability of the findings to clinical practice remains unclear.
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    • "one ( mean dosage 4Á6 mg / day ) was significantly better than placebo in all the studies . Comparison with haloper - idol showed no difference in antimanic efficacy ( Scherk et al . 2007 ) . Additionally , a small head - to head comparison trial against lithium and haloper - idol ( Segal et al . 1998 ) and a larger comparison against olanzapine ( Perlis et al . 2006a ) support the antimanic efficacy of risperidone monotherapy . Two placebo - controlled studies investigated ris - peridone as add on to valproate or lithium ( Sachs et al . 2002 ) or as add on to lithium , valproate or carbamazepine ( Yatham et al . 2003 ) . Whereas the first study demonstrated the superiority of risper - idone add - on"
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