Myrto T Samara1, Yair Goldberg2, Stephen Z Levine3, Toshi A Furukawa4, John R Geddes5, Andrea Cipriani5, John M Davis6, Stefan Leucht7. 1. Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany; 3rd Department of Psychiatry, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. Electronic address: samaramyrto@gmail.com. 2. Department of Statistics, Faculty of Social Sciences, University of Haifa, Haifa, Israel. 3. Department of Community Mental Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel. 4. Department of Health Promotion and Human Behavior and Department of Clinical Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan. 5. Department of Psychiatry, University of Oxford, Oxford, UK; Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK. 6. Psychiatric Institute, University of Illinois at Chicago, Chicago, IL, USA; Maryland Psychiatric Research Center, University of Maryland, Baltimore, MD, USA. 7. Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany.
Abstract
BACKGROUND: The efficacy of antipsychotics across the initial severity range in patients with acute mania remains unclear. Therefore, we examined the influence of baseline severity on the efficacy of olanzapine. METHODS: We did an individual participant data meta-analysis of double-blind, randomised controlled trials that compared olanzapine with placebo, identified through searches of the ClinicalStudyRequest.com database on Feb 2, 2016. We included patients with acute mania associated with bipolar I disorder. We examined the association between baseline and change scores on the Young Mania Rating Scale (YMRS; range 0-60) up to 3 weeks for olanzapine versus placebo groups using eight increasingly complex competing mixed-effects models for repeated measures. FINDINGS: We identified 33 reports, five (15%) of which were eligible and contained data for 939 patients (552 received olanzapine; 387 received placebo). The interaction between baseline severity and treatment was significant (β=0·22, 95% CI 0·05-0·39; p=0·013). The greater the baseline severity, the greater the magnitude of the differences between olanzapine and placebo was expected. The mean estimated YMRS scores were reduced at 3 weeks in both groups, but were greater with olazapine than placebo by 2·56 points for patients with a baseline score of 20-25 (9·26 for olanzapine vs 6·70 for placebo; effect size 0·35, 95% CI 0·11-0·60), by 4·74 points for a baseline score of 25-35 (14·25 vs 9·51; 0·58, 0·34-0·86), and by 8·01 points for a baseline score of 35-60 (21·72 vs 13·71; 0·70, 0·31-1·23). INTERPRETATION: Benefits of olanzapine can be expected for patients across the full spectrum of symptom severity who are likely to be treated for acute mania. Less severely ill patients seem to benefit less in terms of olanzapine efficacy, but still experience the same side-effects as more severely ill patients. Thus, clinicians and patients should carefully consider the benefit-to-risk ratio of olanzapine and its additional, prophylactic effect against relapse in the long term. The generalisability of these results to other antipsychotics, trial designs, and medical conditions remains to be established. FUNDING: None.
BACKGROUND: The efficacy of antipsychotics across the initial severity range in patients with acute mania remains unclear. Therefore, we examined the influence of baseline severity on the efficacy of olanzapine. METHODS: We did an individual participant data meta-analysis of double-blind, randomised controlled trials that compared olanzapine with placebo, identified through searches of the ClinicalStudyRequest.com database on Feb 2, 2016. We included patients with acute mania associated with bipolar I disorder. We examined the association between baseline and change scores on the Young Mania Rating Scale (YMRS; range 0-60) up to 3 weeks for olanzapine versus placebo groups using eight increasingly complex competing mixed-effects models for repeated measures. FINDINGS: We identified 33 reports, five (15%) of which were eligible and contained data for 939 patients (552 received olanzapine; 387 received placebo). The interaction between baseline severity and treatment was significant (β=0·22, 95% CI 0·05-0·39; p=0·013). The greater the baseline severity, the greater the magnitude of the differences between olanzapine and placebo was expected. The mean estimated YMRS scores were reduced at 3 weeks in both groups, but were greater with olazapine than placebo by 2·56 points for patients with a baseline score of 20-25 (9·26 for olanzapine vs 6·70 for placebo; effect size 0·35, 95% CI 0·11-0·60), by 4·74 points for a baseline score of 25-35 (14·25 vs 9·51; 0·58, 0·34-0·86), and by 8·01 points for a baseline score of 35-60 (21·72 vs 13·71; 0·70, 0·31-1·23). INTERPRETATION: Benefits of olanzapine can be expected for patients across the full spectrum of symptom severity who are likely to be treated for acute mania. Less severely ill patients seem to benefit less in terms of olanzapine efficacy, but still experience the same side-effects as more severely ill patients. Thus, clinicians and patients should carefully consider the benefit-to-risk ratio of olanzapine and its additional, prophylactic effect against relapse in the long term. The generalisability of these results to other antipsychotics, trial designs, and medical conditions remains to be established. FUNDING: None.
Authors: Stefan Leucht; S Z Levine; M Samara; A Cipriani; J M Davis; T A Furukawa Journal: Eur Arch Psychiatry Clin Neurosci Date: 2018-10 Impact factor: 5.270
Authors: Rebecca F McKnight; Saïk J G N de La Motte de Broöns de Vauvert; Edward Chesney; Ben H Amit; John Geddes; Andrea Cipriani Journal: Cochrane Database Syst Rev Date: 2019-06-01