An integrated analysis of olanzapine/fluoxetine combination in clinical trials of treatment-resistant depression.
ABSTRACT To evaluate the efficacy of olanzapine/fluoxetine combination (OFC) versus olanzapine or fluoxetine monotherapy across all clinical trials of treatment-resistant depression sponsored by Eli Lilly and Company.
Efficacy and safety data from 1146 patients with a history of nonresponse during the current depressive episode who subsequently exhibited nonresponse during a 6- to 8-week antidepressant open-label lead-in phase and were randomly assigned to OFC (N = 462), fluoxetine (N = 342), or olanzapine (N = 342) for double-blind treatment were analyzed. All patients had a diagnosis of major depressive disorder as defined by DSM-III or DSM-IV criteria. The dates in which the trials were conducted ranged from May 1997 to July 2005.
After 8 weeks, OFC patients demonstrated significantly greater Montgomery-Asberg Depression Rating Scale improvement (mean change = -13.0) than fluoxetine (-8.6, p < .001) or olanzapine (-8.2, p < .001) patients, via a mixed-effects model repeated-measures analysis. Remission rates were 25.5% for OFC, 17.3% (p = .006) for fluoxetine, and 14.0% (p < .001) for olanzapine. Adverse events in >or= 10% of OFC patients were weight gain, increased appetite, dry mouth, somnolence, fatigue, headache, and peripheral edema. Random glucose mean change (mg/dL) was +7.92 for the OFC group, +1.62 for the fluoxetine group (p = .020), and +9.91 for the olanzapine group (p = .485). Random cholesterol mean change (mg/dL) was +12.4 for OFC, +2.3 for fluoxetine (p < .001), and +3.1 for olanzapine (p < .001); incidence of treatment-emergent increase from normal to high cholesterol (baseline < 200 mg/dL and >or= 240 subsequently) was significantly higher for the OFC group (10.2%) than for the fluoxetine group (3.1%, p = .017) but not the olanzapine group (8.0%, p = .569). Mean weight change (kg) was +4.42 for OFC, -0.15 for fluoxetine (p < .001), and +4.63 for olanzapine (p = .381), with 40.4% of OFC patients gaining >or= 7% body weight (vs. olanzapine: 42.9%, p = .515; fluoxetine: 2.3%, p < .001).
Results of this analysis showed that OFC-treated patients experienced significantly improved depressive symptoms compared with olanzapine- or fluoxetine-treated patients following failure of 2 or more antidepressants within the current depressive episode. Safety results for OFC were generally consistent with those for its component monotherapies. The total cholesterol increase associated with OFC was more pronounced than with olanzapine alone.
- SourceAvailable from: Shao-Tsu ChenProgress in Neuro-Psychopharmacology and Biological Psychiatry 01/2011; 35(1):305-6. DOI:10.1016/j.pnpbp.2010.11.024 · 4.03 Impact Factor
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ABSTRACT: To evaluate the efficacy of rEEG(®)-guided pharmacotherapy for the treatment of depression in those circumstances where rEEG and STAR*D provided different recommendations. This was a randomized, single-blind, parallel group, 12 center, US study of rEEG-guided pharmacotherapy vs. the most effective treatment regimens reported in the NIH sponsored STAR*D study. Relatively treatment-resistant subjects ≥18 years who failed one or more antidepressants were required to have a QIDS-16-SR score ≥13 and a MADRS score ≥26 at baseline. All subjects underwent a washout of all current medications (with some protocol-specified exceptions) for at least five half-lives before receiving a QEEG and rEEG report. Subjects randomized to rEEG were assigned a regimen based on the rEEG report. Control subjects who had failed only SSRI's in their current episode were randomized to receive venlafaxine XR. Control subjects who had failed antidepressants from ≥2 classes of antidepressants were randomized to receive a regimen from Steps 2-4 of the STAR*D study. Treatment lasted 12 weeks. The primary outcome measures were change from baseline for self-rated QIDS-SR16 and Q-LES-Q-SF. A total of 114 subjects were randomized and 89 subjects were evaluable. rEEG-guided pharmacotherapy exhibited significantly greater improvement for both primary endpoints, QIDS-SR16 (-6.8 vs. -4.5, p<0.0002) and Q-LES-Q-SF (18.0 vs. 8.9, p<0.0002) compared to control, respectively, as well as statistical superiority in 9 out of 12 secondary endpoints. These results warrant additional studies to determine the role of rEEG-guided psychopharmacology in the treatment of depression. If these results were confirmed, rEEG-guided pharmacotherapy would represent an easy, relatively inexpensive, predictive, objective office procedure that builds upon clinical judgment to guide antidepressant medication choice.Journal of Psychiatric Research 01/2011; 45(1):64-75. DOI:10.1016/j.jpsychires.2010.05.009 · 4.09 Impact Factor
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ABSTRACT: Study objective: this systematic review assessed the safety and efficacy of olanzapine-fluoxetine combination (OFC) for treatment of bipolar depression, specifically in studies of 8 to 12 weeks duration in adults (primary objective) and adolescents (secondary objective). Materials and methods: trials were identified using MEDLINE, EMBASE, Cochrane Library, Web of Knowledge, LILACS, WHOLIS, NEURO, Latindex, and DIALNET (2000 – July 2014). English and Spanish free-text and MeSH terms were used. Searches were supplemented with identified trials (Clinical Trials.gov) and congress abstracts. Evidence from randomized controlled trials (RCTs), nonrandomized trials, and meta-analyses were considered. Results: nine publications reporting 5 RCTs (6 publications), 1 nonrandomized trial, and 2 meta-analyses were included. One RCT was conducted in adolescents and one RCT was conducted in a Latin American population. Studies enrolled from 34 to 833 participants, were conducted for 7 to 8 weeks and up to 6 months, and varied in methodological quality and reporting. The efficacy of OFC (depression rating scales, response and remission rates) was greater compared with olanzapine monotherapy, lamotrigine monotherapy, and placebo. OFC was well tolerated in adults and adolescents. However, there was a greater frequency of weight gain, somnolence, nausea, diarrhea, and elevated metabolic parameters in participants receiving OFC versus active comparators or placebo. Conclusions: this systematic review presents findings that OFC is effective and generally well tolerated for acute treatment of bipolar depression in adults and adolescents. Existing evidence suggests that the efficacy and safety profile of OFC in patients from Latin America is not different to Caucasian populations.Archivos de Neurociencias 04/2015; 20(2):144-158.