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An integrated analysis of olanzapine/fluoxetine combination in clinical trials of treatment-resistant depression.
J Clin Psychiatry. 2009 Mar; 70(3):387-96.JC

Abstract

OBJECTIVE

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.

METHOD

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.

RESULTS

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).

CONCLUSION

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.

Authors+Show Affiliations

Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9119, USA. madhukar.trivedi@utsouthwestern.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19284928

Citation

Trivedi, Madhukar H., et al. "An Integrated Analysis of Olanzapine/fluoxetine Combination in Clinical Trials of Treatment-resistant Depression." The Journal of Clinical Psychiatry, vol. 70, no. 3, 2009, pp. 387-96.
Trivedi MH, Thase ME, Osuntokun O, et al. An integrated analysis of olanzapine/fluoxetine combination in clinical trials of treatment-resistant depression. J Clin Psychiatry. 2009;70(3):387-96.
Trivedi, M. H., Thase, M. E., Osuntokun, O., Henley, D. B., Case, M., Watson, S. B., Campbell, G. M., & Corya, S. A. (2009). An integrated analysis of olanzapine/fluoxetine combination in clinical trials of treatment-resistant depression. The Journal of Clinical Psychiatry, 70(3), 387-96.
Trivedi MH, et al. An Integrated Analysis of Olanzapine/fluoxetine Combination in Clinical Trials of Treatment-resistant Depression. J Clin Psychiatry. 2009;70(3):387-96. PubMed PMID: 19284928.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An integrated analysis of olanzapine/fluoxetine combination in clinical trials of treatment-resistant depression. AU - Trivedi,Madhukar H, AU - Thase,Michael E, AU - Osuntokun,Olawale, AU - Henley,David B, AU - Case,Michael, AU - Watson,Susan B, AU - Campbell,Giedra M, AU - Corya,Sara A, Y1 - 2009/03/10/ PY - 2008/01/18/received PY - 2009/01/02/accepted PY - 2009/3/17/entrez PY - 2009/3/17/pubmed PY - 2009/4/14/medline SP - 387 EP - 96 JF - The Journal of clinical psychiatry JO - J Clin Psychiatry VL - 70 IS - 3 N2 - OBJECTIVE: 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. METHOD: 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. RESULTS: 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). CONCLUSION: 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. SN - 1555-2101 UR - https://www.unboundmedicine.com/medline/citation/19284928/An_integrated_analysis_of_olanzapine/fluoxetine_combination_in_clinical_trials_of_treatment_resistant_depression_ L2 - http://www.psychiatrist.com/jcp/article/pages/2009/v70n03/v70n0311.aspx DB - PRIME DP - Unbound Medicine ER -