Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-23T06:46:07.409Z Has data issue: false hasContentIssue false
  • English
  • Français

Time to response for duloxetine 60 mg once daily versus placebo in elderly patients with major depressive disorder

Published online by Cambridge University Press:  22 June 2007

Joel Raskin ,
Jimmy Y. Xu  and
Daniel K. Kajdasz
Joel Raskin*
Affiliation:
Lilly Research Laboratories, Eli Lilly Canada, Toronto, Canada
Jimmy Y. Xu
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, U.S.A.
Daniel K. Kajdasz
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, U.S.A.
*
Correspondence should be addressed to: Dr. Joel Raskin, Lilly Research Laboratories, Eli Lilly Canada, 3650 Danforth Ave., Toronto, Ontario, Canada MIN 2E8. Phone: +1 416 699 7260; Fax: +1 416 699 7352. Email: [email protected].
Get access

Abstract

Background: Rapid response to antidepressant therapy is desirable and may be particularly critical in elderly patients with major depressive disorder (MDD).

Methods: Findings are based on post-hoc analyses from a double-blind trial of elderly patients with MDD ≥ 65 years, randomly assigned 2:1 to duloxetine 60 mg QD (N = 207) or placebo (N = 104) for 8 weeks. Depression and pain measures included the Geriatric Depression Scale (GDS), 17-item Hamilton Depression Scale (HAMD17), CGI-Severity, and Visual Analog Scale (VAS) for overall pain. The time to response and remission for duloxetine compared with placebo was evaluated using Cox proportional hazards (PH) modeling, Kaplan-Meier estimation, and categorical repeated measures analysis.

Results: Significant improvements of estimated HAMD17 response and remission rates for duloxetine started at week 2 (P = 0.022 and P = 0.033, respectively). Time to HAMD17 response and remission were significantly shorter for duloxetine versus placebo (P < 0.001 and P = 0.004, respectively). Placebo-referenced duloxetine hazard ratios (HR) for HAMD17 response and remission were 2.03 (P = 0.002) and 2.01 (P = 0.006), respectively. Results for GDS-based response (HR = 1.54, P = 0.023) and remission (HR = 1.54, P = 0.104) rates were consistent with the HAMD17 findings. Patients ≥75 years (n = 93) responded with similar rapidity to duloxetine compared with those <75 years (n = 199, P > 0.10 for all PH treatment-by-age interactions). The placebo-referenced duloxetine HR for time to 50% reduction in overall pain was 1.75 (P = 0.024) for patients with moderate to severe pain.

Conclusion: Duloxetine demonstrated a faster time to antidepressant response and improvement in self-reported pain as compared with placebo.

Clinical trial registry number for this study: NCT00062673, at www.clinicaltrials.gov.

Keywords

duloxetineelderlyonset of actiondepression
Type
Research Article
Information
International Psychogeriatrics , Volume 20 , Issue 2 , April 2008 , pp. 309 - 327
Copyright
Copyright © International Psychogeriatric Association 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

American Psychiatric Association 1994. Diagnostic and Statistical Manual of Mental Disorders. 4th edn. Washington, DC: American Psychiatric Association.Google Scholar
Benkert, O. et al. 2006. Mirtazapine orally disintegrating tablets versus venlafaxine extended release: a double-blind, randomized multicenter trial comparing the onset of antidepressant response in patients with major depressive disorder. Journal of Clinical Psychopharmacology, 26, 75–78.CrossRefGoogle ScholarPubMed
Brannan, S. K., Mallinckrodt, C. H., Detke, M. J., Watkin, J. G. and Tollefson, G. D. 2005. Onset of action for duloxetine 60 mg once daily: double-blind, placebo-controlled studies. Journal of Psychiatric Research, 39, 161–172.CrossRefGoogle ScholarPubMed
Bymaster, F. P. et al. 2001. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology, 25, 871–880.CrossRefGoogle ScholarPubMed
DeLoach, L. J., Higgins, M. S., Caplan, A. B. and Stiff, J. L. 1998. The visual analog scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale. Anesthesia and Analgesia, 86, 102–106.Google ScholarPubMed
Depression Guideline Panel 1993. Clinical Practice Guideline Number 5: Depression in Primary Care. Rockville, MD: U.S. Department of Health and Human Services, Agency for Health Policy and Research.Google Scholar
Detke, M. J., Lu, Y., Goldstein, D. J., Hayes, J. R. and Demitrack, M. A. 2002. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. Journal of Clinical Psychiatry, 63, 308–315.CrossRefGoogle ScholarPubMed
Driscoll, H. C. et al. 2005. Late-onset major depression: clinical and treatment-response variability. International Journal of Geriatric Psychiatry, 20, 661–667.CrossRefGoogle ScholarPubMed
Entsuah, R., Derivan, A. and Kikta, D. 1998. Early onset of antidepressant action of venlafaxine: pattern analysis in intent-to-treat patients. Clinical Therapeutics, 20, 517–526.CrossRefGoogle ScholarPubMed
Flint, A. J. and Rifat, S. L. 1997. Effect of demographic and clinical variables on time to antidepressant response in geriatric depression. Depression and Anxiety, 5, 103–107.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
Folstein, M. F., Folstein, S. E. and McHugh, P. R. 1975. “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198.CrossRefGoogle ScholarPubMed
Frank, E. et al. 1991. Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Archives of General Psychiatry, 48, 851–855.CrossRefGoogle ScholarPubMed
Georgotas, A., McCue, R. E., Cooper, T. B., Nagachandran, N. and Friedhoff, A. 1989. Factors affecting the delay of antidepressant effect in responders to nortriptyline and phenelzine. Psychiatry Research, 28, 1–9.CrossRefGoogle ScholarPubMed
Hamilton, M. 1960. A rating scale for depression. Journal of Neurology Neurosurgery, and Psychiatry, 23, 56–62.CrossRefGoogle ScholarPubMed
Hirschfeld, R. M., Mallinckrodt, C., Lee, T. C. and Detke, M. J. 2005. Time course of depression-symptom improvement during treatment with duloxetine. Depression and Anxiety, 21, 170–177.CrossRefGoogle ScholarPubMed
Katz, M. M., Koslow, S. H. and Frazer, A. 1996. Onset of antidepressant activity: reexamining the structure of depression and multiple actions of drugs. Depression and Anxiety, 4, 257–267.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Katz, M. M. et al. 1997. Can the effects of antidepressants be observed in the first two weeks of treatment? Neuropsychopharmacology, 17, 110–115.Google ScholarPubMed
Katz, M. M. et al. 2004. Onset and early behavioral effects of pharmacologically different antidepressants and placebo in depression. Neuropsychopharmacology, 29, 566–579.CrossRefGoogle ScholarPubMed
Katz, M. M., Bowden, C. L., Berman, N. and Frazer, A. 2006. Resolving the onset of antidepressants' clinical actions: critical for clinical practice. Journal of Clinical Psychopharmacology, 26, 549–553.CrossRefGoogle ScholarPubMed
Leon, A. C. et al. 2001. An ideal trial to test differential onset of antidepressant effect. Journal of Clinical Psychiatry, 62, 34–36.Google ScholarPubMed
Mitchell, A. J. 2006. Two-week delay in onset of action of antidepressants: new evidence. British Journal of Psychiatry, 188, 105–106.CrossRefGoogle ScholarPubMed
Mulsant, B. H. et al. 2006. What is the optimal duration of a short-term antidepressant trial when treating geriatric depression? Journal of Clinical Psychopharmacology, 26, 113–120.CrossRefGoogle ScholarPubMed
Nelson, J. C., Mazure, C. M., Bowers, M. B. Jr. and Jatlow, P. I. 1991. A preliminary, open study of the combination of fluoxetine and desipramine for rapid treatment of major depression. Archives of General Psychiatry, 48, 303–307.CrossRefGoogle ScholarPubMed
Nierenberg, A. A. et al. 2007. Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study. Current Medical Research Opinion, 23, 401–416.CrossRefGoogle Scholar
Papakostas, G. I., Perlis, R. H., Scalia, M. J., Petersen, T. J. and Fava, M. 2006. A meta-analysis of early sustained response rates between antidepressants and placebo for the treatment of major depressive disorder. Journal of Clinical Psychopharmacology, 26, 56–60.CrossRefGoogle ScholarPubMed
Parker, G. 1996. On brightening up: triggers and trajectories to recovery from depression. British Journal of Psychiatry, 168, 263–264.CrossRefGoogle ScholarPubMed
Petersen, R. C., Stevens, J. C., Ganguli, M., Tangalos, E. G., Cummings, J. L. and DeKosky, S. T. 2001. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 56, 1133–1142.CrossRefGoogle Scholar
Posternak, M. A. and Zimmerman, M. 2005. Is there a delay in the antidepressant effect? A meta-analysis. Journal of Clinical Psychiatry, 66, 148–158.CrossRefGoogle Scholar
Raskin, J. et al. 2007. Efficacy of duloxetine on cognition, depression, and pain in elderly patients with major depressive disorder: an 8-week, double-blind, placebo-controlled trial. American Journal of Psychiatry, 164, 900–909.CrossRefGoogle ScholarPubMed
Reynolds, C. F. III 1997. Treatment of major depression in later life: a life cycle perspective. Psychiatric Quarterly, 68, 221–246.CrossRefGoogle ScholarPubMed
Roose, S. P. and Sackeim, H. A. 2002. Clinical trials in late-life depression: revisited. American Journal of Geriatric Psychiatry, 10, 503–505.CrossRefGoogle Scholar
Roose, S. P. et al. 2004. Antidepressant pharmacotherapy in the treatment of depression in the very old: a randomized, placebo-controlled trial. American Journal of Psychiatry, 161, 2050–2059.CrossRefGoogle Scholar
Schatzberg, A. and Roose, S. 2006. A double-blind, placebo-controlled study of venlafaxine and fluoxetine in geriatric outpatients with major depression. American Journal of Geriatric Psychiatry, 14, 361–370.CrossRefGoogle ScholarPubMed
Staab, J. P. and Evans, D. L. 2000. Efficacy of venlafaxine in geriatric depression. Depression and Anxiety, 12 (Suppl. 1), 63–68.3.0.CO;2-T>CrossRefGoogle ScholarPubMed
Stahl, S. M., Nierenberg, A. A. and Gorman, J. M. 2001. Evidence of early onset of antidepressant effect in randomized controlled trials. Journal of Clinical Psychiatry, 62, 17–23.Google ScholarPubMed
Stassen, H. H., Angst, J. and Delini-Stula, A. 1997. Delayed onset of action of antidepressant drugs? Survey of recent results. European Psychiatry, 12, 166–176.CrossRefGoogle ScholarPubMed
Taylor, M. J., Freemantle, N., Geddes, J. R. and Bhagwagar, Z. 2006. Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis. Archives of General Psychiatry, 63, 1217–1223.CrossRefGoogle ScholarPubMed
Thompson, C. 1999. Mirtazapine versus selective serotonin reuptake inhibitors. Journal of Clinical Psychiatry, 60, 18–22.Google ScholarPubMed
Thompson, W. L., Brunelle, R. L., Enas, G. G. and Simpson, P. J. 1987. Routine laboratory tests in clinical trials: interpretation of results. Journal of Clinical Research and Drug Development, 1, 95–119.Google Scholar
Walsh, B. T. and Sysko, R. 2005. Placebo control groups in trials of major depressive disorder among older patients. Journal of Clinical Psychopharmacology, 25, S29–S33.CrossRefGoogle ScholarPubMed
Whyte, E. M. et al. 2004. Time course of response to antidepressants in late-life major depression: therapeutic implications. Drugs and Aging, 21, 531–554.CrossRefGoogle ScholarPubMed
Yesavage, J. A. et al. 1982. Development and validation of a geriatric depression screening scale: a preliminary report. Journal of Psychiatric Research, 17, 37–49.CrossRefGoogle Scholar
Zigmond, A. S. and Snaith, R. P. 1983. The hospital anxiety and depression scales. Acta Psychiatrica Scandinavica, 67, 361–370.CrossRefGoogle Scholar