Skip to main content
    • Aa
    • Aa

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

  • Joel Raskin (a1), Jimmy Y. Xu (a2) and Daniel K. Kajdasz (a2)

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

Corresponding author
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:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

O. Benkert 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, 7578.

F. P. Bymaster 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, 871880.

L. J. DeLoach , M. S. Higgins , A. B. Caplan and J. L. Stiff 1998. The visual analog scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale. Anesthesia and Analgesia, 86, 102106.

M. J. Detke , Y. Lu , D. J. Goldstein , J. R. Hayes and M. A. Demitrack 2002. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. Journal of Clinical Psychiatry, 63, 308315.

H. C. Driscoll 2005. Late-onset major depression: clinical and treatment-response variability. International Journal of Geriatric Psychiatry, 20, 661667.

A. J. Flint and S. L. Rifat 1997. Effect of demographic and clinical variables on time to antidepressant response in geriatric depression. Depression and Anxiety, 5, 103107.

M. F. Folstein , S. E. Folstein and P. R. McHugh 1975. “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189198.

A. Georgotas , R. E. McCue , T. B. Cooper , N. Nagachandran and A. Friedhoff 1989. Factors affecting the delay of antidepressant effect in responders to nortriptyline and phenelzine. Psychiatry Research, 28, 19.

M. Hamilton 1960. A rating scale for depression. Journal of Neurology Neurosurgery, and Psychiatry, 23, 5662.

R. M. Hirschfeld , C. Mallinckrodt , T. C. Lee and M. J. Detke 2005. Time course of depression-symptom improvement during treatment with duloxetine. Depression and Anxiety, 21, 170177.

M. M. Katz , S. H. Koslow and A. Frazer 1996. Onset of antidepressant activity: reexamining the structure of depression and multiple actions of drugs. Depression and Anxiety, 4, 257267.

M. M. Katz 2004. Onset and early behavioral effects of pharmacologically different antidepressants and placebo in depression. Neuropsychopharmacology, 29, 566579.

M. M. Katz , C. L. Bowden , N. Berman and A. Frazer 2006. Resolving the onset of antidepressants' clinical actions: critical for clinical practice. Journal of Clinical Psychopharmacology, 26, 549553.

A. J. Mitchell 2006. Two-week delay in onset of action of antidepressants: new evidence. British Journal of Psychiatry, 188, 105106.

B. H. Mulsant 2006. What is the optimal duration of a short-term antidepressant trial when treating geriatric depression? Journal of Clinical Psychopharmacology, 26, 113120.

J. C. Nelson , C. M. Mazure , M. B. Jr. Bowers and P. I. Jatlow 1991. A preliminary, open study of the combination of fluoxetine and desipramine for rapid treatment of major depression. Archives of General Psychiatry, 48, 303307.

A. A. Nierenberg 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, 401416.

G. I. Papakostas , R. H. Perlis , M. J. Scalia , T. J. Petersen and M. Fava 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, 5660.

G. Parker 1996. On brightening up: triggers and trajectories to recovery from depression. British Journal of Psychiatry, 168, 263264.

R. C. Petersen , J. C. Stevens , M. Ganguli , E. G. Tangalos , J. L. Cummings and S. T. DeKosky 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, 11331142.

M. A. Posternak and M. Zimmerman 2005. Is there a delay in the antidepressant effect? A meta-analysis. Journal of Clinical Psychiatry, 66, 148158.

J. Raskin 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, 900909.

C. F. III Reynolds 1997. Treatment of major depression in later life: a life cycle perspective. Psychiatric Quarterly, 68, 221246.

A. Schatzberg and S. Roose 2006. A double-blind, placebo-controlled study of venlafaxine and fluoxetine in geriatric outpatients with major depression. American Journal of Geriatric Psychiatry, 14, 361370.

H. H. Stassen , J. Angst and A. Delini-Stula 1997. Delayed onset of action of antidepressant drugs? Survey of recent results. European Psychiatry, 12, 166176.

M. J. Taylor , N. Freemantle , J. R. Geddes and Z. Bhagwagar 2006. Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis. Archives of General Psychiatry, 63, 12171223.

E. M. Whyte 2004. Time course of response to antidepressants in late-life major depression: therapeutic implications. Drugs and Aging, 21, 531554.

J. A. Yesavage 1982. Development and validation of a geriatric depression screening scale: a preliminary report. Journal of Psychiatric Research, 17, 3749.

A. S. Zigmond and R. P. Snaith 1983. The hospital anxiety and depression scales. Acta Psychiatrica Scandinavica, 67, 361370.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

International Psychogeriatrics
  • ISSN: 1041-6102
  • EISSN: 1741-203X
  • URL: /core/journals/international-psychogeriatrics
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 3
Total number of PDF views: 18 *
Loading metrics...

Abstract views

Total abstract views: 89 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 21st September 2017. This data will be updated every 24 hours.