Geriatric Depression Treatment in Nonresponders to Selective Serotonin Reuptake Inhibitors

Ellen M. Whyte, M.D.; James Basinski, B.S.; Panthea Farhi, B.S.; Mary Amanda Dew, Ph.D.; Amy Begley, M.A.; Benoit H. Mulsant, M.D.; and Charles F. Reynolds III, M.D.

Background: Up to a third of elderly patients with major depressive disorder are treatment resistant, yet little objective evidence is available to guide the clinician in managing these patients. We report here our experience with elderly subjects with prospectively defined treatment-resistant depression in 2 separate research studies: one entailing an augmentation strategy, the other a change to venlafaxine extended release (XR).

Method: Fifty-three elderly subjects with major depressive disorder according to DSM-IV criteria who failed treatment with paroxetine plus interpersonal psychotherapy received 1 to 3 trials of augmentation with bupropion sustained release, nortriptyline, or lithium. Successively fewer subjects entered each sequential trial of augmentation. Twelve subjects subsequently received venlafaxine XR monotherapy. Response to treatment was defined as a 17-item Hamilton Rating Scale for Depression score of < 10 for 3 weeks.

Results: Sixty percent of subjects (N = 32) responded to some form of augmentation, with 45% (24/53), 31% (5/16), and 43% (3/7) responding to the first, second, and third augmentation trials, respectively. The mean time to response after starting the first augmentation trial was 6.0 (SD = 5.8) weeks. Forty-two percent (N = 5) of the venlafaxine XR-treated subjects responded with the mean time to response of 6.4 (SE = 0.9) weeks. Adverse effects leading to treatment discontinuation and falls were more common in the augmentation subjects than in the venlafaxine XR subjects.

Conclusion: We observed similar rates and speed of response with an augmentation strategy and a strategy of switching to venlafaxine XR in elderly subjects with prospectively defined treatment-resistant major depressive disorder. Venlafaxine XR was generally better tolerated than the augmentation strategies. Further investigation of venlafaxine XR as a preferred strategy for treatment-resistant geriatric depression is warranted.

(J Clin Psychiatry 2004;65:1634-1641)

Received March 28, 2004; accepted Sept. 7, 2004. From the Department of Psychiatry (Drs. Whyte, Dew, Mulsant, and Reynolds and Ms. Begley) and the Department of Neurology (Dr. Reynolds), University of Pittsburgh School of Medicine (Mr. Basinski), Pittsburgh; the Geriatric Research Education Clinical Center, Pittsburgh VA Healthcare System, Pittsburgh (Drs. Whyte and Mulsant); and Pennsylvania State University, State College (Ms. Farhi), Pa.

This work was supported by U.S. Public Health Service Grants MH067710, MH069430, MH52247, MH43832, MH37869, and T32MH19986. GlaxoSmithKline provided supplies of paroxetine for the study.

Presented in part at the International Psychogeriatric Association, 11th annual meeting, August 2003, Chicago, Ill.

Dr. Mulsant has served as a consultant for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest, Fox Learning System, GlaxoSmithKline, Janssen, and Pfizer; has received grant/research support from National Institutes of Health, AstraZeneca, Corcept, Eli Lilly, Forest, GlaxoSmithKline, Janssen, and Pfizer/Eisai; has received honoraria from AstraZeneca, Forest, Janssen, Lundbeck, GlaxoSmithKline, and Pfizer/Eisai; has served on the speakers bureau of AstraZeneca, Forest, GlaxoSmithKline, Janssen, and Pfizer/Eisai; and has received other financial or material support from Eli Lilly, Forest, Janssen, and Pfizer.

Corresponding author and reprints: Ellen M. Whyte, M.D., Department of Psychiatry, University of Pittsburgh, TDH/WPIC, Room 886-B, 3811 O'Hara Street, Pittsburgh, PA 15213(e-mail: whyteem@upmc.edu).