A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease

I. H. Richard, M. P. McDermott, R. Kurlan, J. M. Lyness, P. G. Como, N. Pearson, S. A. Factor, J. Juncos, C. Serrano Ramos, M. Brodsky, C. Manning, L. Marsh, L. Shulman, H. H. Fernandez, K. J. Black, M. Panisset, C. W. Christine, W. Jiang, C. Singer, S. HornR. Pfeiffer, D. Rottenberg, J. Slevin, L. Elmer, D. Press, H. C. Hyson, W. McDonald

Research output: Contribution to journalArticlepeer-review

244 Scopus citations


Objective: To evaluate the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI) and a serotonin and norepinephrine reuptake inhibitor (SNRI) in the treatment of depression in Parkinson disease (PD). Methods: A total of 115 subjects with PD were enrolled at 20 sites. Subjects were randomized to receive an SSRI (paroxetine; n = 42), an SNRI (venlafaxine extended release [XR]; n = 34), or placebo (n = 39). Subjects met DSM-IV criteria for a depressive disorder, or operationally defined subsyndromal depression, and scored 12 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Subjects were followed for 12 weeks (6-week dosage adjustment, 6-week maintenance). Maximum daily dosages were 40 mg for paroxetine and 225 mg for venlafaxine XR. The primary outcome measure was change in the HAM-D score from baseline to week 12. Results: Treatment effects (relative to placebo), expressed as mean 12-week reductions in HAM-D score, were 6.2 points (97.5% confidence interval [CI] 2.2 to 10.3, p = 0.0007) in the paroxetine group and 4.2 points (97.5% CI 0.1 to 8.4, p = 0.02) in the venlafaxine XR group. No treatment effects were seen on motor function. Conclusions: Both paroxetine and venlafaxine XR significantly improved depression in subjects with PD. Both medications were generally safe and well tolerated and did not worsen motor function. Classification of Evidence: This study provides Class I evidence that paroxetine and venlafaxine XR are effective in treating depression in patients with PD.

Original languageEnglish (US)
Pages (from-to)1229-1236
Number of pages8
Issue number16
StatePublished - Apr 17 2012

Bibliographical note

Funding Information:
Study funding: Supported by NIH/NINDS R01 NS046487 and the General Clinical Research Center at Johns Hopkins University School of Medicine (National Center for Research Resources/NIH M01-RR00052). Wyeth Pharmaceuticals provided venlafaxine XR and matching placebo. Glaxo-Smith Kline provided paroxetine.


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