1. Depression and Parkinson Disease: An Old Drug Still Works (Better) Summary and Comment by Jonathan Silver, MD Published in Journal Watch Psychiatry February 9, 2009Journal Watch Psychiatry Tricyclics remain a good choice for depressed patients with neurologic disease. CopyrightCopyright © 2009. Massachusetts Medical Society. All rights reserved.Massachusetts Medical Society

2. Covering Menza M et al. A controlled trial of antidepressants in patients with Parkinson disease and depression. Neurology 2008 Dec 17; [e-pub ahead of print]. (http://dx.doi.org/10.1212/01.wnl.0000336340.89821.b3) Okun MS and Fernandez HH. Will tricyclic antidepressants make a comeback for depressed Parkinson disease patients? Neurology 2008 Dec 17; [e-pub ahead of print]. (http://dx.doi.org/10.1212/01.wnl.0000338145.24512.02) CopyrightCopyright © 2009. Massachusetts Medical Society. All rights reserved.Massachusetts Medical Society

3. Background Few double-blind, placebo-controlled treatment trials exist regarding depression in patients with neurological disorders. Using a strong study design with both active and placebo controls, researchers compared outcomes after 8 weeks’ treatment with paroxetine CR, nortriptyline, and placebo in 52 cognitively intact patients with Parkinson disease and major depression (mean age, 63; 25 women). CopyrightCopyright © 2009. Massachusetts Medical Society. All rights reserved.Massachusetts Medical Society

4. The Research Paroxetine was started at 12.5 mg/day (maximum dose, 37.5 mg/day; average dose, 28.4 mg/day). Nortriptyline was started at 25.0 mg/day (maximum dose, 75.0 mg/day; average dose, 48.5 mg/day). Completion rates were similar in the three groups. CopyrightCopyright © 2009. Massachusetts Medical Society. All rights reserved.Massachusetts Medical Society

5. The Research At 8 weeks, nortriptyline was superior to placebo in the main outcome measure (change from baseline on a standardized depression scale) and to both placebo and paroxetine in response rates (53% vs. 24% and 11%, respectively). Remission rates were 41%, 17%, and 12%, respectively. Nortriptyline also had greater efficacy for symptoms of sleep, anxiety, and social functioning. The authors reported no evidence of drug effect on cognitive tests but did not present specific results. Paroxetine was associated with more side effects than placebo. The most common were constipation and dry mouth with nortriptyline and fatigue with paroxetine. CopyrightCopyright © 2009. Massachusetts Medical Society. All rights reserved.Massachusetts Medical Society

6. Comment These results demonstrate the efficacy of an old drug and the importance of using active controls in research. Not all antidepressant classes have equal efficacy, and newer drugs are not necessarily better than older ones. Interestingly, a study of poststroke depression published several years ago showed that nortriptyline was more effective than fluoxetine, which was only as effective as placebo. Unfortunately, tricyclic antidepressants are infrequently used today, and psychiatric trainees seem to have little experience in prescribing this class of medication. CopyrightCopyright © 2009. Massachusetts Medical Society. All rights reserved.Massachusetts Medical Society

7. Comment The anticholinergic properties of nortriptyline can be problematic to patients with cognitive problems. Paroxetine’s anticholinergic profile, however, is similar to nortriptyline’s and is greater than that of any other SSRI. Editorialists discuss issues related to design of this study and others on antidepressants in Parkinson disease. CopyrightCopyright © 2009. Massachusetts Medical Society. All rights reserved.Massachusetts Medical Society

8. About Journal Watch Journal Watch helps physicians and allied heath professionals save time and stay informed by providing brief, clearly written, clinically focused perspectives on the medical developments that affect practice. Journal Watch is an independent, trustworthy source, from the publishers of the New England Journal of Medicine. These slides were derived from Journal Watch Psychiatry.Journal Watch Psychiatry The best way to stay informed with Journal Watch, is through our alerts. To sign up, visit the My Alerts page.My Alerts page CopyrightCopyright © 2009. Massachusetts Medical Society. All rights reserved.Massachusetts Medical Society