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