Internal Medicine News - Nortriptyline may beat SSRIs for depression in Parkinson’s
PHOENIX–Nortriptyline was more effective than paroxetine or placebo in treating depression in patients with Parkinson’s disease, an 8-week pilot study of 52 patients found.
The study, while small, is the largest placebo-controlled trial of treating depression in patients with Parkinson’s disease and the first in this population to compare a tricyclic antidepressant–nortriptyline–with a selective serotonin reuptake inhibitor (SSRI), in this case controlled-release paroxetine (paroxetine CR).
The results raise questions about current clinical practice, which seems to favor SSRIs as first-line medications for depression in Parkinson’s disease, Dr. Matthew A. Menza said at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.
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Only 7% of patients with Parkinson’s disease and depression are on a tricyclic antidepressant, noted Dr. Menza, professor of psychiatry and neurology at the University of Medicine and Dentistry of New Jersey, Newark.
More research is needed to confirm these pilot results and to provide guidance to clinicians on treating depression in Parkinson’s disease, he added.
The National Institute of Neurological Disorders and Stroke funded the study. Dr. Menza has been a consultant or speaker or received research grant support from Eli Lilly & Co., which makes a brand of nortriptyline, and for GlaxoSmithKline, which makes paroxetine CR and provided the drug and matching placebo for the study.
The study randomized patients to 8 weeks of blinded treatment with nortriptyline, paroxetine CR, or placebo. Approximately a third of the patients in each group discontinued treatment before the end of the trial, including 29% on nortriptyline, 39% on paroxetine CR, and 35% on placebo. Of those who completed the study, the average dose by the end of 8 weeks was 63 mg/day nortriptyline, 32 mg/day paroxetine CR, or two pills of placebo.
The nortriptyline group showed better results on the two primary end points–Hamilton Depression Rating Scale (HAM-D) scores and the proportion that showed a response to therapy, Dr. Menza and his associates reported.
Scores on the HAM-D changed by about 11 points in the nortriptyline group, 7 in the paroxetine CR group, and 3 in the placebo group. The differences between the nortriptyline and paroxetine groups were significant at weeks 2 and 4, with a trend toward significance at week 8. Scores in the nortriptyline group were significantly different from those in the placebo group at all visits.
The proportion of patients who responded to therapy was 53% in the nortriptyline group, 11% in the paroxetine group, and 24% in the placebo group. The nortriptyline response rate was significantly higher, compared with the paroxetine group, but not compared with placebo.
The total number of side effects did not differ significantly between groups, but the nortriptyline group had more anticholinergic effects, including constipation and dry mouth. No worsening in cognition or movement was seen.
Among the patients who showed an improvement in depression scores, 20 continued therapy in a 4-month blinded extension period after the 8 weeks ended. Two measures suggested that quality of life improved in these patients, whose depression improved, compared with baseline, he said.
The study excluded patients with dementia, psychosis, or motor fluctuations. Patients averaged 62 years in age and had had Parkinson’s disease for 6 years on average. The cohort included 25 women and 27 men.
From 40% to 50% of the approximately 1 million U.S. residents with Parkinson’s disease have a major depressive disorder or dysthymia. Depression often precedes motor impairment in the disease.
In two small previous trials of 12 and 37 patients with Parkinson’s disease, an SSRI showed no advantage over placebo in treating depression, he said. A few double-blind trials of other antidepressive agents were poorly designed, with significant methodological problems, he added.
BY SHERRY BOSCHERT San Francisco Bureau
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