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 is the largest placebo-controlled trial of depression treatment in PD and the first in this population to compare a tricyclic antidepressant with a selective serotonin reuptake inhibitor (SSRI), in this case, controlled-release paroxetine (paroxetine CR), Dr. Matthew A. Menza said at a meeting of the New Clinical Drug Evaluation Unit.
Only 7% of patients with PD 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.
The National Institute of Neurological Disorders and Stroke funded the study. Dr. Menza has financial ties to Eli Lilly & Co., which makes a brand of nortriptyline, and to 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. About one-third of patients in each group discontinued treatment. 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, reported Dr. Menza and his associates.
Scores on the HAM-D changed by 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 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% on placebo. 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 PD for 6 years on average. The cohort included 25 women and 27 men.
In two previous trials of 12 and 37 patients with PD, an SSRI showed no advantage over placebo, he said.
Total side effects did not differ between groups, but nortriptyline was tied to more anticholinergic effects. DR. MENZA