NEW YORK (Reuters Health) – Nortriptyline is more effective than paroxetine CR in reducing symptoms of depression in patients with Parkinson’s disease, according to results of a small randomized trial.

Writing in the March 10 issue of Neurology, Dr. Matthew Menza and co-investigators note that depression is common in Parkinson’s disease (PD), and “in fact, depression appears to be more predictive of distress than motor disability.”

However, despite the fact that many of these patients are treated with antidepressants, particularly selective serotonin reuptake inhibitors, there have been few head-to-head trials of different antidepressants.

Dr. Menza’s group conducted an 8-week, double-blind trial with 52 patients (mean age 62.8 years, mean PD duration 6.6 years) who had a diagnosis of major depression or dysthymia. Eighteen patients were randomized to paroxetine CR (12.5-37.5 mg), 17 to nortriptyline (25-75 mg), and 17 to placebo. The trial was completed by 11, 12, and 11 in each arm, respectively. Analysis was by intent-to-treat with last observation carried forward.

At 8 weeks, mean changes in the Hamilton Depression Rating Scale significantly favored nortriptyline, but not paroxetine CR, over placebo (p = 0.002 and 0.165, respectively). There was a trend for superiority of nortriptyline over paroxetine CR (p = 0.079).

Response rates, defined as a 50% change in the HAM-D score, was 53% for nortriptyline, 11% for paroxetine CR, and 24% for placebo (p = 0.024). Nortriptyline remained significantly more effective than paroxetine CR after adjustment for multiple confounders (p = 0.034). Patients on nortriptyline also had significant improvements in social functioning, sleep, and anxiety.

The number needed to treat with nortriptyline to obtain a 50% response was 3.5.

“With depression reported to occur in 40% or more of patients with PD, this is an important clinical study,” Drs. Michael S. Okun and Hubert H. Fernandez at the McKnight Brain Institute in Gainesville, Florida, write in a related editorial.

They note that time to response tends to be longer for paroxetine CR, so the outcomes may have been different if the study had been of longer duration. Also, they say, the patients were fairly young, with relatively short disease duration and mild disease severity.

“The safety issues of older subjects with PD with longer disease durations, greater cognitive difficulties, and those on higher doses of levodopa will need to be carefully factored into future trials, since more advanced and cognitively challenged patients with PD may be more susceptible to tricyclic antidepressant-induced mental status problems, cardiac issues, and orthostatic hypotension,” the editorialists point out.

Reference:
Neurology 2009;72:886-892.