Monday, January 5, 2009
Neurology has published a randomized controlled comparison of nortriptyline with paroxetine for depression in patients with Parkinson's disease. It's a rare treat to see a decently designed, controlled trial of depression treatment in a palliative-care-relevant population (when was the last time we've seen a controlled drug trial of depression therapy in advanced cancer patients?).
This was an 8 week, NIH-funded, randomized comparison of nortiptyline (starting dose 25 mg), paroxetine CR (starting dose 12.5 mg), and placebo in 52 patients (median age ~63 years) with Parkinson's disease. Patients were seen at 2, 4, and 8 weeks and doses were titrated per the treating physician's discretion (mean doses at the end of the study were ~50 mg of nortriptyline and 30 mg of paroxetine). They used changes in depression symptoms measured by the Hamilton Depression Rating Scale for their primary outcome. No power analysis was done.
Overall, nortriptyline looked better than paroxetine. At 2 and 4 weeks nortriptyline patients had significantly greater decreases in depression symptoms compared to paroxetine; by 8 weeks this was a non-significant trend. Nortriptyline was superior to placebo at all points; paroxetine was not (trended better; not statistically significant). Again - no power analysis was done and so there's a good risk of 'type II' error here in concluding paroxetine is genuinely 'no better' than placebo. In looking at the percent of patients who had a 50% reduction in their HDRS score, nortriptyline again looked much better than paroxetine (~50% of patients vs. 11% with paroxetine being no better than placebo for this outcome). Symptoms/side effects/drop-outs were similar across all groups, including orthostatic hypotension, although the study was certainly not powered to detect any differences.
The authors note in their discussion that the other controlled trials of SSRIs in Parkinson's disease patients did not support their efficacy either. Despite the small size of the study nortriptyline seemed to be consistently, and by different analyses, better than paroxetine, without any obvious differences in side effects, although one wonders if those would have emerged in a larger trial. The authors speculate that norepinephrine (and not serotonin) may have a particular role in the pathophysiology of depression in Parkinson's disease which is why nortriptyline was more effective. Given that, a trial of norepinephrinergic antidepressants (duloxetine, venlafaxine) seems to be in order. Overall I think the findings are pretty compelling.
M. Menza, R. DeFronzo Dobkin, H. Marin, M. H. Mark, M. Gara, S. Buyske, K. Bienfait, A. Dicke (2008). A controlled trial of antidepressants in patients with Parkinson disease and depression Neurology DOI: 10.1212/01.wnl.0000336340.89821.b3