Out of the million or so Americans who have Parkinson's disease, about a
half also suffer from depression. Yet depression in Parkinson's disease is
often underrecognized, underappreciated, and undertreated. Commonly the
attitude is "Of course you are depressed; you have a serious
Moreover, there is not much scientific evidence demonstrating that
parkinsonian depression can be successfully treated pharmacologically, and if
so, by which antidepressant.
So Matthew Menza, M.D., a professor and interim chair of psychiatry at the
Robert Wood Johnson Medical School, and his colleagues undertook a trial to
answer this question. Although the trial included only 52 subjects, it appears
to be the largest placebo-controlled trial to date exploring this
Subjects were randomized to receive for eight weeks an SSRI antidepressant
(paroxetine), a dual reuptake inhibitor (nortriptyline), or a placebo. They
were evaluated for depression at the start of the trial, during the trial, and
at the end of the trial with the Hamilton Rating Scale for Depression. Menza
and his colleagues compared the outcomes for the three groups. The response
rate at the end of the study, based on a 50 percent change in the Hamilton
depression score, was 53 percent for subjects on nortriptyline, 24 percent for
subjects on a placebo, and 11 percent for subjects on paroxetine.
This finding, Menza told Psychiatric News, demonstrates, first of
all, that Parkinson's patients do respond to antidepressants and, second, that
the dual reuptake inhibitor nortriptyline is superior to the SSRI paroxetine
for treating parkinsonian depression. "This is not to say that the SSRIs
won't work in some patients," he said, "just that percentage-wise,
you may be better off started with a dual-action drug."
The study also revealed that nortriptyline was superior to a placebo on
secondary outcomes such as anxiety, sleep, and social functioning, whereas
paroxetine was not. This finding is important because such symptoms are common
in Parkinson's patients and cause considerable distress, Menza
Furthermore, nortriptyline, like paroxetine, was well tolerated by subjects
and had no adverse effects on subjects' hearts, even though it has been
associated with cardiac arrhythmias.
Thus, this study appears to suggest that nortriptyline is superior to
paroxetine in treating depression, anxiety, and sleep problems in Parkinson's
patients and to be quite safe for such patients, Menza and his team concluded
in their study report, which was published in the March 10
The challenge now, they pointed out in their report, is to find out whether
the newer dual reuptake inhibitors venlafaxine and duloxetine are as effective
as nortriptyline, or perhaps even more so, for such indications, and how their
safety profiles compare with that of nortriptyline in Parkinson's patients.
Neither venlafaxine nor duloxetine has been linked with cardiac arrhythmias.
Two different groups of researchers—one in Rochester, N.Y., and the
other in Italy—are undertaking trials to answer these questions, Menza
told Psychiatric News.
Also to be answered is why nortriptyline seems to be superior to paroxetine
in countering parkinsonian depression, Menza and his colleagues stated in
their report. A recent study showed that Parkinson's subjects with depression
had a deficiency in neurons that use norepinephrine in the limbic area of
their brains. So one possible explanation for why nortriptyline counters
parkinsonian depression better than paroxetine, they speculated, is because
nortriptyline, being a dual reuptake inhibitor, replenishes not only
serotonin, but norepinephrine in the limbic area of the brain, whereas
paroxetine, being an SSRI, only replenishes serotonin.
This trial was funded by the National Institute of Neurological Disorders
and Stroke. GlaxoSmithKline provided the paroxetine and placebo.
An abstract of "A Controlled Trial of Antidepressants in
Patients With Parkinson's Disease and Depression" is posted at<www.neurology.org/cgi/content/abstract/72/10/886>.▪