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Ask the Mental Health Expert Archives 2001-2004

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Paxil Patient

Q. I have a patient with chronic depression who has been on Paxil for 5 years with good results. The patient was recently diagnosed with Parkinson's disease. I was told that other SSRIs are better with Parkinson's disease. Can you give me any references on this?

A. I think it's premature to claim that any one of the serotonergic antidepressants (so-called SSRIs) is the drug of choice for depressed Parkinson's patients. The truth is, the research on Parkinson's Disease (PD) and antidepressant treatment is pretty poor; i.e., we have mainly open, short-term studies involving small numbers of patients, and few if any head-to-head comparison studies of different SSRIs. (see Zesiewicz etal, Am J Geriatric Psychiatry Spring 1999 for a review).

What we do know for sure is that any of the SSRIs can sometimes provoke extrapyramidal symptoms (EPS) and/or worsen PD in some especially sensitive patients (see review by Leo in J Clin Psychiatry 1996; 57:449-54). Most neurologists, nevertheless, find that in the lower dosage range, PD patients often do well on an SSRI. A recent review by IH Richard (Current treatment options in neurology. 2000 May;2:263-274) concluded that "a very reasonable first-choice antidepressant is either sertraline or paroxetine...if the SSRIs are...not tolerated, nortriptyline is a good next choice."

Bupropion has also been used successfully in a few cases. Ceravolo et al (Neurology 2000 55:1216-8) found that 6 months of therapy with paroxetine 20 mg/day in a group of depressed PD patients generally did not worsen parkinsonian motor symptoms, except for one case of fully reversible worsening of tremor. Moreover, depression improved in this cohort. On the other hand, there are reports of worsening PD with several of the SSRIs; e.g., in one study of paroxetine in PD (Tesai et al, Mov Disor 2000 15:986-9), 13 of 65 outpatients stopped the drug because of adverse reactions, including two cases of increased off time and tremor. (Nevertheless, the authors concluded that "paroxetine is a safe and effective drug to treat depression in PD.").

Fluoxetine has also been reported to worsen motor disability in PD patients (Steur, Neurology 1993; 43:211-3). Experience is still very limited with nefazodone, venlafaxine, and mirtazepine in depressed PD patients, though there is at least one report of nefazodone-related akathisia. In my experience, EPS due to SSRIs are almost always dose-related, so, "start low, go slow", and monitor carefully for EPS.

Finally, you may be interested in a study of tolcapone, a COMT inhibitor used in Parkinson's disease. In one study, it was effective in major depression at 400 mg bid (Fava et al, J Clin Psychopharmacol August 1999). But-I would certainly not jump immediately to a different agent in a patient who had done well on paroxetine.

July 2001

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