Parkinson’s Treatment Tips on the Worst Drugs for Parkinson’s Disease

A Critical Reappraisal of the Worst Drugs in Parkinson’s Disease

What are the worst drugs for Parkinson’s disease patients?  Couldn’t a simple list be assembled and disseminated to the Parkinson community?  Recently Ed Steinmetz, an experienced neurologist in Ft. Meyers, FL pointed out to me, a list approach published in the Public Citizen Newsletter (  The approach was to list every drug associated with a single confirmed or unconfirmed symptom of Parkinson’s disease or parkinsonism.  Parkinson’s disease is defined as a neurodegenerative syndrome (common symptoms include tremor, stiffness, slowness, posture and gait issues), whereas parkinsonism encompasses a wider net of drug induced and other potential causes. In parkinsonism symptoms are similar to Parkinson’s disease, but patients do not have Parkinson’s disease.  Patients and family members confronted with a simple “drug list” approach may falsely conclude that most medicines are bad for Parkinson’s disease, and that any medicine may cause parkinsonism.  This concept is in general, incorrect.  Although the approach is well-meaning, it is in need of a major revision, as Parkinson’s disease and parkinsonism are too complex to summarize by simple lists. In this month’s column I will try to summarize the key information that patients and family members need to know about the “worst pills,” for Parkinson’s disease and parkinsonism.

It is well known that drugs that block dopamine worsen Parkinson’s disease and also worsen parkinsonism, whereas dopamine replacement therapy (Carbidopa/Levodopa, Sinemet) may improve symptoms.  One of the big issues facing many Parkinson’s disease patients is psychosis (hallucinations, illusions, and behavioral changes such as paranoia).  How does one concomitantly administer dopamine replacement therapy, which may in some cases induce psychosis, and at the same time administer dopamine blocker drugs aimed at alleviating psychosis?  Will the drugs cancel each other out?  There are two dopamine blockers that will not cancel out dopamine replacement, and therefore not appreciably worsen Parkinson’s disease.  One is Quetiapine (Seroquel), and the other is Clozapine (Clozaril).  Clozapine is the more powerful of the two drugs, but it requires weekly blood monitoring.  Other classical dopamine blocking drugs, also referred to as neuroleptics (e.g. Haldol), worsen Parkinson’s disease and parkinsonism.

Patients may not be aware that some common drugs used for conditions such as headache or gastrointestinal dysmotility may also block dopamine, and concomitantly worsen Parkinson’s disease, or alternatively result in parkinsonism.  These drugs include Prochlorperazine (Compazine), Promethazine (Phenergan), and Metoclopramide (Reglan).  They should be avoided.  Also, drugs that deplete dopamine such as reserpine and tetrabenazine may worsen Parkinson’s disease and parkinsonism and should be avoided in most cases.  Substitute drugs that do not result in worsening of parkinsonism can be utilized, and these include Ondansetron (Zofran) for nausea, and erythromycin for gastrointestinal motility.

Antidepressants, anxiolytics, mood stabilizers, thyroid replacement drugs, and antihypertensives are in general safe, and do not worsen Parkinson’s disease and parkinsonism.  They appear commonly on lists such as that provided by the Public Citizen, but these lists are misleading.  There may be rare reactions that lead to worsening of Parkinson’s disease or parkinsonism with these drugs, but these are very rare occurrences.   The bigger issue is drug-drug interactions.  The most commonly encountered in Parkinson’s disease is mixing a MAO-B Inhibitor (Selegline, Rasagiline, Azilect, Zelapar, Selegiline Hydrochloride Dissolvable) with a pain medicine such as Meperidine (Demerol).  Also, MAO-A Inhibitors (e.g. Pirlindole) should not be taken with antidepressants.  And finally it should be kept in mind that in rare instances mixing an antidepressant with another class of drugs can in select cases result in a serotonin syndrome.  Finally, remember, there are very common “other” side effects of antidepressants, anxiolytic drugs, mood stabilizers, thyroid replacement drugs, and antihypertensives.

In summary, the list approach to the worst pills in Parkinson’s disease and parkinsonism needs a critical reappraisal.  A more refined approach would take into consideration the complexities of Parkinson’s disease and parkinsonism, and would appreciate that with physician guidance, and with few exceptions, most drugs can be safely and effectively administered in Parkinson’s disease and parkinsonism.

*Portions of this post have previously appeared on Dr. Okun NPF What’s Hot in Parkinson’s Treatment blog.

A Florida Parkinson’s Treatment Blog by Michael S. Okun, M.D.

UF Center for Movement Disorders & Neurorestoration, Gainesville FL



About the Author


Michael Okun

Professor of Neurology, expert on Parkinson's disease and other basal ganglia disorders, deep brain stimulation, author of over 300 research papers and the bestselling book…

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