Drugs reported to cause/aggravate parkinsonism

Prescribed drugs and neurological complications K.A.Grosset, D.G.Grosset J Neurol Neurosurg Psychiatry 2004;75(Suppl III):iii2–iii8.
Drug induced movement disorders are common. In epidemiological studies between a third and a half of parkinsonism is caused by medication.

Parkinson’s disease: an overview The Pharmaceutical Journal 26 FEB 2000 By David Burn Last updated 12 Feb.2021
Perhaps the most important differential diagnosis to consider when a patient presents with parkinsonism is whether their symptoms and signs may be drug-induced. This is because drug-induced parkinsonism (DIP) is potentially reversible upon cessation of the offending agent.

CHAPTER 2 Approach to History Taking and Examination of the Movement Disorder Patient David J. Burn (in Oxford Textbook of Movement Disorders 2013)

Drug history: Always consider drugs, both past and present, as a potential cause for the movement disorder… A full list of medications previously taken by the patient should be obtained from the primary care practitioner if necessary. A high index of suspicion is required…If relevant, enquire about a history of drug abuse/‘recreational’ drug use.

Extrapyramidal effects of neuroleptics. A.D.Korczyn and G.J.Goldberg J Neurol Neurosurg Psychiatry. 1976 Sep; 39(9): 866–869.
The recognition of persistent orofacial dyskinesia as a syndrome connected with prolonged treatment with these drugs raises the possibility of irreversible toxic effects on the brain, particularly the extrapyramidal system (Korczyn, 1972). There have been suggestions that the Parkinsonism effects, frequently observed with these drugs, might become irreversible after prolonged treatment (McGeer et al., 1961) or, conversely, disappear (Cahan and Parish, 1960; Mandell and Oliver, 1961).

https://www.researchgate.net/publication/14117968_Drug-Induced_Movement_Disorders (& download)
Drug-Induced Movement Disorders F.J.Jimenez-Jimenez, P.J.Garcia-Ruiz and J.A.Molina Drug Safety 1997 Mar: 16 (3): 180-204
Parkinsonism, tremor, chorea-ballismus, dystonia, tardive dyskinesia, myoclonus, tics and akathisia can be induced by many drugs…It is possible for a single drug to induce 2 or more types of movement disorders in the same patient. …In Spain, several studies have reported that drug-induced parkinsonism accounts for 24 to 35% of parkinsonian syndromes. Movement disorders are not always reversible after drug withdrawal.

The persistence of parkinsonian symptoms might reflect the fact that the patient have subclinical idiopathic parkinsonism, a condition that was unmasked by the offending drug. On the other hand, this could also represent the onset of Parkinson’s disease in the patients while they were taking the drug, and a direct toxic effect on the dopaminergic system cannot be ruled out.

Table I. Drugs associated with induction or aggravation of parkinsonism
Calcium antagonists: flunarizine, cinnarizine, diltiazem, verapamil, amlodipine, manidipine
Orthopramides and substituted benzamides: metoclopramide, sulpiride, clebopride, cisapride, domperidone, veralipride
Dopamine storage and transport inhibitors: reserpine, tetrabenazine
Antiemetic/antivertiginous agents: thiethylperazine, prochlorperazine
Antidepressants: fluoxetine, paroxetine, trazodone, phenelzine, amfebutomone (bupropion)
Anticonvulsants: valproic acid (sodium valproate), phenytoin
Cholinergic agents bethanechol, pyridostigmine
Other agents: amiodarone, procaine, pethidine (meperidine), amphotericin, cefaloridine, naproxen, ethanol, oral contraceptives, indeloxazine, captopril, cytarabine

Chapter 11 Movement Disorders Induced by Selective Serotonin Reuptake Inhibitors and other Antidepressants K.J. Barucha & K.D. Sethi (in Drug-Induced Movement Disorders ed. K.D. Sethi.Marcel Dekker 2004)

Antidepressant therapy in neurological disorders: Parkinson’s disease There are two separate issues to be addressed here. The first is whether parkinsonism appears de novo in patients with depression treated with antidepressants. The second is whether antidepressants significantly worsen the motor symptoms in patients with established PD…It has also been noted that SSRIs may in isolated instances worsen the motor symptoms in PD and can also induce parkinsonism in patients who have not had symptoms previously

I had drug induced Parkinsonism when I was taking Amitriptyline, as well as sensitivity to the hydrochloride in it. I had to figure out by myself that this was the problem. I stopped taking it, and within two days the Parkinsonism was totally gone. Then after a couple of months symptoms slowly started returning, although this time I had tremors which I didn’t have before. I was diagnosed with possible Parkinson’s in July. I found a medical report online which stated that after having drug induced Parkinsonism, in 16% of cases it can lead to permanent idiopathic Parkinson/s, either caused by damage to the brain from the medication, or it rapidly bringing on something was going to happen in the future.

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Hi @Appletree, :wave:t5:

Thanks for sharing these links.

I thought it might be worth pointing out that the first link is very old (1997). I think this paper has some more up to date information and should be readily accessible - https://tremorjournal.org/article/10.5334/tohm.554/

I also thought I’d point you in the direction of some of the pages that we have on drug-induced Parkinsonism:

Best wishes,

I just haD blepharospasm (after Domperidone) when my gp gave me sertraline then amitriptyline. This might be the original article reporting 16% but much higher figures can be found. It is wise to do your own research. Drug-induced movement disorders are common and can be caused by a wide range of drugs across various classes.

Drug-induced or aggravated parkinsonism: clinical signs and the changing pattern of implicated drugs J F Martí Massó , J J Poza Neurologia. 1996 Jan;11(1):10-5.

Retrospective study of DIP patients seen between January 1981 and December 1993. Of the 306 cases of parkinsonism seen, 56.8% were induced or aggravated by drugs. Parkinsonism disappeared completely within a mean of 5 months in 142 (82%) patients. Twenty-eight (16%) developed Parkinson’s disease. Six of them were symptom-free for 12 to 72 months (mean 40 months), whereas 22 never experienced relief from parkinsonism.

Drug-Induced Parkinsonism Hae-Won Shin and Sun Ju Chung J Clin Neurol. 2012 Mar; 8(1): 15–21.

The exact prevalence and incidence of DIP are unclear because it is frequently unrecognized or misdiagnosed as PD… DIP usually resolves within weeks to months after stopping the offending drug; however, parkinsonism may persist or progress in 10-50% of patients.

CYP 2D6 PM phenotype hypothesis of antidepressant extrapyramidal side-effects. Vandel P, Bonin B, Vandel S, Sechter D, Bizouard P. Med Hypotheses. 1996 Dec;47(6):439-42.

Extrapyramidal symptoms occur as side-effects of neuroleptics. For many years, case reports of such side-effects, linked to antidepressant treatments, have been published, but this phenomenon is not well known. Tricyclic and serotonergic antidepressants are both involved. The authors present an hypothesis which provides one possible neurobiochemical explanation for the aetiology of these side-effects. The proposed explanation is related to the inhibition of the CYP 2D6 isoenzyme by antidepressants (or neuroleptics) that may be involved in the genesis of the observed extrapyramidal side-effects.

SSRI-Induced extrapyramidal side-effects and akathisia: implications for treatment Roger M. Lane Volume 12, Issue 2 1998

The selective serotonin reuptake inhibitors (SSRIs) may occasionally induce extrapyramidal side-effects (EPS) and/or akathisia. This maybe a consequence of serotonergically-mediated inhibition of the dopaminergic system. Manifestations of these effects in patients may depend on predisposing factors such as the presence of psychomotor disturbance, a previous history of drug-induced akathisia and/or EPS, concurrent antidopaminergic and/or serotonergic therapy, recent monoamine oxidase inhibitor discontinuation, comorbid Parkinson’s disease and possibly deficient cytochrome P450 (CYP) isoenzyme status.

Drug-Induced Diseases: Prevention, Detection, and Management J.E.Tisdale, D.A. Miller 2010 American Society of Health System Pharmacists
P.211 Chapter 12 Movement disorders Jack Chen & David Swope

DIMDs [Drug-induced movement disorders] are a significant source of distress and discomfort resulting in medication nonadherence or refusal, subsequent relapse and hospitalization, and increased use of healthcare resources. DIMDs are underrecognized iatrogenic conditions. In one study, resident physicians failed to detect or recognize more than 50% of cases of Tdk [tardive DYSKINESIA] and drug-induced parkinsonism. In one study of elderly patients, 51% of newly referred cases of parkinsonism were believed to be caused by drugs.