An Evidence-Based Update on Anticholinergic Use for Drug-Induced Movement Disorders

Abstract

Drug-induced movement disorders (DIMDs) are associated with use of dopamine receptor blocking agents (DRBAs), including antipsychotics. The most common forms are drug-induced parkinsonism (DIP), dystonia, akathisia, and tardive dyskinesia (TD). Although rare, neuroleptic malignant syndrome (NMS) is a potentially life-threatening consequence of DRBA exposure. Recommendations for anticholinergic use in patients with DIMDs were developed on the basis of a roundtable discussion with healthcare professionals with extensive expertise in DIMD management, along with a comprehensive literature review. The roundtable agreed that "extrapyramidal symptoms" is a non-specific term that encompasses a range of abnormal movements. As such, it contributes to a misconception that all DIMDs can be treated in the same way, potentially leading to the misuse and overprescribing of anticholinergics. DIMDs are neurobiologically and clinically distinct, with different treatment paradigms and varying levels of evidence for anticholinergic use. Whereas evidence indicates anticholinergics can be effective for DIP and dystonia, they are not recommended for TD, akathisia, or NMS; nor are they supported for preventing DIMDs except in individuals at high risk for acute dystonia. Anticholinergics may induce serious peripheral adverse effects (e.g., urinary retention) and central effects (e.g., impaired cognition), all of which can be highly concerning especially in older adults. Appropriate use of anticholinergics therefore requires careful consideration of the evidence for efficacy (e.g., supportive for DIP but not TD) and the risks for serious adverse events. If used, anticholinergic medications should be prescribed at the lowest effective dose and for limited periods of time. When discontinued, they should be tapered gradually.

Fig. 1

Selected common medications with strong anticholinergic properties, based on American Geriatric Society Beers^® criteria [110]. Medications that have a level 3 rating on the Anticholinergic Drug Scale (*) or a 3-point score on the Anticholinergic Risk Scale (†) are also noted [88, 89]

Fig. 2

Hypokinetic movement disorders, such as drug-induced parkinsonism, are characterized by a decrease in dopamine signaling, which amplifies cholinergic activity. Anticholinergics can be effective in treating these disorders by restoring dopamine–acetylcholine balance. Hyperkinetic disorders, such as tardive dyskinesia, are characterized by an increase in dopamine signaling, which dampens cholinergic activity. Thus, anticholinergic medications are not effective in treating these disorders and may even worsen hyperkinetic symptoms

Fig 3

Dopamine (DA) is released from the substantia nigra to the striatum. Within the striatum, antipsychotics prevent DA from binding to D₂ receptors on indirect medium spiny neurons (MSNs) and cholinergic interneurons (CINs). Anticholinergics prevent the binding of acetylcholine (ACh) to muscarinic M₁ and M₄ receptors on direct MSNs and to M1 receptors on indirect MSNs. Adapted with permission from Lester 2010 [15] and Paz 2021 [17]