Medication-Induced Dystonic Reactions

Updated: Jun 27, 2022
  • Author: J Michael Kowalski, DO; Chief Editor: David Vearrier, MD, MPH  more...
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Overview

Practice Essentials

Dystonic reactions are reversible extrapyramidal effects that can occur after administration of a neuroleptic drug. Symptoms may begin immediately or can be delayed hours to days. Although a wide variety of medications can elicit symptoms, the typical antipsychotics are most often responsible.

Dystonic reactions (ie, dyskinesias) are characterized by intermittent spasmodic or sustained involuntary contractions of muscles in the face, neck, trunk, pelvis, extremities, and even the larynx. [1, 2] Although dystonic reactions are rarely life threatening, the adverse effects often cause distress for patients and families.

Medical treatment is usually effective to abate acute symptoms. With treatment, motor disturbances resolve within minutes, but they can reoccur over subsequent days.

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Pathophysiology

Although dystonic reactions are occasionally dose related, these reactions are more often idiosyncratic and unpredictable. They reportedly arise from a drug-induced alteration of dopaminergic-cholinergic balance in the nigrostriatum (ie, basal ganglia). Most drugs produce dystonic reactions by nigrostriatal dopamine D2 receptor blockade, which leads to an excess of striatal cholinergic output. High-potency D2 receptor antagonists are most likely to produce an acute dystonic reaction. [3, 4]

Older individuals may carry less risk for the development of dystonia because of diminished numbers of D2 receptors with aging. [5] Agents that balance dopamine blockade with muscarinic M1 receptor blockade, like atypical antipsychotics, are less likely to elicit dystonic reactions. Paradoxically, dystonic reactions may be increased through nigrostriatal dopaminergic activity that occurs as a compensatory response to dopamine receptor blockade.

Cases of acute dystonic reactions to drugs (eg, metoclopramide) that are metabolized by the cytochrome P450 2D6 (CYP2D6) enzyme have been reported in patients carrying CYP2D6 alleles associated with poor CYP2D6 metabolism. Such patients may have a family history of medication-related acute dystonia. [6]

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Etiology

Neuroleptics (antipsychotics), antiemetics, and antidepressants are the most common causes of drug-induced dystonic reactions. [7, 8, 9, 10, 11]  Acute dystonic reactions have been described with every antipsychotic. Alcohol and cocaine use increase risk. [12, 13]  Cases involving other drugs have been reported, including methylphenidate, carbamazepine, and duloxetine. [14, 15, 16]

Predisposing factors include a family history of dystonia and viral infection.

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Epidemiology

The incidence of acute dystonic reactions varies according to individual susceptibility, drug identity, dose, and duration of therapy. The actual incidence of dystonic reactions is unknown, owing to misdiagnosis and underreporting.  Variations in incidence are as follows:

  • There is no identified increased risk of dystonic reaction attributable to race.
  • The incidence of dystonic reactions is greater in males than in females.
  • These reactions are more common in children, teens, and young adults (ie, 5-45 years. [17, 18] ; the risk of reaction decreases as age increases.
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Prognosis

In rare instances, as with laryngeal involvement, airway management may be necessary. Dystonic reactions are typically not life threatening and result in no long-term effects. Complete resolution of symptoms is expected following treatment. However, symptoms may reoccur up to 72 hours later. No long-term sequelae are expected from acute dystonic reactions once the inciting agent is discontinued.

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