Medication-Induced Dystonic Reactions


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.


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]

Older individuals may carry less risk for the development of dystonia because of diminished numbers of D2 receptors with aging.[4] 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.



United States

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.


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.

Race-, Sex-, and Age-related Demographics

Variations in incidence are as follows:


Dystonic reactions most often occur shortly after initiation of drug treatment or an increase in drug dose; 50% occur within 48 hours of initiation of treatment, and 90% occur within 5 days. A literature review by Hawthorne and Caley found among published reports of extrapyramidal reactions associated with serotonergic antidepressant therapy—not only dyskinesia but also akathisia, dyskinesia, parkinsonism, and mixed extrapyramidal reactions—that the reactions typically developed within 30 days of either the start of treatment or a dosage increase.[7]

Risk factors for drug-induced dystonic reactions include a family history of dystonia, a recent history of cocaine or alcohol use, or treatment with a potent dopamine D2 receptor antagonist (eg, fluphenazine, haloperidol).[8, 9] Incecik et al report a case in which albendazole induced a dystonic reaction that cleared up with discontinuation of the drug.[6]

Obtain history from others if patient is not able to speak.

Obtain medication history, including new medications and/or dosage increases.


Physical examination findings may include any of the following:

Mental status is unaffected.

Vital signs are usually normal.

Remaining physical examination findings are normal.


Neuroleptics (antipsychotics), antiemetics, and antidepressants are the most common causes of drug-induced dystonic reactions.[10, 11, 12, 13, 14] Acute dystonic reactions have been described with every antipsychotic. Alcohol and cocaine use increase risk.[15, 16] Cases involving other drugs have been reported, including methylphenidate and carbamazepine.[17, 18]

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

Laboratory Studies

The diagnosis is usually apparent from the history and physical examination. A history of medication exposure is usually obtained. Even when a supporting history is not obtained, the clinical picture alone is enough to strongly suggest the diagnosis. A predictable, rapid resolution of symptoms following treatment confirms the diagnosis. Failure to improve, however, should prompt the clinician to consider alternative diagnosis.[20] In most cases, laboratory and imaging tests are not needed.

Emergency Department Care

Emergency interventions other than pharmacologic treatment rarely are required.

Securing the airway is rarely necessary. Laryngeal and pharyngeal dystonic reactions may place the patient at risk of imminent respiratory arrest.

Pharmacologic treatment, typically with anticholinergic agents, resolves the reaction.


Arrange psychiatric follow-up care if patient has a dystonic reaction while taking neuroleptic medication. When continued neuroleptic therapy is necessary, maintain patient on an anticholinergic agent or switch to a neuroleptic less likely to produce an acute dystonic reaction.

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications. Anticholinergic agents and benzodiazepines are most often used.

Benztropine (Cogentin)

Clinical Context:  By blocking striatal cholinergic receptors, benztropine may help in balancing cholinergic and dopaminergic activity.

Diphenhydramine (Benadryl)

Clinical Context:  Although an antihistamine, diphenhydramine also possesses significant anticholinergic properties. The mechanism of action is identical to that of benztropine.

Class Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications. The most commonly used agents are benztropine and diphenhydramine. Both are effective treatments, and data do not support one over the other.

IV is the route of choice, with signs and symptoms often resolving within 10 minutes. The medication can be delivered IM if an IV line cannot be established, but medications will take 30 min to be absorbed. More than 1 dose may be necessary for complete resolution of dystonia.

Diazepam (Valium)

Clinical Context:  Some recommend using diazepam for patients with dystonic reactions refractory to anticholinergic therapy or when such therapy is contraindicated.

Class Summary

Normal balance between dopamine and acetylcholine in the basal ganglia involves modulation from GABA-containing striatonigral neurons. GABA-ergic neurons are inhibitory and antagonize excitatory dopaminergic neurons. GABA agonists (eg, benzodiazepines) may be helpful for acute dystonic reactions when anti-muscarinic agents are not approporiate.

Further Outpatient Care

Consider discontinuing the inciting agent.

Further Inpatient Care

In cases with respiratory compromise, as with laryngeal involvement, patients should be observed for a prolonged period (12-24 h).[21]

Inpatient & Outpatient Medications

Continue medication for 48-72 hours to prevent relapse, as follows:


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.


John Michael Kowalski, DO, Attending Physician, Division of Medical Toxicology, Department of Emergency Medicine, Einstein Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Michael J Burns, MD, Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center

Disclosure: Nothing to disclose.

Chief Editor

David Vearrier, MD, MPH, Associate Professor, Medical Toxicology Clerkship Director, Medical Toxicology Fellowship Director, Department of Emergency Medicine, Drexel University College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Samuel M Keim, MD, MS, Professor and Chair, Department of Emergency Medicine, University of Arizona College of Medicine

Disclosure: Nothing to disclose.


Geofrey Nochimson, MD Consulting Staff, Department of Emergency Medicine, Sentara Careplex Hospital

Geofrey Nochimson, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.


  1. Fahn S. The varied clinical expressions of dystonia. Neurol Clin. 1984 Aug. 2(3):541-54. [View Abstract]
  2. Christodoulou C, Kalaitzi C. Antipsychotic drug-induced acute laryngeal dystonia: two case reports and a mini review. J Psychopharmacol. May 2005. 19:307-11. [View Abstract]
  3. Marsden CD, Jenner P. The pathophysiology of extrapyramidal side-effects of neuroleptic drugs. Psychol Med. 1980 Feb. 10(1):55-72. [View Abstract]
  4. Volkow N, Ruben C, Wang G-J, Fowler J, Moberg P, Ding Y-S, et al. Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. Am J Psychiatry. March 1998. 155:344-9. [View Abstract]
  5. Derinoz O, Caglar AA. Drug-induced movement disorders in children at paediatric emergency department: 'dystonia'. Emerg Med J. 2012 Mar 7. [View Abstract]
  6. Incecik F, Hergüner MO, Ozcan K, Altunbasak S. Albendazole-induced dystonic reaction: a case report. Turk J Pediatr. 2011 Nov-Dec. 53(6):709-10. [View Abstract]
  7. Hawthorne JM, Caley CF. Extrapyramidal Reactions Associated with Serotonergic Antidepressants. Ann Pharmacother. 2015 Oct. 49 (10):1136-52. [View Abstract]
  8. Zakariaei Z, Taslimi S, Tabatabaiefar MA, Arghand Dargahi M. Bilateral dislocation of temporomandibular joint induced by haloperidol following suicide attempt: a case report. Acta Med Iran. 2012. 50(3):213-5. [View Abstract]
  9. Digby G, Jalini S, Taylor S. Medication-induced acute dystonic reaction: the challenge of diagnosing movement disorders in the intensive care unit. BMJ Case Rep. 2015 Sep 21. 2015:[View Abstract]
  10. Elliott ES, Marken PA, Ruehter VL. Clozapine-associated extrapyramidal reaction. Ann Pharmacother. 2000 May. 34(5):615-8. [View Abstract]
  11. Jhee SS, Zarotsky V, Mohaupt SM, et al. Delayed onset of oculogyric crisis and torticollis with intramuscular haloperidol. Ann Pharmacother. 2003 Oct. 37(10):1434-7. [View Abstract]
  12. Roberge RJ. Antiemetic-related dystonic reaction unmasked by removal of a scopolamine transdermal patch. J Emerg Med. 2006 Apr. 30(3):299-302. [View Abstract]
  13. Schumock GT, Martinez E. Acute oculogyric crisis after administration of prochlorperazine. South Med J. 1991 Mar. 84(3):407-8. [View Abstract]
  14. Demetropoulos S, Schauben JL. Acute dystonic reactions from "street Valium". J Emerg Med. 1987 Jul-Aug. 5(4):293-7. [View Abstract]
  15. Fines RE, Brady WJ, DeBehnke DJ. Cocaine-associated dystonic reaction. Am J Emerg Med. 1997 Sep. 15(5):513-5. [View Abstract]
  16. Kumor K. Cocaine withdrawal dystonia. Neurology. 1990 May. 40(5):863-4. [View Abstract]
  17. Tekin U, Soyata AZ, Oflaz S. Acute focal dystonic reaction after acute methylphenidate treatment in an adolescent patient. J Clin Psychopharmacol. 2015 Apr. 35 (2):209-11. [View Abstract]
  18. Bansal S, Gill M, Bhasin C. Carbamazepine-induced dystonia in an adolescent. Indian J Pharmacol. 2016 May-Jun. 48 (3):329-30. [View Abstract]
  19. Barach E, Dubin LM, Tomlanovich MC, Kottamasu S. Dystonia presenting as upper airway obstruction. J Emerg Med. 1989 May-Jun. 7(3):237-40. [View Abstract]
  20. Piecuch S, Thomas U, Shah BR. Acute dystonic reactions that fail to respond to diphenhydramine: think of PCP. J Emerg Med. 1999 May-Jun. 17(3):527. [View Abstract]
  21. Juurlink D. Antipsychotics. In: Hoffman RS, Howland MA, Lewin NA, Nelson LS, Goldfrank LR, eds. Goldfrank's Toxicologic Emergencies. 10th ed. New York: McGraw-Hill Education; 2015.