Medication-Induced Dystonic Reactions

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Background

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.

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] Increased age may carry less risk for the development of dystonia because of diminished numbers of D2 receptors.[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.

Epidemiology

Frequency

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.

Mortality/Morbidity

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

There is no identified increased risk of dystonic reaction attributable to race.

Sex

Incidence of dystonic reactions is greater in males than in females.

Age

These reactions are more common in children, teens, and young adults (ie, 5-45 years).[5, 6]

The risk of reaction decreases as age increases.

History

Dystonic reactions most often occur shortly after initiation of drug treatment; 50% occur within 48 hours and 90% occur within 5 days of initiation of treatment. Risk factors include family history of dystonia, recent history of cocaine or alcohol use, or treatment with a potent dopamine D2 receptor antagonist (eg, fluphenazine, haloperidol).[7] Incecik et al report a case in which albendazole induced a dystonic reaction that cleared up with discontinuation of the drug.[6]

Onset of symptoms is early, occurring within minutes to days of initiating a causative agent or increasing the dose of a causative agent.

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

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

Physical

Physical examination findings may include any of the following:

Mental status is unaffected.

Vital signs are usually normal.

Remaining physical examination findings are normal.

Causes

Drug-related adverse effects[8, 9, 10, 11, 12]

Neuroleptics (antipsychotics), antiemetics, and antidepressants are the most common causes of drug-induced dystonic reactions.

Acute dystonic reactions have been described with every antipsychotic.

Alcohol and cocaine use increase risk.[13, 14]

Predisposing factors

Predisposing factors include (1) a family history of dystonia and (2) 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.[16] 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 resolves the reaction.

Consultations

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.

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 Inpatient Care

In cases with respiratory compromise, as with laryngeal involvement, patients should be observed for a prolonged period (12-24 h).[17]

Further Outpatient Care

Consider discontinuing the inciting agent.

Inpatient & Outpatient Medications

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

Prognosis

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.

Author

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

Disclosure: Nothing to disclose.

Specialty Editors

Samuel M Keim, MD, Associate Professor, Department of Emergency Medicine, University of Arizona College of Medicine

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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

Disclosure: Nothing to disclose.

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

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.

References

  1. Fahn S. The varied clinical expressions of dystonia. Neurol Clin. Aug 1984;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. Feb 1980;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. Mar 7 2012;[View Abstract]
  6. Incecik F, Hergüner MO, Ozcan K, Altunbasak S. Albendazole-induced dystonic reaction: a case report. Turk J Pediatr. Nov-Dec 2011;53(6):709-10. [View Abstract]
  7. 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]
  8. Elliott ES, Marken PA, Ruehter VL. Clozapine-associated extrapyramidal reaction. Ann Pharmacother. May 2000;34(5):615-8. [View Abstract]
  9. Jhee SS, Zarotsky V, Mohaupt SM, et al. Delayed onset of oculogyric crisis and torticollis with intramuscular haloperidol. Ann Pharmacother. Oct 2003;37(10):1434-7. [View Abstract]
  10. Roberge RJ. Antiemetic-related dystonic reaction unmasked by removal of a scopolamine transdermal patch. J Emerg Med. Apr 2006;30(3):299-302. [View Abstract]
  11. Schumock GT, Martinez E. Acute oculogyric crisis after administration of prochlorperazine. South Med J. Mar 1991;84(3):407-8. [View Abstract]
  12. Demetropoulos S, Schauben JL. Acute dystonic reactions from "street Valium". J Emerg Med. Jul-Aug 1987;5(4):293-7. [View Abstract]
  13. Fines RE, Brady WJ, DeBehnke DJ. Cocaine-associated dystonic reaction. Am J Emerg Med. Sep 1997;15(5):513-5. [View Abstract]
  14. Kumor K. Cocaine withdrawal dystonia. Neurology. May 1990;40(5):863-4. [View Abstract]
  15. Barach E, Dubin LM, Tomlanovich MC, Kottamasu S. Dystonia presenting as upper airway obstruction. J Emerg Med. May-Jun 1989;7(3):237-40. [View Abstract]
  16. Piecuch S, Thomas U, Shah BR. Acute dystonic reactions that fail to respond to diphenhydramine: think of PCP. J Emerg Med. May-Jun 1999;17(3):527. [View Abstract]
  17. Juurlink DN. Antipsychotics. In: Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE. Goldfrank's Toxicologic Emergencies. 9. New York: McGraw-Hill; 2011:1007-8.