eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Medication-Induced Dystonic Reactions

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

Updated: Sep 30, 2008

Introduction

Background

Dystonic reactions are adverse extrapyramidal effects that often occur shortly after the initiation of neuroleptic drug therapy. These reactions may occur with a wide variety of medications. Dystonic reactions (ie, dyskinesias) are characterized by intermittent spasmodic or sustained involuntary contractions of muscles in the face, neck, trunk, pelvis, and extremities. Dystonic reactions are rarely life threatening, yet are very uncomfortable and often produce significant anxiety and distress for patients. Fortunately, treatment is extremely effective, and motor disturbances resolve within minutes.

Pathophysiology

Although dystonic reactions are occasionally dose related, these reactions are more often idiosyncratic and not predictable. They appear to result from 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. Agents that balance dopamine blockade with muscarinic M1 receptor blockade are less likely to produce a dystonic reaction. Paradoxically, an alternative cause of dystonic reactions may be increased nigrostriatal dopaminergic activity that occurs as a compensatory response to dopamine receptor blockade.

Frequency

United States

Incidence of acute dystonic reactions varies according to individual susceptibility, drug identity, dose, and duration of therapy. For patients on neuroleptics, the overall incidence of dystonic reactions is approximately 2%.

Mortality/Morbidity

• In rare instances, airway management may be needed.
• Dystonic reactions typically are not life threatening and result in no long-term effects.

Sex

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

Age

• These reactions are most common in children, teens, and young adults (ie, 5-45 years).
• The risk of reaction decreases as age increases.

Clinical

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).

• Onset of symptoms is sudden, usually within minutes to days of initiating or increasing dose of 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:
  • Oculogyric crisis, deviation of eyes in all directions
  • Buccolingual crisis
  • Protrusion of tongue
  • Trismus
  • Forced jaw opening
  • Difficulty in speaking
  • Facial grimacing
  • Torticollis, usually associated with oculogyric and buccolingual crisis
  • Opisthotonic crisis
  • Lordosis or scoliosis
  • Tortipelvic crisis - Typically involves hip, pelvis, and abdominal wall muscles, causes difficulty with ambulation
• Mental status is unaffected.
• Vital signs are usually normal.
• Remaining physical examination findings are normal.

Causes

• Drug-related adverse effects
  • 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.
• Predisposing factors
  • Family history of dystonia
  • Viral infections

Differential Diagnoses

Other Problems to Be Considered

Metabolic or respiratory alkalosis
Toxicity, strychnine
Oropharyngeal infections

Treatment

Emergency Department Care

• Emergency interventions other than pharmacologic treatment rarely are required.
• Securing the airway is necessary only rarely, when laryngeal and pharyngeal dystonic reactions place the patient at risk of imminent respiratory arrest.
• Pharmacologic treatment resolves the reaction.

Medication

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Anticholinergic agents

Intravenous anticholinergic agents are the treatment of choice. 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.

Benztropine (Cogentin)

By blocking striatal cholinergic receptors, may help in balancing cholinergic and dopaminergic activity.

Dosing

Adult

1-2 mg PO/IV/IM qd or bid; IV has most rapid onset

Pediatric

<3 years: Not established
>3 years: 0.02-0.05 mg/kg PO/IV/IM; not to exceed 2 mg/d

Interactions

Decreases effects of levodopa; increases effects of narcotic analgesics, phenothiazines, quinidine, tricyclic antidepressants, and anticholinergics

Contraindications

Documented hypersensitivity; angle-closure glaucoma; stenosing peptic ulcers; prostatic hypertrophy or bladder neck obstructions; myasthenia gravis; pyloric or duodenal obstruction; achalasia (megaesophagus); megacolon

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May exacerbate hypertension, tachycardia, cardiac arrhythmias, liver or kidney disorders, hypotension, prostatic hypertrophy, urinary retention, and obstructive disease of GI/GU tracts; may cause toxic psychosis in psychiatric patients with extrapyramidal reactions resulting from phenothiazine

Diphenhydramine (Benadryl)

Although an antihistamine, also possesses significant anticholinergic properties. Mechanism of action is identical to that of benztropine.

Dosing

Adult

50-100 mg IV/IM repeat prn

Pediatric

1-2 mg/kg IV/IM repeat prn

Interactions

Potentiates effect of CNS depressants; alcohol content of syrup dosage form may cause disulfiramlike reaction in patients taking medications that can cause these reactions

Contraindications

Documented hypersensitivity; MAOIs; angle-closure glaucoma

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction

Benzodiazepines

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.

Diazepam (Valium)

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

Dosing

Adult

2.5-10 mg IV slow push

Pediatric

0.1 mg/kg IV slow push repeat prn

Interactions

Phenothiazines, barbiturates, alcohols, and MAOIs may increase CNS toxicity

Contraindications

Documented hypersensitivity; narrow-angle glaucoma

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity)

Follow-up

Inpatient & Outpatient Medications

• Continue medication for 48-72 hours to prevent relapse.
  • Benztropine 1-2 mg PO bid
  • Diphenhydramine 25-50 mg PO qid
  • Trihexyphenidyl 2 mg PO bid

Miscellaneous

Medicolegal Pitfalls

• Failure to consider other diagnoses if symptoms have not abated after 2 IV doses of appropriate medication
• Failure to continue treatment for 48-72 hours to prevent relapse

Special Concerns

• 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.

References

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8. Kumor K. Cocaine withdrawal dystonia. Neurology. May 1990;40(5):863-4. [Medline].

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10. McCormick MA, Manoguerra AS. Dystonic reaction. In: Harwood-Nuss A, et al, eds. Clinical Practice of Emergency Medicine. Lippincott Williams & Wilkins; 1991:510-511.

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Keywords

medication-induced dystonic reactions, dystonic reaction, neuroleptic drug therapy, drug treatment, neuroleptics, neuroleptic agents, dyskinesia, acute dystonic reaction, neuroleptic drugs, involuntary muscle contractions

Contributor Information and Disclosures

Author

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.

Medical Editor

Samuel M Keim, MD, Associate Professor, Department of Emergency Medicine, University of Arizona College of Medicine
Samuel M Keim, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Public Health Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Michael J Burns, MD, Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center
Michael J Burns, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

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
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

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