Basics
Description
- Normal pattern of CNS neurotransmission maintained by balance between dopaminergic and cholinergic receptors:
- Certain drugs antagonize dopamine receptors in the basal ganglia resulting in an imbalance of dopaminergic and cholinergic stimulation
- This imbalance leads to acute involuntary muscle spasms of the face or neck (the trunk, pelvis, or extremities can also be affected)
- Although the spasms are uncomfortable and frightening, they are not life threatening except in very rare cases when laryngeal muscles are involved
- Usually occurs within hours of ingestion:
- Almost always within 1st wk after exposure to offending drug
- Risk factors:
- Children and young adults are at higher risk
- Rarely occurs in patients over 45 yr of age
- Males more often affected
- Prior episodes of dystonia significantly increase risk
- Recent cocaine use increases risk
Etiology
- Usually occurs after patient has taken antipsychotic, antiemetic, or antidepressant drug
- Incidence of dystonic reactions varies widely (2-25%) depending on the potency of the agent
- Higher with more potent drugs (haloperidol, fluphenazine)
- Lower with less potent drugs (chlorpromazine, thioridazine)
- Lowest with atypical antipsychotics (quetiapine, olanzapine, risperidone)
- Antiemetic agents:
- Metoclopramide (Reglan)
- Prochlorperazine (Compazine)
- Promethazine (Phenergan)
- Droperidol (Inapsine)
- Other agents:
- Cyclic antidepressants
- H2 blockers
- Some antimalarial agents
- Antihistamines
- Some anticonvulsants
- Doxepin
- Lithium
- Phencyclidine
Children are particularly vulnerable to dystonic reactions when dehydrated or febrile
Diagnosis
Signs and Symptoms
History
- Ingestion of neuroleptic, antiemetic, or other drug within week of symptom onset
- May occur in patients on neuroleptic agents who increase their dose of neuroleptics or reduce medications (anticholinergic agents) used to treat extrapyramidal symptoms
- Difficulty with vocalization
- Completely alert and able to answer questions, although facial muscle involvement may make speech difficult.
- Involuntary muscle contractions or spasms usually involving the face or neck (see "Physical Exam"):
- Muscles of the trunk, pelvis, or extremities can also be involved
Physical Exam
- Characteristic involuntary muscle spasms occur
- Oculogyric crisis
- Involves eye and periorbital muscles
- Evolves into painful upward or lateral deviation of the eyes
- Blepharospasm
- Involuntary eyelid closure
- Buccolingual crisis
- Involves facial muscles and the tongue
- May have difficulty speaking
- Facial grimacing
- Trismus
- Tongue protrusion
- Dysphagia
- Spasmodic torticollis
- Torticopelvic crisis
- Abdominal wall muscle spasm
- Opisthotonos
- Involves muscles of trunk and back
- Twisting and arching of spine
- Laryngeal dystonia
- Very rare but potentially life threatening
- May develop airway obstruction due to laryngospasm
- Presents as dysphonia or stridor
Essential Workup
- Clinical diagnosis is based on characteristic signs and symptoms with history of possible drug exposure
- Diagnosis is confirmed by response to treatment
- Lack of response to treatment should lead one to consider alternative diagnosis
Diagnosis Tests & Interpretation
Lab
- Lab testing not routinely indicated
- If no response to treatment, hypocalcemia should be considered and calcium level obtained
Imaging
No imaging studies needed
Differential Diagnosis
- Tardive dyskinesia:
- Complication of chronic antipsychotic therapy
- Usually choreiform movements
- Does not rapidly improve with administration of anticholinergic drug
- Akathisia:
- Involuntary motor restlessness
- May appear agitated
- Seizure:
- History of prior seizures
- Not responsive to verbal stimuli
- Tonic-clonic-type motor movements rather than spasm
- Hysteria or pseudoseizure:
- History of precipitating emotional event
- Tonic-clonic motor activity rather than sustained spasm
- Tetanus
- Strychnine poisoning
- Chronic dystonias:
- Cerebral palsy, familial choreas
- Usually history of dystonia is associated with chronic neurologic process
- Scorpion envenomation:
- Oculogyric crisis and opisthotonos are common manifestations of scorpion envenomation
- Patient lacks history of drug exposure.
- Meningitis and encephalitis may present with atypical seizures that mimic dystonic reaction
- Mandible dislocation
- Hypocalcemia
Treatment
Pre-Hospital
- Rarely life threatening
- Direct attention toward spasm of larynx and tongue to be sure dystonic reaction is not causing respiratory compromise
- Ask family and friends about ingestions of antipsychotic medications, antiemetics, and recreational drugs
- Transport pill bottles
Initial Stabilization/Therapy
Stabilize airway to prevent spasm of larynx or tongue from causing respiratory compromise.
Ed Treatment/Procedures
- Administer diphenhydramine (Benadryl) or benztropine mesylate (Cogentin):
- Rapid resolution of muscular spasm by restoring cholinergic-dopaminergic balance in CNS
- IV administration is preferred route of treatment
- Onset of relief in 2-5 min
- Complete resolution of symptoms in 30 min
- IM administration is alternate route of treatment
- Begins to work in 15-30 min
- Continue oral administration for 3 days to prevent redevelopment of symptoms
- Diazepam (Valium):
- Administer in cases of dystonia unresponsive to adequate doses of anticholinergic medications
- Failure to respond to standard treatment should lead physician to consider other diagnoses
Medication
- Benztropine mesylate (Cogentin): 1-2 mg either IV (over 2 min) or IM followed by 1-2 mg PO BID for 3 days:
- Not to be used in children <3 yr old
- For children >3 yr old: 0.02 mg/kg IV (over 2 min) or IM followed by 0.02 mg/kg PO BID for 3 days
- Diphenhydramine (Benadryl): 1-2 mg/kg up to 100 mg either IV (over 2 min) or IM followed by 25-50 mg (peds: 1-2 mg/kg) PO q6-8h for 3 days, or
- Diazepam: 5-10 mg IV followed by 5 mg PO q4-6h as necessary for 3 days
First Line
Diphenhydramine (Benadryl)
Second Line
Benztropine mesylate (Cogentin):
- Not to be used in children <3 yr old
- Diazepam
Follow-Up
Disposition
Admission Criteria
- Patients are not admitted unless symptoms do not resolve with treatment, there are concerns about maintaining the airway, or the diagnosis is not certain
- If the dystonic reaction causes laryngospasm patient should be observed for 12-24 hr after symptoms resolve
Discharge Criteria
- Discharge after resolution of symptoms
- The offending agent should be discontinued
- Patient should not drive or perform tasks that require full alertness while taking sedating medications
Followup Recommendations
Patients should follow-up with the prescribing physician of the causative agent
Pearls and Pitfalls
- The diagnosis of acute dystonia is made based on the history of ingestion coupled with complete resolution of the symptoms after appropriate treatment
- 1st line of therapy is diphenhydramine
- Failure to respond should lead you to consider other diagnoses
Additional Reading
- Derinoz O, Caglar AA. Drug-induced movement disorders in children at paediatric emergency department: "Dystonia'. Emerg Med J. 2013;30:130-133.
- Goldfrank LR, Lewin NA, Howland MA, et al. Pathophysiology and clinical manifestations. In: Nelson LS, Lewin NA, Howland MA, et al., eds. Goldfranks Toxicologic Emergencies. 9th ed. New York, NY: McGraw Hill; 2011;9:1007-1010.
- Sachdev PS. Neuroleptic-induced movement disorders: An overview. Psychiatr Clin North Am. 2005;28:255-274.
- Vena J, Dufel S, Paige T. Acute olanzapine-induced akathisia and dystonia in a patient discontinued from fluoxetine. J Emerg Med. 2006;30:311-317.
- Wolfson AB, Hendey GW, Ling LJ, et al., eds. Harwood Nuss' Clinical Practice of Emergency Medicine. 5th ed. Philadelphia, PA: Lippincott; 2010.
Codes
ICD9
333.72 Acute dystonia due to drugs
ICD10
- G24.01 Drug induced subacute dyskinesia
- G24.02 Drug induced acute dystonia
- G24.09 Other drug induced dystonia
- G24.0 Drug induced dystonia
SNOMED
- 230315008 Drug-induced dystonia (disorder)