11th August 2024

Acute drug reactions to medications affecting dopaminergic transmission

Acute dystonia

Dystonia describes an involuntary muscle contraction, which can be primary or secondary. Cervical dystonia, also known as torticollis, is the most common focal dystonia.

Acute dystonia is rare and usually secondary to anti-dopaminergic agents, including metoclopramide. It is often painful and can be life threatening due to occlusion of the airway depending on the muscle groups affected. Examples include oculogyric crisis causing intermittent deviation of the eyes, often upwards, or laryngeal dystonia, which causes intermittent contractions of the muscles in the larynx and therefore difficulty speaking or changes/hoarseness to the voice.

If the patient has been exposed to an anti-dopaminergic treatment then benztropine or diphenhydramine should be given intravenously and the offending agent should be discontinued or weaned. It is important to assess for concurrent pathology such as neuroleptic malignant syndrome or metabolic, infectious or toxin causes.

Of note, dopa-responsive dystonia, which presents in childhood, is a rare disorder but one which is treatable, responding to L-dopa or dopamine agonists and is therefore important not to miss.

Tardive dyskinesia

Hyperkinetic movement disorders (including tardive dystonia, myoclonus and tremor) that develop due to prolonged anti-dopaminergic treatment, usually antipsychotic medication but also metoclopramide. Tardive, derived from the Latin for ‘slow’, describes the slow, writhing (choreiform or athetoid) movements often seen in the face, commonly lip smacking, lip puckering and intermittent blinking. The diagnosis is clinical and requires the movements to have been present for at least 4 weeks.

The offending drug should be withdrawn, however that may involve a weaning regime while an alternative medication is uptitrated. Symptoms can last up to 6 months after the offending medication is discontinued, and in unfortunate cases may be irreversible. First-line treatment is tetrabenazine (also used in the management of chorea in Huntington’s disease).

Neuroleptic malignant syndrome

Neuroleptic malignant syndrome, also known as parkinsonism hyperpyrexia syndrome, is a drug reaction that presents similarly to severe parkinsonism with rigidity along with a high fever, confusion or altered behaviour and autonomic dysfunction resulting in labile blood pressures, dilated pupils, tachycardia and sweating. In severe cases the airway may be compromised due to loss of consciousness, or severe rigidity may prevent adequate ventilation. It most commonly occurs in patients recently started on antipsychotic treatment, but can also develop in those whose dopaminergic treatment is abruptly withdrawn. Clinically it can look quite similar to serotonin syndrome and thus it is important to take a thorough drug history.

Treatment involves addressing the precipitant, i.e. stopping the offending antipsychotic medication or restarting the necessary dopamine agonist, alongside managing the fever and any kidney injury or rhabdomyolysis. In severe cases dantrolene, a muscle relaxant, and bromocriptine, a dopamine agonist, can be used.