Tardive dyskinesia

Tardive dyskinesia is a neurological disorder caused by the long-term or high-dose use of dopamine antagonists, usually antipsychotics. These neuroleptic drugs are generally prescribed for psychiatric disorders. Other dopamine antagonists that can cause tardive dyskinesia are drugs for gastrointestinal disorders (for example metoclopramide) and neurological disorders. Some drugs that are not intended to affect dopamine, such as SSRI antidepressants, may also cause tardive dyskinesia. While newer atypical antipsychotics such as olanzapine and risperidone appear to have less dystonic effects, only clozapine has been shown to have a lower risk of tardive dyskinesia than older antipsychotics.

The term tardive dyskinesia was introduced in 1964. Dyskinesia refers to an impairment of voluntary movement. The resultant tics and other movements are often referred to as dyskinesias. Dyskinesia is sometimes caused by long-term use of anti-psychotic drugs or other dopamine antagonists like the antiemetic metoclopramide. The effect of these drugs can be tardive, meaning the dyskinesia continues or appears even after the drugs are no longer taken. As far as treatment of iatrogenic tardive dyskinesia is concerned, neuroleptic drugs should be withdrawn for a period of 3-6 months to see if this resolves the issue, but the problem may fail to improve or may even exacerbate. In this situation, it would be sensible to trial the patient on tetrabenazine 25-50 mg/8h PO.(Oxford Handbook of Clinical Medicine).

In context of Parkinson's disease, dyskinesias are often the result of chronic levodopa (L-dopa) therapy. These motor fluctuations occur in more than half of PD patients after 5 to 10 years of levodopa therapy, with the percentage of affected patients increasing over time.

Dyskinesias most commonly occur at the time of peak L-dopa plasma concentrations and are thus referred to as peak-dose dyskinesias. As patients advance, they may evidence diphasic dyskinesias, which occur when the drug concentration rises or falls.

The use of MDMA has been shown to enhance the effects of L-Dopa while reducing the associated dyskinesia in primates with simulated Parkinson's disease.