Drug-induced Movement Disorders

Epidemiology

The true incidence and prevalence of drug-induced movement disorders is unknown and likely vastly underappreciated because of lack of recognition. Even among neurologists, drug-induced parkinsonism, for example, is often not recognized and, therefore, not appropriately treated.2 Studies have shown that most parkinsonism in patients in nursing homes is not recognized,3 and, even among psychiatrists, tardive dyskinesia and akathisia are frequently overlooked.4 In addition, identifying the exact prevalence and incidence of DIMD has proven to be difficult because of factors such as fluctuation in symptoms; the use of drugs that can mask drug-induced movement disorders, thereby causing an underestimation of the prevalence; and a lack of validated criteria for the diagnosis of DIMD.

Factors affecting the rate of DIMD related to the use of antipsychotic drugs include age of the population, the drug being used, the definition of the movement being employed in the study, and the design of the study.5 DIMD related to exposure to antipsychotic drugs is estimated to occur in 19% and 42% of patients receiving atypical (second-generation) and typical (first-generation) antipsychotic drugs, respectively.6 With the increasing use of antipsychotic drugs in young children, the incidence of DIMD is growing in this population. In one study, 9% of children who had received an antipsychotic drug for six months or longer developed OBLD (as opposed to none in a control population), including those children who had only received atypical antipsychotics.

The package insert for metoclopramide, which has been approved by the Food and Drug Administration to treat symptomatic gastroesophageal reflux and diabetic gastroparesis, has separate warnings for the risk of OBLD; parkinsonian symptoms (usually beginning within the first six months of treatment, with reversal of symptoms within two to three months after discontinuation of the drug); and "extrapyramidal symptoms," (EPS) which usually occur within the first 24 to 48 hours of treatment and are primarily manifest as acute dystonic reactions (involuntary limb movements, facial grimacing, torticollis, oculogyric crisis, rhythmic tongue protrusion, bulbar speech, trismus, and, rarely, stridor and dyspnea). The risk for the development of EPS (1 in 500 people treated with the drug) is highest in infants and children and adults younger than 30 years of age. Cumulative dose is also related to risk of developing EPS.7 Kaplan et al found that 15% of people on metoclopramide therapy remained on the drug for longer than 90 days,8 even though the safety of the drug has been evaluated only up to 90 days and even though the labeling of the drug clearly states that the risk and likely irreversibility of tardive dyskinesia are related to the length of exposure and total accumulative exposure to the drug.

A variety of populations have been determined to be at increased risk for developing DIMD. Not all DRBDs carry the same risk, but, in general, these populations overall have increased risks of developing DIMD.

Populations at High Risk for Developing DIMD	Potential Reasons
Elderly	Decreased functional reserve
Elderly women	Decreased estrogen levels
Patients who have used DRBD for more than 3 months	Increased exposure to DRBD
Diabetics, independent of their use of DRBD, although the risk increases with the use of DRBD	Impaired glucose metabolism
Persons with phenylketonuria	Increased phenylalanine levels