To the Editor:             

Antipsychotics all share the property of blocking dopamine receptors in the brain.1 Almost all, including the “atypical antipsychotics, ” have been associated with extrapyramidal side effects.1,2 These drugs have been almost exclusively prescribed by psychiatrists who are aware of the risks involved. They have been trained in recognizing tardive dyskinesia (TD), and counsel their patients about this risk. They document their examination for TD with the Abnormal Involuntary Movement Scale as a standard routine.

When counseling for TD risk and routine evaluations are not performed, doctors are open to liability suits. Metoclopramide is widely used to treat gastric reflux disorders, gastroparesis, and nausea, and can cause the same extrapyramidal adverse effects, including TD, as caused by antipsychotics. It now carries a “black box” warning. Since it often produces dramatic improvement in gastrointestinal symptoms, is well tolerated, and is inexpensive, it is often continued for years, increasing the risk of TD. Since most doctors are unaware of the risk, patients are rarely told about the potential for TD and chart notes documenting an evaluation for movement disorders are rare. Potential suitors are recruited in television advertisements by personal injury law firms.

Aripiprazole, the most recently approved atypical antipsychotic has recently been implicated as a cause of TD in patients never exposed to other dopamine receptor-blocking agents3,4 and at the low doses recommended for treating depression.4 We are concerned that the recent Food and Drug Administration approval of aripiprazole for use in treating depression may result in an increase in the number of cases of TD. Primary care physicians (PCPs) often treat depression without consultation with psychiatrists. The addition of aripiprazole into the depression arena, assisted by mass market advertising, especially on television, may lull unsuspecting non-psychiatrists into believing that this drug, and possibly similar drugs in the future, are as risk-free in terms of TD as the selective serotonin reuptake inhibitors. The medical-legal issues that PCPs are currently facing with metoclopramide law suits may occur again in a few years with aripiprazole.

There are few data concerning the incidence of TD in neuroleptic-naïve patients starting aripiprazole. Although the atypical antipsychotics are believed to be “relatively” free of extrapyramidal side effects, the results of the Clinical Antipsychotic Trials in Intervention Effectiveness studies5 have questioned this belief. In a recent review6 of studies using comparable doses of antipsychotics, the annualized incidence of TD was estimated to be 3.9% for atypical antipsychotics compared with 5.5% for conventional antipsychotics—only a modest improvement.

Aripiprazole may produce TD, which may be permanent. It should therefore be used only when necessary. We believe that it should only be used for refractory cases by doctors knowledgeable about antipsychotics. The dose should be as low as possible and attempts to wean off the drug should be made once the patient has achieved a stable improvement. Alternatives include switching to other antidepressants, including the tricyclics; combined therapy with drugs of different chemical families; adjunctive exercise; and psychotherapy. Other alternatives such as lithium or thyroid augmentation should be considered by psychiatrists. TD should be specifically evaluated and commented upon at each office visit so that the drug may be stopped if TD begins.

Sincerely,

Joseph H. Friedman, MD, and Daniel Tarsy, MD

Dr. Friedman is professor and chief of the Division of Movement Disorders in the Department of Neurology at Warren Alpert Medical School of Brown University/Butler Hospital in Providence, Rhode Island. Dr. Tarsy is professor in the Department of Neurology at Harvard Medical School/Beth Israel Deaconess Medical Center in Boston, Massachusetts.

Disclosures: Dr. Friedman is a consultant to Acadia and EMD serono; on the speakers’ bureaus of GlaxoSmithKline and Ingelheim-Boehringer; and receives research support from Cephalon, EMD Serono, Epivax, the National Institutes of Health, and The Michael J. Fox Foundation. Dr. Tarsy is a consultant to Esai Neuroscience; receives grant support from Allergan and Schwarz Pharma; and receives foundation support from The Michael J. Fox Foundation and the National Parkinson Foundation.

References

1. Tarsy D, Baldessarini RJ. Epidemiology of tardive dyskinesia: is risk declining with modern antipsychotics? Mov Disord. 2006;21(5):589-598.
2. Kane JM. Tardive dysinesia rates with atypical antipsychotics in adults: prevalence and incidence. J Clin Psychiatry. 2004;65(suppl 9):16-20.
3. Lungu C, Aia PG, Shih LC et al. Tardive dyskinesia due to aripiprazole: report of 2 cases. J Clin Psychopharmacol. 2009;29(2):185-186.
4. Friedman JH. Aripiprazole induced tardive dystonia in a neuroleptic naïve patient. J Clin Psychiatry. In press.
5. Miller DD, Caroff SN, Davis SM, et al. Extrapyramidal side effects of antipsychotics in a randomised trial. Br J Psychiatry. 2008;193(4):279-288.
6. Correll CU, Schenk EM. Tardive dyskinesia and new antipsychotics. Curr Opin Psychiatry. 2008;21(2):151-156.

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