Letters to the Editor
Improvement in Tardive Dyskinesia With Aripiprazole Use
Dear Editor:
We wish to report the case of a patient with tardive dyskinesia (TD) whose improvement with the introduction of aripiprazole is quite similar to a case recently reported in the Journal by Duggal (1).
Case Report
Mrs SR, aged 45 years, was initially diagnosed with bipolar disorder 16 years prior to this report and, more recently, with schizoaffective disorder, bipolar type. She took oral and then depot haloperidol for many years, along with lithium and then divalproex. For 6 years, she was consistently treated in our clinic with risperidone 4 mg and divalproex 2000 mg daily. On 3 occasions, she discontinued all medications, was admitted to the state hospital, and returned to our clinic taking haloperidol decanoate 100 mg intramuscularly every 3 weeks. Each time, we gradually returned her to the risperidone and divalproex combination. On the last occasion, when most recently changed from haloperidol to risperidone, she was noted to have mild TD and an Abnormal Involuntary Movement Scale (AIMS) score of 8. Clonazepam 1 mg daily was added with little improvement. For the next year and a half, her AIMS score varied between 7 and 9, with no trend toward improvement.
In December 2003, her family took her to see a physician in Mexico, who recommended that she stop all psychiatric medications and who gave her an unknown drug or drugs to take in their place. She was apparently without her usual medications for no more than 10 days. Upon her return to the US, her TD had worsened dramatically, and her AIMS score was 26. Risperidone and divalproex were immediately restarted, but no improvement in TD occurred over the next 4 weeks. Finally, aripiprazole 15 mg daily was added to her other medications. Within 3 days, choreoathetosis was dramatically reduced, and 1 week after starting aripiprazole, her AIMS score was 7.
Like Duggal, we speculate that the partial agonist status of aripiprazole may offer a unique remedy for some patients who develop TD after prolonged use of first- generation antipsychotics, particularly when substitution of a second-generation antipsychotic does not reduce TD severity (2). We are somewhat reassured that the preclinical data available for aripiprazole seem to argue against progressive hypersensitization of D2 receptors with prolonged exposure (3,4).
Finally, we note the ratchet-like impact on the severity of our patient’s TD of briefly discontinuing risperidone and divalproex. We initially anticipated that resuming her usual medications would at least substantially undo the abrupt increase in TD. No such improvement was seen over a period of 4 weeks, prior to the addition of aripiprazole. We have found no reference in the literature either to such an abrupt and dramatic worsening of TD after brief discontinuation of a second- generation antipsychotic or to its failure to improve following reinstitution of the same drug.
Funding and Support
No funding or support was received in the preparation of this manuscript, and none is anticipated. Dr Witschy is a member of the Speakers’ Bureau for Eli Lilly and for Pfizer. Dr Winter is a member of the Speakers’ Bureaus for AstraZeneca, Bristol- Myers Squibb, Eli Lilly, Forrest, GlaxoSmithKline, and Pfizer.
References
1. Duggal HS. Aripiprazole-induced improvement in tardive dyskinesia. Can J Psychiatry 2003;48:771–2.
2. Kane JM, Carson WH, Saha AR, McQuade RD, Ingenito GG, Zimbroff DL, and others. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and Schizoaffective disorder. J Clin Psychiatry 2002;63:763–71.
3. Toru M, Miura S, Kudo Y. Clinical experiences of OPC-14597, a dopamine autoreceptor agonist in schizophrenic patients. Neuropsychopharmacology 1994;10:122S.
4. Inoue A, Miki S, Seto M, Kikuchi T, Morita S, Ueda H, and others. Aripiprazole, a novel antipsychotic drug, inhibits quinpirole-evoked GTPase activity but does not up-regulate dopamine D2 receptor following repeated treatment in the rat striatum. Eur J Pharmacol 1997;321:105–11.
James K Witschy, MD
A Scott Winter, MD
Fort Worth, Texas
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