Letters to the Editor
Aripiprazole-Induced Improvement in Tardive Dyskinesia
Dear Editor:
Atypical antipsychotics, particularly clozapine, have been reported effective in the treatment of tardive dyskinesia (TD) (1). We report the case of a patient with schizoaffective disorder who showed remarkable improvement in TD following treatment with aripiprazole (APZ).
Case Report
Mrs A, aged 41 years, suffered from chronic schizoaffective disorder of 20 years’ duration and was admitted with psychotic exacerbation. The patient had been free of antipsychotics for the last 6 months but had significant TD in the form of choreoathetoid movement of her upper extremities and truncal dyskinesia. TD was first noticed about 2 years ago, while she was taking haloperidol. Discontinuation of haloperidol and subsequent sequential trials of risperidone, olanzapine, ziprasidone, and quetiapine did not improve the TD. Quetiapine exacerbated the TD and olanzapine, ziprasidone, and risperidone had to be discontinued owing to weight gain, EKG changes, and hyperprolactinemia, respectively. Before her current admission, Mrs A was maintained only on valproate 1000 mg daily. Her score on the Abnormal Involuntary Movement Scale (AIMS) was 12. In view of her intolerance for atypical antipsychotics and failed trials with conventional antipsychotics, APZ was started at 15 mg daily and increased to 30 mg daily after 2 weeks. While Mrs A’s symptoms showed modest improvement, more notable was the dramatic improvement in TD within 48 hours of starting APZ. This improvement continued despite augmentation with chlorpromazine at 100 mg thrice daily. Four weeks after APZ was started, she showed only occasional choreic movements of her fingers and scored 2 on the AIMS. She maintained that improvement at the time of discharge and also displayed significantly decreased psychotic symptoms.
APZ, a dopamine–serotonin system stabilizer, is unique in having a partial dopamine agonist and antagonist effect (2). It causes dopamine receptor super- sensitivity to a lesser extent after repetitive administration, compared with haloperidol (3). Dopaminergic supersensitivity is currently the most accepted hypothesis for TD (4), and we can speculate that APZ has less potential to cause TD. This is supported by a recent study showing that APZ was not associated with any significant changes in AIMS score (2). TD has been associated with upregulation of the D2 receptors, and another finding favouring a beneficial role of APZ in TD is that it does not upregulate these receptors (5). An interesting observation was that dyskinesia did not remerge after augmentation with a conventional antipsychotic. APZ may have inherent capacity to prevent reemergence of TD caused by conventional antipsychotics because it acts as a functional agonist at dopamine receptors under hypo- dopaminergic states (2) occurring with conventional antipsychotics. Thus, further trials of APZ in cases of TD are encouraged. Moreover, augmenting APZ with conventional antipsychotics in partial responders deserves more attention, considering recent reports of optimizing treatment using combined typical and atypical antipsychotics (6).
References
1. Uzun O, Cansever A, Ozsahin A. A case of relapsed tardive dyskinesia due to clozapine dose reduction. Int Clin Psychopharmacol 2001;16:369–70.
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. Marangell LB, Yudofsky SC, Silver JM. Psychopharmacology and electroconvulsive therapy. In: Hales RE, Yudofsky SC, Talbott JA, editors. The American Psychiatric Press textbook of psychiatry. 3rd ed. Washington (DC): American Psychiatric Press; 1999. p 1070.
5. 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.
6. Freudenreich O, Goff DC. Antipsychotic combination therapy in schizophrenia. A review of efficacy and risks of current combinations. Acta Psychiatr Scand 2002;106:323–30.
Harpreet S Duggal, MD
Pittsburgh, Pennsylvania
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