Aripiprazole-Induced Tardive Dystonia

Abstract

Sir: Tardive dystonia is a persistent syndrome of sustained muscle contraction that produces twisting and repetitive movements or abnormal postures. It usually involves the head and neck, producing torticollis, retrocollis, or anterocollis, but sometimes it involves back muscles, giving rise to opisthotonus and gait disturbances.1 The most common causes for development of tardive dystonia are exposure to neuroleptics or other medications like metaclorpromide, prochloroperazine, or amoxepine.1 Among the new generation of antipsychotics, aripiprazole has a unique receptor binding profile that combines partial agonistic activity at D2 and 5-HT2A receptors.2,3 The risk of movement disorder in people taking aripiprazole has to date been considered insignificant as there is no published report to our knowledge on association of tardive dystonia with aripiprazole. Case report. Ms. A, a 25-year-old woman, presented to the hospital in 2000 with schizoaffective disorder that included a past history of 2 psychotic episodes and 3 manic episodes. During the course of treatment, she developed skin rashes with the use of carbamazepine, experienced significant weight gain with the use of olanzapine, developed galactorrhea and severe extra-pyramidal symptoms with the use of risperidone, and experienced severe tremors and excessive daytime drowsiness with the use of valproate. These side effects led to frequent changes in medications. While treated with quetiapine, she developed recurrence of mania. She was also given a trial of lithium with which she complained of memory loss and vomiting. The lithium dosage was reduced to 450 mg/day, and she remained on treatment with that dosage for the 8 months preceding the current episode. For the current manic episode, in 2005, aripiprazole 10 mg/day was added to her lithium treatment, which she had been taking for the last 8 months without any significant problem. After 4 weeks, aripiprazole was increased to 15 mg/day. After 2 months of administration of aripiprazole, she developed backward arching of her body with spasm over the origin of latissimus dorsi muscle near vertebrae L1 and L2. These effects worsened while she was standing and lifting her arms. The arching increased when she was asked to engage in physical activity. These symptoms were absent during sleep, caused significant dysfunction in her occupation and embarrassment in public, and gradually worsened. She did not experience perioral tongue movements, facial grimacing, or difficulty in chewing or breathing. Ms. A had no history of head injury or loss of consciousness or a family history of movement disorders. A thorough neurologic examination, including neuroimaging, revealed no pathology. She was rated with the Extrapyramidal Symptom Rating Scale (ESRS)4 and was found to suffer from moderate to severe levels of extrapyramidal symptoms. Aripiprazole was stopped and tablet trihexyphenidyl 6 mg/day was started with continued lithium treatment (450 mg/day) in view of worsening dystonic symptoms. She showed improvement in dystonia, and after 2 weeks, her ESRS score was zero. Four weeks after the start of trihexyphenidyl treatment, in view of her mood and psychotic symptoms, she was started on treatment with clozapine, which was increased to 150 mg/day. Currently, 1 year after discontinuing aripiprazole, she is symptom free. This patient had several features suggestive of tardive dystonia following exposure to aripiprazole. The symptoms started after about 2 months of exposure to aripiprazole and worsened subsequently. They improved only after the stoppage of aripiprazole and addition of trihexyphenidyl. The neurologic examinations revealed no other causes of dystonia, and previous antipsychotic exposure was at least a year earlier. Association of lithium with tardive dystonia has been reported in literature,5 but in this case she took lithium for 8 months with no dystonic symptoms. Studies have reported no increase in incidence of extrapyra-midal symptoms in patients treated with aripiprazole compared with those treated with placebo.6,7 Moreover, treatment with aripiprazole has shown remarkable improvement in tardive dyskinesia.8 But, as seen in this case, the possibility of developing dystonia, though remote, is present even with a safe drug like aripiprazole. It is even more likely to occur in a patient who is vulnerable to side effects with other neuroleptics.