Tardive dyskinesia (TD) is a potentially irreversible and socially stigmatising adverse effect caused by long-term use of antipsychotics. The prevalence of TD among chronically antipsychotic-treated patients is about 10–30% (Reference Jeste and Caligiuri1–Reference Margolese, Chouinard, Kolivakis, Beauclair, Miller and Annable2). Compared to the first generation antipsychotics, the second-generation antipsychotics have a lower liability to develop TD (Reference Tarsy and Baldessarini3–Reference Malhi and Pantelis5).
We present one female schizophrenic patient who developed TD after risperidone treatment and experienced a remarkable improvement with aripiprazole.
Mrs C, a 39-year-old divorced female, was diagnosed with DSM-IV paranoid schizophrenia for 5 years. She had abused amphetamine for several months at the age of 27 years, but did not develop any psychotic symptoms at that time. There was no history of systemic disease, brain damage, or other substance abuse. She became socially withdrawn and irritable, and had persecutory delusion and auditory hallucinations when she was 34 years old. A trial of risperidone 3 mg/day was initiated to treat her psychotic symptoms. No obvious extrapyramidal symptoms were found. Then she maintained on risperidone 3 mg/day in the following 4 years and the symptoms obtained significant improvement. The Positive And Negative Syndrome Scale (PANSS) total score was 58 at that time.
She showed abnormal movements of the cheeks, lips, jaw, mouth, neck and hands after 4-year use of risperidone. The Abnormal Involuntary Movement Scale (AIMS) score was 20 at that time. The antipsychotic medication was then switched to olanzapine 10 mg/day. She also received anticonvulsant (valproic acid 500 mg/day), benzodiazepine (clonazepam 1.5 mg/day), and muscle relaxant (mephenoxalone 600 mg/day). The severity of TD symptoms showed mild improvement and the AIMS scores were fluctuated between 15 and 18 under these combined medications. The severity of psychopathology remained stationary and the PANSS score fluctuated between 56 and 62 during that period.
Her body weight was increased 12 kg (from 56 to 68 kg) after 6 months of olanzapine treatment. The serum levels of fasting glucose, cholesterol and triglyceride were 98, 227 and 322 mg/dl, respectively. Because of the metabolic adversity, aripiprazole was then substituted and titrated to 20 mg/day, and olanzapine, valproic acid, clonazepam and mephenoxalone were gradually tapered off and discontinued. Dyskinetic symptoms gradually disappeared over the following 3 months (AIMS score: 4). Her psychopathology remained unchanged after the antipsychotic switch (PANSS total score: 56) and her body weight was decreased to 62 kg The follow-up serum levels of fasting glucose, cholesterol and triglyceride were 95, 191 and 235 mg/dl, respectively. Six months after the antipsychotic switch, the PANSS and AIMS scores were further decreased to 52 and 3, respectively.
Risperidone seems to have a causative role in the development of TD in our case. Evidence suggests that TD may result primarily from neuroleptic-induced dopamine supersensitivity in the nigrostriatal pathway, with the D2 dopamine receptor being most affected Reference Jeste and Caligiuri(1). The antipsychotics switch from risperidone to olanzapine only produced mild improvement in TD severity. It appeared that our patient was very sensitive to elevated dopamine D2 occupancy.
Aripiprazole exhibits a novel mechanism of action combining partial agonist activity at dopamine D2, dopamine D3 and serotonin 5-HT1A receptors with antagonist activity at serotonin 5-HT2AReference Shapiro, Renock and Arrington(6). Aripiprazole acts as a stabiliser on the dopaminergic function as an agonist in hypodopaminergic states and as an antagonist in hyperdopaminergic states. The unique pharmacologic profile of aripiprazole may protect against the emergency of extrapyramidal symptoms Reference Hirose, Uwahodo and Yamada(7). In animal study, aripiprazole treatment does not upregulate rat striatal dopamine D2 receptors following long-term administration Reference Inoue, Miki and Seto(8). These pharmacologic characteristics of aripiprazole can normalise dopamine D2 supersensitivity and upregulation. This propensity of aripiprazole may explain the beneficial effect that exerts in TD symptoms induced by other antipsychotics.
Though some studies had reported aripiprazole-related TD Reference Lim, Pae, Lee and Lee(9,Reference Hettema and Ross10), we found nine cases of improvement in antipsychotic-induced TD during treatment with aripiprazole in the literature (Reference Rizos, Douzenis, Gournellis, Christodoulou and Lykouras11–Reference Duggal19). However, Miller et al. Reference Miller del, Eudicone, Pikalov and Kim(20) also reported that the incidence of new-onset TD is 0.45% per year for aripiprazole. Therefore, the risk of TD seems to be distinguishable from the impact on preexisting TD. Aripiprazole might have a paradoxical effect in this regard; it could both induce TD and reduce preexisting TD in clinical settings. Therefore, larger sample size and more rigorously designed studies are needed to address the efficacy of aripiprazole on TD.
TD is not only painful and disfiguring, but also contributes to poor compliance and ultimately poor treatment outcome in psychotic patients. The present case is to emphasise on the need to carefully monitor the development of TD, even in those patients treated with second-generation antipsychotics. It also provides a rationale for antipsychotic drug management in TD patients, suggesting that partial dopamine agonists, like aripriprazole, may have beneficial effects on TD.
