Tardive dyskinesia (TD) is a hyperkinetic abnormal involuntary movement disorder induced mostly by conventional antipsychotics possibly through a mechanism of a chronic blocking of striatal D2 and D3 receptors. In addition, patients suffering from schizophrenia with genetically abnormal D2 and D3 receptors were found to present an even greater likelihood towards the emergence of TD Reference Lerer, Segman and Fangerau(1). TD's treatment options include switching from a typical to an atypical antipsychotic (2–Reference Llorca, Cherau, Bayle and Lancon4).
We present a case of a 47-year-old male with schizophrenia who developed TD after chronic administration of haloperidol and risperidone, and his TD and psychotic symptoms were substantially ameliorated by sertindole administration.
Mr A, a 47-year-old unmarried male was referred to our department complaining of mild anxiety and severe tremor. He was diagnosed on the basis of Structured Clinical Interview for DSM-IV Axis I (SCID-I/P) as suffering from DSM-IV schizophrenia of paranoid type with onset of his disorder at the age of 32. The patient had been taking haloperidol from the onset of his disorder with doses ranging from 20 to 30 mg. During the previous 9 months risperidone was added to his medication regimen. Thus his daily medication at referral consisted of 30 mg of haloperidol, 9 mg of risperidone and 6 mg of biperiden. His total Positive and Negative Syndrome Scale (PANSS) score was 21. In addition, he had extra-pyramidal symptoms: tremor, cogwheel rigidity as well as a severe syndrome of TD consisted of abnormal movements of the jaw, lips, mouth and the upper extremities (Abnormal Involuntary Movement Scale – AIMS: 28). The onset of his TD was 2 years before his referral and the onset of extra-pyramidal symp- toms followed immediately risperidone administration. The patient underwent a comprehensive physical, neurological and laboratory work-up as well as brain computed tomography which did not reveal any additional abnormalities.
He was genotyped and found to be DRD3ser-gly heterozygous, whereas, no polymorphisms in 5-HT2C receptor gene area were found. Haloperidol, risperidone and biperiden gradually discontinued in order to control his extra-pyramidal and TD symptoms, and the patient had administrated quetiapine titrated up to 800 mg/day. Six weeks later, his extra-pyramidal symptoms were totally eliminated (AIMS: 11). Although TD symptoms were not remitted, his daily dose of quetiapine was kept unchanged because of the stabilization of his mental state. Four months later he severely relapsed manifesting positive and negative symptoms (PANSS: 51). He was admitted to our department and quetiapine titrated up to 1200 mg/day. Two weeks later, there was no improvement in his psychotic symptoms and there was also a worsening in TD symptoms (PANSS: 50, AIMS: 19).
Quetiapine was gradually discontinued and he had been administrated clozapine titrated up to 125 mgday within 14 days. However, 3 days later his white blood cell count fell to 1.700/mm3 and his neutrophil count to 870/mm3. Thus, the treatment with clozapine was suspended.
Sertindole was initiated with a dose of 4 mg/day and gradually titrated up to 16 mg/day within 2 weeks. There was no prolongation of QTc on the ECGs (Q − T = 340 ms). His mental state improved progressively, and 2 weeks later, his psychotic and TD symptoms were ameliorated (PANSS score: 39, AIMS score: 8). After an 8-week-hospitalization the patient was discharged and his medication remained unchanged. The assessment of his TD symptoms revealed further improvement (PANSS: 29, AIMS: 0).
Mr A has been followed-up monthly and within a year his level of improvement of both psychotic and TD symptoms was wholly preserved (PANSS: 28, .AIMS score: 0).
In our case, haloperidol is considered to have played a causative role in the development of TD. Our patient was genotyped and he was found to be DRD3ser-gly heterozygous, a finding associated with an increased likelihood towards emergence of TD in patients suffering from schizophrenia or schizoaffective disorder Reference Steen, Lovelie, MacEvan and McCreadie(5). Following TD's treatment guidelines (2,Reference Taylor, Paton and Kerwin3), the patient had been switched to atypical antipsychotics. However, quetiapine failed to remit both the psychotic and TD symptoms, and clozapine induced severe hematological side effects.
Sertindole is a new atypical antipsychotic characterized by a high affinity of serotoninergic 5-HT2 receptors and high selectivity for dopaminergic D2 receptors in the mesolimbic region. Sertindole is also well tolerated and there is evidence that it presents a favourable extra-pryramidal symptoms profile (Reference Spina and Zoccali6–Reference Perquin8). We consider that the specific action of sertindole (low D2–D3 occupancy) on dopaminergic system in the striatum on the genetically abnormal DRD3 receptors may have led to down regulation and desensitization of them and thus to a remission of TD symptoms.
To the best of our knowledge, this is the first case study which suggests that sertindole as a monotherapy might be beneficial in the treatment of TD in patients who have genetically abnormal D3 receptors. Although sertindole is not a first-line treatment option in schizophrenia because of the QTc prolongation, its beneficial effect in TD appears promising. More controlled clinico-pharmacogenetic studies including adequate number of patients suffering from TD and schizophrenia are warranted to establish sertindole's propertities in the TD symptoms.
