Tardive dyskinesia with low dose amisulpride.

In recent years, there has been an increasing trend to use amisulpride in the treatment of dysthymia and also as an adjunct treatment in patients with major depression. At low doses (50 mg), amisulpride preferentially blocks presynaptic auto receptors, enhances dopamine release, and therefore acts as a dopaminergic compound able to resolve the dopaminergic hypo activity that characterizes depression. Based on experimental data, amisulpride is the drug of choice for dopaminergic transmission disorders, both in depression and in schizophrenia. This case highlights the development of dyskinesia in a depressed patient treated with low dose amisulpride and fluvoxamine.

INTRODUCTION

Amisulpride is a substituted benzamide that, at low doses, selectively blocks D2 and D3 presynaptic dopamine receptors, enhancing dopaminergic transmission in frontal cortex and limbic areas.[1] Many clinical studies versus placebo, tricyclic antidepressants and selective serotonin reuptake inhibitors showed amisulpride antidepressant effect, supporting its safety and rapid onset of action.[2] The proposed mechanism of action of substituted benzamides implies a selective modulation of the dopaminergic system in the mesocorticolimbic area, important for cognitive processing of internal and external cues, related to survival.[3] The compound is very selective for mesolimbic D2 and D3 receptors and therefore has a dual mechanism of action, which is associated with two different indications. Based on experimental data, amisulpride is the drug of choice for dopaminergic transmission disorders, both in depression and in schizophrenia.[4] Preliminary research findings suggest that adjunctive amisulpride to fluvoxamine may be a potential strategy for an early onset of SSRI activity in the treatment of major depressive disorder.[5] Tardive dystonia with low dose amisulpride in schizophrenia has been reported.[6] However, dyskinesia and dystonias of jaw associated with serotonin specific reuptake inhibitors (SSRI) treatment have also been reported.[7] Fluvoxamine induced complex movement disorders, mandibular dystonia and dyskinesia have also been noted over the years.[8]

CASE REPORT

A 56-year-old female presented to the Schizophrenia Foundation Hospital (SCARF) outpatient services with a seven-year on and off history of sub syndromal anxiety and depressive symptoms related to marital stressors and a one-month exacerbation of symptoms following her son's marriage. Patient was diagnosed as a case of mixed anxiety and depression as per International Classification of Diseases (ICD)-10 criteria. Treatment was initiated with escitalopram 10 mg for a week and discontinued due to gastritis. Subsequently patient was started on amisulpride 50 mg/day and hiked to 100 mg when she gradually reported improvement in mood in 6 weeks. During the next follow up at week 12 of 100 mg amisulpride therapy, she was first noticed to have orofacial dyskinetic movements and amisulpride was discontinued. However, patient was prescribed fluvoxamine 25-50 mg for 8 weeks because of worsening of anxiety and depressive symptoms. During her subsequent hospital visits, patient reported progressively severe dyskinetic movements of the face, neck, right forearm, wrist, and fingers and opisthotonic posturing of the chest. She was evaluated in detail and diagnosed with dyskinesia (drug induced) as per ICD-10. Her Abnormal Involuntary Movement Scale (AIMS) score was 15. A score of 4 on the Naranjo adverse drug reaction probability scale indicates a possible cause of dyskinesia related to amisulpride. Her medical co morbidity also included diabetes mellitus, which was not well controlled. There was no past or current history of substance use or neurological disorder, or any family history of movement disorders or any previous antipsychotic use. Magnetic resonance imaging (MRI) done did not reveal any abnormal finding. To treat drug-induced dyskinesia, fluvoxamine was stopped and patient was started on tetrabenazine. Two months later, tardive dyskinesia persisted and there was no improvement in dyskinetic movement. Patient has recently been started on clozapine for dyskinesia.

DISCUSSION

This case highlights and aims to raise awareness that low dose amisulpride causes dyskinesia contrary to the reports of higher doses of amisulpride and movement disorders.[9] The risk factors for tardive dyskinesia in our patient were old age, female gender, diabetes mellitus, exposure to amisulpride and fluvoxamine. Tardive dyskinesia in our patient had appeared after initiating treatment with amisulpride and worsened with fluvoxamine and had persisted and remained unchanged despite the withdrawal of both drugs from treatment regimen. The introduction of amisulpride was associated with development of dyskinesia and worsened with fluvoxamine. All previous cases have reported development of tardive dyskinesia 8-24 months after the patients were started on amisulpride.[10]

In contrast, this case is unique because of the occurrence of movement disorder within 3-4 months of treatment with low dose amisulpride for depression. It signifies how SSRI can additionally worsen the movements. The implications of this case have been to create awareness that low doses of amisulpride can possibly trigger dyskinetic movements and may worsen further to more complex movements in combination or in monotherapy with fluvoxamine.