Amisulpride induced mania.

Amisulpride is an atypical antipsychotic used for the management of schizophrenia and other conditions like dysthymia. It has also been used for the management of bipolar disorders as an add on therapy. Here, we report a patient of schizophrenia who developed a manic episode while on amisulpride.

Introduction

Amisulpride is a second generation antipsychotic and is chemically a substituted benzamide derivative. It is an unusual "atypical" antipsychotic,[1] as the "atypical" profile of the new antipsychotics clozapine, olanzapine, quetiapine, and risperidone has been linked to combined antagonism of serotonin 2 (5-HT2) and dopamine 2 (D2) receptors, whereas amisulpride has negligible affinity for 5 HT2 receptors and is specific for dopamine D2 and D3 receptors in the limbic rather than striatal structures.[2] There are reports of amisulpride being used for the management of bipolar disorders. However, there are very few reports of mania induced by amisulpride. Here we describe a young male who developed mania while on amisulpride, a newer antipsychotic drug introduced in India.

Case Report

A 18-year-old unmarried Hindu male presented with a history suggestive of schizophrenia for the last 2 years. The illness had an acute onset with complaints of suspiciousness, hearing voices not heard by others, violent abusive behavior, disturbed biological functions, and decreased self care. He was started on risperidone 4 mg along with trihexyphenidyl 2 mg and lorazepam 6 mg per day. Gradually, over a period of 1 month, he showed improvement in the symptoms. Subsequently, trihexyphenidyl and lorazepam were tapered and he was maintained on risperidone 4 mg per day for the next 1 and a half year. However, he would still be lethargic, would prefer to remain alone and would be inattentive at class. He would not interact with others and not take active part in various household functions. He would also not interact much with his younger siblings. He would deny sadness of mood or depressive cognitions. His mental status examination revealed decreased speech output and restricted affect. His past and family history were non-contributory to his present state. He was prescribed amisulpride for the negative symptoms along with risperidone 4 mg that was continued. It was initiated at 50 mg per day and was increased to 100 mg per day after 4 days of initiation it. After 10 days of 100 mg dose, the patient developed a manic episode, characterized by decreased need for sleep, over talkativeness, hyperactivity, persistent elevated mood, disinhibited behavior, over-grooming, and distractibility. His Young Mania Rating Scale (YMRS) score was 33. He reported on the third day of these symptoms. Amisulpride was stopped and he was prescribed lorazepam 4 mg on as and when required basis. Risperidone was continued in the same dose i.e. 4 mg per day. The patient was followed up after 1 week and during this time there was substantial improvement in his manic symptoms with YMRS score of 17. His symptoms resolved completely over the next week.

Discussion

To the best of our knowledge of mania due to first amisulpride was reported by Murphy in 2003.[3] However, in the case described by Murphy, the patient was also on citalopram, an antidepressant, though its discontinuation did not led to improvement in manic symptoms. Also, the patient was initiated on olanzapine immediately which would also probably have antimanic effects.

In our case, use of the Naranjo Adverse drug reaction Probability Scale and Edward's criteria both indicate a probable relationship between the manic episode and short-term exposure to amisulpride therapy.[45] The manic symptoms with amisulpride can be postulated to be due to the fact that amisulpride in low doses (<10 mg/kg), preferentially blocks presynaptic D2/D3 receptors, resulting in enhanced dopamine transmission.[2] Increased dopamine metabolites and increased dopamine transmission have been reported in patients with mania.[67]

This case report highlights the fact that close monitoring of patients on amisulpiride should be done for manic symptoms. This is also important because of the fact that atypical antipsychotic drugs (including amisulpride) are used for the treatment for bipolar disorder.[8] Open label studies have shown that amisulpride may be useful for patients with bipolar disorder.[9] Also, as low doses enhance dopamine transmission, and high doses reduce dopamine transmission, it might be prudent to start amisulpride at the recommended target dose at the initiation of therapy. The upward dose titration, in fact, may be harmful.