Augmenting amisulpride with clozapine had led to unmasking of akathisia
A 20-year-old man presented with akathisia with psychomotor agitation. He had a 5-year history of schizophrenia and was previously partially controlled on risperidone 6 mg with trihexyphenidyl 4 mg in two equally divided doses daily in the last 2 years. Then he was switched to amisulpride 200 mg twice daily, that initially controlled the akathisia and agitation symptoms. However, this dose of amisulpride (400 mg in two divided doses) for 2 months did not achieve full symptom remission although he was better than before with akathisia remitted and psychomotor agitation controlled but still had disorganized behavior, fleeting delusion and hallucination. In an attempt to achieve complete symptom remission the patient was switched to amisulpride 200 mg thrice daily (600 mg/day) for next 6 weeks. Unfortunately, the patient did not achieve any further symptom remission, but did not deteriorate either. At this juncture, clozapine was definitely a strong choice. However, as the patient has already partially responded to amisulpride without much side-effect and amisulpride augmentation of clozapine is a proven effective procedure,[] to achieve further clinical improvement this augmentation strategy were thought of. Here reverse augmentation strategy i.e., to augment amisulpride with clozapine (25 mg to start with, which then escalated to 75 mg with 25 mg increments every 3 days) was tried, with an expectation of achieving symptom remission, as these two medicines may have synergistic effect. However, within 2 weeks this patient presented severe akathisia, restlessness, hypertonia along with sialorrhoea and tachycardia. These were managed with propranolol 120 mg and trihexyphenidyl 4 mg, but with modest success for 1 week. As clozapine was the medication last introduced, it was withdrawn and the patient continued the other medications, i.e., amisulpride 600 mg/day in three divided doses along with propranolol 120 mg and trihexyphenidyl 4 mg. Moderate improvement of akathisia and agitation symptoms was noted after 1 month, but it did not reach the base level, which were present before start of clozapine. Sialorrhoea was completely subsided on this regime. In order to achieve total side effect remission, amisulpride was completely withdrawn under the cover of lorazepam 6 mg and propranolol 120 mg. In another 2 weeks, akathisia symptoms drastically remitted but psychotic symptoms like aggressiveness, disorganized speech and behavior, use of abusive language severely increased.\nIt is known that clozapine has one of the least tendencies to cause akathisia symptoms on its own[] and withdrawal of clozapine did not remit akathisia and agitation completely, led to a hypothesis that it may not be clozapine per se, but its interaction with amisulpride might be instrumental in generation of the akathisia symptoms. So it was decided to give clozapine as a mono therapy a try, as it is a proven effective agent in treatment resistant schizophrenia. Hence clozapine was reintroduced without amisulpride at 50 mg/day, which was increased to 150 mg/day with small increments of 25 mg weekly. This regime showed very significant symptom control without any akathisia, along with propranolol 120 mg and lorazepam 4 mg. Even after slow withdrawal of supportive medications like propranolol and lorazepam the patient maintained effective symptom control without any akathisia or other unwanted side effect.