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 , 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 as clozapine was the medication last introduced , it was withdrawn and the patient continued the other medications , i.e. , amisulpride 600 mg / day in three divided doses along with propranolol 120 mg and trihexyphenidyl 4 mg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 in order to achieve total side effect remission , amisulpride was completely withdrawn under the cover of lorazepam 6 mg and propranolol 120 mg .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 . it 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 . only one case report and another case in a case series report have reported positive results attempting clozapine augmentation of patients after non successful treatment of amisulpride . however , this case reported here have shown an occurrence of unwanted side effects in the form of akathisia , dystonia and sialorrhoea after addition of clozapine . whereas , sialorrhoea can solely be due to clozapine , which was subsided after withdrawal of clozapine , akathisia , and dystonia is very unlikely to be caused by clozapine at a dose of 75 mg / day . it is rather more likely to be caused by amisulpride , especially after an escalation of dose . here amisulpride dose was not escalated but side effects occurred , which was time related to addition of clozapine . though amisulpride serum level could not be measured in this case , from clinical setting , it was very evident that most probably there may be increase in amisulpride serum level due to drug interaction with clozapine . it is known that amisulpride is only sparingly metabolized by liver enzymes and thus it is not known to participate in many drug interaction . however , an article had already reported that there was increase of blood level of amisulpride on addition of clozapine . this interaction might be a probable explanation for this case 's adverse effect . as the symptoms persisted even after complete withdrawal of clozapine and administration of supportive medications in proper doses . it also raises the question , whether elevation of amisulpride blood level is instrumental in obtaining good result in augmentation strategy , as a study has already shown that amisulpride does nt seem to increase the blood level of clozapine . interestingly these two pharmacokinetic observations can not fully explain the reason , why patients resistant to both the medication alone , can respond to their combination therapy but question may be raised whether sequence of introduction of medications may have some role in this augmentation strategy , as clearly it is safer to augment a partial responder with optimal dose of clozapine with amisulpride than the reverse , because there are more chances of producing side effects in the later schedule . further systematic research is required to study , whether it is mere association or sequence of introduction of medications may have some role in augmentation strategies and also the exact nature of amisulpride , clozapine drug interaction and possible reasons behind it .