cognitive impairment is associated with poor functional outcome and long - term prognosis [ 4 , 5 ] . these impairments also determine quality of life and medical and social cost of schizophrenia [ 6 , 7 ] . systematic analyses have shown that conventional antipsychotics have a modest benefit in improving cognitive dysfunctions . also , current treatment of schizophrenia with these typical antipsychotics is limited by the side effects of the drugs . side effects like parkinsonian syndrome [ 9 , 10 ] and tardive dyskinesia   occur in a significant number of patients only to deteriorate the quality of life . with the arrival of newer atypical antipsychotics that are claimed to have low incidence of extrapyramidal effects   and provide a more significant improvement in cognitive dysfunctions than conventional drugs , the scenario of schizophrenia seems to change though results are not entirely consistent . though these atypical drugs share the property of blocking dopamine d2 receptors in limbic system , they have different overall pharmacological profile . amisulpride is an atypical antipsychotic with selective affinity for d2 and d3 receptors , with efficacy in positive and negative schizophrenic symptoms , and with low incidence of extrapyramidal symptoms . this drug also shows improvement in neuropsychological performance in patients of schizophrenia [ 17 , 18 ] . olanzapine , on the other hand , acts on various monoamine receptors like 5-ht2 and d2 receptors . it also shows low incidence of extrapyramidal side effects , efficacy in psychotic symptoms , and improvement in neuropsychological performance [ 21 , 22 ] . we have performed a two - month , double - blind , randomized clinical trial of olanzapine versus amisulpride for treating acute exacerbation of schizophrenia . overall objectives of study were to compare both treatments in terms of efficacy , safety , and impact on cognitive functions . the study was conducted in the government mental hospital , banganga , indore , madhya pradesh , india . patients of either sex in the age group of 1845 years with a diagnosis of schizophrenia according to icd 10 criteria were included . both inpatients and outpatients symptoms were assessed using brief psychiatric rating scale ( bprs scale )   and positive and negative syndrome scale ( panss scale ) . a bprs score of at least 36 and positive panss score more than negative was an essential criterion for randomization of patients . pregnant and lactating women were excluded and women of childbearing age were advised to use adequate means of contraception . each patient was included in the study after applying inclusion and exclusion criteria and through clinical and psychiatric examination . eligible patients were randomized to one of the treatment arms either amisulpride 400  mg / d or olanzapine 10  mg / d . the medicine doses were adjusted to 400800  mg / d orally for amisulpride and olanzapine and 1020  mg / d orally for olanzapine according to individual patient response and tolerability . follow - up visits for efficacy , safety , and cognitive assessment were performed at 4 and 8 weeks . concomitant use of benzodiazepines , nonbenzodiazepine hypnotics ( zolpidem , zopiclone ) , and anti - parkinsonian drug , trihexyphenidyl , was allowed at the investigator 's discretion . the study was conducted according to good clinical practices [ european / icmr guidelines ] . patients were free to withdraw from the study at any time , due to any reason , and without effect on their treatment . , a full clinical examination including recording of vital signs and body weight was done . cognitive assessment involved token test , stroop test [ 27 , 28 ] , digit vigilance test , animal names test , and triads test . subjects exposed to efficacy analysis were the intention - to - treat population , that is , all patients randomized and exposed to treatment and providing at least one postbaseline evaluation . missing data due to premature discontinuation mean change in bprs and panss scale over the study period was compared in both the treatment arms using mann whitney u test for independent samples because of low sample size . mean change in scores of cognitive tests was compared in both the arms using mann whitney u test for independent samples . total of 81 patients were included ( 40 in amisulpride group and 41 in olanzapine group ) with comparable baseline characteristics ( table 1 ) . out of these 74 patients provided at least one post treatment reading and these were the intention to treat population . 32 patients in amisulpride ( 80% ) as well as olanzapine ( 78.04% ) group completed the two months treatment . incidence of premature discontinuation was not different in both the groups . during the study period change observed in bprs score in amisulpride group was 16.80 ( sd : 3.61 ) and in olanzapine group was 15.30 ( sd : 2.69 ) ( table 3 ) . this improvement was similar in both groups and was not statistically significant ( p = 0.38 ) . symptomatic improvement was also observed on panss scale in both the groups ( p = 0.22 ) ( table 4 ) . only one patient in amisulpride group suffered from adverse event to warrant his removal from the study . there was no difference in score between baseline and end of two months in abnormal voluntary movement scale . there was a more statistically significant ( p < 0.001 ) weight gain observed in olanzapine group ( 2.09  kg ) than in amisulpride group ( 0.94  kg ) . amisulpride group performed significantly better ( p = 0.02 ) than olanzapine group in this test ( table 5 ) . there was statistically significant difference found between these two groups ( p = 0.03 ) ( table 6 ) . amisulpride group performed better than olanzapine group with a p value of 0.02 ( table 7 ) . it is a test of attention , alertness , and mental processing capacity using a rapid visual tracking task . amisulpride group performed better in both aspects of test , that is , time factor ( p < 0.001 ) and number of errors ( p < 0.001 ) than olanzapine group ( table 8) . amisulpride group showed statistically significant ( p < 0.001 ) improvement in this test than olanzapine group ( table 9 ) . a major reason behind performing this study was to gather data on schizophrenic patients in india . cognitive tests used were designed by nimhans institute , banglore , especially for indian population , which helped us to perform this study . the study showed that amisulpride and olanzapine were equally effective in the treatment of acute exacerbation of schizophrenia as shown by bprs scores . both drugs showed comparable improvement over the study period of two months . as far as panss scale is concerned , however , negative symptoms score was low at baseline and did not improve markedly during study in both the groups . the general psychopathology symptom subscale in panss also showed improvement during the study . in case of safety , olanzapine group showed a significant weight gain ( mean of 2.09  kgs ) as compared to amisulpride group ( mean of 0.9  kgs ) . excessive weight gain with olanzapine is a well - characterized side effect of this drug [ 34 , 35 ] and may increase the subsequent risk of cardiovascular disease , diabetes , and hyperlipidemia . difference in weight gain in both the drugs may be explained by the mechanisms of action of both . weight gain is claimed to involve serotonergic mechanism , and olanzapine is a potent antagonist at 5-ht2 receptors . amisulpride being a very specific dopaminergic antagonist may not share the weight gain property . with respect to extrapyramidal side effects , our study did not show emergence of these in both treatment groups . amisulpride group fared better in cognitive aspects of study , that is , divided attention , response inhibition , verbal comprehension , and verbal fluency . previous studies [ 13 , 17 , 38 ] have shown that agents like olanzapine , which have affinity for 5-ht2 , lack effect on learning and memory performance in patients of schizophrenia . while our study shows results consistent with these studies , our results are in disagreement with a large canadian open - label study , which showed improvement with olanzapine , which may be due to low sample size in our study . considering the differences between these two agents in terms of effect on cognition , the following explanation may clear the difference . dopamine projections to the prefrontal cortex comprising the mesocortical dopamine system are essential for normal cognition . amisulpride is a benzamide with high affinity for dopamine d2 , and d3 , receptors without affinity for serotonin , muscarinic , or alpha - adrenergic receptors . at low doses ( 100300  mg / d ) , amisulpride binds preferentially on d2/d3 presynaptic autoreceptors , increasing dopaminergic transmission in the prefrontal cortex , which is believed to be associated with improvement of cognitive symptoms . selective binding of amisulpride also makes it free of side effects like sedation and weight gain seen with blockade of other receptors . it was proved in a previous study [ 38 , 41 ] that serotonin antagonism as in olanzapine was not necessary for improvement in cognitive dysfunctions and was responsible for some of the side effects like weight gain seen with olanzapine . olanzapine improves verbal learning and memory , verbal fluency , and executive function , but not attention , working memory , or visual learning and memory . to conclude , amisulpride and olanzapine show equivalent efficacy in improving psychotic symptoms of schizophrenia . amisulpride gains an upper hand in preserving body weight and in improvement of cognitive functions .
background . impaired 
 cognitive functions in schizophrenia are the major deciding factors in response to treatment . 
 conventional antipsychotics have minimal impact on cognitive dysfunctions and are associated with adverse effects . 
 atypical antipsychotics have shown promise in treatment of cognitive and negative symptoms of schizophrenia . 
 efforts are underway to find out the best drug amongst atypical antipsychotics . objective . to compare efficacy , safety , and cognitive profile of amisulpride and olanzapine in the treatment of acute psychotic exacerbations of schizophrenia 
 . method . 
 a prospective , randomized , double - blind , single - center , 8-week clinical trial we used . 
 subjects and treatments . 
 seventy four patients were treated for two months with either amisulpride ( 400800  mg / d ) or olanzapine ( 1020  mg / d ) . statistics . 
 mann whitney u test we used for independent samples with p < 0.05 taken as significant 
 . results . 
 brief psychiatric rating scale ( bprs ) was used as a primary measure of efficacy . 
 other measures of efficacy and safety were also evaluated . 
 both amisulpride and olanzapine groups showed equivalent improvement in psychotic symptoms on bprs scale . 
 less than five percent of patients suffered adverse effects only to withdraw from the study . 
 olanzapine group showed statistically significant ( p < 0.05 ) weight gain compared with amisulpride group . 
 amisulpride group showed significant improvement ( p < 0.05 ) in various cognitive parameters as compared to olanzapine group .