***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: Purpose / Background Negative symptoms and cognitive impairments tend to co-occur in people with schizophrenia . If their association with each other is due , in part , to shared pathophysiology , then this suggests that a single drug could potentially be effective for both domains . The current study was design ed to examine this hypothesis . Methods / Procedures Fifty-eight participants with either Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Text Revision schizophrenia or schizoaffective disorder entered into a 6-week double-blind , placebo-controlled , double-dummy , r and omized clinical trial of intranasal oxytocin and galantamine .  Seventeen participants were r and omized to intranasal oxytocin  , 20 were r and omized to galantamine  , and 21 were r and omized to placebo .  The Scale for the Assessment of Negative Symptoms total score was used to assess change in negative symptoms ( the primary outcome measure for oxytocin ) . The MATRICS Consensus Cognitive Battery composite score was used to assess cognition ( the primary outcome measure for galantamine ) . Findings / Results There were no significant group differences for negative symptoms ( oxytocin vs placebo : F2,47.4 = 0.19 , P = 0.83 ; galantamine vs placebo : F2,52.5 = 0.41 , P = 0.67 ) . There were no significant group differences for cognitive impairments  ( galantamine vs placebo : t40 = 0.71 , P = 0.48 ; oxytocin vs placebo : t40 = 0.50 , P = 0.62 ) . There were also no significant group differences for the functional capacity or ancillary symptom measures . Implication s/ Conclusions The lack of an efficacy signal for either compound precluded our ability to test whether pharmacological treatment pathways for negative symptoms and cognitive impairments overlap or are independent OBJECTIVE Cognitive impairment and negative signs are common in patients with schizophrenia . Up to 35 % of elderly patients with schizophrenia fulfill the diagnostic criteria of dementia . Donepezil inhibits cholinesterase , thus enhancing cholinergic neurotransmission . We tested the efficacy of donepezil in elderly patients with chronic schizophrenia and severe cognitive impairment . METHOD Following baseline assessment , patients were r and omly assigned to receive either donepezil or placebo . The dose was 5 mg daily for the first week and 10 mg for an additional 11 weeks . The procedure was repeated using the crossover compound . The Positive and Negative Symptom Scale ( PANSS ) , Clinical Global Impression Scale ( CGI ) and Alzheimer Disease Assessment Scale - Cognitive subscale ( ADAS-Cog ) were used to assess the severity of symptoms , cognitive status and intervention effects . RESULTS Twenty subjects were enrolled ( 15 females , five males ) , mean age 70.2 years ( SD 6.5 ) and mean duration of disease 38.5 years ( SD 9.3 ) . A modest treatment effect was found for both placebo and donepezil treatment periods . No crossover effect was found . No statistical differences were demonstrated between the two treatment groups ( CGI p = 0.37 , PANSS p = 0.71 , ADAS-Cog p = 0.86 ) . Two patients died during the study period due to unrelated causes and one patient discontinued participation due to increased agitation . CONCLUSION Donepezil does not seem to improve negative signs and cognitive impairment in elderly patients with chronic schizophrenia BACKGROUND Despite the beneficial effects of atypical antipsychotics on cognition , these improvements will not return most schizophrenic patients to normative st and ards of cognitive functioning . Therefore , other treatments need to be considered . Subtle changes in cholinergic function in schizophrenic patients provide the rationale to test the effectiveness of cholinesterase inhibitors in treating cognitive impairment in schizophrenia . METHODS Given this , a 12-week , double-blind , placebo-controlled trial of donepezil ( 5 mg and 10 mg ) as adjunctive treatment to risperidone was conducted in a total of 36 schizophrenic patients . RESULTS Neither the 5-mg nor 10-mg dose of donepezil produced significant improvements in any cognitive measure compared with placebo . CONCLUSIONS It is possible that nicotinic receptor desensitization produced by chronic tobacco use in these patients rendered their nicotinic receptors refractory to the effects of increased agonist activity produced by donepezil . An alternative treatment is the allosterically potentiating lig and s , which enhance the activity of ( sensitize ) nicotinic receptors in the presence of acetylcholine treatment of schizophrenia , they do n’t adequately address residual positive , negative and depressive symptoms . The aim of the present study is to assess the effect of adjunctive memantine treatment on positive , negative and depressive symptoms of schizophrenia . METHODS This r and omized , placebo-controlled study was conducted in Noor Hospital , Isfahan , Iran , 2013 - 2014 ; 32 patients in maintenance treatment were included in each group , using block sampling ; inclusion criteria were age 18- 65 years , normal intellectual ability , being diagnosed with schizophrenia for the past two years , being treated with fixed doses of atypical antipsychotic for at least three months before r and omization . Exclusion criteria were pregnancy , breast feeding , having received electro-convulsive therapy in the past two weeks , drug or substance abuse and dependence , psychiatric/ neurological comorbidities , and sensitivity to memantine . Patients in the intervention group were treated with memantine plus atypical antipsychotic ; while in the control group , patients received placebo and atypical antipsychotic . Patients were assessed by Positive and Negative Symptom Scale ( PANSS ) and Calgary Depression Scale for Schizophrenia ( CDSS ) initially and every four weeks to the end of the 12th week . Data were analyzed in SPSS 17.0 using t-test , chi square , analysis of variance ( ANOVA ) , and analysis of covariance ( ANCOVA ) . RESULTS Positive symptoms ( p=0.028 ) , negative symptoms ( 0.004 ) , general psychopathology ( p<0.001 ) , depressive symptoms ( p<0.001 ) and total symptom severity ( p<0.001 ) decreased significantly in patients receiving add-on memantine . CONCLUSION This study shows that , add-on memantine would be helpful , in the adjunctive treatment of depressive , positive , negative and general symptoms in patients with schizophrenia BACKGROUND Glutamate deregulation may be involved in the neuropathology of schizophrenia , mainly through N-methyl-d-aspartate ( NMDA ) receptor dysfunction . Memantine , a drug approved by the FDA for the treatment of moderate to severe Alzheimer 's disease , acts as a weak nonselective NMDA receptor antagonist . The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to clozapine in patients with refractory schizophrenia . METHOD In this double-blind , placebo-controlled study , out patients with refractory schizophrenia according to DSM-IV clinical criteria were r and omly assigned , from March 2005 to February 2008 , to receive either 20 mg/d memantine ( n = 10 ) or placebo ( n = 11 ) , in addition to clozapine , for 12 weeks . The primary outcome measure was the total score on the 18-item Brief Psychiatry Rating Scale ( BPRS ) and BPRS subscales of positive and negative symptoms . Secondary outcomes were global severity of disease as measured by the Clinical Global Impressions scale ( CGI ) , cognition as assessed by the Mini-Mental State Examination ( MMSE ) , and extrapyramidal symptoms as assessed by the Simpson-Angus Scale ( SAS ) . RESULTS Twenty-one participants completed the study and were used in the analysis . Significant improvement ( P < .01 ) on the total BPRS score , its subscales of positive ( effect size [ ES ] = -1.38 ) and negative ( ES = -3.33 ) symptoms , the CGI score ( ES = 1.56 ) , and the MMSE score was observed with memantine as compared with placebo . No significant changes in extrapyramidal symptoms were observed . CONCLUSIONS Memantine add-on to clozapine therapy was associated with improvement in negative and positive symptoms in refractory schizophrenia patients . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00757978 Altered expression of central muscarinic and nicotinic acetylcholine receptors in hippocampal and cortical regions may contribute to the cognitive impairment exhibited in patients with schizophrenia . Increasing cholinergic activity through the use of a cholinesterase inhibitor ( ChEI ) therefore represents a possible strategy for cognitive augmentation in schizophrenia . We examined the efficacy and safety of the ChEI donepezil as cotreatment for mild to moderate cognitive impairment in schizophrenia or schizoaffective disorder in a prospect i ve , 12-week , placebo-controlled , double-blind , parallel-group study . In total , 250 patients ( 18–55 years ) with schizophrenia or schizoaffective disorder who were clinical ly stabilized on risperidone , olanzapine , quetiapine , ziprasidone , or aripiprazole , alone or in combination , were enrolled at 38 outpatient psychiatric clinics in the United States . Patients were r and omized to donepezil 5 mg q.d . for 6 weeks then 10 mg q.d . for 6 weeks , or placebo administered as oral tablets . The primary outcome measure was the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) neurocognitive battery composite score . In the intent-to-treat sample ( donepezil , n=121 ; placebo , n=124 ) , both treatments showed improvement in the composite score from baseline to week 12 . At week 12 , cognitive improvement with donepezil was similar to that with placebo ( last-observation-carried-forward effect size , 0.277 vs 0.411 ; p=0.1182 ) and statistically significantly inferior for the observed-cases analysis ( 0.257 vs 0.450 ; p=0.044 ) . There was statistically significant improvement in the Positive and Negative Syndrome Assessment Scale negative symptoms score for placebo compared with donepezil , while total and positive symptom scores were similar between both treatments . Statistically significant improvements in positive symptoms score and Clinical Global Impression-Improvement for donepezil compared with placebo were noted at Week 6 . Treatment-emergent adverse events ( AEs ) were observed for 54.5 % of donepezil- and 61.3 % of placebo-treated patients ; most AEs were rated as mild to moderate in severity . Donepezil was safe and well-tolerated but was not effective compared with placebo as a cotreatment for the improvement of cognitive impairment in this patient population . A significant and surprisingly large placebo/ practice effect was observed among placebo-treated patients , and is a serious consideration in future clinical trial study design s for potential cognitive enhancing compounds in schizophrenia There have been many advancements in the pharmacologic treatment of schizophrenia ; however , negative symptoms and cognitive impairment remain an intractable part of this illness . Donepezil is an anticholinesterase inhibitor with cognitive enhancing effects approved for the treatment of Alzheimer disease that has shown some benefit in the treatment of schizophrenia . In this study , 15 in patients at a state hospital with a history of schizophrenia were administered donepezil in a r and omized , double-blind , crossover design . Neurocognitive testing and psychiatric ratings were completed at baseline and at regular intervals for 18 weeks . Results indicated that donepezil treatment was associated with modest improvements in psychiatric symptoms and improved verbal learning . These results suggest that donepezil may be helpful as adjunctive therapy for the treatment of psychiatric symptoms and cognitive impairment in a subgroup of schizophrenic patients 
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However , it was not superior to placebo+AP in improving composite cognitive test score , which more systematic ally evaluates cognitive impairment than the MMSE score .
Overall , ADD+AP treatment was well tolerated