***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objectives To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate ( quetiapine XR ) monotherapy in patients with major depressive disorder ( MDD ) . Patients and methods This was a 10-week ( 8-week active treatment/2-week post-treatment ) r and omized , double-blind , placebo- and active-controlled study ( D1448C00004 ) . Patients received quetiapine XR 150 mg/day , escitalopram 10 mg/day , or placebo ; patients with an inadequate response ( < 20 % improvement in Montgomery – Åsberg Depression Rating Scale [ MADRS ] total score ) at week two received double-dose treatment . The primary end point was week eight change from r and omization in MADRS total score . Secondary end points included MADRS response ( ≥50 % improvement ) and remission ( score ≤8 ) ; Hamilton Rating Scale for Depression total and item 1 ; Hamilton Rating Scale for Anxiety total , psychic , and somatic ; Clinical Global Impressions – Severity of Illness total ; Pittsburgh Sleep Quality Index ( PSQI ) global ; and Quality of Life Enjoyment and Satisfaction Question naire – Short Form percentage maximum total scores . Tolerability was assessed throughout . Results A total of 471 patients was r and omized . No significant improvements in MADRS total score were observed at week eight ( last observation carried forward ) with either active treatment ( quetiapine XR , −17.21 [ P=0.174 ] ; escitalopram , −16.73 [ P=0.346 ] ) versus placebo ( −15.61 ) . There were no significant differences in secondary end points versus placebo , with the exception of week-eight change in PSQI global score  ( quetiapine XR , −4.96 [ P<0.01 ] versus placebo , −3.37 ) . Mixed-model repeated- measures analysis of observed-case data suggested that the primary analysis may not be robust . Most commonly reported adverse events included dry mouth , somnolence , and dizziness for quetiapine XR , and headache and nausea for escitalopram . Conclusion In this study , neither quetiapine XR ( 150/300 mg/day ) nor escitalopram ( 10/20 mg/day ) showed significant separation from placebo . Both compounds have been shown previously to be effective in the treatment of MDD ; possible reasons for this failed study are discussed . Quetiapine XR was generally well tolerated , with a profile similar to that reported previously OBJECTIVE The authors evaluated the efficacy and safety of lurasidone in the treatment of patients with major depressive episodes associated with bipolar I disorder . METHOD Patients were r and omly assigned to receive double-blind treatment with lurasidone ( 20 - 60 mg/day [ N=166 ] or 80 - 120 mg/day [ N=169 ] ) or placebo ( N=170 ) for 6 weeks . Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale ( MADRS ) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness ( CGI-BP ) , respectively . RESULTS Lurasidone treatment significantly reduced mean MADRS total scores at week 6 for both the 20 - 60 mg/day group ( -15.4 ; effect size=0.51 ) and the 80 - 120 mg/day group ( -15.4 ; effect size=0.51 ) compared with placebo ( -10.7 ) . Similarly , lurasidone treatment result ed in significantly greater endpoint reduction in CGI-BP depression severity scores for both the 20 - 60 mg/day group ( -1.8 ; effect size=0.61 ) and the 80 - 120 mg/day group ( -1.7 ; effect size=0.50 ) compared with placebo ( -1.1 ) . Both lurasidone groups also experienced significant improvements compared with placebo in anxiety symptoms and in patient-reported measures of quality of life and functional impairment . Discontinuation rates due to adverse events were similar in the 20 - 60 mg/day ( 6.6 % ) , 80 - 120 mg/day ( 5.9 % ) , and placebo ( 6.5 % ) groups . The most frequent adverse events associated with lurasidone were nausea , headache , akathisia , and somnolence . Minimal changes in weight , lipids , and measures of glycemic control were observed with lurasidone . CONCLUSION Monotherapy with lurasidone in the dosage range of 20 - 120 mg/day significantly reduced depressive symptoms in patients with bipolar I depression . Lurasidone was well tolerated , with few changes in weight or metabolic parameters OBJECTIVE To evaluate aripiprazole once-monthly ( AOM ) , a long-acting injectable suspension of aripiprazole , as acute treatment in patients with schizophrenia ( DSM-IV-TR ) . METHOD Adults experiencing an acute psychotic episode were r and omized to 12 weeks of double-blind treatment with  AOM 400 mg or placebo ( October 2012-August 2013 ) . The primary efficacy outcome was change from baseline to endpoint ( week 10 ) in Positive and Negative Syndrome Scale ( PANSS ) total score . The key secondary efficacy outcome was change from baseline in Clinical Global Impressions-Severity of Illness scale ( CGI-S ) score . Secondary efficacy outcomes included change from baseline in PANSS positive and negative subscale and Personal and Social Performance Scale ( PSP ) scores . The study took place from October 2012 through August 2013 . RESULTS Patients ( N = 340 ; 79 % male , 66 % black ) were r and omized to AOM ( n = 168 ) or placebo ( n = 172 ) . Least squares ( LS ) mean change from baseline to endpoint ( week 10 ) favored AOM versus placebo in PANSS total ( treatment difference , -15.1 [ 95 % CI , -19.4 to -10.8 ] ; P < .0001 ) and CGI-S ( treatment difference , -0.8 [ 95 % CI , -1.1 to -0.6 ] ; P < .0001 ) scores , as it did at all other timepoints through 12 weeks ( all P ≤ .0005 ) . LS mean change from baseline in PANSS positive and negative subscale and PSP scores favored AOM versus placebo ( P < .0001 ) . Common ( > 10 % ) treatment-emergent adverse events  ( AOM vs. placebo ) were increased weight ( 16.8 % vs 7.0 % ) , headache ( 14.4 % vs. 16.3 % ) , and akathisia ( 11.4 % vs 3.5 % ) . CONCLUSIONS Symptoms and functioning improved with AOM 400 mg versus placebo in patients with acute schizophrenia , with acceptable safety and tolerability . These data suggest that AOM 400 mg is a viable treatment option for patients experiencing an acute schizophrenia episode . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01663532 OBJECTIVE The efficacy , safety , and tolerability of brexpiprazole and placebo were compared in adults with acute schizophrenia . METHOD This was a multicenter , r and omized , double-blind , placebo-controlled study . Patients with schizophrenia experiencing an acute exacerbation were r and omly assigned to daily brexpiprazole at a dosage of 0.25 , 2 , or 4 mg or placebo ( 1:2:2:2 ) for 6 weeks . Outcomes included change from baseline to week 6 in Positive and Negative Syndrome Scale ( PANSS ) total score ( primary endpoint measure ) , Clinical Global Impressions Scale ( CGI ) severity score ( key secondary endpoint measure ) , and other efficacy and tolerability measures . RESULTS The baseline overall mean PANSS total score was 95.2 , and the CGI severity score was 4.9 . Study completion rates were 62.2 % , 68.1 % , and 67.2 % for patients in the 0.25- , 2- , and 4-mg brexpiprazole groups , respectively , versus 59.2 % in the placebo group . At week 6 , compared with placebo , brexpiprazole dosages of 2 and 4 mg produced statistically significantly greater reductions in PANSS total score ( treatment differences : -8.72 and -7.64 , respectively ) and CGI severity score ( treatment differences : -0.33 and -0.38 ) . The most common treatment-emergent adverse event for brexpiprazole was akathisia ( 2 mg : 4.4 % ; 4 mg : 7.2 % ; placebo : 2.2 % ) . Weight gain with brexpiprazole was moderate ( 1.45 and 1.28 kg for 2 and 4 mg , respectively , versus 0.42 kg for placebo at week 6 ) . There were no clinical ly or statistically significant changes from baseline in lipid and glucose levels and extrapyramidal symptom ratings . CONCLUSIONS Brexpiprazole at dosages of 2 and 4 mg/day demonstrated statistically significant efficacy compared with placebo and good tolerability for patients with an acute schizophrenia exacerbation The aim of this study was to evaluate the short-term efficacy and safety of lurasidone in treating irritability associated with autistic disorder . In this multicenter trial , out patients age 6–17 years who met DSM-IV-TR criteria for autistic disorder , and who demonstrated irritability , agitation , and /or self-injurious behaviors were r and omized to 6 weeks of double-blind treatment with lurasidone 20 mg/day ( N = 50 ) , 60 mg/day ( N = 49 ) , or placebo ( N = 51 ) . Efficacy measures included the Aberrant Behavior Checklist Irritability subscale ( ABC-I , the primary endpoint ) and the Clinical Global Impressions , Improvement ( CGI-I ) scale , and were analyzed using a likelihood-based mixed model for repeated measures . Least squares ( LS ) mean ( st and ard error [ SE ] ) improvement from baseline to Week 6 in the ABC-I was not significantly different for lurasidone 20 mg/day ( −8.8 [ 1.5 ] ) and lurasidone 60 mg/day ( −9.4 [ 1.4 ] ) versus placebo ( −7.5 [ 1.5 ] ; p = 0.55 and 0.36 , respectively ) . CGI-I scores showed significantly greater LS mean [ SE ] improvement at Week 6 for lurasidone 20 mg/day versus placebo ( 2.8 [ 0.2 ] vs. 3.4 [ 0.2 ] ; p = 0.035 ) but not for lurasidone 60 mg/day ( 3.1 [ 0.2 ] ; p = 0.27 ) . Discontinuation rates due to adverse events  were : lurasidone 20 mg/day , 4.1 % ; 60 mg/day , 3.9 % ; and placebo , 8.2 % . Adverse events with an incidence ≥10 % ( lurasidone combined , placebo ) included vomiting ( 18.0 , 4.1 % ) and somnolence ( 12.0 , 4.1 % ) . Modest changes were observed in weight and selected metabolic parameters . In this study , once-daily , fixed doses of 20 and 60 mg/day of lurasidone were not demonstrated to be efficacious compared to placebo for the short-term treatment of children and adolescents with moderate-to-severe irritability associated with autistic disorder AIMS Morbidity and mortality from drug overdose has decreased over three decades . This is credited to safer drugs and therefore better outcomes in overdose . We aim ed to investigate changing prescriptions of antipsychotic medications and associated changes in antipsychotic overdoses over a 26-year period . METHODS All antipsychotic poisoning presentations to a tertiary referral toxicology unit between 1987 and 2012 were review ed . Data were collected prospect ively on demographics , ingestion information , clinical effects , complications and treatment . Rates of antipsychotic drug use in Australia were obtained from Australian government publications for 1990 - 2011 and linked to overdose admissions by postcode . RESULTS There were 3180 antipsychotic overdoses : 1235 first generation antipsychotics , 1695 ' atypical ' second generation antipsychotics and 250 lithium overdoses . Over 26 years , antipsychotic overdoses increased 1.8-fold , with first generation antipsychotics decreasing to one-fifth of their peak ( ≈80/year to 16 ) and second generation antipsychotics increasing to double this ( ≈160/year ) , olanzapine and quetiapine accounting for 78 % . All antipsychotic overdoses had a median length of stay of 18.6 h , 15.7 % admitted to intensive care unit , 10.4 % ventilated and 0.13 % died in hospital , which was the same for first generation compared to second generation antipsychotics . There was a 2.3-fold increase in anti 
    Output:
    
The results support previous findings that weight-gain occurs quickly .