Aripiprazole in the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorder in Japan: A Randomized, Double-blind, Placebo-controlled Study A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. A Head-to-Head Comparison of Aripiprazole and Risperidone for Safety and Treating Autistic Disorders, a Randomized Double Blind Clinical Trial Aripiprazole in the Treatment of Irritability in Children and Adolescents With Autistic Disorder Focus on aripiprazole: a review of its use in child and adolescent psychiatry. Safety and tolerability of aripiprazole for irritability in pediatric patients with autistic disorder: a 52-week, open-label, multicenter study. Aripiprazole treatment of irritability associated with autistic disorder and the relationship between prior antipsychotic exposure, adverse events, and weight change. Aripiprazole in juvenile bipolar disorder comorbid with attention-deficit/hyperactivity disorder: an open clinical trial. Aripiprazole in pervasive developmental disorder not otherwise specified and Asperger's disorder: a 14-week, prospective, open-label study. A randomized controlled trial investigating the safety and efficacy of aripiprazole in the long-term maintenance treatment of pediatric patients with irritability associated with autistic disorder. Risperidone for children and adolescents with autism spectrum disorder: a systematic review Effectiveness and tolerability of aripiprazole in child and adolescent inpatients: a retrospective evaluation A 12-week, naturalistic switch study of the efficacy and tolerability of aripiprazole in stable outpatients with schizophrenia or schizoaffective disorder A multicentre, randomized, naturalistic, open-label study between aripiprazole and standard of care in the management of community-treated schizophrenic patients Schizophrenia Trial of Aripiprazole: (STAR) study. Aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder: a pilot randomized clinical trial. Effect of aripiprazole 2 to 15 mg/d on health-related quality of life in the treatment of irritability associated with autistic disorder in children: a post hoc analysis of two controlled trials. A prospective, multicenter, randomized, parallel-group, open-label study of aripiprazole in the management of patients with schizophrenia or schizoaffective disorder in general psychiatric practice: Broad Effectiveness Trial With Aripiprazole (BETA)
We evaluated the efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents ( 6–17 years ) with autism spectrum disorder ( ASD ) in a r and omized , double-blind , placebo-controlled 8-week study in Japan . Patients received flexibly dosed aripiprazole ( 1–15 mg/day ) or placebo .  Ninety-two patients were r and omized to placebo ( n = 45 ) or aripiprazole ( n = 47 ) . Aripiprazole produced a significant improvement in the mean parent/caregiver-rated Aberrant Behavior Checklist Japanese Version irritability subscale score relative to placebo from week 3 through week 8 . Administration of aripiprazole provided significantly greater improvement in the mean clinician-rated Clinical Global Impression-Improvement scores than placebo from week 2 through week 8 . All patients r and omized to aripiprazole completed the study , and no serious adverse events were reported . Three patients in placebo group discontinued . Aripiprazole was effective and generally safe and well-tolerated in the treatment of irritability associated with ASD in Japanese children and adolescents OBJECTIVE To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder . METHOD Two hundred eighteen children and adolescents ( aged 6 - 17 years ) with a diagnosis of autistic disorder , and with behaviors such as tantrums , aggression , self-injurious behavior , or a combination of these symptoms , were r and omized 1:1:1:1 to aripiprazole ( 5 , 10 , or 15 mg/day ) or placebo in this 8-week double-blind , r and omized , placebo-controlled , parallel-group study . Efficacy was evaluated using the caregiver-rated Aberrant Behavior Checklist Irritability subscale ( primary efficacy measure ) and the clinician-rated Clinical Global Impressions-Improvement score . Safety and tolerability were also assessed . RESULTS At week 8 , all aripiprazole doses produced significantly greater improvement than placebo in mean Aberrant Behavior Checklist Irritability subscale scores ( 5 mg/day , -12.4 ; 10 mg/day , -13.2 ; 15 mg/day , -14.4 ; versus placebo , -8.4 ; all p < .05 ) . All aripiprazole doses demonstrated significantly greater improvements in mean Clinical Global Impressions-Improvement score than placebo at week 8 . Discontinuation rates due to adverse events were as follows : placebo 7.7 % , aripiprazole 5 mg/day 9.4 % , 10 mg/day 13.6 % , and 15 mg/day 7.4 % . The most common adverse event leading to discontinuation was sedation . There were two serious adverse events : presyncope ( 5 mg/day ) and aggression ( 10 mg/day ) . At week 8 , mean weight change ( last observation carried forward ) was as follows : placebo + 0.3 kg , aripiprazole 5 mg/day + 1.3 kg , 10 mg/day + 1.3 kg , and 15 mg/day + 1.5 kg ; all p < .05 versus placebo . CONCLUSIONS Aripiprazole was efficacious and generally safe and well tolerated in the treatment of children and adolescents with irritability associated with autistic disorder Abstract Aripiprazole and risperidone are the only FDA approved medications for treating irritability in autistic disorder , however there are no head-to-head data comparing these agents . This is the first prospect i ve r and omized clinical trial comparing the safety and efficacy of these two medications in patients with autism spectrum disorders . Fifty nine children and adolescents with autism spectrum disorders were r and omized to receive either aripiprazole or risperidone for 2 months . The primary outcome measure was change in Aberrant Behavior Checklist ( ABC ) scores . Adverse events were assessed . Aripiprazole as well as risperidone lowered ABC scores during 2 months . The rates of adverse effects were not significantly different between the two groups . The safety and efficacy of aripiprazole ( mean dose 5.5 mg/day ) and risperidone ( mean dose 1.12 mg/day ) were comparable . The choice between these two medications should be on the basis of clinical equipoise considering the patient ’s preference and clinical profile OBJECTIVE : The objective of this study was to evaluate short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder who were manifesting behaviors such as tantrums , aggression , self-injurious behavior , or a combination of these . METHODS : This 8-week , double-blind , r and omized , placebo-controlled , parallel-group study was conducted of children and adolescents ( aged 6–17 years ) with autistic disorder . Patients were r and omly assigned ( 1:1 ) to flexibly dosed aripiprazole ( target dosage : 5 , 10 , or 15 mg/day ) or placebo . Efficacy outcome measures included the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression – Improvement score ( CGI-I ) . Safety and tolerability were also assessed . RESULTS : Ninety-eight patients were r and omly assigned to receive placebo ( n = 51 ) or aripiprazole ( n = 47 ) . Mean improvement in Aberrant Behavior Checklist irritability subscale score was significantly greater with aripiprazole than with placebo from week 1 through week 8 . Aripiprazole demonstrated significantly greater global improvements than placebo , as assessed by the mean CGI-I score from week 1 through week 8 ; however , clinical ly significant residual symptoms may still persist for some patients . Discontinuation rates as a result of adverse events ( AEs ) were 10.6 % for aripiprazole and 5.9 % for placebo . Extrapyramidal symptom-related AE rates were 14.9 % for aripiprazole and 8.0 % for placebo . No serious AEs were reported . Mean weight gain was 2.0 kg on aripiprazole and 0.8 kg on placebo at week 8 . CONCLUSIONS : Aripiprazole was efficacious in children and adolescents with irritability associated with autistic disorder and was generally safe and well tolerated OBJECTIVE To review published literature regarding aripiprazole in child and adolescent psychiatry . METHOD A literature review was conducted using the medline search term : ' aripiprazole ' with limits : Human trials , English language , All Child ( aged 0 - 18 years ) . Additional articles were identified from reference information and poster presentation data . RESULTS Aripiprazole is an atypical antipsychotic which was recently approved for use in Canada , but has been available for several years in the United States . Pharmacologically , aripiprazole is a partial agonist at D(2 ) and 5-HT(1A ) receptors and an antagonist at 5-HT(2A ) receptors . R and omized controlled trial data is available showing efficacy for aripiprazole in the treatment of children and adolescents with schizophrenia , bipolar disorder and behavioural problems associated with autism . Open-label evidence is also available for use of aripiprazole in other disorders such as tic disorders , aggression and disruptive behavior disorders . Unlike some other available atypical antipsychotics , there does not appear to be any effect on QTc interval on the electrocardiogram . Adverse effects including extrapyramidal symptoms ( EPS ) , akathisia , sedation , headache , nausea were significant in clinical trials in children and adolescents . The possibility of aripiprazole causing tardive dyskinesia can not be excluded . In this population , aripiprazole appears to have minimal impact on the metabolic profile compared to most other atypical antipsychotics , with minimal changes in weight or body mass index , no significant changes in glucose or lipid metabolism , and a decrease in serum prolactin . CONCLUSION Aripiprazole may represent an important alternative for some children and adolescents who have experienced poor efficacy or significant metabolic adverse effects with their current antipsychotic treatment regimen OBJECTIVE Evaluate the long-term safety and tolerability of aripiprazole in the treatment of irritability in pediatric subjects ( 6 - 17 years ) with autistic disorder . METHOD A 52-week , open-label , flexibly dosed ( 2 - 15 mg/d ) study of the safety and tolerability of aripiprazole in out patients with a DSM-IV-TR diagnosis of autistic disorder who either had completed 1 of 2 antecedent , 8-week r and omized trials or were enrolled de novo ( ie , not treated in the r and omized trials ) .  Safety and tolerability measures included incidences of adverse events , extrapyramidal symptoms , weight , metabolic measures , vital signs , and other clinical assessment s. RESULTS Subjects were enrolled between September 2006 and June 2009 . Three hundred thirty subjects entered the treatment phase : 86 de novo , 174 prior aripiprazole , and 70 prior placebo . A total of 199 ( 60.3 % ) subjects completed 52 weeks of treatment . Adverse events were experienced by 286/330 subjects ( 86.7 % ) . Common adverse events included weight increase , vomiting , nasopharyngitis , increased appetite , pyrexia , upper respiratory tract infection , and insomnia . Discontinuations due to adverse events occurred in 35/330 r and omized subjects (10.6%)-most commonly aggression and weight increase . One patient discontinued from the study due to a laboratory-related adverse event ( moderately increased alanine transaminase and aspartate transaminase ) . Nine subjects experienced serious adverse events-most frequently aggression . Extrapyramidal symptoms-related adverse events occurred in 48/330 subjects (14.5%)-most commonly tremor ( 3.0 % ) , psychomotor hyperactivity ( 2.7 % ) , akathisia ( 2.4 % ) , and dyskinesia ( not tardive , 2.4 % ) . At > 9 months ' aripiprazole exposure ( n = 220 ) , mean change in body weight z score was 0.33 and body mass index z score was 0.31 . The percentages of subjects with clinical ly significant fasting metabolic abnormalities at > 9 months were 2 % for glucose , 5 % for total cholesterol , 7 % for low-density lipoprotein cholesterol , 30 % for high-density lipoprotein cholesterol , and 5 % for triglycerides . CONCLUSIONS Aripiprazole was generally safe and well tolerated in the long-term treatment of irritability associated with autistic disorder in pediatric subjects . Weight should be proactively monitored during long-term treatment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00365859 OBJECTIVE The purpose of this study was to evaluate the impact of prior antipsychotic exposure ( PAE ) on safety and tolerability outcomes in pediatric subjects receiving aripiprazole treatment . METHODS This study was a post-hoc analysis of pooled data from two 8-week , double-blind , r and omized , placebo-controlled studies evaluating aripiprazole for the treatment of irritability in pediatric subjects with autistic disorder , aged 6 - 17 years . Subjects were stratified by PAE ; adverse events ( AEs ) , and changes in weight , and metabolic measures were evaluated . For subjects receiving aripiprazole , regardless of PAE , baseline weight , age , gender , and symptom severity were evaluated in a regression model predicting body weight change . RESULTS Of 316 r and omized subjects , 259 ( 82.0 % ) were antipsychotic naïve ( AN ) and 57 ( 18.0 % ) had a PAE . Aripiprazole-treated AN subjects were more likely than PAE subjects to report somnolence ( 11.9 % vs. 2.8 % ) , sedation ( 22.7 % vs. 11.1 % ) , or fatigue ( 17.0 % vs. 13.9 % ) . Rates of extrapyramidal disorder and drooling , but not akathisia or tremor , were marginally higher in AN subjects . Overall , 10.8 % of aripiprazole-treated AN subjects had at least one AE leading to discontinuation compared with 8.3 % of aripiprazole-treated PAE subjects . AN subjects receiving aripiprazole had a larger change in weight from baseline to endpoint compared with those receiving placebo ( 1.9 vs. 0.7 kg ; treatment difference 1.2 kg , 95 % CI : 0.5 , 1.9 ) than PAE subjects receiving aripiprazole compared with subjects receiving placebo ( 0.4 vs. -0.4 kg ; treatment difference 0.9 kg , 95 % CI : -0.6 , 2.4 ) . Regression analysis identified that younger subjects with higher baseline weight z-score were at highest risk for weight gain . There were no significant changes in metabolic measures compared with placebo in either group . CONCLUSIONS Weight gain was more pronounced in AN subjects and more likely to occur in younger subjects with a higher baseline weight z-score . AN subjects were more likely to experience AEs related to somnolence . However , based on discontinuations rates from AEs , overall tolerability was good for both AN and PAE groups . CLINICAL TRIAL REGISTRATION Study of aripiprazole in the treatment of  children and adolescents with autistic disorder  . Registry : www . clinical trials.gov . Identifiers : NCT00332241 and NCT00337571 INTRODUCTION Juvenile bipolar disorder ( JBD ) is a highly impairing chronic mental health condition that affects children and adolescents ' overall functioning . Comorbidity with attention-deficit/hyperactivity disorder ( ADHD ) is extremely prevalent and may determine worse response to treatment . Few investigations have addressed the use of recent atypical antipsychotics in JBD , although several guidelines suggest their use . METHODS We conducted a 6-week open trial with aripiprazole in 10 children and adolescents with JBD comorbid with ADHD to assess impact on mania and ADHD symptoms , respectively , by means of the Young Mania Rating Scale and the Swanson , Nolan and Pelham Scale , as well as on global functioning ( Clinical Global Impressions-Severity ) , and adverse events . RESULTS Significant improvement in global functioning scores ( F=3.17 , P=.01 , effect size=0.55 ) , manic symptoms ( F=5.63 , P<.01 ; ES=0.93 ) , and ADHD symptoms ( t=3.42 , P<.01;ES=1.05 ) were detected . Although an overall positive tolerability was reported , significant weight gain ( F=3.07 , P=.05 ) was observed . CONCLUSION Aripiprazole was effective in improving mania and ADHD symptoms , but neither JBD nor ADHD symptom remission was observed in most of the cases . R and omized placebo-controlled trials for JBD and ADHD are needed OBJECTIVE The aim of this study was to determine the effectiveness and tolerability of aripiprazole for irritability in pervasive developmental disorder not otherwise specified ( PDD-NOS ) and Asperger 's disorder . METHOD This is a 14-week , prospect i ve , open-label investigation of aripiprazole in 25 children and adolescents diagnosed with PDD-NOS or Asperger 's disorder . Primary outcome measures included the Clinical Global Impressions-Improvement ( CGI-I ) scale and the Irritability subscale of the Aberrant Behavior Checklist ( ABC-I ) . RESULTS Twenty-five subjects , ages 5 - 17 years ( mean 8.6 years ) received a mean final aripiprazole dosage of 7.8 mg/day ( range 2.5 - 15 mg/day ) . Full-scale intelligence quotient ( IQ ) scores ranged from 48 to 122 ( mean 84 ) . Twenty-two ( 88 % ) of 25 subjects were responders in regard to interfering symptoms of irritability , including aggression , self-injury , and tantrums , with a final CGI-I of 1 or 2 ( very much or much improved ) and a 25 % or greater improvement on the ABC-I. The final mean CGI-I was 1.6 ( p < or= 0.0001 ) . ABC-I scores ranged from 18 to 43 ( mean 29 ) at baseline , whereas scores at week 14 ranged from 0 to 27 ( mean 8.1 ) ( p < or= 0.001 ) . Aripiprazole was well tolerated . Mild extrapyramidal symptoms ( EPS ) were reported in 9 subjects . Age- and sex-normed body mass index ( BMI ) increased from a mean value of 20.3 at baseline to 21.1 at end point ( p < or= 0.04 ) . Prolactin significantly decreased from a mean value of 9.3 at baseline to 2.9 at end point ( p < or= 0.0001 ) . No subject exited the study due to a drug-related adverse event . CONCLUSIONS These preliminary data suggest that aripiprazole may be effective and well tolerated for severe irritability in pediatric patients with PDD-NOS or Asperger 's disorder . Larger-scale placebo-controlled studies are needed to eluci date the efficacy and tolerability of aripiprazole in this understudied population OBJECTIVE To evaluate the efficacy and safety of aripiprazole versus placebo in preventing relapse of irritability symptoms associated with autistic disorder in pediatric patients . METHOD This multicenter , double-blind , r and omized , placebo-controlled , relapse-prevention trial enrolled patients ( 6 - 17 years ) who met the current Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Text Revision ( DMS-IV-TR ) criteria for autistic disorder and who also had serious behavioral problems ( ie , tantrums , aggression , self-injurious behavior , or a combination of these behavioral problems ) between March 2011 and June 2012 . In phase 1 , single-blind aripiprazole was flexibly dosed ( 2 - 15 mg/d ) for 13 - 26 weeks . Patients with a stable response ( ≥ 25 % decrease in Aberrant Behavior Checklist-irritability subscale score and a rating of " much improved " or " very much improved " on the Clinical Global Impressions-Improvement scale ) for 12 consecutive weeks were r and omized into phase 2 to continue aripiprazole or switch to placebo . Treatment was continued until relapse or up to 16 weeks . The primary end point was time from r and omization to relapse . RESULTS Eighty-five patients were r and omized in phase 2 . The difference in time to relapse  between aripiprazole and placebo was not statistically significant ( P = .097 ) . Kaplan-Meier relapse rates at week 16 were 35 % for aripiprazole and 52 % for placebo ( hazard ratio [ HR ] = 0.57 ; number needed to treat [ NNT ] = 6 ) . The most common adverse events during phase 1 were weight increase ( 25.2 % ) , somnolence ( 14.8 % ) , and vomiting ( 14.2 % ) ; and , during phase 2 ( aripiprazole vs placebo ) , they were upper respiratory tract infection ( 10.3 % vs 2.3 % ) , constipation ( 5.1 % vs 0 % ) , and movement disorder ( 5.1 % vs 0 % ) . CONCLUSIONS In this study , there was no statistically significant difference between aripiprazole and placebo in time to relapse during maintenance therapy . However , the HR and NNT suggest some patients will benefit from maintenance treatment . Patients receiving aripiprazole should be periodically reassessed to determine the continued need for treatment . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01227668 Background Various clinical trials suggested that risperidone was beneficial in the treatment of autism spectrum disorder ( ASD ) in children and adolescents . Objective The aim of this systematic review was to determine the efficacy , acceptability and tolerability of risperidone in the treatment of children and adolescents with ASD . Data sources The data bases of Scopus , PubMed , CINAHL and Cochrane Controlled Trials Register were search ed in February 2017 . Study eligibility criteria , participants and interventions Eligible RCTs of risperidone in the treatment of child and adolescent patients with ASD . Language s were not restricted . Study appraisal and synthesis methods The full-text versions of relevant studies were thoroughly assessed and extracted . The primary efficacy of outcome was the pooled response rate and the pooled mean changed scores of the st and ardized rating scales for ASD . Results A total of 372 r and omized subjects from seven RCTs were included in this review . In acute treatment , the pooled mean change score of the Aberrant Behavior Checklist for irritability subscale ( ABC-I ) and response rate for the risperidone-treated group had a greater significance than that of the placebo-treated group . In the long-term treatment , the pooled mean change score of the CARS in the risperidone-treated group was significantly greater than that in the placebo-treated group . According to the discontinuation phase , the overall pooled relapse rate of the risperidone-treated group was significantly less than that of the placebo-treated group . The rates of pooled overall discontinuation and discontinuation due to adverse events rates were not different between the two groups in acute and long-term treatments . Limitations A small study was included in the current review . Conclusion In relation to the current systematic review , risperidone is efficacious in the treatment of symptoms in children and adolescents with ASD . Although its acceptability is comparable to placebo , treatment with risperidone is well tolerated in children and adolescents with ASD The objective of this study was to evaluate the effectiveness and tolerability of aripiprazole use in child and adolescent psychiatric in patients . This was a naturalistic , retrospective evaluation of the discharged patients treated with aripiprazole on the child and adolescent unit at the Austin State Hospital . To be included , patients had to be < 18 years of age and treated with aripiprazole for at least two consecutive weeks during their hospital stay . We used a chart extracted Clinical Global Impression of Improvement , and a chart extracted Clinical Global Impression of Severity of Illness score to determine their effectiveness . Adverse events and side effects recorded in the physician or nursing notes were collected to establish tolerability . Forty-five patients met the criteria and were included in this analysis . Average clinical global impression of severity of illness scores at baseline and endpoint were 5.04±0.91 and 3.33±1.24 respectively . This difference was statistically significant ( Wilcoxon 's signed-rank test : Z=−5.179 , P<0.001 ) . Fifty-one percent of the youth had a clinical global impression of severity of illness score that was much improved or very much improved ( clinical global impression of improvement score of 1 or 2 ) . Significant reduction in clinical global impression of severity of illness scores suggests a decline in the symptom severity for patients treated with aripiprazole . On the basis of the reported adverse events and side effects , aripiprazole was generally well tolerated . R and omized controlled trials of aripiprazole in childhood mental disorders are warranted The objectives of this 12-week multicenter open-label switching study were to evaluate the overall clinical efficacy , safety , and tolerability of aripiprazole in stable patients with schizophrenia or schizoaffective disorder , and to assess , in a naturalistic setting , whether such patients experience symptom worsening when switched from D2 receptor antagonists to aripiprazole ( a D2 receptor partial agonist ) . Patients with schizophrenia or schizoaffective disorder in a symptomatically stable state were r and omized to aripiprazole or st and ard-of-care antipsychotics .  The Clinical Global Impression ( CGI ) , Positive and Negative Syndrome Scale , and Investigator 's Assessment Question naire were used monthly . The Udvalg for Kliniske Undersogelser side-effect rating scale scores and treatment emergent adverse events were recorded to assess the safety and tolerability of switching to aripiprazole from other antipsychotics . A total of 292 patients were r and omly assigned to receive aripiprazole ( N = 245 ) or  non-aripiprazole antipsychotics ( N = 47 )  . Mean CGI-Improvement score at 12 weeks was 3.56±1.29 ( 95 % confidence interval : 3.39–3.73 ) in the aripiprazole group , indicating that aripiprazole was effective in treating schizophrenic patients . Aripiprazole treatment result ed in improvement from baseline on all efficacy outcome measures , including Positive and Negative Syndrome Scale total , positive , negative , and general subscale , and CGI-Severity scores . In addition , after aripiprazole treatment , the remission rate was increased from 43.9 % at baseline to 51.7 % at 12 weeks . The proportion of patients with symptom worsening at 12 weeks was low ( 12.4 % ) . Both Investigator 's Assessment Question naire and Udvalg for Kliniske Undersogelser scores showed that there were fewer prolactin-related adverse events in the aripiprazole group than in the st and ard-of-care antipsychotics group ( P<0.05 ) . There were no significant between-group differences in time to failure to maintain remission and time to dropout . In the naturalistic setting , symptomatically stable out patients with schizophrenia who were switched to aripiprazole showed clinical ly meaningful treatment benefits . The majority of patients was successfully switched from other antipsychotics without serious symptom exacerbation or adverse events over a course of 12 weeks BACKGROUND Naturalistic effectiveness trials of atypical antipsychotics are needed to provide broader information on efficacy , safety , and tolerability in patients with schizophrenia treated in a community practice setting . METHOD In this 26-week , open-label , multicentre study , patients with schizophrenia requiring a switch in antipsychotic medication because current medication was not well tolerated and /or clinical symptoms were not well controlled were r and omized to receive aripiprazole or an atypical antipsychotic st and ard of care ( SOC ) treatment ( i.e. , olanzapine , quetiapine , or risperidone based on the investigator 's judgment of the optimal treatment for the individual patient and the patient 's prior response to antipsychotic medication ) . The primary objective was to compare the effectiveness of a 26-week treatment of aripiprazole versus SOC , as measured by the Investigator Assessment Question naire ( IAQ ) total score at Week 26 last observation carried forward ( LOCF ) ( primary endpoint ) , a vali date d measure that monitors relief or worsening of 10 key symptoms associated with the psychopathology of schizophrenia and side effects of antipsychotic treatment . Secondary objectives were to further assess effectiveness using the Clinical Global Impression - Global Improvement ( CGI-I ) and Clinical Global Impression - Severity of Illness scale , to assess time to treatment discontinuation , patient preference of medication , quality of life , and the tolerability of aripiprazole compared with SOC . RESULTS Aripiprazole treatment ( n=268 ) result ed in significantly better effectiveness than SOC treatment ( n=254 ; P<0.001 ; Week 26 LOCF ) as evidence d by the IAQ total score beginning at Week 4 ( the first assessment point ) and sustained through Week 26 . A similar relationship was demonstrated among patients who completed the study ( observed cases analysis ) ; aripiprazole was associated with significantly better effectiveness at all time points with a greater differential effect from SOC over time . Patients treated with aripiprazole also demonstrated significantly greater improvements on the CGI-I scale ( responder rate , P=0.009 at Week 26 LOCF ) , as well as on quality of life ( Quality of Life scale total score ; P<0.001 at Week 26 ) . Furthermore , a significantly higher proportion of patients receiving aripiprazole rated their study medication as " much better " on the Preference of Medication Question naire ( POM ) scale than their pre- study medication compared with SOC patients ( P<0.001 ; Week 26 ) . Time to treatment discontinuation and rates of discontinuation due to adverse events were similar in both treatment groups . The incidence of patients with one or more extrapyramidal symptom ( e.g. , akathisia , dystonia , parkinsonian events , and residual events ) was higher in patients receiving aripiprazole compared with patients treated with SOC ( 13.5 % vs. 5.6 % ) ; however , a higher proportion of patients in the SOC-treated group had clinical ly significant weight gain ( 21.2 % vs. 7.3 % for aripiprazole ) and potentially clinical ly relevant elevated fasting levels of total cholesterol , low-density lipoprotein cholesterol , triglycerides , and serum prolactin compared with patients receiving aripiprazole . CONCLUSIONS Aripiprazole is an effective atypical antipsychotic for the treatment of schizophrenia , demonstrating better effectiveness than SOC agents used in this study in patients for whom a switch in antipsychotic medication was warranted OBJECTIVE To assess response to treatment with aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder ( ADHD ) . METHOD Children and adolescents were extensively assessed according to DSM-IV criteria for bipolar disorder comorbid with ADHD ( n = 710 ) . Those with this comorbidity who were acutely manic or in mixed states were r and omly assigned in a 6-week double-blind , placebo-controlled trial to aripiprazole ( n = 18 ) or placebo ( n = 25 ) . Primary outcome measures were assessed weekly and included the Young Mania Rating Scale ; the Swanson , Nolan , and Pelham Scale-Version IV ; and weight . Secondary outcome measures were the Clinical Global Impressions-Severity of Illness scale , the Child Mania Rating Scale-Parental Version ( CMRS-P ) , the Children 's Depression Rating Scale-Revised , the Kutcher Adolescent Depression Scale , and adverse events . The trial was conducted at the Hospital de Clínicas de Porto Alegre , Rio Gr and e do Sul , Brazil , from January 2005 to November 2007 . RESULTS The group receiving aripiprazole showed a significantly greater reduction in YMRS scores ( P = .02 , effect size [ ES ] = 0.80 ) , CMRS-P scores ( P = .02 ; ES = 0.54 ) , and CGI-S scores ( P = .04 ; ES = 0.28 ) from baseline to endpoint than the placebo group . In addition , higher rates of response ( P = .02 ) and remission ( P = .01 ) were found for the aripiprazole group . No significant between-group differences were found in weight , ADHD symptoms , and depressive symptoms . Adverse events significantly more frequent in the aripiprazole group were somnolence and sialorrhea . CONCLUSION Aripiprazole was effective in reducing manic symptoms and improving global functioning without promoting severe adverse events or weight gain . No significant treatment effect in ADHD symptoms was observed . Studies are needed to assess psychopharmacologic interventions for improving ADHD symptoms in juvenile bipolar disorder comorbid with ADHD . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00116259 BACKGROUND There are limited published data on the impact of treatment on the health-related quality of life ( HRQOL ) in individuals with autistic disorder . OBJECTIVE The aim of this study was to evaluate the impact of aripiprazole on HRQOL in the treatment of irritability in pediatric patients ( aged 6 - 17 years ) with autistic disorder . METHODS This post hoc analysis assessed data from two 8-week , double-blind , r and omized , placebo-controlled studies that compared the efficacy of aripiprazole ( fixed-dose study , 5 , 10 , and 15 mg/d ; flexible-dose study , 2 - 15 mg/d ) with placebo in the treatment of irritability associated with autistic disorder . HRQOL was assessed at baseline and week 8 using 3 Pediatric Quality of Life Inventory ( PedsQL ™ ) scales . Clinical ly relevant improvement in HRQOL was determined using an accepted distribution-based criterion-1 st and ard error of measurement . RESULTS In total , 316 patients were r and omly assigned to receive treatment with aripiprazole ( fixed-dose study , 166 ; flexible-dose study , 47 ) or placebo ( fixed-dose study , 52 ; flexible-dose study , 51 ) . Aripiprazole was associated with significantly greater improvement  than placebo in PedsQL combined-scales total score ( difference , 7.8 ; 95 % CI , 3.8 - 11.8 ; P < 0.001 ) and in 3 PedsQL scale scores ( differences [ 95 % CI ] : Emotional Functioning , 7.8 [ 3.4 - 12.2 ] ; Social Functioning , 6.2 [ 0.7 - 11.8 ] ; Cognitive Functioning , 9.3 [ 3.8 - 14.9 ] ; all , P < 0.05 ) . Patients who received aripiprazole were significantly more likely than those who received placebo to have a clinical ly meaningful improvement on the combined-scales total score ( odds ratio [ OR ] = 1.9 ; 95 % CI , 1.0 - 3.3 ; P < 0.05 ) , Emotional Functioning scale ( OR = 2.2 ; 95 % CI , 1.2 - 4.0 ; P < 0.05 ) and Social Functioning scale ( OR = 2.2 ; 95 % CI , 1.2 - 4.1 ; P < 0.05 ) , and were significantly less likely to experience deterioration ( OR : 0.3 , 95 % CI : 0.1 - 0.8 ; P < 0.05 ) when " Stable " was used as the reference group . CONCLUSIONS The findings from the present post hoc analysis suggest that aripiprazole was associated with improved HRQOL , as assessed using 3 PedsQL scales , in pediatric patients with irritability associated with autistic disorder OBJECTIVE BETA was design ed to evaluate the overall effectiveness of aripiprazole in patients with schizophrenia or schizoaffective disorder treated in a general psychiatry outpatient practice setting . METHODS In this 8-week , multicenter , open-label study , 1,599 out patients with schizophrenia or schizoaffective disorder were r and omly assigned to receive either aripiprazole ( n=1,295 ) or another antipsychotic medication ( safety control [ SC ] group ; n=304 ) . Aripiprazole was initiated at 15 mg/d with the option to adjust between 10 - 30 mg/d . The SC medication was specifically selected for each patient by the clinician and dosed according to prescribing guidelines for that medication . The primary effectiveness measure was the Clinical Global Impression-Improvement ( CGI-I ) score of the aripiprazole group at study end point . Secondary measures included response rates and preference of medicine ( POM ) ratings by patients and caregivers . RESULTS Sixty-five percent of aripiprazole patients completed the study . The mean aripiprazole dose at end point was 19.9 mg/d , with approximately 39 % of patients starting and remaining at 15 mg/d . At end point , the mean CGI-I score of 2.77 demonstrated that aripiprazole was minimally to moderately effective ; the mean CGI-I score for the SC group was 3.59 indicating minimally effective to no change . Fifty-three percent of aripiprazole patients responded to treatment ( CGI-I score of 1 or 2 ; last-observation-carried-forward [ LOCF ] ) , and approximately 71 % of patients and caregivers rated aripiprazole as better than the pre study medication on the POM ( LOCF ) . Incidence and severity of adverse events ( AEs ) were similar to those reported in double-blind , r and omized , placebo-controlled aripiprazole clinical trials . The most frequent AE in the aripiprazole group was insomnia ( 24 % ) . CONCLUSIONS Aripiprazole was effective for the treatment of schizophrenia and schizoaffective disorder in a general psychiatry outpatient practice setting . Overall , aripiprazole was found to be effective by the treating clinician and well accepted by patients and caregivers over the 8-week treatment course
The pooled mean change scores in aripiprazole-treated group for the Aberrant Behavior Checklist (ABC)-Irritability , ABC-Hyperactivity/noncompliance , ABC-Inappropriate speech and ABC-Stereotypic behavior were significantly greater than those of the placebo-treated group .
Unfortunately , the significant difference between two groups was not found for ABC-Lethargy/social withdrawal .
The pooled overall discontinuation rate in aripiprazole-treated group was significantly better than that of placebo-treated group .
Conclusion Aripiprazole has efficacy in the treatment of behavioral disturbances , including irritability , hyperactivity/noncompliance , inappropriate speech and stereotypic behavior found in ASD children and adolescents ; however , it could not improve the lethargy/social withdrawal in such patients .
The present evidence also indicates that it is safe , acceptable and tolerable in such treatment .
Background Recent r and omized controlled trials indicated that aripiprazole was the effective treatment for children and adolescents with autism spectrum disorder ( ASD ) .
Objective This study systematic ally review ed the efficacy , acceptability and tolerability of aripiprazole in treatment of ASD children and adolescents .