Focus on aripiprazole: a review of its use in child and adolescent psychiatry. An open-label trial of aripiprazole monotherapy in children and adolescents with bipolar disorder. The effects of aripiprazole on electrocardiography in children with pervasive developmental disorders. Aripiprazole in the Treatment of Irritability in Children and Adolescents With Autistic Disorder Efficacy and safety of aripiprazole in the treatment of bipolar disorder: a systematic review An open-label trial of aripiprazole in the treatment of aggression in male adolescents diagnosed with conduct disorder. An open-label study of the efficacy and tolerability of aripiprazole for children and adolescents with tic disorders. A multicenter, randomized, double-blind, placebo-controlled study of aripiprazole in children and adolescents with Tourette's disorder. Aripiprazole in children and adolescents with Tourette's disorder: an open-label safety and tolerability study. Aripiprazole in pervasive developmental disorder not otherwise specified and Asperger's disorder: a 14-week, prospective, open-label study. Aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder: a pilot randomized clinical trial. A Head-to-Head Comparison of Aripiprazole and Risperidone for Safety and Treating Autistic Disorders, a Randomized Double Blind Clinical Trial A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia. Methylphenidate combined with aripiprazole in children and adolescents with bipolar disorder and attention-deficit/hyperactivity disorder: a randomized crossover trial. Open label aripiprazole in the treatment of youth with tic disorders. Aripiprazole in the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorder in Japan: A Randomized, Double-blind, Placebo-controlled Study Efficacy and safety of aripiprazole in the acute treatment of schizophrenia in Chinese patients with risperidone as an active control: a randomized trial. A review of aripiprazole in the treatment of patients with schizophrenia or bipolar I disorder A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. Neuromotor Adverse Effects in 342 Youth During 12 Weeks of Naturalistic Treatment With 5 Second-Generation Antipsychotics. Aripiprazole Versus Risperidone for Treating Children and Adolescents with Tic Disorder: A Randomized Double Blind Clinical Trial Aripiprazole treatment of irritability associated with autistic disorder and the relationship between prior antipsychotic exposure, adverse events, and weight change. Efficacy and safety of paliperidone extended release in adolescents with schizophrenia: a randomized, double-blind study.
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 INTRODUCTION Aripiprazole is a novel second-generation antipsychotic approved for the treatment of bipolar disorder in adults but there is no systematic data available in pediatric bipolar disorder . METHODS This was an 8-week , open-label , prospect i ve study of aripiprazole 9.4+/-4.2 mg/day monotherapy to assess the efficacy and tolerability of this compound in treating pediatric bipolar disorder . Assessment s included the Young Mania Rating Scale , Clinical Global Impressions-Improvement scale , and Brief Psychiatric Rating Scale . Adverse events were assessed through spontaneous self-reports , vital signs weight monitoring , and laboratory analysis . RESULTS Fifteen of the 19 bipolar youth ( 79 % ) completed the study .  Aripiprazole treatment was associated with clinical ly and statistically significant improvement in mean Young Mania Rating Scale scores ( -18.0+/-6.9 , P<.0001 ) . With the important exception of two cases of extrapyramidal symptoms that precipitated dropout , aripiprazole was well tolerated with no statistically significant increase in body weight ( 1.8+/-1.7 kg , P=.2 ) . CONCLUSION Open-label aripiprazole treatment was beneficial in the treatment of mania in youth with bipolar disorder . Future placebo-controlled , double-blind studies are warranted OBJECTIVES Psychotropic medications , including the atypical antipsychotics , have historically been scrutinized for cardiac effects and risk of sudden death .  Aripiprazole is an atypical antipsychotic approved for pediatric use in schizophrenia , bipolar I disorder , and autistic disorder . Adult studies have evaluated aripiprazole 's effects on electrocardiograms , but no pediatric studies have been published to date . METHODS Electrocardiographic data were collected from children and adolescents participating in a 14-week , prospect i ve , open-label study ( n=25 ) of aripiprazole for irritability in pervasive developmental disorder not otherwise specified and Asperger 's disorder . A  12-lead electrocardiogram  was obtained at the baseline and end point visits . The  electrocardiograms  were evaluated for abnormal findings , and the PR , QRS , QT(c ) , and RR intervals were recorded . The QT interval was corrected using Bazett 's , United States Food and Drug Administration ( FDA ) Pharmacology Division , and Fridericia 's formulas . RESULTS Twenty-four subjects received both baseline and posttreatment electrocardiograms . The mean age was 8.6 years ( range 5 - 17 years ) . The average final aripiprazole dose was 7.8 mg/day ( range 2.5 - 15 mg/day ) . There were no significant differences noted with the PR , QRS , RR , and QT(c ) intervals after aripiprazole therapy . Also , there was no significant correlation between the dose given and the percent change in the QT(c ) . No post-treatment QT(c ) exceeded 440 ms . CONCLUSIONS To our knowledge , this is the first systematic evaluation of the cardiac effects of aripiprazole in children and adolescents . The results are consistent with previously published literature in adults that aripiprazole has no significant cardiac effects and can be deemed a low risk for causing sudden death . It will be important to confirm these findings in a r and omized controlled trial 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 Background The current article is a systematic review concerning the efficacy and safety of aripiprazole in the treatment of bipolar disorder . Methods A systematic Medline and repositories search concerning the usefulness of aripiprazole in bipolar disorder was performed , with the combination of the words ' aripiprazole ' and ' bipolar ' . Results The search returned 184 articles and was last up date d on 15 April 2009 . An additional search included repositories of clinical trials and previous systematic review s specifically in order to trace unpublished trials . There were seven placebo-controlled r and omised controlled trials ( RCTs ) , six with comparator studies and one with add-on studies . They assessed the usefulness of aripiprazole in acute mania , acute bipolar depression and during the maintenance phase in comparison to placebo , lithium or haloperidol . Conclusion Aripiprazole appears effective for the treatment and prophylaxis against mania . The data on bipolar depression are so far negative , however there is a need for further study at lower dosages . The most frequent adverse effects are extrapyramidal signs and symptoms , especially akathisia , without any significant weight gain , hyperprolactinaemia or laboratory test changes BACKGROUND The adverse effect profiles of typical and atypical antipsychotics are problematic because of their extrapyramidal and endocrine adverse effects , respectively . METHODS Ten adolescent male patients diagnosed with conduct disorder received aripiprazole in doses of ≤20 mg/d in an open-label , intent-to-treat design to establish and characterize the efficacy of the drug in reducing aggressive behavior . RESULTS Based on clinician and parent observations , aripiprazole was effective in reducing aggressive behavior in adolescent boys . The change in clinician-observed aggression ratings appears to have been driven by a decrease in physical aggression , whereas the change in parent-observed aggression ratings appears to have been driven by a decrease in verbal aggression and aggression against objects and animals . CONCLUSIONS Aripiprazole was an effective and relatively well-tolerated treatment for overall aggression in adolescent males with conduct disorder , in the view of both clinicians and parents . Depending on the observer , aripiprazole improved aggression categorized as physical aggression , verbal aggression , and aggression against objects and animals OBJECTIVES This study aim ed to investigate the efficacy and tolerability of aripiprazole , an atypical antipsychotic with dual agonist and antagonist actions toward dopaminergic imbalance and partial serotonin-2A receptor antagonism , for treating children and adolescents with tic disorders . METHOD Twenty-four out patients aged 7 to 18 years with DSM-IV-diagnosed tic disorders were treated with aripiprazole using an open-label , flexible dosing schedule for 8 weeks from January 2005 to August 2006 . The Korean versions of the Yale Global Tic Severity Scale ( YGTSS ) , the Clinical Global Impressions-Improvement scale ( CGI-I ) , and the CGI-Severity of Illness scale ( CGI-S ) scores were used to measure the drug efficacy . Side effects were assessed using an adverse effect checklist , the Extrapyramidal Symptom Rating Scale , height and weight measurements , laboratory tests , and electrocardiograms . RESULTS Aripiprazole was prematurely discontinued in 6 ( 25 % ) of the 24 subjects due to intolerable adverse effects . After a mean of 9.8 + /- 4.8 mg/day of aripiprazole for 8 weeks , there was a 52.8 % reduction in the mean YGTSS Total Tic scores ( from 26.7 + /- 5.5 to 12.6 + /- 7.6 , p < .001 ) . Nineteen patients ( 79.2 % ) showed either much improved or very much improved status according to the CGI-I. The CGI-S score was also reduced ( from 5.5 + /- 0.5 to 3.0 + /- 1.4 , p < .001 ) . The initial dose of 5 mg/day aripiprazole for 2 weeks was also found to reduce tic symptoms significantly ( Total Tic scores decreased from 26.7 + /- 5.5 to 17.9 + /- 8.7 , p < .001 ) . Fourteen subjects ( 58.3 % ) experienced unwanted side effects , the most common being hypersomnia ( 37.5 % ) , nausea ( 20.8 % ) , and headache ( 16.6 % ) . CONCLUSION This open-label study suggests that aripiprazole is an efficacious and safe treatment for children and adolescents with tic disorders OBJECTIVE To examine the short-term efficacy and tolerability of aripiprazole for children and adolescents with Tourette 's disorder . METHOD This 10-week multicenter , double-blind , r and omized , placebo-controlled trial was conducted from August 2008 to April 2010 . Children and adolescents ( aged 6 - 18 years ) with a DSM-IV diagnosis of Tourette 's disorder and a Yale Global Tic Severity Scale total tic score of 22 or more were r and omly assigned ( 1:1 ratio ) to placebo or aripiprazole . The primary outcome measure was mean change from baseline in the total tic score on the Yale Global Tic Severity Scale ( last observation carried forward ) . Assessment s of safety and tolerability included spontaneously reported adverse events , extrapyramidal symptoms , serum prolactin level , metabolic variables , and other laboratory evaluations . RESULTS Of 61 subjects , 89 % completed the study . Patients who received aripiprazole demonstrated a significant reduction from baseline to end of study on the mean ( SD ) total tic score of the Yale Global Tic Severity Scale compared to those who received placebo ( -15.0 [ 8.4 ] and -9.6 [ 8.8 ] , respectively , P=.0196 ) . Response rate on the Tourette 's Syndrome Clinical Global Impression-Improvement was 66 % and 45 % in the aripiprazole and placebo groups , respectively . Mean decrease in the Tourette 's Syndrome Clinical Global Impression-Severity of Illness score was significantly different between the groups ( P=.0321 ) . In general , aripiprazole was well tolerated and there were no early discontinuations due to adverse events . The incidence of treatment-emergent adverse events between the groups was not significantly different ( P=.7550 ) . While aripiprazole decreased serum prolactin concentration ( P<.0001 ) , it increased mean body weight , body mass index , and waist circumference significantly ( P=.0055 , P=.0142 , and P=.0270 , respectively ) . CONCLUSIONS In comparison with placebo , aripiprazole was efficacious , generally tolerated and safe in the short-term treatment of children and adolescents with Tourette 's disorder . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00706589 OBJECTIVE The aim of this study was to conduct a prospect i ve safety and tolerability study of aripiprazole for the treatment of tics in children and adolescents with Tourette 's disorder ( TD ) . METHOD Eleven subjects ( 10 males ) with TD ( age 9 - 19 years , mean 13.36 , st and ard deviation [ SD ] 3.33 ) who did not respond or were unable to tolerate previous tic medication were treated with aripiprazole in an open-label , flexible-dosing study over 10 weeks . Tic severity was rated using the Yale Global Tic Severity Scale ( YGTSS ) and the Clinical Global Impressions Scale for tics ( CGI-Tics ) at baseline and at follow-up . RESULTS The mean ( + /-SD ) daily dose for aripiprazole was 4.5 + /- 3.0 mg . Mean ( + /-SD ) YGTSS Global Severity scores reduced from 61.82 + /- 13.49 at baseline to 33.73 + /- 15.18 at end point ; mean YGTSS total tic scores reduced from 28.18 + /- 7.74 at baseline to 16.73 + /- 7.54 at end point . Mean ( + /-SD ) CGI-Tic severity scores reduced from 4.45 + /- 0.52 ( moderate-marked ) at baseline to 3.18 + /- 0.60 ( mild ) at end point . On the CGI-Tic improvement scale , 10 ( 91 % ) subjects achieved 1 ( " very much improved " ) or 2 ( " much improved " ) at end point . Most common adverse effects included appetite increase and weight gain in 5 subjects , mild extrapyramidal effects in 7 subjects , and headaches and tiredness/fatigue in 7 subjects ; 1 subject experienced akathisia and muscle cramps . CONCLUSION Aripiprazole appears to be a safe and tolerable treatment in children and adolescents with TD that appears to reduce tics ; it should be further investigated as a treatment option in controlled trials 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 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 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 Aripiprazole is a dopamine partial agonist approved for use in adults for short- and long-term treatment of schizophrenia and bipolar disorder . This study was design ed to examine the acute efficacy , safety , and tolerability of aripiprazole for adolescents with schizophrenia . METHOD This was a 6-week multicenter , double-blind , r and omized , placebo-controlled trial . Subjects 13 to 17 years old with a DSM-IV diagnosis of schizophrenia and a Positive and Negative Syndrome Scale ( PANSS ) total score of 70 or more were r and omly assigned ( 1:1:1 ratio ) to placebo or 10 or 30 mg/day of aripiprazole . The primary endpoint was mean change from baseline to endpoint ( last observation carried forward ) in PANSS total score . Assessment s of safety and tolerability included spontaneously reported adverse events , extrapyramidal symptom scores , serum prolactin concentration , body weight , and metabolic measures . RESULTS Of 302 patients , 85 % completed the 6-week study . The mean baseline PANSS score was 94.1 . At the end of the study , both aripiprazole doses showed statistically significant differences from placebo in reduction in PANSS total score . Adverse events occurring in more than 5 % of either aripiprazole group and with a combined incidence at least twice the rate for placebo were extrapyramidal disorder , somnolence , and tremor . Mean changes in prolactin were -8.45 , -11.93 , and -15.14 ng/ml for placebo and 10 mg and 30 mg of aripirazole , respectively . Mean body weight changes were -0.8 , 0.0 , and 0.2 kg for placebo and 10 mg and 30 mg of aripiprazole , respectively . CONCLUSION Both 10- and 30-mg/day doses of aripiprazole were superior to placebo in the acute treatment of adolescents with schizophrenia .  Aripiprazole was generally well tolerated In clinical sample s , juvenile bipolar disorder ( JBPD ) is frequently accompanied by co-morbid attention-deficit/hyperactivity disorder ( ADHD ) . Clinical trials assessing combined psychopharmacological interventions in this population are scarce , and methylpheni date ( MPH ) may worsen manic symptoms . We conducted a r and omized crossover trial with MPH and placebo ( 2 weeks each ) combined with aripiprazole in children and adolescents ( n = 16 ; 8 - 17 years old ) with JBPD and ADHD who had a significant response in manic symptoms with aripiprazole but still presented clinical ly significant symptoms of ADHD .  ADHD , manic , and depressive symptoms were assessed by means of st and ard scales . Fourteen out of the 16 subjects completed the trial . No significant differences between the effects of methylpheni date and placebo were detected in ADHD ( F(1 , 43.22 ) = 0.00 ; p = 0.97 ) or manic ( F(1 , 40.19 ) = 0.93 ; p = 0.34 ) symptoms . Significant improvement in depressive symptoms was observed in the MPH group ( F(1,19.03 ) = 7.75 ; p = 0.01 ) according to a secondary self-reported outcome measure . One patient using aripiprazole  and MPH discontinued the trial due to the onset of a severe mixed episode . No other significant adverse events were observed . Although MPH did not worsen manic symptoms , it was not more effective than placebo in improving ADHD symptoms in children and adolescents with JBPD co-morbid with ADHD stabilized with aripiprazole . Further investigations are warranted . This study is registered at www . clinical trials.gov under the identifier NCT00305370 BACKGROUND Primarily safe and efficacious treatments for chronic tic disorders are needed . Also needed are such treatments that target co-morbid conditions . Aripiprazole , a dopaminergic/serotonergic agent with partial agonist properties at the D2 dopamine receptor and 5-hydrdoxytryptamine 1A ( 5-HT(1A ) ) receptor and antagonist properties at the 5-HT(2A ) receptor , holds promise in both regards . OBJECTIVE This was an open-label , flexible-dose study to evaluate the safety of aripiprazole in children and adolescents with a primary diagnosis of a chronic tic disorder with/without co-morbid disorder(s ) . METHOD Sixteen children ( 15 males ) aged 8 - 17 years participated in the 6-week trial . Ratings for tic , obsessive compulsive disorder ( OCD ) , attention-deficit/hyperactivity disorder ( ADHD ) , and side effects were administered weekly . Baseline and exit laboratory measures , electrocardiograms ( ECGs ) , weight , and height were obtained . RESULTS The average daily aripiprazole dose was 3.3 mg ( range 1.25 - 7.5 mg ) . Significant pre- and posttreatment differences were ascertained for the Yale Global Tic Severity Scale motor ( p < or = 0.0001 ) , phonic ( p < or = 0.0001 ) , and total tic ( p < or = 0.0001 ) scores . Results of other rating scales suggested significant improvements in co-morbid disorders as well , including OCD , ADHD , and depressive disorders . Although aripiprazole was well tolerated , increases in weight were found . CONCLUSION In this preliminary open-label trial , aripiprazole was a well-tolerated treatment for tics and co-morbid OCD and ADHD symptoms . Improvements in co-morbid conditions may be secondary to tic reduction or to specific to aripiprazole therapy ; however , further study is warranted 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 Asian population s may differ from other races in response to antipsychotics . Studies of aripiprazole in Asian population s are scarce . This study aim ed to investigate the efficacy , safety , and tolerability of aripiprazole in Chinese patients with acute schizophrenia or schizoaffective disorder . METHOD This 4-week , double-blind , r and omized , parallel study was conducted in 5 medical centers in Taiwan between March 2004 and January 2005 . A total of 83 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were r and omly assigned ( with a r and omization ratio of 3:2 ) to 15 mg/day of aripiprazole ( N = 49 ) or 6 mg/day of risperidone ( N = 34 ) . Efficacy measures included the Positive and Negative Syndrome Scale ( PANSS ) total , positive , and negative scores and Clinical Global Impressions-Severity of Illness ( CGI-S ) and -Improvement scale scores . Extrapyramidal symptoms ( EPS ) , weight gain , serum prolactin level , QTc interval , and self-reported adverse events were assessed as measures of safety and tolerability . RESULTS Both the aripiprazole and risperidone groups showed statistical improvement from baseline in PANSS total , PANSS positive , PANSS negative , and CGI-S scores at study endpoint ( all p < .001 ) . Significant improvement was noted in the first week of treatment for both treatment groups . There were no significant differences in efficacy measures between treatment groups . Aripiprazole showed significantly less EPS liability as assessed by the Simpson-Angus Scale ( p < .005 ) and less serum prolactin level elevation ( p < .001 ) than risperidone . Both groups showed mild weight gain . No patients showed clinical ly significant QTc interval prolongation in this study . CONCLUSION Compared with risperidone 6 mg/day , aripiprazole 15 mg/day has comparable efficacy and favorable safety and tolerability profiles in the short-term treatment of Chinese patients with acute schizophrenia . In this group of Chinese patients , the overall response to aripiprazole did not differ from that of white patients . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00283179 Aripiprazole has been approved by regulatory agencies for the treatment of schizophrenia and bipolar I disorder . Although it is a dopamine partial agonist , it also has substantial binding affinity for the serotonin 5HT2A receptor . Several double-blind r and omized clinical trials have established the efficacy and tolerability of aripiprazole within the dose range of 10–30 mg/day for schizophrenia , and 15–30 mg/day for manic or mixed states associated with bipolar I disorder . Relatively few comparative trials with other second-generation antipsychotics have been published for schizophrenia , with none available for bipolar disorder . The evidence so far suggests that in terms of efficacy for schizophrenia , aripiprazole is superior to placebo and haloperidol ( long term ) , similar to perphenazine and risperidone , and inferior to olanzapine .  Its tolerability profile in patients with schizophrenia appears superior to haloperidol , perphenazine , risperidone , and olanzapine .  Efficacy in treating manic or mixed states was established in placebo-controlled trials . Among some patients with bipolar disorder  , akathisia and gastrointestinal ( GI ) complaints can emerge at the start of treatment ; however , the GI symptoms were time-limited in many instances . Appropriate dosing may also be important in individualizing therapy to improve tolerability , with lower starting doses becoming more important when adding to , or switching from , another antipsychotic . Aripiprazole appears to have a low propensity for weight gain , a favorable metabolic profile , and no association with hyperprolactinemia 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 OBJECTIVE Second-generation antipsychotic ( SGA ) effects in youth were monitored to quantify extrapyramidal side effects ( EPS ) and to identify risk profiles for treatment-emergent EPS . METHOD Data were analyzed for the nonr and omized , prospect i ve Second-generation Antipsychotic Treatment Indications , Effectiveness and Tolerability in Youth ( SATIETY ) inception cohort study . EPS were assessed at baseline and 4 , 8 , and 12 weeks after naturalistic SGA initiation for schizophrenia , mood , disruptive behavior , and autism spectrum disorders using the Simpson-Angus Scale ( SAS ) , Barnes Akathisia Scale , Abnormal Involuntary Movement Scale ( AIMS ) , and Treatment Emergent Side Effect Scale . Drug-induced parkinsonism was defined by incident mean SAS score > 0.33 , anticholinergic initiation , or increasing total SAS score ≥2 in patients with baseline EPS . RESULTS In 342 youth aged 13.6 ± 3.5 years ( male = 58.2 % , antipsychotic-naive = 65.8 % ) , 15.2 % developed drug-induced parkinsonism .  Raw SGA-grouped drug-induced parkinsonism rates were as follows : quetiapine = 1.5 % , olanzapine = 13.8 % , risperidone = 16.1 % , ziprasidone = 20.0 % , and aripiprazole = 27.3 % . SGA type , dose , higher age , and lower baseline functioning were jointly associated with drug-induced parkinsonism ( R(2 ) = 0.18 ; p < .0001 ) . Controlling for these factors , drug-induced parkinsonism rates were significantly lower only for quetiapine and olanzapine . Subjectively reported EPS ( 5 % ) , EPS-related treatment discontinuation ( 3.3 % ) , and anticholinergic initiation ( 3 % ) were infrequent . Anticholinergic initiation was most frequent with risperidone ( 10.2 % ; p = .0004 ) . Treatment-emergent dyskinesia ranged from 4.5 % ( aripiprazole ) to 15.5 % ( olanzapine ) . SGA type , younger age , white race/ethnicity , and baseline AIMS were jointly associated with treatment-emergent dyskinesia ( R(2 ) = 0.31 ; p < .0001 ) . Controlling for these factors , treatment-emergent dyskinesia rates differed among SGA subgroups , with higher rates with olanzapine and ziprasidone . At baseline , psychostimulant use was associated with dyskinesia , and number of psychotropic comedications was associated with subjective EPS . CONCLUSION In youth , SGA-related EPS rates did not generally exceed those reported in adults , with particularly low rates with quetiapine and olanzapine There are some uncontrolled studies about the efficacy and safety of both aripiprazole and risperidone for treating tic disorder . Moreover , the efficacy of these medications has never been compared . This is the first double blind r and omized clinical trial comparing the safety and efficacy of aripiprazole and risperidone for treating patients with tic disorder . Sixty children and adolescents with tic disorder were r and omly allocated into one of the two groups to receive either aripiprazole or risperidone for 2 months . The primary outcome measure was the score of Yale Global Tic Severity Scale . In addition , health related quality of life and adverse events were assessed . Both aripiprazole and risperidone decreased the Yale Global Tic Severity Scale score during this trial . Moreover , both medications increased the health related quality of life score . Both aripiprazole and risperidone were tolerated well .  Aripiprazole [ 3.22 ( 1.9 ) mg/day ] decreased tic score as much as risperidone [ 0.6 ( 0.2 ) mg/day ] . Their adverse effects and their effects on health related quality of life were comparable . However , risperidone increased the patients ’ social functioning more than aripiprazole in short term 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 OBJECTIVE To evaluate the efficacy , safety , and tolerability of paliperidone extended release ( ER ) relative to aripiprazole in adolescent schizophrenia . METHOD In this multicenter , double-blind , phase 3 study ( screening [ ≤3 weeks ] , with an acute treatment period [ 8 weeks ] and a maintenance period [ 18 weeks ] ) , adolescents ( 12 - 17 years old ) with schizophrenia ( DSM-IV diagnosis ; Positive and Negative Symptom Score [ PANSS ] total score 60 - 120 ) were r and omized ( 1:1 ) to once-daily paliperidone ER ( 6 mg per day [ days 1 - 7 ] , flexibly dosed 3 , 6 , or 9 mg per day from week 2 to end of study [ EOS ] ) , or to aripiprazole ( 2 mg per day [ days 1 and 2 ] , 5 mg per day [ days 3 and 4 ] , 10 mg per day [ days 5 - 7 ] , flexibly dosed 5 , 10 , or 15 mg per day [ week 2 to EOS ] ) . RESULTS Overall , 76 % of enrolled patients ( 174/228 ) completed the study ( paliperidone ER , 75 % [ 85/113 ] ; aripiprazole , 77 % [ 89/115 ] ) . There was no significant difference in change in PANSS total scores from baseline to day 56 ( primary endpoint ) ( paliperidone ER versus aripiprazole , -19.3 [ 13.80 ] versus -19.8 [ 14.56 ] , p = .935 ) ; responders , 67.9 % versus 76.3 % , p = .119 ) and day 182 ( -25.6 [ 16.88 ] versus -26.8 [ 18.82 ] , p = .877 ; responders , 76.8 % versus 81.6 % , p = .444 ) . All secondary endpoints ( maintenance of clinical stability , change in PANSS-negative symptoms , Clinical Global Impression-Severity , and Personal and Social Performance scores ) were similar in both treatment groups . The most common ( > 10 % patients ) treatment-emergent adverse events for paliperidone ER were akathisia , headache , somnolence , tremor , and weight gain , and  for aripiprazole were worsening of schizophrenia and somnolence . Extrapyramidal symptoms including dystonia and hyperkinesia occurred in > 2 % in paliperidone ER-treated versus aripiprazole-treated patients . CONCLUSION Paliperidone ER did not demonstrate superior efficacy to aripiprazole in treating adolescent schizophrenia . Both drugs showed clinical ly meaningful improvements in symptom and functional measurements and were generally tolerable . Clinical Trial Registration Information-An Efficacy and Safety Study of Extended-Release ( ER ) Paliperidone in Adolescent Participants With Schizophrenia ; http:// clinical trials.gov ; NCT01009047
The side effects ‘ EPS ’ , ‘ parkinsonism ’ , and ‘ tremor ’ were significantly more common in children and adolescents treated with aripiprazole than in those treated with placebo .
Conclusion Our meta- analysis provides evidence for a non-negligible incidence of acute EPS in children and adolescents treated with aripiprazole .
Background Both the US FDA and the European Medicines Agency ( EMA ) have approved aripiprazole for use in adolescents for specific indications .
Given the assumed favorable side-effect profile of aripiprazole , its use in children and adolescents has increased for both official and off-label indications ( anxiety disorders , eating disorders , personality disorders ) .
However , several cases of children and adolescents with new-onset  extrapyramidal symptoms ( EPS )  after commencing treatment with aripiprazole have been reported , and a more systematic appraisal of this possible risk is lacking .
Objective We conducted a systematic review and a meta- analysis to assess the evidence for acute EPS ( acute dystonia , akathisia , Parkinsonism ) associated with the use of aripiprazole in children and adolescents .