Focus on aripiprazole: a review of its use in child and adolescent psychiatry. Aripiprazole in the Treatment of Irritability in Children and Adolescents With Autistic Disorder 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. A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. Atypical Antipsychotics as Augmentation Therapy in Anorexia Nervosa Aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder: a pilot randomized clinical trial. Aripiprazole, a novel atypical antipsychotic drug. Neuromotor Adverse Effects in 342 Youth During 12 Weeks of Naturalistic Treatment With 5 Second-Generation Antipsychotics. Aripiprazole in Children and Adolescents: Clinical Experience A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia. Aripiprazole for the Treatment of Psychosis in Patients With Alzheimer's Disease: A Randomized, Placebo-Controlled Study A Randomized, Open-Label Comparison of 2 Switching Strategies to Aripiprazole Treatment in Patients With Schizophrenia: Add-On, Wait, and Tapering of Previous Antipsychotics Versus Add-On and Simultaneous Tapering Aripiprazole in the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorder in Japan: A Randomized, Double-blind, Placebo-controlled Study Open label aripiprazole in the treatment of youth with tic disorders. The effects of aripiprazole on electrocardiography in children with pervasive developmental disorders. Aripiprazole in juvenile bipolar disorder comorbid with attention-deficit/hyperactivity disorder: an open clinical trial.
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 : 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 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 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 Anorexia nervosa ( AN ) is a life-threatening and difficult to treat mental illness with the highest mortality rates of any psychiatric disorder . We aim ed to garner preliminary data on the real-world use of olanzapine and aripiprazole as augmentation agents of Selective Serotonin Reuptake Inhibitors ( SSRIs ) in adult in patients affected by AN . We retrospectively evaluated the clinical charts of patients who were hospitalized between 2012 and 2014 . Patients were evaluated upon admission and discharge . We investigated eating symptomatology , and both general and eating psychopathology using : Hamilton Rating Scale for Anxiety , Hamilton Rating Scale for Depression , and Yale-Brown-Cornell Eating Disorders Scale .  The charts of 75 patients were included in this study . The sample result ed equally distributed among those receiving SSRIs and either aripiprazole or olanzapine in addition to SSRIs . Notwithst and ing a few baseline clinical differences , upon discharge all groups were significantly improved on all measures . Interestingly , aripiprazole showed the greatest effectiveness in reducing eating-related preoccupations and rituals with a large effect size . The body of evidence on medication management in AN is in dismal condition . Augmentation therapy is a well-established approach to a variety of mental disorders and it is often used in every-day clinical practice with patients affected by AN as well . Nevertheless , to date very little data is available on this topic . Results from our sample yielded promising results on the effectiveness of aripiprazole augmentation in reducing eating-related obsessions and compulsions . R and omized controlled trials are warranted to confirm these encouraging findings 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 Before the 1990s , treatment of psychoses centered on conventional agents whose tolerability was limited by extrapyramidal side effects ( EPS ) . The past decade has seen the emergence of a newer generation of antipsychotic agents , first with clozapine and followed shortly by risperidone , olanzapine , quetiapine , and ziprasidone . These agents have been touted as providing better negative symptom efficacy , less impaired cognition , and lower risk of extrapyramidal syndromes . However , evolving evidence suggests that several drugs in this class may be associated with significant weight gain and lipid abnormalities .  Aripiprazole , a new atypical antipsychotic drug , displayed efficacy similar to that of haloperidol and risperidone and superior to that of placebo in numerous clinical trials . Aripiprazole does not cause significant prolactin elevation and is associated with a low rate of clinical ly significant weight gain compared with other atypical antipsychotics . Patients receiving aripiprazole  experienced EPS at a rate similar to that seen with placebo . Aripiprazole provides a new treatment option with limited adverse effects for patients in need of antipsychotic therapy 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 Despite few supportive data , aripiprazole was being administered to children and adolescents for management of mood instability , aggression , and psychosis . Using a retrospective review ( n = 11 ) and prospect i ve recruitment ( n = 6 ) , 17 children and adolescents received aripiprazole  5 to 20 mg/day . Only 4 of 16 bipolar and autistic subjects ( 25 % ) demonstrated reduced aggression without adverse events , and the symptoms of 2 of 4 psychotic subjects improved . Coadministration of sedative medications ( particularly guanfacine or clonidine ) and weight < 58 kg increased the risk of adverse events , such as increased lability and aggression . All three children < 8.6 years old , all four children < 34 kg , and all five children receiving α2-agonists developed adverse events prior to clinical efficacy . Age > 11 years , weight > 58 kg , and absence of sedative medications were associated with a 56 % ( five of nine ) success rate . Until larger , prospect i ve studies are completed , caution is advised when considering aripiprazole for smaller children and children receiving sedative medications . ( J Child Neurol 2005;20:603—610 ) 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 Abstract : This study compared the efficacy , safety , and tolerability of aripiprazole , a novel antipsychotic , with placebo in patients with psychosis associated with Alzheimer 's Disease ( AD ) . This 10-week , double-blind , multicenter study r and omized 208 out patients ( mean age , 81.5 years ) with AD-associated psychosis to aripiprazole ( n = 106 ) or placebo ( n = 102 ) . The initial aripiprazole dose of 2 mg/d was titrated upwards ( 5 , 10 , or 15 mg/d ) according to efficacy and tolerability . Evaluations included Neuropsychiatric Inventory ( NPI ) Psychosis subscale and Brief Psychiatric Rating Scale ( BPRS ) , adverse event ( AE ) reports , extrapyramidal symptoms ( EPS ) rating scales , and body weight . Overall , 172 patients ( 83 % ) completed the study .  Mean aripiprazole dose at end point was 10.0 mg/d . The NPI Psychosis subscale score showed improvements in both groups ( aripiprazole , −6.55 ; placebo , −5.52 ; P = 0.17 at end point ) . Aripiprazole-treated patients showed significantly greater improvements from baseline in BPRS Psychosis and BPRS Core subscale scores at end point compared with placebo . AEs were generally mild to moderate in severity and included  ( aripiprazole vs. placebo ) : urinary tract infection ( 8 % vs. 12 % ) , accidental injury ( 8 % vs. 5 % ) , somnolence ( 8 % vs. 1 % ) , and bronchitis ( 6 % vs. 3 % ) . Somnolence was mild and not associated with falls or accidental injury . There were no significant differences from placebo in EPS scores , or clinical ly significant ECG abnormalities , vital signs , or weight . In conclusion , aripiprazole showed similar improvements to placebo in psychotic symptoms as assessed by NPI Psychosis subscale scores , but significantly greater effects on BPRS Core and Psychosis assessment s in community-living AD patients with psychosis . Aripiprazole was safe and well tolerated in this patient population Although recent treatment guidelines for schizophrenia recommend that the prior antipsychotic agent should remain stable for at least 2 weeks when aripiprazole is introduced , there is no trial-based evidence to support this strategy . This study was design ed to compare this strategy with another conventional one in patients with schizophrenia . We conducted a r and omized , 14-week , open-label trial to compare the following 2 switching strategies : ( 1 ) add-on of aripiprazole on a current regimen , wait for 4 weeks , and the tapering of prior antipsychotics and ( 2 ) add-on of aripiprazole and the simultaneous tapering of prior antipsychotics in  patients with schizophrenia .  Aripiprazole was initiated at 12 mg/d and then titrated between 12 and 30 mg . The previous antipsychotic medication was reduced biweekly by 25 % . Assessment s included the Clinical Global Impression Scale Schizophrenia version , the Drug-Induced Extrapyramidal Symptoms Scale , and the Subjective Well-being Under Neuroleptics , Short Version , Japanese Edition . Impressions toward their assigned strategy were also subjectively evaluated at baseline and end point . Fifty-three patients were enrolled , and 48 patients completed this trial . No significant differences were found in changes from the baseline in the total Clinical Global Impression Scale Schizophrenia version severity , Drug-Induced Extrapyramidal Symptoms Scale , and Subjective Well-being Under Neuroleptics , Short Version , Japanese Edition scores throughout the study period between the 2 strategies . Both strategies were judged by subjects to be tolerable and favorable without between-group differences . In conclusion , both strategies were found to be objective ly safe and well tolerated . Taken together with similar results from subjective assessment s , it would be reasonable to choose either of these 2 strategies in clinical practice based on a patients ' preference 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 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 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 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
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 .