title: The retrospective chart review: important methodological considerations A prospective open-label study of aripiprazole in fragile X syndrome A methodology for conducting retrospective chart review research in child and adolescent psychiatry. Aripiprazole in children and adolescents with Tourette's disorder: an open-label safety and tolerability study. Aripiprazole in the Treatment of Irritability in Children and Adolescents With Autistic Disorder A Non-randomized, Open Study with Aripiprazole and Ziprasidone for the Treatment of Aggressive Behavior in Youth in a Community Clinic 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. Safety and tolerability of aripiprazole for irritability in pediatric patients with autistic disorder: a 52-week, open-label, multicenter study. Aripiprazole in children with Tourette's disorder and co-morbid attention-deficit/hyperactivity disorder: a 12-week, open-label, preliminary study. An open-label trial of aripiprazole in the treatment of aggression in male adolescents diagnosed with conduct disorder. 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. Focus on aripiprazole: a review of its use in child and adolescent psychiatry. An open-label study of aripiprazole in children with a bipolar disorder. Paediatric Atypical Antipsychotic Monitoring Safety (PAMS) Study Aripiprazole in Children and Adolescents: Clinical Experience Aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder: a pilot randomized clinical trial. Neuromotor Adverse Effects in 342 Youth During 12 Weeks of Naturalistic Treatment With 5 Second-Generation Antipsychotics. Acute treatment of pediatric bipolar I disorder, manic or mixed episode, with aripiprazole: a randomized, double-blind, placebo-controlled study. An open-label trial of aripiprazole monotherapy in children and adolescents with bipolar disorder. Open label aripiprazole in the treatment of youth with tic disorders. A RATING SCALE FOR EXTRAPYRAMIDAL SIDE EFFECTS 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. A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. Effectiveness and tolerability of aripiprazole in child and adolescent inpatients: a retrospective evaluation A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia. Aripiprazole in the treatment of the psychosis prodrome: an open-label pilot study.
abstract: In this paper , we review and discuss ten common method ological mistakes found in  retrospective chart review s. The retrospective chart review is a widely applicable research methodology that can be used by healthcare disciplines as a means to direct subsequent prospect i ve investigations . In many cases in this review , we have also provided suggestions or accessible re sources that research ers can apply as a “ best practice s ” guide when planning , conducting , or review ing this investigative method Rationale Fragile X syndrome ( FXS ) is the most common inherited form of developmental disability and most common single gene cause of autism . Persons with FXS frequently exhibit irritable behavior marked by aggression , self-injury , and severe tantrums . Despite frequent clinical use of atypical antipsychotic drugs to target this behavioral cluster , no systematic trials to date have assessed the efficacy and safety of these drugs in persons with FXS . Methods We conducted a prospect i ve open-label 12-week trial of aripiprazole in 12 persons aged 6–25 years ( mean age , 14.3 years ) with FXS who were free of concomitant psychoactive drugs .  Results Aripiprazole use ( mean dose , 9.8 mg/day ) was associated with treatment response ( defined by a Clinical Global Impressions-Improvement scale score of much improved or very much improved and a ≥25 % improvement on the Aberrant Behavior Checklist-Irritability subscale ) in 10 of 12 ( 87 % ) persons . Two individuals ( 13 % ) discontinued aripiprazole prior to study completion due to adverse events . One discontinuation was due to akathisia , mild drooling , and mild tiredness and the other due to moderate tiredness and moderate drooling . No significant changes in vital signs including weight or laboratory measures occurred during treatment with aripiprazole . Conclusions Aripiprazole was generally safe and well tolerated and was associated with significant improvement in irritable behavior . Given these findings , a double-blind , placebo-controlled study of aripiprazole in FXS is warranted INTRODUCTION Retrospective research has become largely undervalued and underutilized in child and adolescent psychiatry with the increasing singular focus on r and omized control trials , despite the wealth of clinical ly relevant data available in historical medical records . In this paper a systematic and scientific approach to chart review research methodology for psychiatry is described . METHOD Informed by available literature , a method ological stepwise approach for retrospective chart review was developed . RESULTS A nine step method aim ed at maximizing benefits and minimizing limitations is discussed . CONCLUSIONS Retrospective chart review is an important methodology with distinct advantages and has the potential to provide psychiatry with valuable research opportunities . This method of study should not be lost in the field of psychiatry 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 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 Forty-six patients ( 36 male , mean age 11.9 ± 2.6 ) with a variety of diagnoses and with significant aggressive behavior were treated in an open , non-r and omized fashion with Aripiprazole or Ziprasidone . Patients were diagnosed with the Mini International Neuropsychiatric Interview and the Child/Adolescent Symptom Inventory . The primary outcome measure was the Overt Aggression Scale ( OAS ) . After 2 months , 34 patients were still in treatment . The average improvement of the OAS in these 34 patients was 63 % . Clinical Global Impression-Improvement Scale was 2.1 ± 1.2 . Neither at baseline , nor at 2 months , were there any statistically significant differences between the Aripiprazole and Ziprasidone groups . Sedation was the most common side effect 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 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 Tourette 's disorder ( TD ) in children and adolescents is frequently co-morbid with attention-deficit/hyperactivity disorder ( ADHD ) . Dopamine-blockers are the first line treatment for TD , whereas dopamine-agonists , such as stimulants , are the gold-st and ard in the treatment of ADHD . These contrasting effects supported concerns about the risk that stimulants for treating ADHD may trigger or worsen co-morbid tics . Aripiprazole , a partial dopamine agonist , acts as an antagonist at dopamine D2 receptors in hyperdopaminergic conditions and displays agonist properties under hypodopaminergic conditions . The present study describes the use of aripiprazole ( 10.0 ± 4.8 mg/day ) in a consecutive group of 28 patients with a primary diagnosis of TD and co-morbid ADHD , combined subtype .  The Yale Global Tic Severity Scale ( YGTSS ) and the ADHD-Rating Scale ( ADHD-RS-IV ) were used as primary outcome measures and both significantly improved ( p<0.001 ) after the treatment . Global measures of severity ( Clinical Global Impressions-Severity ) and of functional impairment ( Children 's Global Assessment Scale ) also significantly improved during the treatment ( p<0.001 ) . At the YGTSS there was a reduction of 42.5 % , in motor tics , of 47.9 % in phonic tics ( 44.7 % for the combined scores ) , and of 32.3 % in tic impairment . Nineteen patients ( 67.9 % ) had a reduction of at least 50 % of the YGTSS score ( motor+phonic tics ) . The improvement at the ADHD-RS-IV score was 22.5 % , 12 patients ( 42.8 % ) presented an improvement of 30 % , but only 2 ( 7.1 % ) an improvement greater than 50 % . Using a logistic regression model , a reduction of at least 30 % in ADHD-RS-IV score was more likely to occur in the obsessive-compulsive disorder co-morbid group . Aripiprazole was well tolerated and none of the patients discontinued medication because of side effects . In summary , aripiprazole result ed in an effective treatment for TD , but it was only moderately effective on co-occurring ADHD symptomatology . Our preliminary data suggest that aripiprazole may represent a possible therapeutic option , among other possible monotherapies addressing both tics and ADHD 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 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 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 purpose of this open-label study was to describe the effectiveness of aripiprazole ( APZ ) in the treatment of children with bipolar disorders suffering from manic symptomatology . METHOD Symptomatic out patients ( Young Mania Rating Scale [ YMRS ] score ≥15 ) meeting strict , unmodified , Diagnostic and Statistical Manual of Mental Disorders , 4th edition , diagnostic symptom criteria for a bipolar disorder , ages 4 - 9 years , were eligible . Subjects were treated prospect ively with flexible doses of APZ ( maximum daily dose of 15 mg/day ) , for up to 16 weeks or until a priori response criteria were met . Outcome measures included the YMRS , Clinical Global Impressions Scale-Severity , Children 's Global Assessment Scale ( CGAS ) , and the Children 's Depression Rating Scale-Revised ( CDRS-R ) . A priori response criteria consisted of 3 of 4 consecutive weeks with ( 1 ) CDRS-R < 29 ; ( 2 ) YMRS < 10 ; and ( 3 ) CGAS > 50 . RESULTS Ninety-six children ( 62 males ; mean age of 6.9 ( SD = 1.7 ) , received APZ for an average length of treatment of 12.5 ( SD = 3.9 ) weeks . Significant improvements in YMRS , CDRS-R , CGAS , and Clinical Global Impressions Scale-Severity scores ( p < 0.001 ) were noted at the end of study participation . Sixty of the subjects ( 62.5 % ) met a priori response criteria at study 's end . The most common side effects noted were stomachache , increased appetite , and headache . Two subjects were removed from the study due to side effects [ epistaxis ( n = 1 ) ; akathisia ( n = 1 ) ] . Subjects experienced an average weight gain of 2.4 ( SD = 1.9 ) kg . CONCLUSION APZ may be effective in the acute treatment of symptoms of children with bipolar illnesses Abstract Background : In the UK , treatment with  antipsychotic medications  for children is usually initiated by specialists in secondary care . Recent studies have shown an increase in the prescribing of atypical antipsychotics in children . The severity of possible adverse effects to antipsychotics in adults has lead to awareness of the importance of investigating the potential adverse effects of these agents in children . Additionally , there have been many reports proposing that the newer atypical antipsychotics are associated with many of the same adverse effects seen with the older generation drugs in children . The aim of the Paediatric Atypical Antipsychotic Monitoring Safety ( PAMS ) study was to determine the feasibility of conducting a prospect i ve targeted pharmacovigilance study to monitor adverse drug reactions ( ADRs ) associated with atypical antipsychotic therapy in children seen in secondary - and tertiary-care setting s. Methods : Participants were identified from the clinical members of the UK Paediatric Psychopharmacology Groups in London and the West Midl and s. Participating clinicians reported the number of patients ( aged ≤18 years ) taking atypical antipsychotic treatment who were under their care and any reportable ADRs experienced by these patients during the period September 2006–September 2007 . Participants contributed data via password protected online data collection forms . Results : A total of 35 clinicians consented to participate in the study . However , data from 22 of the participating clinicians were excluded because of incomplete reporting . Data from the remaining 13 ( 37 % ) clinicians were eligible for the final analysis . There were 281 patients who received atypical antipsychotic treatment under the care of the 13 participating clinicians . From these 281 patients , 40 ADR reports ( 0.14 ADR reports per patient ; 95 % CI 0.10 , 0.19 ) from 37 patients were entered into the data base . Of the 37 patients , 13 experienced more than one ADR , bringing the total number of ADRs to 56 ( 0.20 ADR per patient ; 95 % CI 0.15 , 0.25 ) . The most commonly reported ADRs were weight gain , extrapyramidal symptoms and hyperprolactinaemia . Rare ADRs , including neuroleptic malignant syndrome , were also reported . The duration s of atypical antipsychotic drug exposure were recorded for 54 of the 56 ADRs reported . The median duration of exposure was 42 days ( interquartile range 23.25–90 days ) . Conclusions : Our study demonstrates that a clinician-based targeted pharmacovigilance study on  atypical antipsychotics in children provides useful qualitative data . However , this pilot study raised many method ological issues , which should be addressed for the study to be extended nationally . Specifically , significant funding is needed to improve the reporting rate and the overall data obtained . Furthermore , the study yielded a very high incidence of serious ADRs , thus supporting the need for a larger and improved pharmacovigilance study to evaluate the safety of atypical antipsychotics in children 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 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 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 OBJECTIVES To determine the efficacy and safety of aripiprazole for the treatment of pediatric bipolar I disorder , manic or mixed episode , with or without psychotic features . METHOD Subjects were enrolled between March 2005 and February 2007 in a r and omized , multicenter , double-blind 4-week study of aripiprazole 10 mg/d , aripiprazole 30 mg/d , and placebo .  Subjects ( n = 296 ) were 10 to 17 years old with a DSM-IV diagnosis of bipolar I disorder with current manic or mixed episodes , with or without psychotic features , and a Young Mania Rating Scale ( YMRS ) score > or = 20 . The primary efficacy variable was change from baseline in the YMRS total score . RESULTS Both doses of aripiprazole were superior to placebo on the YMRS total score beginning at week 1 and continuing through week 4 . Aripiprazole 10 mg and 30 mg were more effective than placebo on global improvement , mania , and overall bipolar illness outcome measures . Response ( > or = 50 % reduction in YMRS total score ) at week 4 was achieved by 44.8 % , 63.6 % , and 26.1 % of subjects in the aripiprazole 10 mg , aripiprazole 30 mg , and placebo groups , respectively ( P < .01 both doses vs placebo ) . Both doses were generally well tolerated . The most common adverse events were extrapyramidal disorder and somnolence ; rates were higher for aripiprazole 30 mg compared with aripiprazole 10 mg . Average weight gain was not significantly different between the aripiprazole 10 mg ( + 0.82 kg ) or 30 mg ( + 1.08 kg ) groups compared with the placebo group ( + 0.56 kg ) ( P = .35 and P = .13 , respectively ) . CONCLUSIONS Aripiprazole in daily doses of 10 mg or 30 mg is an effective and generally well-tolerated acute treatment for pediatric subjects with bipolar I mania or mixed episodes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00110461 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 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 A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors 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 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 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 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 BACKGROUND Research studies for the treatment of the putative prodromal phase of psychotic disorders have begun to appear . AIMS To obtain preliminary evidence of the short-term efficacy and safety of aripiprazole treatment in people with the psychosis prodrome . METHOD Fifteen participants meeting prodrome criteria ( mean age 17.1 years , s.d.=5.5 ) enrolled in an open-label , single-site trial with fixed-flexible dosing of aripiprazole ( 5 - 30 mg/day ) for 8 weeks . RESULTS In the mixed-effects repeated- measures analysis , improvement from baseline on the Scale of Prodromal Symptoms total score was statistically significant by the first week . No participant converted to psychosis and 13 completed treatment . Neuropsychological measures showed no consistent improvement ; mean weight gain was 1.2 kg . Akathisia emerged in 8 participants , but the mean Barnes Akathisia Scale score fell to baseline levels by the final visit . Adverse events were otherwise minimal . CONCLUSIONS Aripiprazole shows a promising efficacy and safety profile for the psychosis prodrome . Placebo-controlled studies are indicated
target: 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: 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 .