Journal of Child and Adolescent Psychopharmacology : Pharmacological treatment of autism (Novembre 2016)

mardi 6 décembre 2016

Le Journal of Child and Adolescent Psychopharmacology consacre intégralement son numéro de novembre 2016 au traitement pharmacologique de l’autisme.

1. Koplewicz HS. From the Editor-in-Chief’s Desk. Journal of Child and Adolescent Psychopharmacology ;2016 (2016/11/01) ;26(9):773-773.

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2. Hendren RL, James SJ, Widjaja F, Lawton B, Rosenblatt A, Bent S. Randomized, Placebo-Controlled Trial of Methyl B12 for Children with Autism. Journal of Child and Adolescent Psychopharmacology ;2016 (2016/11/01) ;26(9):774-783.

Abstract Objective : Children with autism spectrum disorder (ASD) have been reported to have reduced ability to methylate DNA and elevated markers of oxidative stress. We sought to determine if methyl B12, a key metabolic cofactor for cellular methylation reactions and antioxidant defense, could improve symptoms of ASD. Methods : A total of 57 children with ASD were randomly assigned to 8 weeks of treatment with methyl B12 (75 ??g/kg) or saline placebo every 3 days in a subcutaneous injection. The primary outcome measure was overall improvement in symptoms of ASD as measured by the Clinical Global Impressions-Improvement (CGI-I) score. Secondary outcome measures included changes in the Aberrant Behavior Checklist (ABC) and the Social Responsiveness Scale (SRS). Laboratory measures of methionine methylation and antioxidant glutathione metabolism were assessed at baseline and 8 weeks. Results : A total of 50 children (mean age 5.3 years, 79% male) completed the study. The primary outcome measure ? the clinician rated CGI-I score ? was statistically significantly better (lower) in the methyl B12 group (2.4) than in the placebo group (3.1) (0.7 greater improvement in the methyl B12 group, 95% CI 1.2 ?0.2, p ?= ?0.005). Clinical improvement among children treated with methyl B12 was positively correlated with increases in plasma methionine (p ?= ?0.05), decreases in S-adenosyl-l-homocysteine (SAH) (p ?= ?0.007) and improvements in the ratio of S-adenosylmethionine (SAM) to SAH (p ?= ?0.007), indicating an improvement in cellular methylation capacity. No improvements were observed in the parent-rated ABC or SRS. Conclusions : Methyl B12 treatment improved clinician-rated symptoms of ASD that were correlated with improvements in measures of methionine metabolism and cellular methylation capacity. Clinical Trial Registry : Efficacy Study of Subcutaneous Methyl B12 in Children with Autism : NCT01039792 (clinicaltrials.gov1).
Objective : Children with autism spectrum disorder (ASD) have been reported to have reduced ability to methylate DNA and elevated markers of oxidative stress. We sought to determine if methyl B12, a key metabolic cofactor for cellular methylation reactions and antioxidant defense, could improve symptoms of ASD. Methods : A total of 57 children with ASD were randomly assigned to 8 weeks of treatment with methyl B12 (75 ??g/kg) or saline placebo every 3 days in a subcutaneous injection. The primary outcome measure was overall improvement in symptoms of ASD as measured by the Clinical Global Impressions-Improvement (CGI-I) score. Secondary outcome measures included changes in the Aberrant Behavior Checklist (ABC) and the Social Responsiveness Scale (SRS). Laboratory measures of methionine methylation and antioxidant glutathione metabolism were assessed at baseline and 8 weeks. Results : A total of 50 children (mean age 5.3 years, 79% male) completed the study. The primary outcome measure ? the clinician rated CGI-I score ? was statistically significantly better (lower) in the methyl B12 group (2.4) than in the placebo group (3.1) (0.7 greater improvement in the methyl B12 group, 95% CI 1.2 ?0.2, p ?= ?0.005). Clinical improvement among children treated with methyl B12 was positively correlated with increases in plasma methionine (p ?= ?0.05), decreases in S-adenosyl-l-homocysteine (SAH) (p ?= ?0.007) and improvements in the ratio of S-adenosylmethionine (SAM) to SAH (p ?= ?0.007), indicating an improvement in cellular methylation capacity. No improvements were observed in the parent-rated ABC or SRS. Conclusions : Methyl B12 treatment improved clinician-rated symptoms of ASD that were correlated with improvements in measures of methionine metabolism and cellular methylation capacity. Clinical Trial Registry : Efficacy Study of Subcutaneous Methyl B12 in Children with Autism : NCT01039792 (clinicaltrials.gov1).

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3. Ghaleiha A, Alikhani R, Kazemi M-R, Mohammadi M-R, Mohammadinejad P, Zeinoddini A, Hamedi M, Shahriari M, Keshavarzi Z, Akhondzadeh S. Minocycline as Adjunctive Treatment to Risperidone in Children with Autistic Disorder : A Randomized, Double-Blind Placebo-Controlled Trial. Journal of Child and Adolescent Psychopharmacology ;2016 (2016/11/01) ;26(9):784-791.

Abstract Objective : This is an investigation of minocycline efficacy and safety as an adjuvant to risperidone in management of children with autism. Methods : Forty-six children with diagnosis of autistic disorder, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria and a score of ≥12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale, who were already drug-free for at least 6 months participated in a randomized controlled trial and underwent 10 weeks of treatment with either minocycline (50 ?mg twice per day) or placebo in addition to risperidone titrated up to 2 ?mg/day (based on bodyweight). Patients were evaluated using ABC-C at baseline and at weeks 5 and 10. Results : General linear model repeated measures showed significant effect for time ? treatment interaction on the irritability [F(2, 88) ?= ?3.94, p ?= ?0.02] and hyperactivity/noncompliance [F(1.50, 66.05) ?= ?7.92, p ?= ?0.002], but not for lethargy/social withdrawal [F(1.61, 71.02) ?= ?0.98, p ?= ?0.36], stereotypic behavior [F(1.34, 58.80) ?= ?1.55, p ?= ?0.22], and inappropriate speech subscale scores [F(1.52, 66.88) ?= ?1.15, p ?= ?0.31]. By week 10, 21 (91.3%) patients in the minocycline group and 15 (65.5%) patients in the placebo group achieved at least partial response (p ?= ?0.03). Frequencies of adverse events were not significantly different between groups. Conclusions : Minocycline seems to be a safe and effective adjuvant in management of patients with autistic disorder. Future studies with larger sample sizes, longer follow-ups, and inflammatory cytokine measurements are warranted to confirm these findings and provide insight into minocycline mechanism of action in autistic disorder.
Objective : This is an investigation of minocycline efficacy and safety as an adjuvant to risperidone in management of children with autism. Methods : Forty-six children with diagnosis of autistic disorder, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria and a score of ≥12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale, who were already drug-free for at least 6 months participated in a randomized controlled trial and underwent 10 weeks of treatment with either minocycline (50 ?mg twice per day) or placebo in addition to risperidone titrated up to 2 ?mg/day (based on bodyweight). Patients were evaluated using ABC-C at baseline and at weeks 5 and 10. Results : General linear model repeated measures showed significant effect for time ? treatment interaction on the irritability [F(2, 88) ?= ?3.94, p ?= ?0.02] and hyperactivity/noncompliance [F(1.50, 66.05) ?= ?7.92, p ?= ?0.002], but not for lethargy/social withdrawal [F(1.61, 71.02) ?= ?0.98, p ?= ?0.36], stereotypic behavior [F(1.34, 58.80) ?= ?1.55, p ?= ?0.22], and inappropriate speech subscale scores [F(1.52, 66.88) ?= ?1.15, p ?= ?0.31]. By week 10, 21 (91.3%) patients in the minocycline group and 15 (65.5%) patients in the placebo group achieved at least partial response (p ?= ?0.03). Frequencies of adverse events were not significantly different between groups. Conclusions : Minocycline seems to be a safe and effective adjuvant in management of patients with autistic disorder. Future studies with larger sample sizes, longer follow-ups, and inflammatory cytokine measurements are warranted to confirm these findings and provide insight into minocycline mechanism of action in autistic disorder.

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4. Mostafavi M, Hardy P, Arnold LE. Varenicline in Autism : Theory and Case Report of Clinical and Biochemical Changes. Journal of Child and Adolescent Psychopharmacology ;2016 (2016/11/01) ;26(9):792-797.

Abstract Objective : To explore the potential benefits of varenicline (CHANTIX ?), a highly specific partial agonist of neuronal α4 ?2 nicotinic acetylcholine receptors (nAChR), for autistic symptoms, and present resulting biochemical changes in light of dopamine-related genotype. Methods : The clinical and biochemical changes exhibited by a 19-year-old severely autistic man following the use of low-dose varenicline in an ABA experiment of nature, and his genotype, were extracted from chart review. Clinical outcome was measured by the Ohio Autism Clinical Impression Scale and 12 relevant urine and saliva metabolites were measured by Neuroscience Laboratory. Results : With varenicline, this patient improved clinically and autonomic biochemical indicators in saliva and urine normalized, including dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), epinephrine, norepinephrine, taurine, and histamine levels. In addition, with varenicline, the dopamine D1 receptor (DRD1) antibody titer as well as the percent of baseline calmodulin-dependent protein kinase II (CaM KII) activity dropped significantly. When varenicline stopped, he deteriorated ; when it was resumed, he again improved. Doses of 0.5, 1, and 2 ?mg daily were tried before settling on a dose of 1.5 ?mg daily. He has remained on varenicline for over a year with no noticeable side effects. Conclusion : This report is, to the best of our knowledge, only the second to demonstrate positive effects of varenicline in autism, the first to show it in a severe case, and the first to show normalization of biochemical parameters related to genotype. As with the previous report, these encouraging results warrant further controlled research before clinical recommendations can be made.
Objective : To explore the potential benefits of varenicline (CHANTIX ?), a highly specific partial agonist of neuronal α4 ?2 nicotinic acetylcholine receptors (nAChR), for autistic symptoms, and present resulting biochemical changes in light of dopamine-related genotype. Methods : The clinical and biochemical changes exhibited by a 19-year-old severely autistic man following the use of low-dose varenicline in an ABA experiment of nature, and his genotype, were extracted from chart review. Clinical outcome was measured by the Ohio Autism Clinical Impression Scale and 12 relevant urine and saliva metabolites were measured by Neuroscience Laboratory. Results : With varenicline, this patient improved clinically and autonomic biochemical indicators in saliva and urine normalized, including dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), epinephrine, norepinephrine, taurine, and histamine levels. In addition, with varenicline, the dopamine D1 receptor (DRD1) antibody titer as well as the percent of baseline calmodulin-dependent protein kinase II (CaM KII) activity dropped significantly. When varenicline stopped, he deteriorated ; when it was resumed, he again improved. Doses of 0.5, 1, and 2 ?mg daily were tried before settling on a dose of 1.5 ?mg daily. He has remained on varenicline for over a year with no noticeable side effects. Conclusion : This report is, to the best of our knowledge, only the second to demonstrate positive effects of varenicline in autism, the first to show it in a severe case, and the first to show normalization of biochemical parameters related to genotype. As with the previous report, these encouraging results warrant further controlled research before clinical recommendations can be made.

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5. Kilincaslan A, Mutluer TD, Pasabeyoglu B, Tutkunkardas MD, Mukaddes NM. Effects of Atomoxetine in Individuals with Attention-Deficit/Hyperactivity Disorder and Low-Functioning Autism Spectrum Disorder. Journal of Child and Adolescent Psychopharmacology ;2016 (2016/11/01) ;26(9):798-806.

Abstract Objectives : This naturalistic, retrospective study investigated the effects of atomoxetine (ATX) on attention-deficit/hyperactivity disorder (ADHD) symptoms and autistic features in children with autism spectrum disorders (ASDs) and intellectual disability (ID). Methods : Participants (n ?= ?37, age range 6 ?17 years, mean : 10.16 ?± ?3.60) were assessed at baseline, 4th and 12th weeks using Clinical Global Impressions (CGI) scales, DSM-IV-based ADHD-rating scale (ADHD-RS), and amended Turkish version of Aberrant Behavior Checklist (ABC). The primary outcome measure was a treatment response defined by a CGI-improvement score of 1 or 2 together with a decrease of at least 25% in the parent-rated ADHD-RS total score at the end of 12th week. Results : Five patients (13.5%) stopped medication at 4 weeks due to ineffectivity (2) and intolerable side effects (increased motor activity and talkativeness [n ?= ?1], irritability [n ?= ?2], temper outbursts [n ?= ?2], and increased blood pressure [n ?= ?1]). Sixteen patients (43.2%) were judged to be responders according to primary outcome measure. Improvement rate on CGI scale was 48.8%. On ADHD-RS, there were significant reductions between baseline and 4th week and between baseline and 12th week in both hyperactivity and inattention, and between baseline and 12th week in impulsivity scores. Decrease was significant in hyperactivity and social withdrawal subscales of the parent-reported ABC. Responders based on primary outcome measure were not significantly different from nonresponders in terms of sociodemographic features or clinical parameters, including intellectual, language, autism symptom, and ADHD symptom levels. Conclusion : In this chart review, ATX appears to be safe and effective for social withdrawal and ADHD symptoms in children with ASD and ID.
Objectives : This naturalistic, retrospective study investigated the effects of atomoxetine (ATX) on attention-deficit/hyperactivity disorder (ADHD) symptoms and autistic features in children with autism spectrum disorders (ASDs) and intellectual disability (ID). Methods : Participants (n ?= ?37, age range 6 ?17 years, mean : 10.16 ?± ?3.60) were assessed at baseline, 4th and 12th weeks using Clinical Global Impressions (CGI) scales, DSM-IV-based ADHD-rating scale (ADHD-RS), and amended Turkish version of Aberrant Behavior Checklist (ABC). The primary outcome measure was a treatment response defined by a CGI-improvement score of 1 or 2 together with a decrease of at least 25% in the parent-rated ADHD-RS total score at the end of 12th week. Results : Five patients (13.5%) stopped medication at 4 weeks due to ineffectivity (2) and intolerable side effects (increased motor activity and talkativeness [n ?= ?1], irritability [n ?= ?2], temper outbursts [n ?= ?2], and increased blood pressure [n ?= ?1]). Sixteen patients (43.2%) were judged to be responders according to primary outcome measure. Improvement rate on CGI scale was 48.8%. On ADHD-RS, there were significant reductions between baseline and 4th week and between baseline and 12th week in both hyperactivity and inattention, and between baseline and 12th week in impulsivity scores. Decrease was significant in hyperactivity and social withdrawal subscales of the parent-reported ABC. Responders based on primary outcome measure were not significantly different from nonresponders in terms of sociodemographic features or clinical parameters, including intellectual, language, autism symptom, and ADHD symptom levels. Conclusion : In this chart review, ATX appears to be safe and effective for social withdrawal and ADHD symptoms in children with ASD and ID.

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6. Hollway JA, Aman MG, Mendoza-Burcham MI, Silverman L, Arnold LE, Tumuluru R, Handen BL, Lecavalier L, Page K, Sayre P, Smith T. Caregiver Satisfaction with a Multisite Trial of Atomoxetine and Parent Training for Attention-Deficit/Hyperactivity Disorder and Behavioral Noncompliance in Children with Autism Spectrum Disorder. Journal of Child and Adolescent Psychopharmacology ;2016 (2016/11/01) ;26(9):807-814.

Abstract Objective : The purpose of this study was to examine caregiver satisfaction with the research experience in a randomized clinical trial of atomoxetine (ATX) and parent training (PT) for attention-deficit/hyperactivity disorder (ADHD) and behavioral noncompliance co-occurring with autism. Methods : The Children with Hyperactivity and Autism Research Treatment Study (CHARTS) randomly assigned 128 children 5.00 ?14.11 years of age to four treatment groups (ATX + PT, ATX alone, PT + placebo[PBO], and PBO). Caregivers completed an 18 item questionnaire about their satisfaction with the research experience. We summarized caregiver responses with descriptive statistics and examined whether the responses were associated with demographic variables, treatment assignment, or the child’s response to treatment (positive or negative). Results : Ninety-three percent of caregivers (119) completed the questionnaire. When asked if they would join the study again if given the chance, 87% (103) responded ?yes, ? 13% (15) responded ?maybe, ? and 1% (1) responded ?no.? When asked if they would recommend the study to other caregivers of children with similar problems, 92% (109) responded ?yes ? and 8% responded (10) ?maybe.? Of the 59 Parent Satisfaction Questionnaire (PSQ) respondents who received PT, 75% (44) felt more confident in managing current child behaviors, 24% (14) felt that their level of confidence was unchanged, and 2% (1) felt less confident. Most caregivers expressed satisfaction with the study procedures, including the number of visits and the safety monitoring protocols. Conclusions : In general, caregivers were highly satisfied with their research experience. These findings may be useful for informing human subject committees and for designing study protocols that are appealing to families.
Objective : The purpose of this study was to examine caregiver satisfaction with the research experience in a randomized clinical trial of atomoxetine (ATX) and parent training (PT) for attention-deficit/hyperactivity disorder (ADHD) and behavioral noncompliance co-occurring with autism. Methods : The Children with Hyperactivity and Autism Research Treatment Study (CHARTS) randomly assigned 128 children 5.00 ?14.11 years of age to four treatment groups (ATX + PT, ATX alone, PT + placebo[PBO], and PBO). Caregivers completed an 18 item questionnaire about their satisfaction with the research experience. We summarized caregiver responses with descriptive statistics and examined whether the responses were associated with demographic variables, treatment assignment, or the child’s response to treatment (positive or negative). Results : Ninety-three percent of caregivers (119) completed the questionnaire. When asked if they would join the study again if given the chance, 87% (103) responded ?yes, ? 13% (15) responded ?maybe, ? and 1% (1) responded ?no.? When asked if they would recommend the study to other caregivers of children with similar problems, 92% (109) responded ?yes ? and 8% responded (10) ?maybe.? Of the 59 Parent Satisfaction Questionnaire (PSQ) respondents who received PT, 75% (44) felt more confident in managing current child behaviors, 24% (14) felt that their level of confidence was unchanged, and 2% (1) felt less confident. Most caregivers expressed satisfaction with the study procedures, including the number of visits and the safety monitoring protocols. Conclusions : In general, caregivers were highly satisfied with their research experience. These findings may be useful for informing human subject committees and for designing study protocols that are appealing to families.

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7. Yalcin O, Kaymak G, Erdogan A, Tanidir C, Karacetin G, Kilicoglu AG, Mutlu C, Adaletli H, Gunes H, Bahali K, Ayik B, Uneri OS. A Retrospective Investigation of Clozapine Treatment in Autistic and Nonautistic Children and Adolescents in an Inpatient Clinic in Turkey. Journal of Child and Adolescent Psychopharmacology ;2016 (2016/11/01) ;26(9):815-821.

Abstract Objective : The aim of this retrospective study is to examine the clinical outcomes and safety of clozapine in children and adolescents with schizophrenia or other psychotic disorders/autism spectrum disorder (ASD) or affective disorders. Methods : The inpatient and outpatient files of all children and adolescents treated with clozapine over a period of 34 months (from October 2011 to July 2014) were reviewed. Demographic and clinical data were examined to describe clinical and metabolic findings, dosing, and tolerability of clozapine treatment in youth with schizophrenia, other psychotic disorders, ASD, or bipolar disorder. Results : The 37 pediatric patients included 26 patients with schizophrenia or other psychotic disorders, 7 patients with ASD complicated by schizophrenia or other psychotic disorders or affective disorders, and 4 patients with ASD only. In all groups (n ?= ?37) there was a significant reduction (p ? <?0.001) in Brief Psychiatric Rating Scale (BPRS) points after clozapine treatment during the inpatient period (38.78?±?27.75 days). In patients with schizophrenia or other psychotic disorders co-occurring with ASD or not (n?=?31), there was a significant improvement in psychotic symptoms according to Positive and Negative Syndrome Scale (PANSS) total scores and subscores (p?<?0.001). Of the 26 patients with schizophrenia or other psychotic disorders, 8 (30.8%) showed a positive response (>30% symptom reduction on BPRS). In patients with ASD complicated by schizophrenia or other psychotic disorders or bipolar disorders (n?=?7), there was a significant reduction (p?=?0.017) in BPRS scores after clozapine treatment. The discontinuation rate for clozapine was 10.8%, and the most frequently observed side effect was hypersalivation (54.1%). Neutropenia associated with clozapine was observed in only one patient (2.7%). Conclusions: Clozapine seems to be effective and safe in children and adolescents with schizophrenia or other psychotic disorders co-occuring with ASD or not. There is a need for further studies for determining the efficacy of clozapine in children and adolescents with bipolar affective disorder or ASD.
Objective: The aim of this retrospective study is to examine the clinical outcomes and safety of clozapine in children and adolescents with schizophrenia or other psychotic disorders/autism spectrum disorder (ASD) or affective disorders. Methods: The inpatient and outpatient files of all children and adolescents treated with clozapine over a period of 34 months (from October 2011 to July 2014) were reviewed. Demographic and clinical data were examined to describe clinical and metabolic findings, dosing, and tolerability of clozapine treatment in youth with schizophrenia, other psychotic disorders, ASD, or bipolar disorder. Results: The 37 pediatric patients included 26 patients with schizophrenia or other psychotic disorders, 7 patients with ASD complicated by schizophrenia or other psychotic disorders or affective disorders, and 4 patients with ASD only. In all groups (n?=?37) there was a significant reduction (p?<?0.001) in Brief Psychiatric Rating Scale (BPRS) points after clozapine treatment during the inpatient period (38.78?±?27.75 days). In patients with schizophrenia or other psychotic disorders co-occurring with ASD or not (n?=?31), there was a significant improvement in psychotic symptoms according to Positive and Negative Syndrome Scale (PANSS) total scores and subscores (p?<?0.001). Of the 26 patients with schizophrenia or other psychotic disorders, 8 (30.8%) showed a positive response (>30% symptom reduction on BPRS). In patients with ASD complicated by schizophrenia or other psychotic disorders or bipolar disorders (n?=?7), there was a significant reduction (p?=?0.017) in BPRS scores after clozapine treatment. The discontinuation rate for clozapine was 10.8%, and the most frequently observed side effect was hypersalivation (54.1%). Neutropenia associated with clozapine was observed in only one patient (2.7%). Conclusions: Clozapine seems to be effective and safe in children and adolescents with schizophrenia or other psychotic disorders co-occuring with ASD or not. There is a need for further studies for determining the efficacy of clozapine in children and adolescents with bipolar affective disorder or ASD.

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8. Yoon Y, Wink LK, Pedapati EV, Horn PS, Erickson CA. {{Weight Gain Effects of Second-Generation Antipsychotic Treatment in Autism Spectrum Disorder}}. {Journal of Child and Adolescent Psychopharmacology};2016 (2016/11/01);26(9):822-827.


Abstract Objective: Irritability (aggression, self-injury, and severe tantrums) associated with autism spectrum disorder (ASD) is often treated with second-generation antipsychotics (SGAs), which are well known for their associated risk of weight gain in youth. Recent reports suggest that youth with ASD treated with SGAs may suffer more pronounced weight gain than typically developing children. In this study, we present a comprehensive comparison of weight gain effects of five SGAs in a clinical population of youth with ASD. Methods: We completed a subanalysis of demographic and treatment data describing 202 youth with ASD treated at two large, subspecialty psychiatry clinics. Included subjects were between 2 and 20 years of age and were treated with one of five SGAs (risperidone, aripiprazole, olanzapine, quetiapine, or ziprasidone) for up to 4 years. We calculated change in each participant's body?mass index (BMI) z-score during the treatment period using a linear model where the dependent variable was change in BMI z-score and the independent variables were SGA used and duration of treatment. First, these models were run for each drug separately, then the SGA groups were run together to estimate differences between groups. We also adjusted these models for weight gain-attenuating concomitant medications. Results: Treatment with risperidone, aripiprazole, and olanzapine resulted in statistically significant increase in BMI z-score (p?=?0.03, 0.05, and <0.01 respectively). Ziprasidone and quetiapine were not associated with an increase in BMI z-score in this analysis (p?=?0.47 and p?=?0.11). Subjects treated with olanzapine showed a statistically significant greater increase in BMI z-score when compared with the other SGAs (all p-values <0.05). These results did not change when adjusted for multiple testing or weight gain-attenuating medication as covariate. Conclusion: Clinicians treating youth with ASD may be able to use this information to balance the risks and benefits of SGA treatment when managing ASD-associated irritability.
Objective: Irritability (aggression, self-injury, and severe tantrums) associated with autism spectrum disorder (ASD) is often treated with second-generation antipsychotics (SGAs), which are well known for their associated risk of weight gain in youth. Recent reports suggest that youth with ASD treated with SGAs may suffer more pronounced weight gain than typically developing children. In this study, we present a comprehensive comparison of weight gain effects of five SGAs in a clinical population of youth with ASD. Methods: We completed a subanalysis of demographic and treatment data describing 202 youth with ASD treated at two large, subspecialty psychiatry clinics. Included subjects were between 2 and 20 years of age and were treated with one of five SGAs (risperidone, aripiprazole, olanzapine, quetiapine, or ziprasidone) for up to 4 years. We calculated change in each participant's body?mass index (BMI) z-score during the treatment period using a linear model where the dependent variable was change in BMI z-score and the independent variables were SGA used and duration of treatment. First, these models were run for each drug separately, then the SGA groups were run together to estimate differences between groups. We also adjusted these models for weight gain-attenuating concomitant medications. Results: Treatment with risperidone, aripiprazole, and olanzapine resulted in statistically significant increase in BMI z-score (p?=?0.03, 0.05, and <0.01 respectively). Ziprasidone and quetiapine were not associated with an increase in BMI z-score in this analysis (p?=?0.47 and p?=?0.11). Subjects treated with olanzapine showed a statistically significant greater increase in BMI z-score when compared with the other SGAs (all p-values <0.05). These results did not change when adjusted for multiple testing or weight gain-attenuating medication as covariate. Conclusion: Clinicians treating youth with ASD may be able to use this information to balance the risks and benefits of SGA treatment when managing ASD-associated irritability.

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9. Osunsanmi S, Turk J. {{Influence of Age, Gender, and Living Circumstances on Patterns of Attention-Deficit/Hyperactivity Disorder Medication Use in Children and Adolescents With or Without Intellectual Disabilities}}. {Journal of Child and Adolescent Psychopharmacology};2016 (2016/11/01);26(9):828-834.


Abstract Aims and Objectives: The aim of the study was to determine whether there are differences in psychopharmacological practice for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents dependent on the presence or absence of associated intellectual disability; and if there are, whether the differences are influenced by factors such as age, gender, and living circumstances. Methodology: A case?control cross-sectional design was used. Each arm of the study had a total of 107 children and adolescents aged 5?18 years. Case participants had diagnoses of having intellectual disability and ADHD; comparison participants had diagnoses of having ADHD, but no intellectual disability. Outcome measurements were (1) concurrent use of medications?single medication event as against concurrent multiple medication events?and (2) type of medication used?stimulants versus nonstimulants. Demographic factors considered were gender, age, and living circumstances. Results: Male-to-female ratio in each group was 90:17. Mean age in the case group was 10.93 years (standard deviation [SD]: 3.39 years) and in the comparison group, 12.34 years (SD: 3.22 years). Seventy percent of the case group lived with their biological families, while 84% of the comparison group did so. In the case group, 7.5% were in residential school placements compared with only 0.9% of the comparison group. There were no statistically significant differences in broad measurements of outcomes between the case and comparison groups. Age appeared to be an important moderating factor for type of medication prescribed. Younger children with intellectual disabilities and ADHD were more likely to be established on nonstimulant medications than those with ADHD and no intellectual disabilities (p?=?0.024, odds ratio: 1.8; 95% CI: 1.2?2.7). Conclusions: Being between the ages of 5 and 12 years and having intellectual disability and ADHD are associated with raised likelihood of being prescribed nonstimulant medications for ADHD. This difference is maintained irrespective of gender and living circumstances. Reasons for these differences in prescribing practice require further exploration.
Aims and Objectives: The aim of the study was to determine whether there are differences in psychopharmacological practice for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents dependent on the presence or absence of associated intellectual disability; and if there are, whether the differences are influenced by factors such as age, gender, and living circumstances. Methodology: A case?control cross-sectional design was used. Each arm of the study had a total of 107 children and adolescents aged 5?18 years. Case participants had diagnoses of having intellectual disability and ADHD; comparison participants had diagnoses of having ADHD, but no intellectual disability. Outcome measurements were (1) concurrent use of medications?single medication event as against concurrent multiple medication events?and (2) type of medication used?stimulants versus nonstimulants. Demographic factors considered were gender, age, and living circumstances. Results: Male-to-female ratio in each group was 90:17. Mean age in the case group was 10.93 years (standard deviation [SD]: 3.39 years) and in the comparison group, 12.34 years (SD: 3.22 years). Seventy percent of the case group lived with their biological families, while 84% of the comparison group did so. In the case group, 7.5% were in residential school placements compared with only 0.9% of the comparison group. There were no statistically significant differences in broad measurements of outcomes between the case and comparison groups. Age appeared to be an important moderating factor for type of medication prescribed. Younger children with intellectual disabilities and ADHD were more likely to be established on nonstimulant medications than those with ADHD and no intellectual disabilities (p?=?0.024, odds ratio: 1.8; 95% CI: 1.2?2.7). Conclusions: Being between the ages of 5 and 12 years and having intellectual disability and ADHD are associated with raised likelihood of being prescribed nonstimulant medications for ADHD. This difference is maintained irrespective of gender and living circumstances. Reasons for these differences in prescribing practice require further exploration.

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10. Kim SH, Kim YS, Koh Y-J, Lim E-C, Kim S-J, Leventhal BL. {{Often Asked but Rarely Answered: Can Asians Meet DSM-5/ICD-10 Autism Spectrum Disorder Criteria?}}. {Journal of Child and Adolescent Psychopharmacology};2016 (2016/11/01);26(9):835-842.


Abstract Objectives: To evaluate whether Asian (Korean children) populations can be validly diagnosed with autism spectrum disorder (ASD) using Western-based diagnostic instruments and criteria based on Diagnostic and Statistical Manual on Mental Disorders, 5th edition (DSM-5). Methods: Participants included an epidemiologically ascertained 7?14-year-old (N?=?292) South Korean cohort from a larger prevalence study (N?=?55,266). Main outcomes were based on Western-based diagnostic methods for Korean children using gold standard instruments, Autism Diagnostic Interview-Revised, and Autism Diagnostic Observation Schedule. Factor analysis and ANOVAs were performed to examine factor structure of autism symptoms and identify phenotypic differences between Korean children with ASD and non-ASD diagnoses. Results: Using Western-based diagnostic methods, Korean children with ASD were successfully identified with moderate-to-high diagnostic validity (sensitivities/specificities ranging 64%?93%), strong internal consistency, and convergent/concurrent validity. The patterns of autism phenotypes in a Korean population were similar to those observed in a Western population with two symptom domains (social communication and restricted and repetitive behavior factors). Statistically significant differences in the use of socially acceptable communicative behaviors (e.g., direct gaze, range of facial expressions) emerged between ASD versus non-ASD cases (mostly p?<?0.001), ensuring that these can be a similarly valid part of the ASD phenotype in both Asian and Western populations. Conclusions: Despite myths, biases, and stereotypes about Asian social behavior, Asians (at least Korean children) typically use elements of reciprocal social interactions similar to those in the West. Therefore, standardized diagnostic methods widely used for ASD in Western culture can be validly used as part of the assessment process and research with Koreans and, possibly, other Asians.
Objectives: To evaluate whether Asian (Korean children) populations can be validly diagnosed with autism spectrum disorder (ASD) using Western-based diagnostic instruments and criteria based on Diagnostic and Statistical Manual on Mental Disorders, 5th edition (DSM-5). Methods: Participants included an epidemiologically ascertained 7?14-year-old (N?=?292) South Korean cohort from a larger prevalence study (N?=?55,266). Main outcomes were based on Western-based diagnostic methods for Korean children using gold standard instruments, Autism Diagnostic Interview-Revised, and Autism Diagnostic Observation Schedule. Factor analysis and ANOVAs were performed to examine factor structure of autism symptoms and identify phenotypic differences between Korean children with ASD and non-ASD diagnoses. Results: Using Western-based diagnostic methods, Korean children with ASD were successfully identified with moderate-to-high diagnostic validity (sensitivities/specificities ranging 64%?93%), strong internal consistency, and convergent/concurrent validity. The patterns of autism phenotypes in a Korean population were similar to those observed in a Western population with two symptom domains (social communication and restricted and repetitive behavior factors). Statistically significant differences in the use of socially acceptable communicative behaviors (e.g., direct gaze, range of facial expressions) emerged between ASD versus non-ASD cases (mostly p?<?0.001), ensuring that these can be a similarly valid part of the ASD phenotype in both Asian and Western populations. Conclusions: Despite myths, biases, and stereotypes about Asian social behavior, Asians (at least Korean children) typically use elements of reciprocal social interactions similar to those in the West. Therefore, standardized diagnostic methods widely used for ASD in Western culture can be validly used as part of the assessment process and research with Koreans and, possibly, other Asians.

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11. Wink LK, Badran I, Pedapati EV, Sorensen R, Benton SC, Johnson MC, Wissel G, Erickson CA. {{Clozapine for Drug-Refractory Irritability in Individuals with Developmental Disability}}. {Journal of Child and Adolescent Psychopharmacology};2016 (2016/11/01);26(9):843-846.


Abstract Objectives: In this case series, we describe the acute clinical impact and tolerability of rapid titration of clozapine for treatment of refractory irritability in five hospitalized youth with developmental disability. We offer this descriptive report in an effort to expand the evidence base guiding treatment of refractory aggression in this population. Methods: Five youth with developmental disability and severe irritability were admitted to a 10-bed psychiatric crisis stabilization unit where they received thorough psychiatric and medical evaluation. Informed consent was obtained in each case, and each patient underwent rapid titration onto clozapine. Clozapine monitoring guidelines were followed for all patients throughout treatment, and clinical severity at baseline and improvement with treatment was measured by use of the Clinical Global Impressions-Severity scale (CGI-S) and the Clinical Global Impressions-Improvement scale (CGI-I). Results: One female and four males diagnosed with developmental disability and at least one other psychiatric diagnosis, mean age of 13.1?±?2.1 years, and mean CGI-S at baseline of 5.8, each received clozapine treatment by rapid titration. The mean therapeutic total daily dose of clozapine was 380?±?200?mg. All patients demonstrated acute clinical improvement with the mean final CGI-I of 2.0, or ?much improved.? Conclusion: These initial results support the potential utility of clozapine rapid titration for treatment of severe refractory irritability in youth with developmental disability. These patients tolerated clozapine treatment in the short term. Future studies are needed to thoroughly evaluate the long-term safety of clozapine treatment in this population.
Objectives: In this case series, we describe the acute clinical impact and tolerability of rapid titration of clozapine for treatment of refractory irritability in five hospitalized youth with developmental disability. We offer this descriptive report in an effort to expand the evidence base guiding treatment of refractory aggression in this population. Methods: Five youth with developmental disability and severe irritability were admitted to a 10-bed psychiatric crisis stabilization unit where they received thorough psychiatric and medical evaluation. Informed consent was obtained in each case, and each patient underwent rapid titration onto clozapine. Clozapine monitoring guidelines were followed for all patients throughout treatment, and clinical severity at baseline and improvement with treatment was measured by use of the Clinical Global Impressions-Severity scale (CGI-S) and the Clinical Global Impressions-Improvement scale (CGI-I). Results: One female and four males diagnosed with developmental disability and at least one other psychiatric diagnosis, mean age of 13.1?±?2.1 years, and mean CGI-S at baseline of 5.8, each received clozapine treatment by rapid titration. The mean therapeutic total daily dose of clozapine was 380?±?200?mg. All patients demonstrated acute clinical improvement with the mean final CGI-I of 2.0, or ?much improved.? Conclusion: These initial results support the potential utility of clozapine rapid titration for treatment of severe refractory irritability in youth with developmental disability. These patients tolerated clozapine treatment in the short term. Future studies are needed to thoroughly evaluate the long-term safety of clozapine treatment in this population.

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12. Garcia-Delgar B, Morer A, Luber MJ, Coffey BJ. {{Obsessive-Compulsive Disorder, Tics, and Autoinflammatory Diseases: Beyond PANDAS}}. {Journal of Child and Adolescent Psychopharmacology};2016 (2016/11/01);26(9):847-850.



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13. Chen F. {{Risperidone-Induced Acute Respiratory Distress in an Adolescent with Autism}}. {Journal of Child and Adolescent Psychopharmacology};2016 (2016/11/01);26(9):851-852.



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14. Fluegge K. {{Methyl B12 and Autism Spectrum Disorders: Any Clues to Etiology?}}. {Journal of Child and Adolescent Psychopharmacology};2016 (2016/11/01);26(9):853-853.



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15. Hor A, Purtell L. {{Influence of Naltrexone/Bupropion Combination Treatment on Body Mass Index in Prader–Willi Syndrome Re: “Prader–Willi Syndrome, Management of Impulsivity, and Hyperphagia in an Adolescent” by Puri et al. (J Child Adolesc Psychopharmacol 26:403–404, 2016)}}. {Journal of Child and Adolescent Psychopharmacology};2016 (2016/11/01);26(9):854-854.



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16. Percinel I, Yazici KU. {{The Use of Aripiprazole in Young Children with Autism Spectrum Disorders: The Treatment and 16 Week Follow-Up of a 23-Month-Old Male Patient}}. {Journal of Child and Adolescent Psychopharmacology};2015 (2016/11/01);26(9):855-857.



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17. Pinnaka S, Roberto AJ, Giordano A, Siller P, Lapidus K. {{Aripiprazole-Induced Transient Morning Pseudoneutropenia in an 11-Year-Old Male}}. {Journal of Child and Adolescent Psychopharmacology};2015 (2016/11/01);26(9):858-859.



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18. Mutlu C, Bahalı K, Gunes H, Adaletli H. {{Increase in Menstrual Cycle Length Induced by Extended-Release Methylphenidate in an Adolescent with Attention-Deficit/Hyperactivity Disorder}}. {Journal of Child and Adolescent Psychopharmacology};2015 (2016/11/01);26(9):860-861.



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Annonces

Accès direct au catalogue en ligne !

Vous pouvez accéder directement au catalogue en ligne du centre de documentation du CRA Rhône-Alpes en cliquant sur l’image ci-dessous :

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Formations pour les Familles et les Proches

le détail des programmes de formation à l’attention des familles et des proches de personnes avec TSA est disponible en cliquant sur l’image ci-dessous.

Formation pour les Aidants Familiaux {JPEG}


Sensibilisation à l’usage des tablettes au CRA !

Toutes les informations concernant les sensibilisations du CRA aux tablettes numériques en cliquant sur l’image ci-dessous :


1-Formation à l’état des connaissances de l’autisme

Plus d’information sur la formation gratuite que dispense le CRA en cliquant sur l’image ci-dessous :

Formation à l'état des connaissances de l'autisme {JPEG}


4-Livret Autisme Rhône-Alpes® (LARA) - Message à l’attention des directeurs

Prenez connaissance du Livret Autisme Rhône-Alpes, projet de répertoire régional des structures médico-sociales. En cliquant sur l’image ci-dessous :

Cliquez sur l'image pour découvrir le Livret LARA