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Risperidone: a review of its use in the treatment of irritability associated with autistic disorder in children and adolescents. Scott Lesley J,Dhillon Sohita Paediatric drugs Risperidone (Risperdal), a psychotropic atypical antipsychotic agent, is thought to act via dopamine D(2) and serotonin (5-HT [5-hydroxytryptamine])(2A) receptor antagonism. The clinical efficacy of oral risperidone in the treatment of bipolar mania and schizophrenia in adult patients is well established. In the US, risperidone is also approved for the treatment of irritability associated with autistic disorder in children and adolescents aged 5-16 years, for the treatment of schizophrenia in adolescents aged 13-17 years and, as monotherapy, for the short-term treatment of acute manic and mixed episodes associated with bipolar I disorder in children and adolescents aged 10-17 years. Oral risperidone treatment was better than placebo treatment in reducing irritability and other behavioral symptoms associated with autistic disorder in children and adolescents in two well designed short-term trials, with these benefits maintained in those receiving risperidone for up to 6 months. The drug had a clinically manageable tolerability profile, with most adverse events being of mild to moderate intensity. There are some aspects of treatment, such as weight gain, somnolence, and hyperglycemia, that require monitoring, and the long-term safety of risperidone in children and adolescents with autistic disorder remains to be fully determined. With these issues in mind, risperidone offers a valuable emerging option for the treatment of irritability associated with autistic disorder in children and adolescents. 10.2165/00148581-200709050-00006
A randomized controlled trial of 25 sessions comparing music therapy and music listening for children with autism spectrum disorder. Rabeyron Thomas,Robledo Del Canto Juan-Pablo,Carasco Emmanuelle,Bisson Vanessa,Bodeau Nicolas,Vrait François-Xavier,Berna Fabrice,Bonnot Olivier Psychiatry research BACKGROUND:Music therapy is based on the use of musical elements by a trained and qualified therapist. Clinical researches have suggested that children with Autism Spectrum Disorders (ASD) may benefit from MT. In this regard, this study examines if MT is more effective than simply listening to music for children with ASD. METHOD:A 8-month RCT has been carried out comparing music therapy (MT) to music listening (ML) for children with ASD aged from 4 to 7 years old. Thirty-seven participants were randomly assigned to one of the two groups (MT vs. ML). The outcome measures were the Clinical Global Impression (CGI), the Childhood Autism Rating Scale (CARS) and the Aberrant Behavior Checklist (ABC) in each condition (MT and ML). RESULTS:CGI scores decreased more for participants in the MT than in the ML condition. This clinical improvement was associated with an improvement of autistic symptoms on lethargy and stereotypy ABC subscales. CONCLUSION:Our findings suggest that music therapy is more efficient than music listening for children with ASD. The present study thus supports the consideration of MT as a rightful add-on to ASD healthcare programs. 10.1016/j.psychres.2020.113377
Aripiprazole in the treatment of irritability in pediatric patients (aged 6-17 years) with autistic disorder: results from a 52-week, open-label study. Marcus Ronald N,Owen Randall,Manos George,Mankoski Raymond,Kamen Lisa,McQuade Robert D,Carson William H,Corey-Lisle Patricia K,Aman Michael G Journal of child and adolescent psychopharmacology AIM:To report the long-term efficacy of aripiprazole in the treatment of irritability in children and adolescents (ages 6-17 years) with autistic disorder. METHODS:This was a 52-week, open-label, flexible-dose (2-15 mg/day) study of aripiprazole for the treatment of children and adolescents with irritability associated with autistic disorder. Eligible subjects were enrolled from two 8-week randomized trials or were enrolled as de novo subjects. "Prior aripiprazole" subjects had received treatment with aripiprazole for 8 weeks before entering this study. Evaluation of efficacy, a secondary objective after evaluation of safety and tolerability in this study, was conducted using the caregiver-rated Aberrant Behavior Checklist-Irritability subscale and the clinician-rated Clinical Global Impression-Improvement score. RESULTS:Three hundred thirty subjects received treatment (de novo, n = 86; prior aripiprazole, n = 174; prior placebo, n = 70) and 199 subjects (60.3%) completed 52 weeks of treatment. At their last study visit, 38.2% of subjects were receiving concomitant central nervous system medications (commonly antidepressants, 13.4%; psychostimulants, 11.5%; antiepileptics, 5.9%). At week 52 (observed cases data set), the mean change from baseline in Aberrant Behavior Checklist Irritability subscale scores was -8.0 in de novo subjects and -6.1 in prior placebo subjects; prior aripiprazole subjects maintained symptom improvement that was achieved with treatment in the prior study. At endpoint, the majority of subjects had a Clinical Global Impressions-Improvement score of 2 (much improved) or 1 (very much improved). CONCLUSION:Aripiprazole reduced symptoms of irritability associated with autistic disorder in pediatric subjects ages 6-17 years who were studied for up to 1 year. 10.1089/cap.2009.0121
Effectiveness of switching from oral ziprasidone to risperidone in a patient with comorbid autistic disorder, profound intellectual disability, Gilbert syndrome, and exacerbation of psychosis. Del Casale Antonio,Kotzalidis Georgios D,Sacco Michele,Rapinesi Chiara,De Giorgi Riccardo,Giardini Marco,D'Andreagiovanni Michele,Carlino Nicola,Brugnoli Roberto,Girardi Paolo Psychiatria Danubina
Bumetanide in the management of autism. Tunisian experience in Razi Hospital. Hajri Melek,Ben Amor Arwa,Abbes Zeineb,Dhouib Soumeyya,Ouanes Sami,Mrabet Ali,Daghfous Riadh,Bouden Asma La Tunisie medicale BACKGROUND:Autism is a multifactorial disease with multiple etiologic hypotheses. Some studies suggest changes in brain GABA mediated inhibition in autism, and a higher intracellular chlorine levels in autistic children. Given these data, clinical trials are conducted to test the efficacy of diuretics in improving clinical symptoms in autism. AIM:The aim of our study was to evaluate the effectiveness of Bumetanide in autistic children. METHODS:This is an experimental study of cross-type. We included children older than 5 years, with autistic disorder according to the diagnostic criteria of DSM- IV (Diagnostic and Statistical Manual of Mental Disorders, IV) and ADI-R (Autism Diagnostic Interview Revised), followed by the child psychiatry consultation Razi hospital. The subjects underwent assessment using the ADI-R, the behavioral scale CARS (Childhood autistic rating scale) and CGI (Clinical Global printing) prior to take diuretic (Bumetanide). In the protocol, the children received checks to day7, day14, day30, day60, day90 comprising: a clinical evaluation (weight gain, blood pressure, general examination for potential adverse effects); biological evaluation; and evaluations by scales (CARS and CGI) after every 3 months of evolution to objectively assess effectiveness. RESULTS:Twenty-nine children were included in our study. The average age was 7.9 years.Initiation of medication was carried out with a dose of    1 mg / day, in all children. The average duration of the protocol was 12 months. Sixteen children were excluded from the study for the following reasons: appearance of hypokalemia, poor tolerance of treatment, insufficient efficacy as estimated by parents. Measuring the effectiveness of diuretic, by studying correlations in the CARS showed an efficacy of this treatment at 3 months (p˂10-3), 6 months (p˂10-3), at 9 months (p = 0.010) and 12 months (p = 0.04), and this compared to the initial assessment. Significant improvement (p˂10-3) was found between the 3rd and 6th month. CONCLUSION:While our results seem to be promising. A larger sample and a medium and long-term evaluation after the end of treatment are needed.
Cyproheptadine in the treatment of autistic disorder: a double-blind placebo-controlled trial. Akhondzadeh S,Erfani S,Mohammadi M R,Tehrani-Doost M,Amini H,Gudarzi S S,Yasamy M T Journal of clinical pharmacy and therapeutics OBJECTIVE:Autism is a childhood-onset disorder of unknown, possibly of multiple aetiologies. The core symptoms of autism are abnormalities in social interaction, communication and behaviour. The involvement of neurotransmitters such as 5-HT has been suggested in neuropsychiatric disorders and particularly in autistic disorder. Increased platelet 5-HT levels were found in 40% of the autistic population, suggesting that hyperserotonaemia may be a pathologic factor in infantile autism. Therefore, it is of interest to assess the efficacy of cyproheptadine, a 5-HT2 antagonist in the treatment of autistic disorder. In this 8-week double-blind, placebo-controlled trial, we assessed the effects of cyproheptadine plus haloperidol in the treatment of autistic disorder. METHODS:Children between the ages 3 and 11 years (inclusive) with a DSM IV clinical diagnosis of autism and who were outpatients from a specialty clinic for children at Roozbeh Psychiatric Teaching Hospital were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to cyproheptadine + haloperidol (Group A) or haloperidol + placebo (Group B) for an 8-week, double-blind, placebo-controlled study. The dose of haloperidol and cyproheptadine was titrated up to 0.05 and 0.2 mg/kg/day respectively. Patients were assessed by a third-year resident of psychiatry at baseline and after 2, 4, 6 and 8 weeks of starting medication. The primary measure of the outcome was the Aberrant Behaviour Checklist-Community (ABC-C) and the secondary measure of the outcome was the Childhood Autism Rating Scale (relating to people and verbal communication). Side effects and extrapyramidal symptoms were systematically recorded throughout the study and were assessed using a checklist and the Extrapyramidal Symptoms Rating Scale, administered by a resident of psychiatry during weeks 1, 2, 4, 6 and 8. RESULTS:The ABC-C and the Childhood Autism Rating Scale scores improved with cyproheptadine. The behaviour of the two treatments was not homogeneous across time (groups-by-time interaction, Greenhouse-Geisser correction; F = 7.30, d.f. = 1.68, P = 0.002; F = 8.21, d.f. = 1.19, P = 0.004 respectively). The difference between the two treatments was significant as indicated by the effect of group, and the between-subjects factor (F = 4.17, d.f. = 1, P = 0.048; F = 4.29, d.f. = 1, P = 0.045 respectively). No significant difference was observed between the two groups in terms of extrapyramidal symptoms (P = 0.23). The difference between the two groups in the frequency of side effects was not significant. CONCLUSION:The results suggest that the combination of cyproheptadine with a conventional antipsychotic may be superior to conventional antipsychotic alone for children with autistic disorder. However the results need confirmation by a larger randomized controlled trial. 10.1111/j.1365-2710.2004.00546.x
The effectiveness of hyperbaric oxygen therapy (HBOT) in children with autism spectrum disorders. Kostiukow Anna,Samborski Włodzimierz Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego Research based on neuro-imaging findings indicate the presence of cerebral hypoperfusion (decreased blood flow) in children with autism spectrum disorders (ASD). One of modern therapeutic methods that can counteract cerebral hypoperfusion in those children is hyperbaric oxygen therapy (HBOT). AIM:The aim of the present study was to examine whether a series of hyperbaric oxygen therapy sessions can improve selected psychosomatic parameters in children with ASD. MATERIALS AND METHODS:The study group comprised 35 boys and 4 girls with ASD, who undertook 40 HBOT sessions consisting of breathing hyperbaric oxygen (1.5 atm.). Each session lasted 60 min. The following questionnaire tests were used to assess the effects of the therapy: Clinical Global Impression Scale (CGIS), Autism Treatment Evaluation Checklist (ATEC), and Childhood Autism Rating Scale (CARS). RESULTS:Eight components of the ATEC and CARS scales as well as the CARS total score revealed statistically significant improvements. One out of all examined items - ATEC Speech/language/communication - "Can follow some commands" revealed a decline after the HBOT sessions (p = 0.0431). CONCLUSIONS:In younger children under study post-therapy improvements were found for the ATEC Sociability - "Does not imitate", ATEC Sensory/cognitive awareness - "Shows imagination", and ATEC Health/physical/behavior - "Sound-sensitive" items. In older children improvements were noted for ATEC Health/physical/behavior - "Obsessive speech" and CARS emotional response, adaptation to change, and total score.
Aripiprazole treatment of irritability associated with autistic disorder and the relationship between prior antipsychotic exposure, adverse events, and weight change. Mankoski Raymond,Stockton Gwen,Manos George,Marler Sabrina,McQuade Robert,Forbes Robert A,Marcus Ronald Journal of child and adolescent psychopharmacology OBJECTIVE:The purpose of this study was to evaluate the impact of prior antipsychotic exposure (PAE) on safety and tolerability outcomes in pediatric subjects receiving aripiprazole treatment. METHODS:This study was a post-hoc analysis of pooled data from two 8-week, double-blind, randomized, placebo-controlled studies evaluating aripiprazole for the treatment of irritability in pediatric subjects with autistic disorder, aged 6-17 years. Subjects were stratified by PAE; adverse events (AEs), and changes in weight, and metabolic measures were evaluated. For subjects receiving aripiprazole, regardless of PAE, baseline weight, age, gender, and symptom severity were evaluated in a regression model predicting body weight change. RESULTS:Of 316 randomized subjects, 259 (82.0%) were antipsychotic naïve (AN) and 57 (18.0%) had a PAE. Aripiprazole-treated AN subjects were more likely than PAE subjects to report somnolence (11.9% vs. 2.8%), sedation (22.7% vs. 11.1%), or fatigue (17.0% vs. 13.9%). Rates of extrapyramidal disorder and drooling, but not akathisia or tremor, were marginally higher in AN subjects. Overall, 10.8% of aripiprazole-treated AN subjects had at least one AE leading to discontinuation compared with 8.3% of aripiprazole-treated PAE subjects. AN subjects receiving aripiprazole had a larger change in weight from baseline to endpoint compared with those receiving placebo (1.9 vs. 0.7 kg; treatment difference 1.2 kg, 95% CI: 0.5, 1.9) than PAE subjects receiving aripiprazole compared with subjects receiving placebo (0.4 vs. -0.4 kg; treatment difference 0.9 kg, 95% CI: -0.6, 2.4). Regression analysis identified that younger subjects with higher baseline weight z-score were at highest risk for weight gain. There were no significant changes in metabolic measures compared with placebo in either group. CONCLUSIONS:Weight gain was more pronounced in AN subjects and more likely to occur in younger subjects with a higher baseline weight z-score. AN subjects were more likely to experience AEs related to somnolence. However, based on discontinuations rates from AEs, overall tolerability was good for both AN and PAE groups. CLINICAL TRIAL REGISTRATION:Study of aripiprazole in the treatment of children and adolescents with autistic disorder. Registry: www.clinicaltrials.gov . Identifiers: NCT00332241 and NCT00337571. 10.1089/cap.2012.0075
Effect of mild hyperbaric oxygen therapy on children diagnosed with autism. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, Inc INTRODUCTION:Hyperbaric oxygen (HBO2) therapy is emerging internationally as the primary treatment modality for inflammatory pathways related to neurological disorders. Currently, literature concerning its effectiveness in autistic children is limited. Using neurocognitive tests and clinical-diagnostic evaluations, this study evaluates the clinical, cognitive and behavioral effects of HBO2 on children diagnosed with autism. METHODS:An experimental HBO2 group (EXP: F = 1; M = 7; mean age: 7 ± 2.33; years) and a control non-HBO2 group of autistic children (CTRL: F = 2; M= 5; mean age: 6.6 ± 2.7 years) correctly completed the Aberrant Behavior Checklist-Community (ABC) before HBO2 (T0), after 40 sessions of HBO2 (T1), and one month after the end of treatments (T2). Additionally, the experimental HBO2 group was evaluated with the Childhood Autism Rating Scale at T0 and T2. RESULTS:Total ABC score was lower at T2 (mean ± SD: 50.38 ± 18.55; p ⟨ 0.001) compared to scores obtained at T0 (mean ± SD: 57.5 ± 19.01). Similarly, in the control group the total ABC score differed statistically (p ⟨ 0.05) between T0 (103.6 ± 20.38) and (T2: 59 ± 25.25). CONCLUSION:Despite the improvements reported in both groups, our results do not support the utility of HBO2 in children diagnosed with autism..
Impact of Auditory Integration Therapy (AIT) on the Plasma Levels of Human Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Autism Spectrum Disorder. Al-Ayadhi Laila,El-Ansary Afaf,Bjørklund Geir,Chirumbolo Salvatore,Mostafa Gehan Ahmed Journal of molecular neuroscience : MN Neurotrophic factors, including the glial cell line-derived neurotrophic factor (GDNF), are of importance for synaptic plasticity regulation, intended as the synapses' ability to strengthen or weaken their responses to differences in neuronal activity. Such plasticity is essential for sensory processing, which has been shown to be impaired in autism spectrum disorder (ASD). This study is the first to investigate the impact of auditory integration therapy (AIT) of sensory processing abnormalities in autism on plasma GDNF levels. Fifteen ASD children, aged between 5 and 12 years, were enrolled and underwent the present research study. AIT was performed throughout 10 days with a 30-min session twice a day. Before and after AIT, Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Short Sensory Profile (SSP) scores were calculated, and plasma GDNF levels were assayed by an EIA test. A substantial decline in autistic behavior was observed after AIT in the scaling parameters used. Median plasma GDNF level was 52.142 pg/ml before AIT. This level greatly increased immediately after AIT to 242.05 pg/ml (P < 0.001). The levels were depressed to 154.00 pg/ml and 125.594 pg/ml 1 month and 3 months later, respectively, but they were still significantly higher compared with the levels before the treatment (P = 0.001, P = 0.01, respectively). There was an improvement in the measures of autism severity as an effect of AIT which induced the up-regulation of GDNF in plasma. Further research, on a large scale, is needed to evaluate if the cognitive improvement of ASD children after AIT is related or not connected to the up-regulation of GDNF. 10.1007/s12031-019-01332-w
Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children. Saad Khaled,Abdel-Rahman Ahmed A,Elserogy Yasser M,Al-Atram Abdulrahman A,Cannell John J,Bjørklund Geir,Abdel-Reheim Mohamed K,Othman Hisham A K,El-Houfey Amira A,Abd El-Aziz Nafisa H R,Abd El-Baseer Khaled A,Ahmed Ahmed E,Ali Ahmed M Nutritional neuroscience OBJECTIVES:Autism spectrum disorder (ASD) is a developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and non-verbal communication, and stereotyped patterns of interests and activities. Vitamin-D deficiency was previously reported in autistic children. However, the data on the relationship between vitamin D deficiency and the severity of autism are limited. METHODS:We performed a case-controlled cross-sectional analysis conducted on 122 ASD children, to assess their vitamin D status compared to controls and the relationship between vitamin D deficiency and the severity of autism. We also conducted an open trial of vitamin D supplementation in ASD children. RESULTS:Fifty-seven percent of the patients in the present study had vitamin D deficiency, and 30% had vitamin D insufficiency. The mean 25-OHD levels in patients with severe autism were significantly lower than those in patients with mild/moderate autism. Serum 25-OHD levels had significant negative correlations with Childhood Autism Rating Scale (CARS) scores. Of the ASD group, 106 patients with low-serum 25-OHD levels (<30 ng/ml) participated in the open label trial. They received vitamin D3 (300 IU/kg/day not to exceed 5000 IU/day) for 3 months. Eighty-three subjects completed 3 months of daily vitamin D treatment. Collectively, 80.72% (67/83) of subjects who received vitamin D3 treatment had significantly improved outcome, which was mainly in the sections of the CARS and aberrant behavior checklist subscales that measure behavior, stereotypy, eye contact, and attention span. CONCLUSION:Vitamin D is inexpensive, readily available and safe. It may have beneficial effects in ASD subjects, especially when the final serum level is more than 40 ng/ml. TRIAL REGISTRATION NUMBER:UMIN-CTR Study Design: trial Number: R000016846. 10.1179/1476830515Y.0000000019
Riluzole as an adjunctive therapy to risperidone for the treatment of irritability in children with autistic disorder: a double-blind, placebo-controlled, randomized trial. Ghaleiha Ali,Mohammadi Effat,Mohammadi Mohammad-Reza,Farokhnia Mehdi,Modabbernia Amirhossein,Yekehtaz Habibeh,Ashrafi Mandana,Hassanzadeh Elmira,Akhondzadeh Shahin Paediatric drugs BACKGROUND:A hyperglutamatergic state has been shown to play a possible role in the pathophysiology of autistic disorders. Riluzole is a glutamate-modulating agent with neuroprotective properties, which has been shown to have positive effects in many neuropsychiatric disorders. OBJECTIVE:The aim of this study was to assess the efficacy and tolerability of riluzole as an adjunctive to risperidone in the treatment of irritability in autistic children who were not optimally responding to previous medications. STUDY DESIGN:This was a 10-week, randomized, double-blind, parallel-group, placebo-controlled trial. PARTICIPANTS:The study enrolled male and female outpatients aged 5-12 years with a diagnosis of autistic disorder based on the DSM-IV-TR criteria and a score of ≥12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale who had discontinued other medications because of a lack of efficacy. INTERVENTIONS:Subjects received riluzole (titrated to 50 or 100 mg/day based on bodyweight) or placebo in addition to risperidone (titrated up to 2 or 3 mg/day based on bodyweight) for 10 weeks. OUTCOME:Patients were assessed at baseline, week 5, and week 10. The primary outcome measure was the difference in the change in the ABC-C irritability subscale score from baseline to week 10 between the two groups. We also compared changes in other ABC-C subscale scores and Clinical Global Impressions-Improvement (CGI-I) scale scores between the two groups. RESULTS:Forty-nine patients were enrolled in the study, and forty children completed the trial (dropouts: placebo = 4, riluzole = 5). A significantly greater improvement in the study primary outcome (the ABC-C irritability subscale score) was achieved by the riluzole-treated children compared with the placebo group (P = 0.03). Patients in the riluzole group also showed significantly greater improvement on the lethargy/social withdrawal (P = 0.02), stereotypic behavior (P = 0.03), and hyperactivity/non-compliance subscales (P = 0.005), but not on the inappropriate speech subscale (P = 0.20) than patients in the placebo group. Eleven patients in the riluzole group and five patients in the placebo group were classified as responders based on their CGI-I scores [χ(2)(1) = 3.750, P = 0.05]. Children in the riluzole group experienced significantly more increases in their appetite and bodyweight than children in the placebo group by the end of the study. CONCLUSION:Riluzole add-on therapy shows several therapeutic outcomes, particularly for improving irritability, in children with autism. However, its add-on to risperidone also results in significantly increased appetite and weight gain. 10.1007/s40272-013-0036-2
Overview of the Recent Advances in Pathophysiology and Treatment for Autism. Famitafreshi Hamidreza,Karimian Morteza CNS & neurological disorders drug targets BACKGROUND & OBJECTIVE:Autism is a developmental disorder that manifests itself in early childhood. Autism is characterized by inability to acquire social skills, repetitive behaviors and failure of speech and nonverbal communication development. Recent studies have shown that genetic mutations occur in majority of individuals with autism. These mutations cause a variety of disorders that ultimately lead to brain disorders. It is noteworthy that all mutations do not follow the same pattern. They encompass various kinds of mutations. Autism needs to be treated during childhood as untreated patients usually do not progress to the later stages of development. In this regard, many studies have been performed and numerous treatments have been proposed to improve the outcome of this disease. CONCLUSION:In this review, we have discussed new advancements made in understanding the pathophysiology of autism. Furthermore, we have also discussed new treatments which have been proposed and have successfully translated affected children. Overall, it is concluded that new advances have largely helped these patients. 10.2174/1871527317666180706141654
Theory of mind predominantly associated with the quality, not quantity, of pretend play in children with autism spectrum disorder. Lin Shu-Kai,Tsai Ching-Hong,Li Hsing-Jung,Huang Chien-Yu,Chen Kuan-Lin European child & adolescent psychiatry This study aimed to clarify the relationships between theory of mind and pretend play in children with autism spectrum disorder, using refined assessments of theory of mind and pretend play while controlling for autistic behaviors and verbal comprehension. A total of 92 children with autism spectrum disorder aged 4-10 years were enrolled. In two visits, the children were assessed with the Theory of Mind Task Battery, the Child-Initiated Pretend Play Assessment, the Childhood Autism Rating Scale, and the Verbal Comprehension Index of the Wechsler Intelligence Scales, respectively, for their theory of mind, pretend play performance, autistic behaviors, and verbal comprehension. The hierarchical regression models showed that in addition to the contributions of the autistic behaviors and verbal comprehension scores, the theory of mind scores positively predicted (p < 0.001) the elaborateness scores of pretend play in the conventional imaginative and symbolic play contexts, respectively, accounting for an additional 8.1 and 18.5% of the variance, but did not predict the scores for number of object substitutions or imitated actions. The findings demonstrate that theory of mind has a predominant role in the quality, not the quantity, of pretend play of children with autism spectrum disorder, when the children's autistic behaviors and verbal comprehension are considered. This study fills a gap in the previous literature and provides information useful for clinicians and researchers on the relationships between theory of mind and pretend play in children with autism spectrum disorder. 10.1007/s00787-017-0973-3
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. Findling Robert L,Mankoski Raymond,Timko Karen,Lears Katherine,McCartney Theresa,McQuade Robert D,Eudicone James M,Amatniek Joan,Marcus Ronald N,Sheehan John J The Journal of clinical psychiatry 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, randomized, 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 randomized 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 randomization to relapse. RESULTS:Eighty-five patients were randomized 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:ClinicalTrials.gov identifier: NCT01227668. 10.4088/JCP.13m08500
Transcranial direct current stimulation for hyperactivity and noncompliance in autistic disorder. D'Urso Giordano,Bruzzese Dario,Ferrucci Roberta,Priori Alberto,Pascotto Antonio,Galderisi Silvana,Altamura Alfredo Carlo,Bravaccio Carmela The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry OBJECTIVES:To evaluate the safety, efficacy, and feasibility of inhibitory transcranial direct current stimulation (tDCS) for the treatment of behavioural abnormalities of autistic patients. METHODS:Twelve young adult patients with autistic disorder were enrolled. All subjects presented intellectual disability and most of them had speech impairment. The Aberrant Behavior Checklist (ABC) was administered as the primary outcome measure before and after a 2-week tDCS course. All subjects received 10 daily applications of 20 min/1.5 mA/cathodal (inhibitory) tDCS over the left dorso-lateral pre-frontal cortex. RESULTS:Eight out of 10 study completers improved in their abnormal behaviours, reaching an average reduction of 26.7% of the total ABC score. The remaining two patients showed no changes. In the whole group of completers, among the five subscales contributing to the significant reduction of the total score, the most remarkable and statistically significant change was seen in the subscale assessing hyperactivity and non-compliance (-35.9%, P = 0.002). No adverse effects were reported. CONCLUSIONS:Inhibitory tDCS improved the ABC rating scores for autistic behaviours. Owing to its ease of use, cost-effectiveness and the limited availability of specific treatment strategies, tDCS might be a valid therapeutic option to be tested in autistic patients. 10.3109/15622975.2015.1014411
[Clinical effect of vitamin D combined with the Early Start Denver Model in the treatment of autism spectrum disorder in toddlers]. Feng Jun-Yan,Li Hong-Hua,Shan Ling,Wang Bing,Jia Fei-Yong,DU Lin Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics OBJECTIVE:To study the clinical effect of vitamin D (VitD) combined with the Early Start Denver Model (ESDM) in the treatment of autism spectrum disorder (ASD) in toddlers. METHODS:A total of 102 toddlers with ASD, aged 1 to 3 years, were enrolled. According to the wishes of their parents, they were divided into conventional rehabilitation, ESDM and ESDM+VitD groups. Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used evaluate behavior problems before treatment and after 3 months of treatment. RESULTS:The conventional rehabilitation group had significant reductions in the total score and the scores on somatic movement and self-care subscales of the ABC scale after 3 months of treatment (P<0.05). After 3 months of treatment, the ESDM group had significant reductions in the total score and the scores on somatic movement, self-care, social interaction and language subscales of the ABC scale (P<0.05), as well as a significant reduction in the total score of the CARS (P<0.05). After 3 months of treatment, the ESDM+VitD group had a significant increase in the level of 25(OH)D and significant reductions in the total score and the scores on self-care, sensation, social interaction and language subscales of the ABC scale (P<0.05), as well as a significant reduction in the total score of the CARS (P<0.05). The ESDM group had a significantly greater reduction in the score on social interaction subscale than the conventional rehabilitation group (P<0.05). The ESDM+VitD group had a significantly greater reduction in the score on social interaction subscale than the other two groups (P<0.05). CONCLUSIONS:ESDM can effectively improve the clinical symptoms of toddlers with ASD, with a significantly better clinical effect in improving social interaction and somatic movement than conventional rehabilitation. ESDM combined with VitD has a significantly better clinical effect in improving social communication skills and may be one of the best strategies for improving the clinical symptoms of toddlers with ASD.
Natural Products and Their Therapeutic Effect on Autism Spectrum Disorder. Deb Satarupa,Phukan Banashree Chetia,Dutta Ankumoni,Paul Rajib,Bhattacharya Pallab,Manivasagam Thamilarasan,Thenmozhi Arokiasamy Justin,Babu Chidambaram Saravana,Essa Musthafa Mohamed,Borah Anupom Advances in neurobiology Autism is a complex neurodevelopmental disorder that is evident in early childhood and can persist throughout the entire life. The disease is basically characterized by hurdles in social interaction where the individuals demonstrate repetitive and stereotyped interests or patterns of behavior. A wide number of neuroanatomical studies with autistic patients revealed alterations in brain development which lead to diverse cellular and anatomical processes including atypical neurogenesis, neuronal migration, maturation, differentiation, and degeneration. Special education programs, speech and language therapy, have been employed for the amelioration of behavioral deficits in autism. Although commonly prescribed antidepressants, antipsychotics, anticonvulsants, and stimulants have revealed satisfactory responses in autistic individuals, adverse side effects and increased risk of several other complications including obesity, dyslipidemia, diabetes mellitus, thyroid disorders, etc. have compelled the researchers to turn their attention toward herbal remedies. Alternative approaches with natural compounds are on continuous clinical trial to confirm their efficacy and to understand their potential in autism treatment. This chapter aims to cover the major plant-based natural products which hold promising outcomes in the field of reliable therapeutic interventions for autism. 10.1007/978-3-030-30402-7_22
Childhood autism and auditory system abnormalities. Hitoglou Magdalini,Ververi Athina,Antoniadis Alexandros,Zafeiriou Dimitrios I Pediatric neurology Hearing disorders are common among children with autism, ranging from peripheral and sensorineural hearing deficit or loss to auditory hypersensitivity with bizarre reactions to sounds. The auditory abnormalities and consequent sensory deprivation exacerbate the communication deficit of autism, and early auditory assessment holds an important place in the planning of intervention and the overall prognosis of patients. Physiologic, pathologic, imaging, and neurochemical studies have revealed an array of aberrations in the perception and processing of the audiologic stimuli, including (among others) maturational defects, atypical lateralization, and serotonin dysfunction. 10.1016/j.pediatrneurol.2009.10.009
l-Carnosine As an Adjunctive Therapy to Risperidone in Children with Autistic Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial. Hajizadeh-Zaker Reihaneh,Ghajar Alireza,Mesgarpour Bita,Afarideh Mohsen,Mohammadi Mohammad-Reza,Akhondzadeh Shahin Journal of child and adolescent psychopharmacology OBJECTIVES:This study aimed at investigating the efficacy and tolerability of l-carnosine as an add-on to risperidone in the management of children with autism. METHODS:This was a 10-week, randomized, double-blind, placebo-controlled study. Seventy drug-free children aged 4-12 years old with a diagnosis of autism spectrum disorder (ASD), according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. (DSM-5) who had an Aberrant Behavior Checklist-Community (ABC-C) scale irritability subscale score of ≥12, entered the study. The patients were randomly assigned to l-carnosine (800 mg/day in 2 divided doses) or placebo in addition to risperidone titrated up to 2 mg/day (based on body weight) for 10 weeks. The children were assessed by using ABC-C at baseline and weeks 5 and 10 post-baseline. The primary outcome measure was the mean change in the ABC-C irritability subscale score, and other subscale scores were defined as secondary outcomes. RESULTS:Using the general linear model repeated measures, no significant effect was observed for time × treatment interaction on the irritability subscale scores. However, significant effect was detected on the hyperactivity/noncompliance subscale [F (1.62, 64.96) = 3.53, p-value = 0.044]. No significant improvements were obtained on the lethargy/social withdrawal, stereotypic behavior, and inappropriate speech subscale scores. Significantly greater score reduction in the hyperactivity/noncompliance subscale occurred in the l-carnosine group compared with the placebo group at the end of the trial. Extrapyramidal Symptom Rating Scale Scores and its changes did not differ between the two groups. The frequency of other side effects was not significantly different between the two groups. CONCLUSIONS:Although no significant difference was detected on the irritability subscale scores, l-carnosine add-on can improve hyperactivity/noncompliance subscales of the ABC-C rating scale in patients with ASD. 10.1089/cap.2017.0026
Autistic traits in mentalization-based treatment for concurrent borderline personality disorder and substance use disorder: Secondary analyses of a randomized controlled feasibility study. Kaltenegger Helena C,Philips Björn,Wennberg Peter Scandinavian journal of psychology Autism is suggested to be a dimensional construct and often represents a comorbid state. However, research on the clinical implications of the presence of autistic traits is scarce. This study aimed to investigate the impact of subclinical autistic traits in mentalization-based treatment (MBT) for concurrent borderline personality disorder (BPD) and substance use disorder (SUD). Based on the data of a randomized controlled feasibility study by Philips, Wennberg, Konradsson, and Franck (2018), secondary analyses were conducted. It was tested, if patients' (N = 46) levels of autistic traits were associated with treatment outcome measured in the course of and after treatment using interviews and self-report measures. Participants' autistic traits were not associated with the change in the severity of BPD throughout and at the end of the treatment. However, results showed associations between autistic traits and the change in patients' consumption of alcohol in the course of MBT. Furthermore, there was an association between autistic traits and the change in mentalizing capacity at the end of MBT, indicating that elevated autistic traits were associated with an improvement in mentalizing capacity. Autistic traits on a subclinical level do not appear to be a complicating factor in MBT for concurrent BPD and SUD. On the contrary, in terms of mentalizing capacity autistic traits might be associated with a larger potential for improvement or facilitate treatment outcome. Further research is needed to explore the role of higher autistic traits in treatment of this special patient group. 10.1111/sjop.12595
Long-term oxytocin administration improves social behaviors in a girl with autistic disorder. Kosaka Hirotaka,Munesue Toshio,Ishitobi Makoto,Asano Mizuki,Omori Masao,Sato Makoto,Tomoda Akemi,Wada Yuji BMC psychiatry BACKGROUND:Patients with autism spectrum disorders (ASDs) exhibit core autistic symptoms including social impairments from early childhood and mostly show secondary disabilities such as irritability and aggressive behavior based on core symptoms. However, there are still no radical treatments of social impairments in these patients. Oxytocin has been reported to play important roles in multiple social behaviors dependent on social recognition, and has been expected as one of the effective treatments of social impairments of patients with ASDs. CASE PRESENTATION:We present a case of a 16-year-old girl with autistic disorder who treated by long-term administration of oxytocin nasal spray. Her autistic symptoms were successfully treated by two month administration; the girl's social interactions and social communication began to improve without adverse effects. Her irritability and aggressive behavior also improved dramatically with marked decreases in aberrant behavior checklist scores from 69 to 7. CONCLUSION:This case is the first to illustrate long-term administration of oxytocin nasal spray in the targeted treatment of social impairments in a female with autistic disorder. This case suggests that long-term nasal oxytocin spray is promising and well-tolerated for treatment of social impairments of patients with ASDs. 10.1186/1471-244X-12-110
Hyperbaric oxygen in the treatment of childhood autism: a randomised controlled trial. Sampanthavivat Mayuree,Singkhwa Wararat,Chaiyakul Thanasawat,Karoonyawanich Sangdaw,Ajpru Haruthai Diving and hyperbaric medicine BACKGROUND:Promising results with hyperbaric therapy for children with autism have been reported, but most involved the use of only mild pressure with oxygen supplementation. To date, there has been no randomised, blinded trial of 100% oxygen administered at hyperbaric pressure. This study evaluated the efficacy of hyperbaric oxygen therapy (HBOT). METHODS:Sixty Thai children with autism, aged three to nine years, were randomly assigned to receive 20 one-hour sessions of either HBOT at 153 kPa (1.5 ATA) or sham air at 116 kPa (1.15 ATA). Effects on behaviour were measured using the Autism Treatment Evaluation Checklist score (ATEC) and clinical improvement was measured with the Clinical Global Impression (CGI) system; in particular the clinical change (CGIC) and severity (CGIS) sub-scores. These were evaluated by parents and clinicians, both of whom were blinded to the actual exposure. RESULTS:The mean total ATEC scores by both parents and clinicians were significantly improved after intervention in both arms of the study compared to the score before intervention (P < 0.001 in both groups by parents, P = 0.015 in HBOT group and P = 0.004 in sham group by clinician). There were no statistically significant differences in average percentage changes of total ATEC score and all subscales scores when comparing the HBOT and sham air groups, either by parents or clinicians. Changes in the CGI scores following intervention were inconsistent between parents and clinicians. For severity scores (CGIS), parents rated their children as more improved following HBOT (P = 0.005), while the clinicians found no significant differences (P = 0.10). On the other hand, for change scores (CGIC) the clinicians indicated greater improvement following HBOT (P = 0.03), but the parents found no such difference (P = 0.28). CONCLUSIONS:Children with autism who received 20 sessions of either HBOT or a sham air exposure had significant improvements in overall behaviour but there were no significant differences in improvement between groups. The inconsistent changes on CGI sub-scores between parents and clinicians are difficult to interpret, but no overall clinically significant benefit from HBOT could be shown. Both interventions were safe and well tolerated with minimal side effect from middle ear barotraumas.
Nasal oxytocin for social deficits in childhood autism: a randomized controlled trial. Dadds Mark R,MacDonald Elayne,Cauchi Avril,Williams Katrina,Levy Florence,Brennan John Journal of autism and developmental disorders The last two decades have witnessed a surge in research investigating the application of oxytocin as a method of enhancing social behaviour in humans. Preliminary evidence suggests oxytocin may have potential as an intervention for autism. We evaluated a 5-day 'live-in' intervention using a double-blind randomized control trial. 38 male youths (7-16 years old) with autism spectrum disorders were administered 24 or 12 international units (depending on weight) intranasal placebo or oxytocin once daily over four consecutive days. The oxytocin or placebo was administered during parent-child interaction training sessions. Parent and child behaviours were assessed using parent reports, clinician ratings, and independent observations, at multiple time points to measure side-effects; social interaction skills; repetitive behaviours; emotion recognition and diagnostic status. Compared to placebo, intranasal oxytocin did not significantly improve emotion recognition, social interaction skills, or general behavioral adjustment in male youths with autism spectrum disorders. The results show that the benefits of nasal oxytocin for young individuals with autism spectrum disorders may be more circumscribed than suggested by previous studies, and suggest caution in recommending it as an intervention that is broadly effective. 10.1007/s10803-013-1899-3
Evaluating the effectiveness of electro-acupuncture as a treatment for childhood autism using single photon emission computed tomography. Zhao Zheng-qin,Jia Shao-wei,Hu Shu,Sun Wen Chinese journal of integrative medicine OBJECTIVE:To explore the effectiveness of electro-acupuncture (EA) in the treatment of childhood autism (CA) and evaluate its effectiveness using single photon emission computed tomography (SPECT). METHODS:A total of 55 CA patients (4.52±2.73 years) were enrolled in this study. All patients received EA treatments and were examined by SPECT before and after treatments. RESULTS:Following treatment, the intracerebral multiple focal radioactivity distribution defect areas of CA patients were observed to be partially filled. Specifically, significant differences in the ratios of regional cerebral blood flow and global cerebral blood flow before (Fb) and after (Fe) EA treatment in different lesions were observed (in the left prefrontal cortex, t=5.01, P<0.01; in the right prefrontal cortex, t=2.32, P<0.05; in the left temporal lobe, t=4.54, P<0.01; in the right temporal lobe, t=2.90, P<0.05; in the left Broca's area, t=5.82, P<0.01). After EA treatment, the patients exhibited symptomatic relief. CONCLUSION:EA is useful to treat CA and SPECT can be used to evaluate the effectiveness of this treatment. 10.1007/s11655-014-1680-2
Minocycline as Adjunctive Treatment to Risperidone in Children with Autistic Disorder: A Randomized, Double-Blind Placebo-Controlled Trial. Ghaleiha Ali,Alikhani Rosa,Kazemi Mohammad-Reza,Mohammadi Mohammad-Reza,Mohammadinejad Payam,Zeinoddini Atefeh,Hamedi Mehdi,Shahriari Mona,Keshavarzi Zahra,Akhondzadeh Shahin Journal of child and adolescent psychopharmacology 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. 10.1089/cap.2015.0175
Comparing Efficacy and Side Effects of Memantine vs. Risperidone in the Treatment of Autistic Disorder. Nikvarz Nikvarz,Alaghband-Rad Javad,Tehrani-Doost Mehdi,Alimadadi Abbas,Ghaeli Padideh Pharmacopsychiatry This study was aimed to compare the efficacy and side effects of memantine, an antagonist of the NMDA receptor of glutamate, with risperidone given the fact that glutamate has been noted for its possible effects in the pathogenesis of autism. Risperidone, an atypical antipsychotic, has been approved by FDA for the management of irritability associated with autism. 30 children, aged 4-17 years, entered an 8-week, randomized trial. Patients were randomly assigned to receive either risperidone or memantine. Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Clinical Global Impressions - Improvement (CGI-I) and Clinical Global Impression-Severity (CGI-S) scales were used to assess behavioral symptoms of the patients. Both risperidone and memantine reduced the scores of 4 subscales of ABC as well as the 10-item and the total score of CARS significantly. However, differences between the 2 drugs in the scores of each evaluating scale were not found to be significant. Relatively, larger number of patients on risperidone showed "very much improvement" when assessed by CGI-I scale when compared with those on memantine. The present study suggests that memantine may have beneficial effects in the treatment of many core symptoms of autism. Therefore, memantine may be considered as a potential medication in the treatment of those autistic children who do not respond or cannot tolerate side effects of risperidone. 10.1055/s-0042-108449