N-Acetylcysteine Plus Risperidone for Autistic Disorders
N-Acetylcysteine Plus Risperidone for Autistic Disorders
This study was an eight week randomized double-blind placebo-controlled clinical trial with two parallel groups. The patients, parents, and independent assessor were blind to the allocation of patients. The patients were randomly allocated into one of the two groups using a random number generator.
The participants were a convenient sample of outpatients children aged between 3.5 to 16 years old from both genders. The sample was recruited from the Child and Adolescent Psychiatriy Clinics affiliated with Shiraz University of Medical Sciences, Iran.
The diagnosis of autism was made using DSM-IV-TR criteria. The diagnosis was in accordance with Autism Diagnostic Interview-Revised (ADI-R). All the interviews were conducted by an expert child and adolescent psychiatrist (A.G.). Assessments were performed by a resident of psychiatry trained to use the questionnaire and checklist. The level of intelligence was not considered as an exclusion criterion. However, the participants should be able to take the medications.
The patients were free from any concomitant medication. Otherwise, the dose of medication should not be markedly changed during two weeks prior entering into this study. The dose of concomitant medication was not markedly changed during this trial.
Patients with psychotic disorders, active substance abuse or dependence, unstable medical condition, evidence of active liver disease, seizure disorder, unstable hypertension or cardiac disease, unstable asthma, and kidney disease as determined by the investigator were not included. Taking concomitant medications with glutamatergic effects (e.g., dextromethorphan, D-cycloserine, amantadine, memantine, lamotrigine, riluzole) was not allowed. In addition, those with hypersensitivity/allergy to NAC were not included.
One of the two groups received risperidone plus N-Acetylcysteine (1200 mg/day). The patients received 1200 mg/day NAC in two divided doses. Both NAC and placebo tablets were administered in the form of effervescent. The other group received risperidone plus placebo tablets. The shape, size, taste, and color of NAC and placebo were identical.
The dose was titrated up during two weeks. The dose was not fixed. In addition, all the patients in both groups received risperidone. Risperidone started at the dose of 0.5 mg/day and it was titrated up to 2 mg/day during three weeks for children less than 30 kg. The dose for children more than 30 kg was up to 3 mg/day. The dose of risperidone was not fixed and it could be changed considering the clinical symptoms and adverse effects.
The primary outcome measure was Aberrant Behavior Checklist. ABC consists of 58 items and includes 5 subscales. The subscales are Irritability, Lethargy and Social Withdrawal, Stereotypic Behavior, Hyperactivity and Noncompliance, and Inappropriate Speech.
The changes of Irritability subscale score was considered as the main outcome of the current trial.
It was completed at pre-intervention, 4 weeks after the beginning of intervention, and 8 weeks after the beginning of intervention. In addition, the adverse effects and extrapyramidal symptoms were systematically examined and assessed using checklists. The patients and their parents were also asked regarding possible adverse effects.
This trial's protocol and procedures were approved by Ethics Committee of Shiraz University of Medical Sciences, Iran. Then, this trial was registered at http://www.irct.ir. The registration number of this trial was IRCT201106103930N6. This trial was performed in 2011 and 2012. The parents of children provided written informed consent.
SPSS was used to perform statistical analyses. Chi-Square test was used to compare the gender ratio between the two groups. The mean of age was compared between the two groups using independent t-test. Repeated Measures of ANOVA was used to examine the effect of interventions on the subscales scores of ABC. Intent-to-Treat (ITT) using Last Observed Carried Forward (LOCF) with at least one post-treatment evaluation was used to handle missing data. The Cohen's d was calculated to measure effect size. P value less than 0.05 was set for being statistically significant. This is an exploratory small sample size trial.
Methods
This study was an eight week randomized double-blind placebo-controlled clinical trial with two parallel groups. The patients, parents, and independent assessor were blind to the allocation of patients. The patients were randomly allocated into one of the two groups using a random number generator.
The participants were a convenient sample of outpatients children aged between 3.5 to 16 years old from both genders. The sample was recruited from the Child and Adolescent Psychiatriy Clinics affiliated with Shiraz University of Medical Sciences, Iran.
The diagnosis of autism was made using DSM-IV-TR criteria. The diagnosis was in accordance with Autism Diagnostic Interview-Revised (ADI-R). All the interviews were conducted by an expert child and adolescent psychiatrist (A.G.). Assessments were performed by a resident of psychiatry trained to use the questionnaire and checklist. The level of intelligence was not considered as an exclusion criterion. However, the participants should be able to take the medications.
The patients were free from any concomitant medication. Otherwise, the dose of medication should not be markedly changed during two weeks prior entering into this study. The dose of concomitant medication was not markedly changed during this trial.
Patients with psychotic disorders, active substance abuse or dependence, unstable medical condition, evidence of active liver disease, seizure disorder, unstable hypertension or cardiac disease, unstable asthma, and kidney disease as determined by the investigator were not included. Taking concomitant medications with glutamatergic effects (e.g., dextromethorphan, D-cycloserine, amantadine, memantine, lamotrigine, riluzole) was not allowed. In addition, those with hypersensitivity/allergy to NAC were not included.
One of the two groups received risperidone plus N-Acetylcysteine (1200 mg/day). The patients received 1200 mg/day NAC in two divided doses. Both NAC and placebo tablets were administered in the form of effervescent. The other group received risperidone plus placebo tablets. The shape, size, taste, and color of NAC and placebo were identical.
The dose was titrated up during two weeks. The dose was not fixed. In addition, all the patients in both groups received risperidone. Risperidone started at the dose of 0.5 mg/day and it was titrated up to 2 mg/day during three weeks for children less than 30 kg. The dose for children more than 30 kg was up to 3 mg/day. The dose of risperidone was not fixed and it could be changed considering the clinical symptoms and adverse effects.
The primary outcome measure was Aberrant Behavior Checklist. ABC consists of 58 items and includes 5 subscales. The subscales are Irritability, Lethargy and Social Withdrawal, Stereotypic Behavior, Hyperactivity and Noncompliance, and Inappropriate Speech.
The changes of Irritability subscale score was considered as the main outcome of the current trial.
It was completed at pre-intervention, 4 weeks after the beginning of intervention, and 8 weeks after the beginning of intervention. In addition, the adverse effects and extrapyramidal symptoms were systematically examined and assessed using checklists. The patients and their parents were also asked regarding possible adverse effects.
This trial's protocol and procedures were approved by Ethics Committee of Shiraz University of Medical Sciences, Iran. Then, this trial was registered at http://www.irct.ir. The registration number of this trial was IRCT201106103930N6. This trial was performed in 2011 and 2012. The parents of children provided written informed consent.
Analysis
SPSS was used to perform statistical analyses. Chi-Square test was used to compare the gender ratio between the two groups. The mean of age was compared between the two groups using independent t-test. Repeated Measures of ANOVA was used to examine the effect of interventions on the subscales scores of ABC. Intent-to-Treat (ITT) using Last Observed Carried Forward (LOCF) with at least one post-treatment evaluation was used to handle missing data. The Cohen's d was calculated to measure effect size. P value less than 0.05 was set for being statistically significant. This is an exploratory small sample size trial.
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