This study was a double-blind clinical trial. The population of the study was children with ADHD and ODD, who were selected based on DSM-5 criteria amongst those who visited in Psychiatric Clinic of Be’sat Hospital, Sanandaj-Iran in 2018. The sample size for each group was determined by considering a 5% first-type error and a 2% second-type error. The sample size was 60 (40 for the intervention group and 20 for the control group).
Sample selection
This is a double-blind clinical trial and experimental intervention (the patient and physician were not aware that patients are in case and control groups) on ADHD and ODD children. The disorder was diagnosed by the paediatric physiatrist or psychiatric expert by using a non-structured clinical interview based on DSM-5 criteria. The study population consisted of 60 children with ADHD who visited the psychiatric clinic of Be’sat hospital in Sanandaj by considering inclusion and exclusion criteria. After an explanation about the steps and attaining the written consent of parents and oral consent of children, the patients entered into the study and excited when they wish. The harshness of symptoms before beginning was assessed by the ADHD Rating Scale. Before starting the treatment, physical examination was done in order to measure heartbeat, blood pressure and weight.
Grouping, Allocation, and Blinding
Regarding the nature of the study, the researcher distributed the patients into three groups i.e. group 1, 2, and 3 and referred them to the treatment authority with this code. Risperidone, Aripiprazole, and placebo (starch) were placed in the same capsules, and delivered to the patients in the pre-prepared packets based on the codes of 1 to 60 by the pharmacy. Therapeutic dose of 10mg Methylphenidate, made by Novartis Company, was prescribed for the first week (daily, one-fourth in the morning and one-fourth in the evening), second week (daily, 1/2 in the morning and 1/2 in the evening) and then (daily, one dose in the morning and one in the evening) based on the tolerance of patient. Therapeutic dose of 1mg Risperidone, made by Sobhan Company, was prescribed for the first week (daily, one-fourth in the morning and one-fourth in the evening), second week (daily, 1/2 in the morning and 1/2 in the evening) and then (daily, one dose in the morning and one in the evening) based on the tolerance of patient along with Methylphenidate. Therapeutic dose of 5mg Aripiprazole, made by Sobhan Company, was prescribed for the first week (daily, one-fourth in the morning and one-fourth in the evening), second week (daily, 1/2 in the morning and 1/2 in the evening) and then (daily, one dose in the morning and one in the evening) based on the tolerance of patient along with Methylphenidate.
Therapeutic dose of placebo (starch), was prescribed for the first week (daily, one-fourth in the morning and one-fourth in the evening), and second week (daily, 1/2 in the morning and 1/2 in the evening) and then (daily, one dose in the morning and one in the evening) along with Methylphenidate. Clinical global impression and Parent ADHD Rating Scale were accomplished by the participants before starting the cure and in weeks 2, 4, and 8 in order to determine the severity of ADHD symptoms. The side-effects were also documented in weeks 2, 4, and 8 after starting the study in side-effects form. Other observed side-effects that were not in the form were also documented.
Measurement
A) Parent's ADHD Rating Scale
It is a valid and reliable tool to evaluate the severity of ADHD symptoms and the response of children, which has two versions: parent and teacher. This scale contains 18 phrases about attention deficit and impulsivity-hyperactivity. The respondent should specify the rate of recurrence of each phrase or symptom in a Likert 4-point scale (0 to 3). From the results of this scale, we acquire three scores (inattention, hyperactivity-impulsivity and total). The internal consistency of this scale was 85% in 92% and its retest reliability in the interval of 4 weeks (28, 29).
B) Clinical Global Impression Severity (CGI-S)
This scale measures the severity of disease and the response rate to treatment of the psychological disorders, especially in the studies (30). Therapists use CGI-S to measure the disease' severity that has 7 sub-scales including: Normal, not at all ill; Borderline mentally ill; mildly ill; moderately ill; markedly ill; severely ill and extremely ill.
C) Demographic Information Checklist
This checklist includes the information like age, gender, education, occupation of parents and weight which was completed by the interviewer during the interview.
D) Side-effects checklist
This checklist is provided to check the probable side-effects in which previously reported side-effects of Methylphenidate, Risperidone, and Aripiprazole are documented.
Data analysis
The descriptive and inferential statistical methods are used to analyze the data in this research. Mean, frequency and standard deviation were applied in descriptive level in this research. Repeated measurement multivariate test was used to compare the quantitative variables in both intervention and study groups using SPSS-18 Software in inferential statistical method. The significance level was 0.05.
Ethical considerations
This study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committees of the Kurdistan Universities of Medical Sciences (Iran) with number (IR.MUK.REC.1395.135). Also this study is registered in clinical trial of Iran site (http:.irct.ir/) with code IRCTID: IRCT20160530028182N5. Prior to participation, participants provided written informed consent.