This is a randomized double-blind clinical trial with control group conducted in 2019. The statistical population includes all children with ADHD referred to Be’sat Hospital in Sanandaj who were selected using a convenience sampling method. Based on the results of a study by Mohammadi et al. (2015) (13), and considering a type 1 error of 0.05 and mean ADHD scores of 4.8±13.9 and 4.4±10.8 in the two groups at the end of the study, and using the following formula a sample size of n=36 was calculated for each study group that was increased to 38 due to possible attrition. ADHD was diagnosed by three child and adolescent psychiatrists based on the DSM-5 criteria and the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) as a semi-structured diagnostic interview. Aged 6-12 years and diagnosis of ADHD based on the diagnostic criteria of DSM-5 were the inclusion criteria. In addition, the exclusion criteria were as follows: serious physical disorders, such as cardiovascular disease; asthma; peptic ulcer disease; pheochromocytoma and G6PD according to family health history of the patient and clinical examination; comorbid psychiatric disorders, except oppositional defiant disorder; mental retardation according to clinical examination; taking ADHD medications during the past month; history of allergy to Betahistine; and systolic blood pressure above 125 mmhg or a resting pulse of fewer than 60 BPM or more than 115 BPM.
Before starting the study, the study objectives and procedure were explained to the patients and their families, and they were reassured that they could leave the study at any time. In addition, they were given a phone number to contact the researcher. Moreover, they were not required to spend any money during the study. Furthermore, written and verbal consent for participation in the study were obtained from parents and children, respectively. The present study was approved by the ethics committee at Kurdistan University of Medical Sciences according to the declaration of Helsinki (No. IR.MUK.REC.1396.263). In addition, it was registered in the Iranian Registry of Clinical Trials (www.irct.ir) (No. IRCT Id: IRCT20160530028182N6).
The data was gathered using the demographic form, a researcher-made form assessing the reported complications of Methylphenidate and BetahistineADHD Rating Scale, and the Clinical Global Impression – Severity scale (CGI-S).
The ADHD Rating Scale is used to measure the severity of ADHD symptoms and respond to treatment in children and adolescents. It has 18 items in two dimensions, including attention deficit and hyperactivity. The items are rated on a 4-point Likert-type scale ranging from 0 to 3. In order to reduce response bias, items assessing attention deficit have odd numbers and those assessing hyperactivity/impulsivity have even numbers. Total score is the sum of raw scores on the two dimensions. Raw scores are converted to standard scores (percent scores) according to the normative table of the scale that is based on the child’s age and gender. The scale has an internal consistency of 0.92 and a one-month test-retest reliability of 0.85 (14).
The CGI-s requires the clinician to assess the severity of the patient's condition. It was used in the presents study to assess the severity of ADHD and patient’s response to treatment. It has 7 subscales, including normal, borderline mentally ill, mildly ill, moderately ill, markedly ill, severely ill, extremely ill.
The severity of symptoms before the intervention was assessed using the ADHD Rating Scale and the CGI-s. Before the intervention, the participants have undergone a physical examination in terms of heart rate, blood pressure, and weight. In the next step, the patients were divided into two groups, a Methylphenidate (Ritalin made by Novartis) plus Betahistine (Betaserc by Abbott) group and another Methylphenidate plus placebo group. The patients were randomly divided into the two groups. Then a pharmacist put the required drugs in boxes with closed doors and codes written on them, and gave them to the patients in the order in which they arrived. Neither the physician nor the patients were aware of the content of each box. Methylphenidate and Betahistine pills were crushed and put into similar capsules. Ritalin 10mg and Betahistine 8mg tablets were prescribed as follows: during the first week, once a day (Half of tablet at 8 am and another half at 2 pm), and from the second week, 2 tablets once a day (One tablet at 8 am and another at 2 pm). The patients were assessed again using the ADHD Rating Scale and the CGI-s in the week zero, and then in the second, fourth, and sixth weeks of the intervention period. In addition, the form assessing drug complications was completed in the second, fourth, and sixth weeks of the intervention period. If a patient could not tolerate the complications of a drug, the dosage of it was reduced and increased in smaller increments; all these details were recorded in patient medical records.
Descriptive statistics, including relative and absolute frequencies, mean, median, standard deviation, and range were used to describe the data. In addition, at the inferential statistics level, the repeated measures ANOVA was used to compare the means of quantitative variables between the intervention and control groups. All the analyses were performed using SPSS v.18. The significance level was set at p<0.05.