Which of the following is a side effect of medication treatment for ADHD eg Ritalin?

J Res Pharm Pract. 2014 Oct-Dec; 3[4]: 130–136.

Abstract

Objective:

The aim of the current study was to determine various aspects of methylphenidate adverse reactions in children with attention deficit-hyperactivity disorder [ADHD] in Iran.

Methods:

During the 6 months period, all children under methylphenidate treatment alone or along with other agents attending a university-affiliated psychology clinic were screened regarding all subjective and objective adverse drug reactions [ADRs] of methylphenidate. Causality and seriousness of detected ADRs were assessed by relevant World Health Organization definitions. The Schumock and Thornton questionnaire was used to determine preventability of ADRs.

Findings:

Seventy-one patients including 25 girls and 46 boys with ADHD under methylphenidate treatment were enrolled within the study period. All [100%] ADHD children under methylphenidate treatment developed at least one ADR. Anorexia [74.3%], irritability [57.1%], and insomnia [47.2%] were the most frequent methylphenidate-related adverse reactions. Except for one, all other detected ADRs were determined to be mild. In addition, no ADR was considered to be preventable and serious.

Conclusion:

Our data suggested that although methylphenidate related adverse reactions were common in children with ADHD, but they were mainly mild and nonserious.

Keywords: Adverse drug reactions, attention deficit-hyperactivity disorder, Methylphenidate

INTRODUCTION

Attention deficit and impulsivity is one of the prevalent disorders in school-aged children with a prevalence rate of about 3–5% in this age group.[1,2,3] Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV] defines attention deficit-hyperactivity disorder [ADHD] as symptoms of attention deficit, high activity and impulsivity in daily actions and speaking too much.[2,4] Children with ADHD are at greater risk for self-injury, motor vehicle accidents, impaired academic functioning, and antisocial personality disorder in the future.[5]

Long-term treatment plan for children with ADHD, especially at school ages includes pharmacotherapy combined with behavioral/psychological interventions.[6] Among different pharmacologic interventions, stimulants are generally considered as a first-line agent for school-aged children or adolescents with ADHD. Several studies have demonstrated that stimulants such as methylphenidate and dextroamphetamine can help ADHD symptoms like agitation, inattention, and excitation. Although the effect of discontinuation of medication is short and it may go away.[1]

Among different stimulants that have been used for treatment of children with ADHD so far, methylphenidate is a popular one.[7,8] In therapeutic doses, methylphenidate can cause anorexia, insomnia, headache, abdominal pain, nausea and irritability.[9,10] Insomnia and loss of appetite are dose-related, but its other adverse effects appear not to be dose-dependent.[11] Weight loss and developmental delay are adverse effects, which may occur in long-term methylphenidate consumption.[4,12] Data also exist about cardiovascular adverse effects of methylphenidate such as tachycardia and hypertension especially in chronic users.[13] Methylphenidate, even in therapeutic dose range, may also lower seizure threshold.[14] These adverse reactions of methylphenidate may compromise the treatment course of ADHD in children and also raise parents’ concerns over them.

The Iranian Pharmacovigilance Center [IPC], as a full member of World Health Organization [WHO] International Drug Monitoring Program, was established in 1998 with the main goal of increasing drug safety and preventing drug-related morbidity and mortality. Currently, more than 80 countries are involved in this program as full or associate members.[15] Shalviri et al. have described the 10 years activities of IPC.[15] According to this report, a total number of 17,967 adverse drug events has been collected and evaluated by the IPC. Ceftriaxone, tramadol, and streptokinase are the three most common medicinal products suspected to cause adverse drug reactions [ADRs]. Based on the WHO standards, countries with the best reporting rates generate over 200 reports per 1,000,000 inhabitants per year. Considering the population of Iran [over 60 million], it is expected to receive at least 12,000 reports per year.[16] However, this rate was only 2330 in 2006.[17] Hanafi et al. demonstrated that about 68% of the nurses in teaching university hospital in Tehran did not even know the correct definition of the term pharmacovigilance and only 2.2% of them had sent the reports to IPC.[16] These findings highlight the importance and prevalence of ADR under-reporting in our country. To obviate this problem, the IPC has been conducted several strategies such as developing spontaneous reporting system and training over 30,000 health care professionals through drug safety workshops. Other achievements of the IPC are as follows: Issuing 86 drug safety alerts to health care professionals, recalling 23 pharmaceutical products and changing the labeling of 30 others, suspending the distribution of 8 medicines, and withdrawing 4 different products from the national drug list.[15]

Regarding the fact that methylphenidate side effects can adversely affect adherence to treatment, clinical outcome and quality of life of its recipients, determining different features of methylphenidate side-effects are crucial for clinicians to develop optimal preventive as well as management strategies. Therefore, we conducted the current study to assess various aspects of methylphenidate adverse reactions, including incidence, causality relationship, preventability, and severity in children with ADHD in Iran.

METHODS

During the 6 months period from mid-September 2013 to mid-March 2014, a cross-sectional study was conducted on children and adolescents with ADHD under methylphenidate therapy attending the office of Children Medical Center psychology clinic affiliated to the Tehran University of Medical Sciences, Tehran, Iran. The diagnosis of ADHD was performed by an expert pediatric psychologist based on DSM-IV diagnostic criteria. The Medical Ethics Committee of the Tehran University of Medical Sciences approved the study, and informed consent was obtained from all patients. No specific inclusion-exclusion criteria regarding duration of methylphenidate treatment course, methylphenidate dose, and probable co-administered medications for management of ADHD were used for patient selection. The regimen of the study population included methylphenidate, alone or with an antipsychotic agent [including risperidone] or other relevant medications [e.g, clonidine].

All ADRs that occurred after starting methylphenidate therapy were recorded by a well-educated and qualified pharmacist. Detection of ADRs was performed by face-to-face interview with patients or his/her parents at regular follow-up office visits through a checklist of methylphenidate adverse reactions in relevant scientific literature and reviewing their brief office charts. Required data including patients’ age, sex, weight and height at the beginning of methylphenidate therapy, and at the present, comorbidities, ADHD treatment, drug regimen and co-administered medications [name, dosage, frequency, indication, and route of administration] and detected ADRs [clinical manifestation and the causative drug[s]] were registered in a predesigned form. ADRs reported by the patient daily [on a daily basis] and 2–3 times a week within the recent 1–2 weeks were classified as “always” and “sometimes,” respectively.

The WHO definition of ADR was used in the present study.[18] The WHO probability scale was used to assess the causality relation between reported ADRs and methylphenidate administration[s].[19] The seriousness of ADRs was determined by WHO definition. Based on this definition, any ADR resulting in death, life-threatening situation, persistent or significant disability/incapacity, hospital admission, or prolonged hospital stay was classified as serious.[20] The severity of ADRs was determined by Hartwig et al. definition.[21] The Schumock and Thornton questionnaire was used to evaluate the preventability of reported ADRs.[22]

Categorical variables were expressed as a percentage. Continuous variables were reported as mean ± standard deviation [SD]. Frequency of methylphenidate-related adverse reactions was expressed as the number of patients developed a certain ADR. Descriptive analyses were performed using the SPSS version 15 software [SPSS, Inc. Chicago, IL, USA].

RESULTS

Demographic characteristics of the cohort are shown in Table 1. Within the study period, 71 patients including 25 girls and 46 boys with ADHD under methylphenidate treatment were enrolled. Table 2 lists the comorbidities of the cohort. Forty-four [61.9%] of patients had no underling diseases. Among comorbidities, neonatal jaundice [25.4%] and seizure [4.2%] were most common. Treatment regimens of ADHD are listed in Table 3. More than half of [56.3%] the study population received methylphenidate alone. About 63.1% of patients received methylphenidate for at least 6 months and in only 2.8%, the treatment duration was