Title

 

Authors

C. Rafaniello

PhD Student in Pharmacology and Clinical and Experimental Medicine
Department of Experimental Medicine, Section of Pharmacology “Leonardo Donatelli”. Center of Pharmacosurveillance and Pharmacoepidemiology, Faculty of Medicine and Surgery, Second University of Naples, Naples, Italy

 

Abstract

Background Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most common childhood disorders and can continue into adolescence and adulthood. ADHD is a neurobehavioral condition characterized by excessive restlessness, inattention, distraction, and impulsivity. In addition, these often exhibit comorbid behaviour such as depression, anxiety, oppositional defiant disorders, and compulsive behaviours ⁽¹⁾. These core symptoms lead to impairment in home, school and peer contexts. Treatment should be limited to the individual child's needs. Evidence-based treatments for ADHD include medication management (generally with stimulant medications), behavioral interventions or the combination of pharmacological and behavioral approaches ⁽²⁾. Stimulant drugs, such as methylphenidate (MPH), and non-stimulant drugs, such as atomoxetine (ATX), are used for the treatment of ADHD in children ⁽³⁾. Because ADHD is a chronic condition and typically requires effective treatment for several years or more, information on the benefits and risks of long-term pharmacotherapy for ADHD is essential for clinicians. In response to these needs, a registry for the treatment of ADHD has been created in Italy, which is coordinated by the National Institute of Health, in collaboration with the Italian Medicine Agency (AIFA). According to the Determination of AIFA General Director, reference centers for prescription of MPH and ATX in the pediatric population have been identified. In the Campania Region, five reference centers for prescription have been identified, with the Centre of Pharmacosurveillance and Pharmacoepidemiology of the Second University of Naples as a centre for monitoring the risk/benefit ratio.  Objective To monitor the safety of MPH and ATX in ADHD patients in the Campania Region. Methods An intensive monitoring programme was conducted in the Campania Region from September 2007 to October 2010. Children data were extracted from National ADHD Registry. Information ADHD diagnosis, medical history, clinical event data, adverse events and any cause of discontinuation of pharmacological therapy. In particular, data about drug therapy (MPH or ATX), dosages, changes in dosage during treatment, duration of treatment, patterns of therapy, comorbidity and use of concomitant medications were collected. Results 92 Campania patients who have had a diagnosis of ADHD, on the basis of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV TR) criteria, were recorded into the ADHD Registry by the Campania Reference Centre for Prescription, but only 76 started treatment. The majority of patients was treated with ATX (90%), was male (86.8%) and was aged between 10-13 years (34.2%). The mean treatment period was about 38 days. The most frequent cause for discontinuation of therapy were improvement of clinical conditions and adverse drug reactions (ADRs). 25 patients (about 33%) reported at least one ADR (2 MPH, 23ATX). Among these, 16 patients reported 1 ADR, 8 reported 2 ADRs and 1 reported 3 ADRs, for a total of 35 ADRs reported to the National Pharmacovigilance Network (3 related to MPH and 32 to ATX). The ADRs included: 9 (22.5%) cases of weight loss; 7 (17.5%) cases of therapy inefficacy; 5 (10%) cases of hepatotoxicity; 4 (10%) cases of abdominal pain; 3 (7.5%) cases of sleep disorders; single cases (2,5%) of oral facial dystonia, suicidal thoughts, tachycardia, hyperidrosis, aggressiveness, weight increase, oppositive disease, depression, gastralgia, vomiting and impulsiveness. Conclusions Our results on ATX and MPH risk/benefit profile are largely similar to what reported in previous clinical trials. Particularly, we observed some rare ADRs that randomized controlled trials have only limited ability to detect such as a case of ATX induced suicidal ideation, a case of bucco-facial distonia an atypical case of weight increaselinked to ATX treatment.