Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents : assessment of harmful effects in non-randomised studies

Abstract

Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated childhood psychiatric disorders (Scahill 2000). The estimated prevalence in children and adolescents is between 3% and 5% (Polanczyk 2007), depending on the classification system used, with boys two to four times more likely to be diagnosed than girls (Schmidt 2009). Prevalence rates have remained stable over the past 30 years and do not appear to vary between countries (Polanczyk 2014). Individuals with ADHD show difficulties in attention and cognitive functions, for example, problem-solving, planning, orienting, flexibility, response inhibition, and working memory (Pasini 2007; Sergeant 2003). Children and adolescents also have high rates of problems involving affective components such as motivational delay and mood dysregulation (Castellanos 2006; Nigg 2005; Schmidt 2009). Many studies have examined environmental risk factors for ADHD development, however, no specific factor seems to predict who is and is not at high risk of developing ADHD. At the population level, poverty (families living under the poverty level) is more likely to be a feature among American children and adolescents diagnosed with ADHD (CDC 2015). In a Swedish cohort of 811,803 individuals, low family income in early childhood was highly associated with ADHD (Larsson 2014). Low birth weight (Indredavik 2004; Van Lieshout 2015), prematurity (Bhutta 2002; Burnett 2014; Elgen 2015), maternal exposure to tobacco (Kovess 2015; Obel 2015), and chemical components like lead (Hong 2015) and manganese (Hong 2014) remain questionable risk factors for ADHD development. To be diagnosed with ADHD, a child must display, before 12 years of age, excessive inattention, hyperactivity and impulsivity that impairs his/her functioning or development (APA 2013; WHO 1992). There are 18 symptoms of ADHD according to the principal diagnostic classification systems:the International Classification of Diseases Tenth Revision (ICD-10; WHO 1992), and the Diagnostic and Statistical Manual of Mental Disorders (DSM) Fourth Edition (DSM-IV; APA 1994); Fourth Edition, Text Revision (DSM-IV-TR; APA 2000); and FiPh Edition (DSM-5; APA 2013). The DSM–5 and ICD-10 criteria require that the inattention, hyperactivity, and impulsivity are pervasive (for example, maladaptive symptoms of hyperactivity-impulsivity or inattention that are present at home and at school, before 6 (ICD-10;WHO 1992) or 12 (DSM-5; APA 2013) years of age, and that persist for at least 6 months. There must also be clear evidence of clinically-significant impairment in social, academic, and occupational functioning (APA 1994; APA 2000; WHO 1992). The diagnostic criteria set out in the DSM-IV and DSM-5 divide ADHD into three different subtypes each with their own particular set of symptoms: 'predominantly inattentive type', the 'predominantly hyperactive-impulsive type', and the 'combined type'- a combination of both hyperactive-impulsive and inattentive symptoms (APA 2013; Willcut 2012). Children, adolescents and adults with ADHD are at increased risk of a broad spectrum of comorbid psychiatric disorders, which frequently result in negative outcomes later in life (Newcorn 2008; Schmidt 2009). The Multimodal Treatment of Attention Deficit Hyperactivity Disorder (MTA) trial identified one or more comorbid disorders in almost 40% of the participants (MTA 1999). These included oppositional defiant disorder, conduct disorder, depression, anxiety, tics, learning disorders, and verbal and cognitive difficulties (Jensen 2001; Kadesjö 2001). More recently, studies have confirmed such comorbidity (Czamara 2013; Yoshimasu 2012), and noted that excess weight and obesity (Cortese 2016) are found with ADHD. Depending on the severity, the presence of these comorbid conditions may modify the medication treatment, adding new classes of medications.