Pediatric pharmacoepidemiology - safety and effectiveness of medicines for ADHD

ABSTRACT

Introduction: Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder in children and adolescents that comprises core symptoms of developmentally inappropriate levels of inattention and/or hyperactivity and impulsivity. Stimulant (methylphenidate, amphetamines) and non stimulant (atomoxetine, clonidine and guanfacine) are the treatment usually prescribed for ADHD.

Area covered: This review covers the safety of ADHD medications in children and adolescents.

MEDLINE, EMBASE and PsycINFO databases were searched with the aim to retrieve prospective studies that monitored the incidence of adverse events (AEs) in children receiving drug therapy for ADHD. Many of the studies investigated the risk of specific AEs. In particular, the cardiovascular safety, the impact on growth and on sleep pattern, the risk of substance use disorders and of suicidal ideation are among the topics more studied.

Expert opinion: Effective drugs for ADHD appears to be safe and well tolerated. Most of the adverse events reported in the randomised controlled trials are mild and transient. Decreased appetite, growth decrease and the impact on sleep (insomnia for stimulants and somnolence for alpha2-agonists) are among the most common events. Concerns exist about cardiovascular and psychiatric AEs, even if the available evidence does not support an association with medications.

KEYWORDS:

• Amphetamines
• attention deficit hyperactivity disorder
• atomoxetine
• drug-related side effects and adverse reactions
• methylphenidate
• pediatrics

Article highlights

• Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder in children and adolescents that comprises core symptoms of developmentally inappropriate levels of inattention and/or hyperactivity and impulsivity, with a world-wide prevalence estimated around 7.2%.

• Current drug treatment approaches for ADHD comprises stimulant medications (methylphenidate, amphetamines) and non stimulant medications (atomoxetine, clonidine and guanfacine). Intervention in ADHD should be based on multimodal treatment combining psychosocial interventions with pharmacological therapies. There is a consensus in the international guidelines on the treatment of ADHD on recommending psychostimulant drugs as first line treatment

• According to clinical trials, decreased appetite and emotional disturbances were common adverse events (AEs) in children taking stimulants or atomoxetine, while headache and gastrointestinal pain were among the most frequent AEs independently from medication. Irritability, crying, sleeping problems, daydreams and anxiety were the most frequent AEs reported for stimulant users, with somnolence and fatigue more commonly reported with the use of atomoxetine and alpha2-agonists

• Prescribers need to be aware of uncommon adverse events that should be monitored in children and adolescent receiving ADHD medications, in particular: cardiovascular and psychiatric adverse events, the impact on growth and development, the potential increased risk of seizures and of suicidal ideation.

• Scant data on long term safety of ADHD medications are available as well on the safety and effectiveness of drug therapy in patients with co-morbidity. Moreover, the role of genetics in influencing the response to therapy and the risk of adverse events need to be investigated.

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Acknowledgments

The authors would like to acknowledge Chiara Pandolfini for manuscript language editing.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The paper is part of the work done for ‘Sharing diagnostic-therapeutic approaches for ADHD in Lombardy’ project partially funded by the Healthcare Directorate of the Lombardy Region (D.G. Sanità n.1077, 02/02/2017).