Understanding the Risk of Using Medications for Attention Deficit Hyperactivity Disorder with Respect to Physical Growth and Cardiovascular Function

https://doi.org/10.1016/j.chc.2007.11.010Get rights and content

The effects of stimulant medications and atomoxetine on physical growth and on cardiovascular function are reviewed in light of the most recent data, with attention to clinical implications and research needs. Although these medications have a favorable benefit/risk profile and do not induce clinically significant changes in growth or cardiovascular function in the majority of cases, careful patient monitoring is needed to identify individuals at risk for negative outcomes. More research is needed to elucidate the mechanism of growth suppression to estimate better the risk for rare but life-threatening events and test the effectiveness of monitoring procedures.

Section snippets

Stimulants and physical growth

That long-term stimulant treatment of children can decrease growth velocity has been recognized for more than 30 years [9]. Several studies conducted in the 1970s and 1980s investigated the extent, persistence, and possible mechanisms of stimulant-induced growth suppression [10], [11], [12], [13], [14], [15], [16]. It was observed that the effect on weight typically emerges in the first few months of treatment, followed by attenuation, whereas the effect on height takes at least 1 year to

Atomoxetine and physical growth

Atomoxetine is a nonstimulant, selective noradrenergic reuptake inhibitor approved for the treatment of ADHD since 2003. Gastrointestinal adverse effects, such as appetite decrease, vomiting, gastric upset, and abdominal pain, frequently emerge early in treatment but seldom lead to drug discontinuation [45]. Acute treatment is on average accompanied by a slight decrease in weight of approximately 1 kg over a period of 2 to 3 months. Several open-label studies of atomoxetine administered for 2

Stimulants and cardiovascular function

Stimulants are sympathomimetic agents that increase noradrenergic and dopaminergic transmission. An effect on heart rate and blood pressure can be considered an intrinsic feature of their pharmacologic activity [48]. Hypertension and tachycardia are common in case of overdosing with these compounds [49]. Several placebo-controlled studies have documented a slight, but statistically significant, increase in blood pressure and heart rate in children and adults during short-term administration of

Atomoxetine and cardiovascular function

Atomoxetine is a selective norepinephrine reuptake inhibitor and an effect on the cardiovascular system can be expected given its pharmacologic properties. A review of five placebo-controlled clinical trials involving 612 children, adolescents, or adults treated with therapeutic doses of atomoxetine up to 10 weeks confirmed an increase 5 to 9 bpm in mean heart rate with suggestions of a dose-effect relationship [69]. Moreover, 3.6% of the children and adolescents on atomoxetine versus 0.5% of

α2-Agonists and cardiovascular function

Clonidine and guanfacine are marketed as antihypertensive drugs and do not have an official indication for the treatment of ADHD. They are, however, prescribed off-label alone or in combination with stimulants to children who have ADHD, especially in the presence of tic disorders or when other treatments prove insufficient [71]. Clonidine and guanfacine have prominent cardiovascular effects. They decrease blood pressure and can cause orthostatic hypotension, with dizziness, palpitations, and

Tricyclics and cardiovascular function

Although their use in children has decreased, tricyclic antidepressants still may be prescribed off-label for the treatment of ADHD in particular cases when stimulants or atomoxetine do not prove effective [71]. Tricyclics delay cardiac conduction and their use requires special attention to possible cardiotoxicity. Before starting treatment, children should receive a complete physical examination with ECG recording. Treatment should be considered only if the following limits are not exceeded on

Summary

In past few years, there has been a flurry of studies investigating growth in children treated with stimulants because of ADHD. Overall, the findings confirm that stimulants cause a slowing in growth velocity for weight and height, which can persist, although attenuated, for at least to 4 years, during continuous treatment. A slight decrease in weight and height velocity also is observed during treatment with atomoxetine. The clinical and practical significance of this effect on growth is

References (72)

  • T.J. Spencer et al.

    Does prolonged therapy with a long-acting stimulant suppress growth in children with ADHD?

    J Am Acad Child Adolesc Psychiatry

    (2006)
  • S.R. Pliszka et al.

    Comparative effects of methylphenidate and mixed salts amphetamine on height and weight in children with attention-deficit/hyperactivity disorder

    J Am Acad Child Adolesc Psychiatry

    (2006)
  • A. Charach et al.

    Stimulant treatment over 5 years: effect on growth

    J Am Acad Child Adolesc Psychiatry

    (2006)
  • D.A. Zachor et al.

    Effects of long-term psychostimulant medication on growth of children wth ADHD

    Res Dev Disabil

    (2006)
  • T. Farietta-Murray et al.

    Effects of stimulants on Hispanic boys' height and weight

    J Am Acad Child Adolesc Psychiatry

    (2007)
  • B. Vitiello et al.

    Methylphenidate dosage for children with ADHD over time under controlled conditions: lessons from the MTA

    J Am Acad Child Adolesc Psychiatry

    (2001)
  • R. Bosse et al.

    Anterior pituitary hypoplasia and dwarfism in mice lacking the dopamine transporter

    Neuron

    (1997)
  • C.J. Kratochvil et al.

    Effects of long-term atomoxetine treatment for young children with attention-deficit/hyperactivity disorder

    J Am Acad Child Adolesc Psychiatry

    (2006)
  • R.L. Findling et al.

    Short-term cardiovascular effects of methylphenidate and Adderall

    J Am Acad Child Adolesc Psychiatry

    (2001)
  • J. Biederman et al.

    A randomized, placebo-controlled trial of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder

    Biol Psychiatry

    (2006)
  • T. Spencer et al.

    A large, double-blind, randomized clincial trial of methylphenidate in the treatment of adults with ADHD

    Biol Psychiatry

    (2005)
  • R. Donner et al.

    Cardiovascular effects of mixed amphetamine salts extended release in the treatment of school-aged children with attention-deficit/hyperactivity disorder

    Biol Psychiatry

    (2007)
  • W.C. Roberts

    Sudden cardiac death: definitions and causes

    Am J Cardiology

    (1986)
  • H. Gutgesell et al.

    AHA scientific statement: cardiovascular monitoring of children and adolescents receiving psychotropic drugs

    J Am Acad Child Adolesc Psychiatry

    (1999)
  • T. Wilens et al.

    Combining methylphenidate and clonidine: a clinically sound medication option

    J Am Acad Child Adolesc Psychiatry

    (1999)
  • S.R. Pliszka et al.

    The Texas children's medication algorithm project: revision of the algorithm for pharmacotherapy of attention-deficit/hyperactivity disorder

    J Am Acad Child Adolesc Psychiatry

    (2006)
  • D. Efron et al.

    Side effects of methylphenidate and dexamphetamine in children with attention deficit hyperactivity disorder: a double-blind, crossover trial

    Pediatrics

    (1997)
  • Research Units on Pediatric Psychopharmacology (RUPP)

    Autism network. A randomized controlled crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity

    Arch Gen Psychiatry

    (2005)
  • S.H. Zuvekas et al.

    Recent trends in stimulant medication use among U.S. children

    Am J Psychiatry

    (2006)
  • R.M. Scheffler et al.

    The global market for ADHD medications

    Health Aff

    (2007)
  • R.G. Ross

    Psychotic and manic-like symptoms during stimulant treatment of attention deficit hyperactivity disorder

    Am J Psychiatry

    (2006)
  • T.E. Wilens et al.

    Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature

    Pediatrics

    (2003)
  • D.J. Safer et al.

    Depression of growth in hyperactive children with stimulant drugs

    N Engl J Med

    (1972)
  • J.A. Mattes et al.

    Growth of hyperactive children on maintenance regimen of methylphenidate

    Arch Gen Psychiatry

    (1983)
  • R.G. Klein et al.

    Methylphenidate and growth in hyperactive children. A controlled withdrawal study

    Arch Gen Psychiatry

    (1988)
  • R.G. Klein et al.

    Hyperactive boys almost grown up. III. Methylphenidate effects on ultimate height

    Arch Gen Psychiatry

    (1988)
  • Cited by (94)

    • Long term methylphenidate exposure and growth in children and adolescents with ADHD. A systematic review and meta-analysis

      2021, Neuroscience and Biobehavioral Reviews
      Citation Excerpt :

      Time of follow-up represents another important variable, when evaluating the possible impact of stimulants on growth: medication effects tend to attenuate over time both for weight and height. According to the results of previous reviews (Poulton, 2005; Vitiello, 2008), effects on height would manifest later in time with respect to weight (Faraone and Giefer, 2007; Spencer et al., 2006; Lisska and Rivkees, 2003), with a similar trend of generally remitting in time (Poulton and Cowell, 2003; Klein and Mannuzza, 1988; Safer and Allen, 1973), and time of follow up appears to be influenced by the condition of drug-naïvity at the beginning of the study. Drug naïve subjects have been shown to present a greater weight and BMI loss with MPH transdermal delivery system (Faraone and Giefer, 2007).

    • Reducing the Clinical and Socioeconomic Burden of Narcolepsy by Earlier Diagnosis and Effective Treatment

      2017, Sleep Medicine Clinics
      Citation Excerpt :

      Sodium oxybate can cause nausea and abnormal neuropsychiatric effects and its use may be limited because of potential interactions with alcohol, sedative hypnotics, and other central nervous system depressants.66 As mentioned earlier, methylphenidate and amphetamines are associated with a potential for tolerance, abuse, and side effects that include growth suppression in children and cardiovascular disease in adults.41,42 In addition, nondrug therapies such as scheduled naps, diet modifications, and exercise play an important role in helping patients with narcolepsy manage their condition, but they do not eliminate the symptoms.51

    View all citing articles on Scopus

    The opinions and assertions contained in this report are the private views of the author and are not to be construed as official or as reflecting the views of the Department of Health and Human Services, the National Institutes of Health, or the National Institute of Mental Health.

    View full text