Complications
Monitoring of weight, giving medication with meals, and adding high-calorie snacks and supplements are recommended.[206]
Meta-analysis of studies with children/adolescents who had ADHD found that stimulant medication leads to longer sleep latency, worse sleep efficiency, and shorter sleep duration.[207] However, insomnia can often be treated first with sleep hygiene techniques including elimination of caffeine, avoidance of all screen use for at least 1 hour prior to bedtime, avoidance of exercise late in the day, and strict adherence to regular sleep and wake times. Adjustment of medication timing, dose, and formulation (e.g., exchanging a long-acting for an intermediate-acting stimulant) may also be tried.[91] Finally, adjuvant medications can be helpful, e.g., melatonin.[91]
Stimulants and atomoxetine: in 2006, the Food and Drug Administration (FDA) issued a warning about the cardiovascular risks of stimulant drugs.[211] However, in healthy children, the evidence for medication-induced cardiac effects is minimal.[212] One article demonstrated that there was no evidence that current use of an ADHD drug was associated with an increased risk of serious cardiovascular event.[137] Another study found a slightly increased relative risk of myocardial infarction and arrhythmias in the early period after starting methylphenidate treatment for ADHD in children and young people, mostly in those with a history of congenital heart disease. This raises the importance of risk-benefit analysis, particularly in children with mild ADHD.[140]
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[Evidence C] Children with preexisting heart disease, symptoms suggestive of heart disease (e.g., syncope, palpitations, chest pain, postexercise symptoms, heart murmur heard on auscultation, signs of heart failure), or a strong family history for sudden death should be referred to a cardiologist for examination before a stimulant trial.[90][91] If patients develop any cardiac adverse effects on stimulants, they should also be referred to a cardiologist. There is no need to obtain routine ECGs or echocardiograms for healthy patients on stimulants, but the American Heart Association recommends that it is reasonable to consider an ECG in selected children prior to stimulant treatment, depending on any positive findings suggestive of cardiovascular risk in the history and physical exam.[98]
Alpha-2-adrenergic agonists: these are antihypertensives and thus have rare cardiac complications including hypotension, bradycardia, and rebound hypertension. There has been debate in the literature about risk of sudden death when combining clonidine with stimulants, but studies show this combination to be safe.[213]
Mood lability is a rare adverse effect of ADHD medications; if this occurs, clinicians may consider changing the dose of the medications or switching to an alternative class of medications.
The Pediatric Advisory Committee of the FDA has found very rare reports of aggression and psychotic symptoms (specifically visual and tactile hallucinations of insects) in postmarketing safety data. The analysis of these data is problematic as information about dose, comorbid diagnoses, and concomitant medication use is often unavailable. One study of adolescents and young adults (13-25 years old) who started taking prescription stimulants for ADHD found that amphetamines were associated with a greater risk of new-onset psychosis than methylphenidate.[132] A population-based cohort study found no evidence that methylphenidate increases the risk of psychotic events in adolescents and young adults with ADHD, including in those with a history of psychosis.[133] Clinicians with patients who develop psychotic symptoms should likely discontinue the medication.
There is conflicting evidence regarding whether stimulants increase the rate of tics relative to placebo; however, double-blind clinical trials have not found any increase.[214][215] In fact, children with comorbid tic disorders generally have a decline in tic frequency when stimulants are initiated, presumably because there is reduction of tic-promoting stress and anxiety.[216][217] If tics emerge following stimulant initiation or increase and are experienced as unacceptable, options include a trial of discontinuation of the stimulant with later rechallenge, addition of an intervention to address tics, for example, comprehensive behavioral intervention for tics (CBIT) or a tic-reducing medication such as clonidine or guanfacine, or a change to a nonstimulant ADHD medication such as atomoxetine.[110][145]
Young people with ADHD are at increased risk of alcohol and other substance use disorders.[27] Parents are often concerned that stimulant treatment will increase this risk further. In fact, a review of this topic concluded that treatment for ADHD actually decreased the risk for substance use disorders.[28][29] All healthcare professionals involved in the treatment of ADHD should be alert to the signs of misuse and/or diversion.[112] Diversion and misuse of stimulants can be reduced by prescribing long-acting forms with the least potential for diversion and misuse, and keeping close track of prescriptions.[218] Evidence has suggested that patients with ADHD have a significantly higher risk of cigarette smoking. However, consistent stimulant treatment of ADHD appeared to reduce smoking risk, with a larger effect in samples with more severe psychopathology, in one meta-analysis.[219] The majority of studies included in the meta-analysis were naturalistic (precluding causal inferences) and most did not provide sufficient data to examine the influence of sample demographics, treatment effectiveness, or other comorbidities.
A meta-analysis found that compared with people without ADHD, children and adolescents with unmedicated ADHD were about 20% more likely to be overweight or obese.[220] Another meta-analysis found that people with unmedicated ADHD were around 40% more likely to be obese, but that those who were receiving medication were indistinguishable in BMI from those without ADHD.[221]
Fairly frequent but not clinically significant except when severe enough to require reduction in dose or change to another agent. Treatment is symptomatic.
Children and adolescents with ADHD have been found to be at greater risk of accidental injury including burn injury and repeated concussion.[226][227] Driving poses a particular risk for adolescents with ADHD, and there is a substantial body of evidence to suggest that ADHD medication mitigates against this.[228][229] It is important that clinicians and patients consider medication coverage for symptom control when driving, for example, with longer-acting or late-afternoon short-acting medications.[90]
There have been inconsistent findings regarding effects of stimulants and atomoxetine on growth, with some studies demonstrating some small decrease in expected height gain and others demonstrating no effect on adult height.[32][208] The Multimodal Treatment Study of AD/HD (MTA), a 3-year follow-up of children with ADHD combined presentation, showed that the group treated with stimulants had an average of 2.0 cm less height and 2.7 kg less weight than the unmedicated subgroup.[209] A proposed mechanism is that stimulants cause blockade of the dopamine transporter, leading to increased dopamine in different brain regions such as the hypothalamus and striatum, which mediate decreased growth. It is unclear if this translates to a reduction in adult height or instead represents a slower tempo of growth, as proposed in a large review and cross-sectional analysis.[210] If growth delay occurs, physicians consider a dose reduction, change to an alternative agent, or may consider a drug holiday during weekends, vacations, and the summer.[112]
A Taiwanese study of over 20,000 adolescents and young adults with ADHD and over 61,000 age- and sex-matched non-ADHD individuals found that those with ADHD were almost four times as likely to attempt suicide, and over six times as likely to repeat suicide attempts.[177] A separate Taiwanesse study of 85,000 youths found that treatment with methylphenidate was associated in a 60% lower risk of suicide attempts in those on treatment for 3-6 months, and a 70% reduction in the risk of attempting suicide in those using methylphenidate for 6 months or more.[178]
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