information:extraction
Stimulants

Methylphenidate and amphetamine or its derivatives are often first-line treatments for ADHD. About 70 per cent respond to the first stimulant tried and as few as 10 per cent respond to neither amphetamines nor methylphenidate. Stimulants may also reduce the risk of unintentional injuries in children with ADHD. Magnetic resonance imaging studies suggest that long-term treatment with amphetamine or methylphenidate decreases abnormalities in brain structure and function found in subjects with ADHD. A 2018 review found the greatest short-term benefit with methylphenidate in children, and amphetamines in adults. Studies and meta-analyses show that amphetamine is slightly-to-modestly more effective than methylphenidate at reducing symptoms, and they are more effective pharmacotherapy for ADHD than α2-agonists but methylphenidate has comparable efficacy to non-stimulants such as atomoxetine.In a Cochrane clinical synopsis, Dr Storebø and colleagues summarised their meta-review on methylphenidate for ADHD in children and adolescents. The meta-analysis raised substantial doubts about the drug's efficacy relative to a placebo. This led to a strong critical reaction from the European ADHD Guidelines Group and individuals in the scientific community, who identified a number of flaws in the review. Since at least September 2021, there is a unanimous and global scientific consensus that methylphenidate is safe and highly effective for treating ADHD. The same journal released a subsequent systematic review (2022) of extended-release methylphenidate for adults, concluding similar doubts about the certainty of evidence. Other recent systematic reviews and meta-analyses, however, find certainty in the safety and high efficacy of methylphenidate for reducing ADHD symptoms, for alleviating the underlying executive functioning deficits, and for substantially reducing the adverse consequences of untreated ADHD with continuous treatment. Clinical guidelines internationally are also consistent in approving the safety and efficacy of methylphenidate and recommending it as a first-line treatment for the disorder.

Safety and efficacy data have been reviewed extensively by medical regulators (e.g., the US Food and Drug Administration and the European Medicines Agency), the developers of evidence-based international guidelines (e.g., the UK National Institute for Health and Care Excellence and the American Academy of Pediatrics), and government agencies who have endorsed these guidelines (e.g., the Australian National Health and Medical Research Council). These professional groups unanimously conclude, based on the scientific evidence, that methylphenidate is safe and effective and should be considered as a first-line treatment for ADHD. The likelihood of developing insomnia for ADHD patients taking stimulants has been measured at between 11 and 45 per cent for different medications, and may be a main reason for discontinuation. Other side effects, such as tics, decreased appetite and weight loss, or emotional lability, may also lead to discontinuation. Stimulant psychosis and mania are rare at therapeutic doses, appearing to occur in approximately 0.1% of individuals, within the first several weeks after starting amphetamine therapy. The safety of these medications in pregnancy is unclear. Symptom improvement is not sustained if medication is ceased.

The long-term effects of ADHD medication have yet to be fully determined, although stimulants are generally beneficial and safe for up to two years for children and adolescents. A 2022 meta-analysis found no statistically significant association between ADHD medications and the risk of cardiovascular disease (CVD) across age groups, although the study suggests further investigation is warranted for patients with preexisting CVD as well as long-term medication use. Regular monitoring has been recommended in those on long-term treatment. There are indications suggesting that stimulant therapy for children and adolescents should be stopped periodically to assess continuing need for medication, decrease possible growth delay, and reduce tolerance. Although potentially addictive at high doses, stimulants used to treat ADHD have low potential for abuse. Treatment with stimulants is either protective against substance abuse or has no effect.

The majority of studies on nicotine and other nicotinic agonists as treatments for ADHD have shown favorable results; however, no nicotinic drug has been approved for ADHD treatment. Caffeine was formerly used as a second-line treatment for ADHD but research indicates it has no significant effects in reducing ADHD symptoms. Caffeine appears to help with alertness, arousal and reaction time but not the type of inattention implicated in ADHD (sustained attention/persistence). Pseudoephedrine and ephedrine do not affect ADHD symptoms.

Modafinil has shown some efficacy in reducing the severity of ADHD in children and adolescents. It may be prescribed off-label to treat ADHD.