Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults [Review] (2018)

Background: Attention deficit hyperactivity disorder (ADHD) is a childhood-onset psychiatric disorder that can persist into adulthood in up to 50% of patients. From a clinical point of view, ADHD is characterised by hyperactivity, mood instability, irritability, difficulties in maintaining attention, lack of organisation, and impulsive behaviours. Occurrence of other disorders at the the same time is common, especially mood disorders and substance abuse. Amphetamines (a type of stimulant) are thought to improve ADHD symptoms, but there are concerns about how safe they are for regular use by patients with ADHD.
Review question: We examined whether treatment with amphetamines improves the symptoms of ADHD in adults.
Study characteristics: Reviewers found 19 studies, which enrolled 2521 patients. Most patients were male (57.2%), middle-aged (mean age 35.3 years) Caucasians (84.5%). These studies compared amphetamines to placebo (something that looks like an amphetamine but with no active ingredient), and three studies also compared amphetamines with other drugs such as guanfacine, modafinil, and paroxetine. In this review, we assessed the effects of three different kinds of amphetamines: dexamphetamine (from 10.2 to 21.8 mg/d), lisdexamfetamine (from 30 to 70 mg/d), and mixed amphetamine salts (MAS) (from 12.5 to 80 mg/d). Treatment length ranged from one to 20 weeks. Eighteen studies were conducted in the USA and one study in Canada and the USA. Ten studies were conducted at multiple sites. Study funding was reported in all but two studies. Sixteen studies were funded by the manufacturer, and one was funded by government agencies.
All amphetamines reduced the severity of ADHD symptoms as rated by patients. Lisdexamfetamine and MAS also reduced the severity of ADHD symptoms as rated by clinicians, but dexamphetamine did not. Overall, amphetamines did not make people more likely to stay in treatment and were associated with higher risk of treatment ending early as the result of adverse events. We found no evidence suggesting that higher doses worked better than lower ones. We did not find any difference in effectiveness between amphetamines that act for longer periods of time versus those that act for shorter periods of time. Therefore, it appears that short-term treatment with amphetamines reduces the severity of ADHD symptoms, but studies assessing the effects of amphetamines for longer periods of time are needed. We found no differences in effectiveness between amphetamines and guanfacine, modafinil, or paroxetine.
Quality of the evidence: The quality of the evidence was low to very low for all outcomes for several reasons, namely, it was possible for patients to know the treatment they were taking; the number of studies and included patients was low, leading to imprecise results for many outcomes; the studies had problems in their design; and, for some outcomes, results varied across trials.