Amphetamines for Attention Deficit Hyperactivity Disorder in adults

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 characterized by hyperactivity, mood instability, irritability, difficulties in maintaining attention, lack of organization and impulsive behaviours. The presence of other disorders occurring at the the same time is also common, especially mood disorders and substance abuse. It seems that amphetamines could reverse the underlying neurological problems that feature in ADHD, and so improve ADHD symptoms.

We found seven studies, which enrolled 1091 patients. These studies compared amphetamines to placebo and three of them also compared amphetamines with other drugs: guanfacine, modafinil and paroxetine. Three amphetamine derivatives were investigated: dexamphetamine, lisdexamphetamine and mixed amphetamine salts (MAS). Treatment length ranged from two to 20 weeks.

All amphetamines improved ADHD symptoms but overall they did not make people more likely to stay in treatment and were associated with a higher risk of treatment ending early due to adverse events. One type of amphetamine, mixed amphetamine salts, did, however, increase retention in treatment. We found no evidence that higher doses worked better than lower ones. We did not find any difference in effectiveness between immediate-release and sustained-release formulations. Therefore, it appears that short-term treatment with amphetamines reduces ADHD symptoms, but studies assessing the effects of amphetamines for longer periods of time are needed.

Authors' conclusions: 

Amphetamines improved short-term ADHD symptom severity. MAS also increased retention in treatment. Amphetamines were associated with higher attrition due to adverse events. The short study length and the restrictive inclusion criteria limit the external validity of these findings. Furthermore, the possibility that the results of the included studies were biased was high, which could have led to an overestimation of amphetamine efficacy.

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Background: 

Attention Deficit Hyperactivity Disorder (ADHD) is a childhood onset disorder that can persist into adulthood. Amphetamines are used to treat adult ADHD, but uncertainties persist about their efficacy and safety.

Objectives: 

To examine the efficacy and safety of amphetamines for adults with ADHD, as well as the influence of dose, drug type and release formulation type.

Search strategy: 

We searched CENTRAL, PubMed, EMBASE, CINAHL, PsycINFO, clinicaltrials.gov, UK Clinical Trials Gateway and references obtained from articles and experts in the field. We conducted the electronic searches on 25 February 2010.

Selection criteria: 

Randomized controlled trials comparing the efficacy of amphetamine derivatives against placebo or an active intervention.

Data collection and analysis: 

Two authors extracted data from each included study. We used the standardized mean difference (SMD) and the risk ratio (RR) to assess continuous and dichotomous outcomes, respectively. We conducted a stratified analysis to determine the influence of moderating variables. We assessed the trials for risk of bias and drew a funnel plot to investigate the possibility of publication bias.

Main results: 

We included seven studies, which enrolled 1091 participants. All studies were placebo-controlled and three included an active comparator: guanfacine, modafinil and paroxetine. Most studies had short-term follow-up, with a mean study length of 8.1 weeks. Amphetamines improved ADHD symptom severity (SMD = -0.72; 95% CI -0.87 to -0.57) but did not improve retention in treatment overall and were associated with increased dropout due to adverse events (RR 3.03; 95% CI 1.52 to 6.05). The three amphetamine derivatives investigated (dextroamphetamine, lisdexamphetamine and mixed amphetamine salts (MAS)) were all efficacious for reducing ADHD symptoms, but MAS also increased retention in treatment. Different doses did not appear associated with differences in efficacy. We investigated immediate and sustained drug release formulations but found no difference between them on any outcome. When amphetamines were compared to other drug interventions, no differences were found. We did not find any study to be at low risk of bias overall, mainly because amphetamines have powerful subjective effects that may reveal the assigned treatment.

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