• Xavier Castells, Josep Antoni Ramos-Quiroga, Rosa Bosch, Mariana Nogueira, and Miguel Casas.
• Unit of Clinical Pharmacology, Department of Medical Sciences, Faculty of Medicine, Universitat de Girona, Girona, Catalonia, Spain.
• Cochrane Db Syst Rev. 2011 Jun 15 (6): CD007813CD007813.

BackgroundAttention 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.ObjectivesTo 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 StrategyWe 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 CriteriaRandomized controlled trials comparing the efficacy of amphetamine derivatives against placebo or an active intervention.Data Collection And AnalysisTwo 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 ResultsWe 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.Authors' ConclusionsAmphetamines 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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