OBJECTIVES: The aim of this review was to evaluate comparative efficacy and tolerability of atomoxetine (ATX), bupropione (BUP), lisdexamfetamine (LDX), methylphenidate (MPH) and mixed amphetamine salts (MAS) in adults with attention deficit hyperactivity disorder (ADHD).

METHODS: A systematic search was conducted using MEDLINE, Clinical Trials Register, ClinicalTrials.gov and the Cochrane Library. Inclusion criteria were restricted to randomised, double-blind, parallel-group clinical trials with at least 2 weeks in duration. Studies in patients with severe comorbidities were excluded. The effect of MPH was separately assessed for immediate release (IR-MPH) and modified release (MR-MPH) formulation. The evaluated outcomes were severity of ADHD symptoms as measured by ADHD rating scale (ADHD-RS) and tolerability (the proportion of patients who left a study early due to adverse effects). OpenBUGS 3.2.3 was used to calculate pairwise Bayesian estimates of pooled standardized mean differences (SMD) for ADHD-RS and pooled odds ratios for tolerability.

RESULTS: In total 31 studies were identified: 1 head-to-head study with two arms, 27 placebo-controlled studies with two arms and 3 studies with three arms. In 30 studies ADHD-RS was assessed, whereas in 27 studies the tolerability was reported. All investigated medicines were superior to placebo. IR-MPH (SMD vs. placebo: -0.94; 95% CI: -1.25 to -0.64), LDX (SMD vs. placebo: -0.90; 95% CI: -1.11 to -0.71) and BUP (SMD vs. placebo: -0.74; 95% CI: -0.96 to -0.52) were significantly more efficacious than MR-MPH (SMD vs. placebo: -0.48; 95% CI: -0.56 to -0.40) or ATX (SMD vs. placebo: -0.42; 95% CI: -0.51 to -0.33) but not than MAS (SMD vs. placebo: -0.64; 95% CI: -0.83 to -0.43). Inconsistency was not detected. Tolerability of the medicines was inferior to placebo.

CONCLUSIONS: Methylphenidate and atomoxetine are most commonly investigated medicines for adults with ADHD. Further research is needed to better evaluate the efficacy of other medicines.