To date, psychostimulants constitute the most efficacious drugs in the treatment of ADHD with variable response rates ranging from 25% to 76%. Although remarkably safe, stimulant treatment is associated with potential shortcomings. Furthermore, adults with ADHD often suffer from concurrent disorders (anxiety, depression, tics and drug dependence)and stimulants are potentially abusable. Therefore a variety of alternative non-stimulants medications have been explored.

All available controlled trials of non-stimulants in adults ADHD patients were retrieved from Pubmed, PsycInfo and Mbase.

Only 17 controlled trials have been published. The compounds used are: desipramine, atomoxetine, modafinil, nicotine, ABT 418, guanfacine, selegiline, bupropion, lithium and pycnogenol. Effects seen in incontrolled studies are in general better than in well designed RCT's. Apart from trials with atomoxetine and bupropion the sample sizes are small. Most studies exclude patients with comorbid disorders, so that the study sample differs considerably from that in clinical practice. Most studies do not include assessment from significant others and some report improvement on a variety of neuropsychological measurements of executive functioning which cannot been translated into better daily functioning.

Sofar the non-stimulants are still hampered by their inferior effectsize compared to stimulants, the need for daily dosing to maintain their clinical efficacy and a delay in the onset of their clinical effects.