Fredriksen M, Dahl AA, Martinsen EW, Klungsoyr O, Haavik J, Peleikis DE “Effectiveness of one-year pharmacological treatment of adult attention-deficit/hyperactivity disorder (ADHD): An open-label prospective study of time in treatment, dose, side-effects and comorbidity.” European Neuropsychopharm 2014 24: 1873-1884.

This new study from Norway provides useful information about the long-term drug treatment of adult ADHD. Prior studies are small, of short duration (e.g. 4-10 weeks) or have problems with high dropout rates or selection biases (i.e. patients with comorbid conditions are often excluded). This naturalistic study examined 250 patients treated with ADHD drugs for one year.
The patients had a mean age of 32.6 years, virtually all of whom (98%) had never been previously diagnosed with ADHD, and none of whom had received prior treatment. Diagnoses and assessments of outcomes were conducted with state-of-the-art methods. Exclusion criteria included any major psychiatric disorder considered to be in immediate need of treatment, any medical contraindications to stimulant treatment, prior use of stimulant medication in adulthood, and the presence of autism spectrum disorder or intellectual disability (IQ < 70).

All study subjects received methylphenidate (MPH) as the first-line medication. Doses were flexibly titrated from 5 mg three times daily to 20 mg three times daily in the in the first six weeks, and to a maximum of 40 mg three times daily during the subsequent study period (one year). Extended-release MPH was offered at the 3-month visit and dosage could be decreased if subjects experienced intolerance. If MPH was not tolerated or ineffective, two alternative medications were offered: d-amphetamine (up to 50 mg daily) or atomoxetine (in doses ranging from 25 mg to 120 mg daily). Outcome measures were obtained at 3, 6 and 12 months after the initiation of treatment. In addition, all subjects received psychoeducational supportive counseling at all follow up visits.

At the end of 12 months, 92% of subjects (N=232) completed the study and 70% (N=163) remained on a medication. Of those on medication, 79% were taking MPH, 15% were taking d-amphetamine, and 6% were on atomoxetine. Mean daily dosages of medications prescribed (60 mg, 30 mg and 40 mg respectively) suggests the subjects were adequately treated. Given the small number of subjects on d- amphetamine or atomoxetine, drug-drug comparisons of treatment effects could not be carried out.

Overall, subjects still taking medication at the end of the 12 month study period were significantly more improved with respect to their ADHD symptoms and had better functional outcomes compared to those who either discontinued treatment or were never medicated. Subjects on the highest doses reported the best outcomes, and an inverse relationship was observed between side effects and effectiveness of treatment. Interestingly, the outcomes of those who discontinued were intermediate between those who never started a medication and those who stayed on one. Prominence of side effects was cited as the most likely reason for stopping medication (almost half), and discontinuation of treatment occurred most often during the first six weeks of treatment. Comorbid anxiety and bipolar disorders, non-alcohol substance use disorders and cumulative amounts of side effects were associated with less effectiveness.

This study was well designed, excellently implemented and comprised of a large enough sample to be of significance to practicing clinicians. While its open-label design makes it possible that patients on medication were over-estimating the effectiveness of treatment, the results appear consistent with prior studies of this type. Naturalistic studies of treatment effectiveness can be helpful in validating current clinical practices and in setting reasonable expectations for patients and clinicians regarding likely treatment outcomes.