Background: Stimulants remain the mainstay of treatment for attention-deficit hyperactivity disorder (ADHD) but are often associated with insufficient response or poor tolerability, leading to many patients not wishing to be treated with controlled substances. Aims: This randomized, placebo-controlled, proof-of-concept study (NCT02327013) evaluated the efficacy of a multimodal antidepressant, vortioxetine, in the treatment of ADHD, using a two-stage sequential parallel comparison design. Methods: Patients aged 18–55 years with a diagnosis of ADHD (DSM-5) and a total score ⩾24 on the Adult ADHD Investigator Symptom Rating Scale (AISRS) were randomized in study stage I with a 1:1:3 ratio to six weeks of treatment with vortioxetine 10 or 20 mg/day, or placebo ( n = 227). In study stage II, placebo non-responders (AISRS total score reduction <30% from stage I baseline) were re-randomized with a 1:1:1 ratio to six weeks of vortioxetine 10 or 20 mg/day, or placebo ( n = 59). Results: Across the two study stages combined, ADHD symptoms improved by approximately eight AISRS points in all treatment groups, showing no difference from placebo for either dose of vortioxetine, the study thus failing to meet its primary endpoint. However, both doses of vortioxetine separated from placebo in improving overall patient functioning, as measured by the Sheehan Disability Scale. Conclusion: Studies are warranted to further investigate this suggested benefit of a multimodal antidepressant for patient functioning in ADHD while addressing issues of non-adherence and placebo response. The study confirmed vortioxetine 10 mg and 20 mg as generally well-tolerated.
Validity and accuracy of the Adult Attention‐Deficit/Hyperactivity Disorder (ADHD) Self‐Report Scale (ASRS) and the Wender Utah Rating Scale (WURS) symptom checklists in discriminating between adults with and without ADHD
