Nonstimulant Treatments for ADHD

Nonstimulants have an important role when response or tolerability to psychostimulants is poor, when certain comorbid disorders are present, or if patients prefer nonstimulants. Here, we discuss monotherapy and combined treatment of ADHD and review mechanism of action, pharmacokinetics, efficacy, tolerability, and safety of approved, off-label, and pipeline nonstimulants. We present detailed information regarding the 4 FDA-approved nonstimulant medications-the norepinephrine reuptake inhibitors, atomoxetine and viloxazine extended release, and the α-2 adrenergic agonists, clonidine XR and guanfacine XR. We additionally review evidence regarding the off-label use of a variety of other medications. Variability across and within drug classes in nature of response, approach to titration, and temporal characteristics of treatment allow a nuanced treatment approach for individuals with comorbid disorders and complicated clinical presentations. Availability of nonstimulant medications enhances our opportunity to offer personalized treatment of ADHD across the lifespan.