Methylphenidate DAT binding in adolescents with Attention-Deficit/ Hyperactivity Disorder comorbid with Substance Use Disorder - a single Photon Emission Computed Tomography with [Tc99m]TRODAT-1 study

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is highly prevalent among adolescents with Substance Use Disorders (SUD). Effects of methylphenidate (MPH) on ADHD are attributed to its properties of blocking the dopamine transporter (DAT) in the striatum. However, it has been demonstrated that drug addiction is associated with dopaminergic system changes that may affect MPH brain effects, emphasizing the need to better understand MPH actions in subjects with ADHD+SUD. Objectives: To evaluate the effect of an extended release formulation of MPH (MPH-SODAS) on DAT availability in 17 stimulant-naive ADHD adolescents with comorbid SUD (cannabis and cocaine). Methods: Subjects underwent two single photon emission computed tomography (SPECT) scans with [Tc99m]TRODAT-1, at baseline and after 3 weeks on MPH-SODAS. Clinical assessment for ADHD relied on the Swanson, Nolan and Pelham Scale - version IV (SNAP-IV). Caudate and putamen DAT binding potential (BP) was calculated. Results: After 3 weeks on MPH-SODAS, there was a significant reduction of SNAP-IV total scores (p < 0.001), and ∼ 52% reductions of DAT BP at the left and right caudate. Similar decreases were found at the left and right putamen (p < 0.001 for all analyses). Discussion: This study shows that the magnitude of DAT blockade induced by MPH in this population is similar to what is found in ADHD patients without SUD comorbidity, providing neurobiological support for trials with stimulants in adolescents with ADHD+SUD, an important population excluded from studies.