Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopment disorder occurring during
childhood. However, ADHD persists into adulthood in 45.7% of cases. The global prevalence of adult ADHD is
estimated to 5.3%, with no difference between Europe and North America. ADHD is often comorbid with substance
use disorder (SUD), with Odds Ratio ranges from 1.5 to 7.9, depending on the substance and the dependence
level. Conversely, the prevalence of ADHD among patients with SUD is 10.8%, versus 3.8% for patients
Methylphenidate (MPH) alleviates ADHD symptoms and, as such, is currently considered as a first choice medication. MPH blocks the
dopamine and norepinephrine transporters leading to an increase in extracellular dopamine. It should be noted that its subjective effects
are highly dependent on the pharmacokinetic and especially on the rate of input, which highlights the importance of choosing a sustainedrelease
formulation. Meanwhile, prescribing MPH to patients with comorbid SUD has always been challenging for clinicians.
The aim of this review is to address the benefits and pitfalls of using MPH in adults with ADHD comorbid SUD, depending on each of
the following types of SUD: amphetamine, cocaine, nicotine, alcohol, cannabis and opiates. Overall, due to the prevalence of ADHD in
SUD and to the benefits of MPH observed in this population, and considering the mild or low side effects observed, the response to MPH
treatment should be evaluated individually in adults with comorbid ADHD and SUD. The choice of the formulation should favor sustained-
release MPH over immediate release MPH. Cardiovascular parameters also have to be monitored during long-term use.