Adults with attention-deficit/hyperactivity disorder (ADHD) often face delays in diagnosis and remain untreated, despite significant negative impacts. To evaluate the safety and efficacy of transdermal treatment options in children, adolescents, and adults, a systematic literature review was conducted, with a focus on the implications of transdermal therapies for ADHD in adults.

A MEDLINE/Embase/BIOSIS/SCOPUS database search was conducted December 4, 2019, for English-language articles of interventional clinical trials using transdermal formulations for the treatment of ADHD without publication date limit. Assessed outcomes included efficacy, safety, adherence, abuse potential, cost efficacy, and health-related quality of life.

Of 23 eligible publications, 18 were in children or adolescents (n = 1699; range 23-305), and 5 in adults (n = 274; range 14-90); all included methylphenidate transdermal system (MTS). All seven pediatric publications reporting change in ADHD symptomology from baseline reported a significant improvement with MTS treatment. Similarly, in three adult publications, ADHD symptoms improved significantly with MTS treatment. Safety findings in pediatric and adult studies were comparable; the most frequently reported treatment-emergent adverse events (TEAEs), namely, headache, decreased appetite, and insomnia, were reported in 13/16 (81%) of publications reporting specific TEAEs. MTS-related dermal reactions were mostly mild and transient. Discontinuation due to dermal reactions was reported in 10 studies (range 0%-7.1% [1 of 14 patients]). MTS compliance was high when assessed (97%-99%).

Transdermal therapies provide a useful treatment formulation for ADHD. Studies of MTS and other transdermal formulations, such as amphetamine, in adult patients are needed in this underserved population.

Functional and mental health impairments that adults with attention-deficit/hyperactivity disorder (ADHD) experience may be exacerbated by regular substance use and co-morbidity with substance use disorders (SUD). This may be especially true during young adulthood, which represents a critical stage of life associated with increased substance use and associated problems. However, previous studies investigating the association between ADHD and substance use and SUD have demonstrated inconsistent results, probably due to methodological limitations (e.g., small and non-representative samples). Thus, the relationship of ADHD with substance use and related disorders remains unclear. The aim of the present study was to examine the association between ADHD and both the use of licit and illicit substances and the presence of SUD in a large, representative sample of young men.

The sample included 5677 Swiss men (mean age 20 ± 1.23 years) who participated in the Cohort Study on Substance Use Risk Factors (C-SURF). ADHD was assessed using the adult ADHD Self Report Screener (ASRS). The association between ADHD and substance use and SUD was assessed for alcohol, nicotine, cannabis and other illicit drugs, while controlling for socio-demographic variables and co-morbid psychiatric disorders (i.e., major depression (MD) and anti-social personality disorder (ASPD)).

Men with ADHD were more likely to report having used nicotine, cannabis and other illicit drugs at some time in their life, but not alcohol. ADHD was positively associated with early initiation of alcohol, nicotine and cannabis use, the risky use of these substances, and the presence of alcohol use disorders, and nicotine and cannabis dependence. Additionally, our analyses revealed that these patterns are also highly associated with ASPD. After adjusting for this disorder, the association between ADHD and licit and illicit substance use and the presence of SUDs was reduced, but remained significant.

Our findings suggest that adult ADHD is significantly associated with a propensity to experiment with licit and illicit substances, especially at earlier ages, to exhibit risky substance use patterns, and to subsequently develop SUDs. Preventive strategies that include early intervention and addressing co-morbidity with ASPD may be crucial to reducing substance use and the development of pathological substance use patterns in young men affected by ADHD and, thus, helping to prevent further illness burden later in life.