30 May 2022

Castellano-García F et al. Brain Sci 2022; 12(5): 590

Sex differences can influence the aetiology and course of mental disorders, but few studies have investigated such differences in patients with mental health disorders (Chandra et al, 2010; Howard, 2010). The objective of this study was to review current literature on sex differences in adolescents with ADHD in terms of substance use, substance use disorder (SUD),* and variables that may be related to substance use and SUDs (e.g. ADHD prevalence, pharmacological therapy and academic performance).

The authors used search terms to identify relevant articles from the PubMed, Web of Science and Scopus databases between October and November 2021. Prior to inclusion, articles were rated for their quality. High-quality articles were included if they reported studies in which:

  1. Participants were 13‒18 years of age.
  2. ADHD was previously diagnosed by questionnaires or clinical interviews according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders – 4th Edition (DSM-IV), 4th Edition – Text Revision (DSM-IV-TR) or 5th Edition (DSM-5TM).
  3. SUD and/or related variables were investigated.
  4. Data were segregated by sex.
  5. Cohorts included ≥100 participants.

There were 559 articles identified by the initial searches, with 21 articles ultimately included in the literature review. Results were grouped according to SUD: nicotine, alcohol, marijuana and cannabis, and other substances.

Regarding SUD in adolescents with ADHD:

  • Nicotine use disorder was more frequent in girls than boys; however, boys smoked more than girls throughout adolescence.
  • In general, boys with SUD drank more alcohol than girls; however, girls with more symptoms of hyperactivity–impulsivity drank more alcohol than boys, and SUDs were more frequent in these girls than boys. Adolescents with more severe ADHD initiated alcohol use earlier and drank alcohol more frequently than those with less severe symptoms, with the risk being similar for both sexes.
  • Girls had more problems with marijuana and cannabis use than boys. Adolescents with more severe ADHD initiated marijuana use earlier and used it more frequently than those with less severe ADHD, with the risk being similar for both sexes.
  • SUDs relating to other substances were more frequent in girls than boys; however, boys with SUDs had more symptoms of ADHD than girls with SUDs.

In terms of ADHD prevalence, girls were diagnosed with ADHD less frequently than boys (1 in 43 vs 1 in 10, respectively) and presented fewer symptoms. In addition, girls with ADHD were less likely to receive treatment (18.7%) than boys with ADHD (28.4%); this may be attributed to the inattentive type ADHD that was more frequent amongst girls and is associated with less disruptive behaviour.

While ADHD negatively impacted academic performance in both boys and girls, girls with ADHD had more impaired cognitive and executive functioning and a higher tendency towards suicidal acts, suicidal ideation and self-harm.

The authors identified some limitations of the study. Firstly, the age range of 13‒18 years was considered narrow; a broader age range may have allowed investigation of SUD in different age categories, such as children and young adults. Secondly, despite sex being the point of interest in this review, most included articles reported studies with higher numbers of boys than girls, which may have influenced the results. The studies were also few and heterogeneous and as a result, the authors could not perform a meta-analysis of the data. Finally, because many of the studies were cross-sectional, it was not possible to explore any causal relationships between ADHD and SUD.

The authors concluded that some girls with ADHD may have a greater risk of developing SUDs than boys with ADHD, particularly girls with mild/moderate ADHD and more symptoms of hyperactivity and impulsivity. This greater risk may be attributed to delays in ADHD diagnosis and lack of treatment of ADHD in girls, and a greater impairment of cognitive and executive functioning in girls with ADHD compared with boys with ADHD. Early diagnosis and treatment of ADHD are suggested to be crucial, particularly in adolescent girls, for the prevention of SUD.

Read more about sex differences in substance use disorder in adolescents with ADHD


*Patients diagnosed with an SUD included abuse (the substance is consumed despite the problems and negative consequences it causes) or dependence (substance use causing tolerance, withdrawal, and/or pattern of compulsive use).
Search terms:
1. (ADHD OR gender differences OR sex differences) AND (adolescents OR teenagers OR teens) AND (dual diagnosis OR dual diagnoses) AND (substance use OR substance addiction).
2. (ADHD) AND (gender differences OR sex differences) AND (substance use OR substance addiction) AND (adolescents OR teenagers OR teens).
3. (ADHD) AND (gender differences OR sex differences) AND (adolescents OR teenagers OR teens).
The methodological quality of case-control or cohort studies was assessed using the Newcastle Ottawa Scale (Wells et al, 2019). The methodological quality of comparative studies was assessed using the adaptation for cross-sectional studies by Modesti et al. (2016).

Disclaimer: The views expressed here are the views of the author(s) and not those of Takeda.

Castellano-García F, Benito A, Jovani A, et al. Sex differences in substance use, prevalence, pharmacological therapy, and mental health in adolescents with attention-deficit/hyperactivity disorder (ADHD). Brain Sci 2022; 12: 590.

Chandra PS, Satyanarayana VA. Gender disadvantage and common mental disorders in women. Int Rev Psychiatry 2010; 22: 513-524.

Howard LM. Gender differences in mental health. Int Rev Psychiatry 2010; 22: 415-416.

Modesti PA, Reboldi G, Cappuccio FP, et al. Working group on CV risk in low resource settings. Panethnic differences in blood pressure in Europe: a systematic review and meta-analysis. PLOS One 2016; 11: e0147601.

Wells G, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of non-randomised studies in meta-analyses. 2019. Available at: https://www.ohri.ca//programs/clinical_epidemiology/oxford.asp. Accessed June 2022.

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