[Skip to Navigation]
Original Investigation
January 4, 2021

Risk of Substance Use Disorder and Its Associations With Comorbidities and Psychotropic Agents in Patients With Autism

Author Affiliations
  • 1Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
  • 2Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
  • 3Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
  • 4Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
  • 5School of Public Health, National Defense Medical Center, Taipei, Taiwan
  • 6Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
  • 7Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
  • 8Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
JAMA Pediatr. 2021;175(2):e205371. doi:10.1001/jamapediatrics.2020.5371
Key Points

Question  Do patients with autism have a higher risk of substance use disorder than the general population, and is this risk associated with psychotropic treatment, comorbidities, or mortality?

Findings  In this cohort study of 6599 individuals with autism spectrum disorder (ASD) and 26 396 controls without ASD, a diagnosis of autism was associated with an increased risk of substance use disorder, and the risk was much higher in those who had behavioral comorbidities and those who did not receive psychotropic agents. The mortality risk was higher in patients with autism and co-occurring substance use disorder than in non-ASD controls with or without substance use disorder.

Meaning  These findings suggest that patients with ASD are vulnerable to the development of substance use disorder, and the use of psychotropic agents for autism is associated with a decreased risk of substance use disorder.


Importance  The risk of substance use disorder (SUD) in patients with autism spectrum disorder (ASD) remains unclear.

Objective  To investigate the risk of SUD in patients with ASD and its associations with comorbidities, psychotropic agents (PAs), and mortality.

Design, Setting, and Participants  This retrospective, population-based, cohort study of 1 936 512 participants used data from the Taiwan National Health Insurance Research Database and was conducted from January 1, 2000, to December 31, 2015. Included participants attended at least 3 outpatient visits within the 1-year study period for symptomatic ASD as determined by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes. Individuals diagnosed with ASD before 2000, those diagnosed with SUD before the first visit for ASD, and those with missing data were excluded from the analysis. Patients with ASD and non-ASD controls were matched 1:4 by age, sex, and index date.

Exposures  Symptomatic ASD evaluated for at least 3 outpatient visits within the 1-year study period.

Main Outcomes and Measures  Adjusted hazard ratios (aHRs) with 95% CIs for SUD, including alcohol use disorder (AUD) and drug use disorder (DUD), and the risk of mortality were calculated. Data were analyzed from March 1 to July 13, 2020.

Results  A total of 6599 individuals with ASD (mean [SD] age, 11.9 [5.1] years; 5094 boys [77.2%]; mean [SD] follow-up period, 8.1 [8.3] years; median follow-up period, 4.3 [interquartile range [IQR], 2.3-5.3] years) and 26 396 controls (mean [SD] age, 12.1 [5.8] years; 20 376 boys [77.2%]; mean [SD] follow-up period, 8.6 [8.9] years; median follow-up period, 4.4 [IQR, 2.4-5.4] years) were enrolled in the study. According to multivariable-adjusted analysis, the aHRs for SUD (2.33; 95% CI, 1.89-2.87), AUD (2.07; 95% CI, 1.60-2.63), and DUD (3.00; 95% CI, 2.15-4.58) were significantly higher in the ASD group than in the non-ASD controls. The aHRs for SUD in the ASD subgroups with 1 PA (0.60; 95% CI, 0.43-0.66) and with multiple PAs (0.37; 95% CI, 0.28-0.49) were significantly lower than those in the ASD subgroup with no PAs. Comparisons between patients with ASD and non-ASD controls with the same comorbidities showed higher aHRs for SUD among patients with ASD (range, 1.17-2.55); moreover, the ASD subgroup not receiving any PAs had an aHR of 6.39 (95% CI, 5.11-7.87) for SUD when they had comorbid tic disorder and aHRs of 5.48 (95% CI, 5.12-5.70) for AUD and 5.42 (95% CI, 5.12-5.80) for DUD when they had comorbid impulse control disorder. The mortality risk was significantly higher in patients with ASD and concomitant SUD than in non-ASD controls without SUD (aHR, 3.17; 95% CI, 2.69-3.89).

Conclusions and Relevance  These findings suggest that patients with ASD are vulnerable to the development of SUD. Comorbid ASD and SUD were associated with an increase in mortality risk.

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    Substance Use/Abuse Acts as Means of Release from Stressors and Trauma Can Be Quite Addictive for ASD Adolescents.
    Frank Sterle Jr. |
    Notable adverse childhood experiences—including immense daily schoolyard stressors like chronic bullying—suffered by adolescents with Autism Spectrum Disorder can readily lead to a substance use disorder. This, of course, can also lead to an adulthood of debilitating self-medicating.

    The greater the drug-induced euphoria or escape one attains from its use, the more one wants to repeat the experience; and the more intolerable one finds their sober reality, the more pleasurable that escape should be perceived. By extension, the greater one’s mental pain or trauma while sober, the greater the need for escape from reality, thus the more addictive the euphoric
    escape-form will likely be.

    If the ASD adolescent is also highly sensitive, both the drug-induced euphoria and, conversely, the come-down effect or return to their burdensome reality will be heightened thus making the substance-use more addicting.

    I strongly feel that not only should all school teachers have received autism spectrum disorder (ASD) and Asperger’s Syndrome (AS) training, but that there should further be an inclusion in standard high school curriculum of a child development course which in part would also teach about the often debilitating condition.

    It would explain to students how, among other aspects of the condition, ASD and AS people, including higher functioning autistics, are often deemed willfully ‘difficult’ and socially incongruent, when such behavior is really not a choice.