Pharmacological treatment of attention deficit hyperactivity disorder with co-morbid drug dependence
Abstract
Background: Drug dependence is frequent in patients with attention deficit hyperactivity disorder (ADHD). Nevertheless, the efficacy and safety of pharmacological treatments in this population are unclear. Methods: A systematic review with meta-analysis was performed. Randomised placebo-controlled clinical trials investigating the efficacy of pharmacological treatment in patients with co-occurring ADHD and substance use disorder (SUD) were included. ADHD symptom severity, drug abstinence and all-cause treatment discontinuation were the primary study endpoints. The effects of patient-, intervention- and study-related covariates over the primary outcomes were investigated by means of meta-regression. Results: Thirteen studies were included, enrolling a total of 1,271 patients. A small to moderate reduction of ADHD symptoms was found. Meta-regression analysis identified the presence of a lead-in period as a covariate associated with reduced efficacy. Conversely, no beneficial effect was observed either on drug abstinence or treatment discontinuation. The efficacy on ADHD symptoms was smaller in studies with a lead-in period. A positive correlation between the efficacy for ADHD and that for SUD was found. Conclusions: The efficacy of pharmacological interventions for co-occurring ADHD and SUD has been little investigated. Mixed results were obtained: while pharmacological interventions improved ADHD symptoms, no beneficial effect on drug abstinence or on treatment discontinuation was noted. The strength of the recommendation of pharmacological treatment for co-occurring ADHD and SUD is therefore modest. The study was registered with the international prospective register of systematic reviews (PROSPERO): CRD 4212003414.
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The Cunill et al. meta-analysis did not distinguish between adolescent and adult patients and did not consider heterogeneity within and between samples, methodological differences between studies, or variations in dosing.
“Unfortunately, this meta-analysis did not distinguish between adolescent and adult patients, and did not consider the heterogeneity within and between samples nor the methodological differences between the studies and the variations in dosing.”
From Treatment of Adolescents with Concurrent Substance Use Disorder and Attention-Deficit/Hyperactivity Disorder: A Systematic Review (2021) · cites this paper as [35]
Age of patients in years did not moderate the effect on ADHD symptoms.
“Age of the patients (in years) did not moderate the effect on ADHD symptoms.”
From Treatment of Adolescents with Concurrent Substance Use Disorder and Attention-Deficit/Hyperactivity Disorder: A Systematic Review (2021) · cites this paper as [35]
None of the medications were effective in increasing abstinence from substances (OR = 1.09).
“None of the medications were effective in increasing abstinence from substances (OR = 1.09).”
From Treatment of Adolescents with Concurrent Substance Use Disorder and Attention-Deficit/Hyperactivity Disorder: A Systematic Review (2021) · cites this paper as [35]
Compared with placebo, methylphenidate (OR = 2.02) and atomoxetine (OR = 1.71) significantly reduced ADHD symptoms, but the other medications did not.
“Compared with placebo, methylphenidate (OR = 2.02) and atomoxetine (OR = 1.71) significantly reduced ADHD symptoms, but the other medications did not [35].”
From Treatment of Adolescents with Concurrent Substance Use Disorder and Attention-Deficit/Hyperactivity Disorder: A Systematic Review (2021) · cites this paper as [35]
Cunill et al. (2014) found a mean pooled effect size on ADHD symptoms of OR = 1.93, a small effect.
“The mean pooled effect size on ADHD symptoms from all of the studies amounted to an odds-ratio (OR) of 1.93 (small effect).”
From Treatment of Adolescents with Concurrent Substance Use Disorder and Attention-Deficit/Hyperactivity Disorder: A Systematic Review (2021) · cites this paper as [35]
Evidence suggests that age plays a minimal role in moderating the efficacy of stimulant treatment in children, adolescents, and adults with ADHD.
“However, evidence suggests that age plays a minimal role in moderating the efficacy of stimulant treatment in children, adolescents, and adults with ADHD [35,81]”
From Treatment of Adolescents with Concurrent Substance Use Disorder and Attention-Deficit/Hyperactivity Disorder: A Systematic Review (2021) · cites this paper as [35]
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The Use of Novel Stimulants in ADHD Self-Medication: A Mixed Methods Analysis
Holborn, T., Schifano, F., Smith, E., & Deluca, P. (2025) · Brain Science · doi:10.3390/brainsci15030292 · Cited by 5 · see citing works
“Furthermore, these individuals are likely to experience increasing difficulties remaining abstinent [87] and may suffer from the reduced effectiveness of standard-dose pharmacotherapy [88].”
van Kernebeek, M. V., Vorspan, F., Crunelle, C., van den Brink, W., Dom, G., Moggi, F., Konstenius, M., Franck, J., Levin, F., van de Glind, G., et al. (2022) · Annales de Toxicologie Analytique · doi:10.1016/j.toxac.2022.02.001 · Cited by 4 · see citing works
“En evanche, la pharmacothérapie du TDAH n’est en soi pas fficace pour réduire l’usage de substances et demeure ssociée, en général, à une fréquence élevée d’effets secndaires et d’arrêt de traitement [7,36].”
BackgroundInfluentialADHS im Erwachsenenalter und substanzbezogene Störungen
Schecke, H., & Mette, C. (2020) · Handbuch Klinische Psychologie · doi:10.1007/978-3-662-45995-9_23-1 · Cited by 4 · see citing works
Scott, K., Becker, S. J., Helseth, S. A., Saldanha, I. J., Balk, E. M., Adam, G. P., Konnyu, K. J., & Steele, D. W. (2022) · Family Practice · doi:10.1093/fampra/cmab096 · Cited by 3 · see citing works
Brynte, C., Konstenius, M., Khemiri, L., Bäcker, A., Guterstam, J., Levin, F. R., Jayaram-Lindström, N., & Franck, J. (2023) · European Addiction Research · doi:10.1159/000535016 · Cited by 3
“Randomized trials utilizing standard doses of MPH have showed limited effects on ADHD symptoms and no demonstrable effects on substance use, compared to placebo, in the comorbid populations [25].”
BackgroundComorbidity of attention deficit-hyperactivity disorder and substance use disorder
Evren, C. (2018) · doi:10.5350/dajpn20183102001 · Cited by 3
“There was a positive correlation between the effects on ADHD and SUD, respectively (62).”
BackgroundBegnaud, A., Cabelguen, C., Challet‐Bouju, G., Leboucher, J., Schreck, B., & Grall‐Bronnec, M. (2025) · Addictive Behaviors · doi:10.1016/j.addbeh.2025.108557 · Cited by 2 · see citing works
OROS-methylphenidate to reduce ADHD symptoms in male prisoners aged 16–25 years: a RCT
Asherson, P. J., Johansson, L., Holland, R., Bedding, M., Forrester, A., Giannulli, L., Ginsberg, Y., Howitt, S., Kretzschmar, I., Lawrie, S. M., et al. (2022) · Efficacy and Mechanism Evaluation · doi:10.3310/thei8200 · Cited by 4 · see citing works
Ozgen, H., Spijkerman, R., Noack, M., Holtmann, M., Schellekens, A., van de Glind, G., Banaschewski, T., Barta, C., Begeman, A., Casas, M., et al. (2021) · Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie · doi:10.1024/1422-4917/a000828 · Cited by 2 · see citing works
Avellaneda-Ojeda, A., Murtaza, S., Shah, A. A., & Moukaddam, N. (2018) · Psychiatric annals · doi:10.3928/00485713-20180719-02 · Cited by 2 · see citing works
ADHS und Sucht im Erwachsenenalter
Ridinger, M. (2016) · Nervenheilkunde · doi:10.1055/s-0037-1616449 · Cited by 2
“Obwohl einige Studiengruppen zeigen konnten, dass mit hohen Dosierungen von Methylphenidat nicht nur positive Effekte auf die Symptome des ADHS, sondern auch auf Tabak-, Amphetamin- oder Kokainabhängigkeit im Sinne einer Verringerung von Craving und Substanzkonsum erreichbar waren (28–30), ergab eine jüngst veröffentl…”
BackgroundThe treatment of dual ADHD: a drop in the ocean.
Cunill, R., & Castells, X. (2016) · Adicciones · doi:10.20882/adicciones.836 · Cited by 2 · see citing works
Self-citationMoodiness in Patients with ADHD and Substance Use Disorders
Bukstein, O., & Roberto, A. (2018) · Springer eBooks · doi:10.1007/978-3-319-64251-2_10 · Cited by 2 · see citing works
Therribout, N., van Kernebeek, M. V., Vorspan, F., Crunelle, C., van den Brink, W., Ozgen, H., Spijkerman, R., Noack, M., Holtmann, M., Schellekens, A., et al. (2022) · Neuropsychiatrie de l'enfance et de l'adolescence · doi:10.1016/j.neurenf.2022.11.004 · Cited by 1 · see citing works
Widinghoff, C., Berge, J., & Håkansson, A. (2021) · International Journal of Mental Health and Addiction · doi:10.1007/s11469-021-00636-6 · Cited by 1 · see citing works
Drugs to Treat Attention Deficit Hyperactivity Disorder (ADHD)
Müller-Sedgwick, U., & Sedgwick-Müller, J. A. (2020) · Cambridge University Press eBooks · doi:10.1017/9781911623465.015 · Cited by 3 · see citing works
ATTENTION-DEFICIT/HYPERACTIVITY DISORDER AND PSYCHIATRIC COMORBIDITY: A REVIEW OF CURRENT EVIDENCE
Glanert, W., Bajer, J. M., Włodarczyk, A., Kulawinek, H., Obersztyn, J., Kasparek, K. M., Czech, M., Kasparek, G., Szczecińska, A., Mliczek, A., et al. (2026) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.3(51).2026.6568
Capusan, A., Zhang, L., Larsson, H., Brikell, I., Martinez, D., D'Onofrio, B., Lichtenstein, P., Kuja-Halkola, R., & Chang, Z. (2026) · BMJ mental health · doi:10.1136/bmjment-2025-302138
Pallucchini, A., Varese, M., Pergentini, I., Gemignani, S., Parapetto, E., Maremmani, I., & Maremmani, A. (2025) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph23010040
“…stimulant treatment have been reported in ADHD patients with co-occurring stimulant use disorders, whereas findings remain mixed or inconclusive in opioid and alcohol use disorder populations, where concerns about misuse, tolerability, and limited impact on substance-related outcomes persist [4,5].”
Tolerability of Chronic Extremely High-dose Use of Methylphenidate. Description of A Clinical Case
Rosenhagen, M. C., Vandenberghe, F., Faida, J. G., & Wavre, S. (2023) · Journal of Medical - Clinical Research & Reviews · doi:10.33425/2639-944x.1348
“Conversely, normal doses of MPH do not show a significant effect in this regard [13].”
Background
- Authors
- Cunill, R., Castells, X., Tobias, A., & Capellà, D.
- Affiliations
- Parc Sanitari Sant Joan de Déu (ES)
- Department of Medical Sciences, Universitat de Girona, Girona, Spain
- Institute of Environmental Assessment and Water Research (IDAEA), Spanish Council for Scientific Research (CSIC), Barcelona, Spain
- Universitat de Girona (ES)
- ORCID
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2014-08-20
- Volume
- 29
- Issue
- 1
- Pages
- 15-23
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- OpenAlex
- W2029873699
- Cited by
- 78
- References
- 0
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 2 · 2023: 4 · 2022: 10 · 2021: 9 · 2020: 10 · 2019: 2 · 2018: 9 · 2017: 10 · 2016: 6 · 2015: 6 · 2014: 2
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- attention deficit hyperactivity disorder, substance use disorders, comorbidities, pharmacotherapy, ADHD symptom severity, drug abstinence, treatment discontinuation, treatment efficacy
- MeSH terms
- Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Humans, Treatment Outcome, Diagnosis, Dual (Psychiatry), Substance-Related Disorders
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