Stimulant Subtype and Transitivity in Pharmacotherapy Rankings for Co-Occurring Attention-Deficit/Hyperactivity Disorder and Stimulant Use Disorder

See reply by Oliva and Angarita and article by Oliva et al

To the Editor: Attention-deficit/hyperactivity disorder (ADHD) and stimulant use disorder (StUD) frequently co-occur. This may reflect shared neurobiological vulnerabilities and, in some individuals, stimulant use as a form of self-medication.¹ Treating co-occurring ADHD and StUD remains challenging because psychostimulants are established treatments for ADHD and are also being investigated as off-label treatments for StUD. The recent network meta-analysis by Oliva et al¹ provides a timely synthesis of the limited randomized evidence and addresses an important therapeutic gap in this population.

Oliva et al¹ found that mixed amphetamine salts (MAS), particularly the 80-mg dose, ranked most favorably for stimulant-use outcomes. For negative urine toxicology, MAS 80 mg ranked highest with a P-score of 0.890. In contrast, methylphenidate (MPH) 180 mg ranked highest for improvement in ADHD symptoms, with a P-score of 0.899. The clinical interpretation of these network rankings, however, depends on the transitivity assumption of network meta-analysis. As discussed by Jansen and Naci,² important treatment-effect modifiers should be sufficiently comparable across the different treatment comparisons.

This assumption may be particularly important when different stimulant disorders are combined within the same network. The American Society of Addiction Medicine/American Academy of Addiction Psychiatry (ASAM/AAAP) guideline³ categorizes pharmacotherapy recommendations by substance type because cocaine and amphetamine-type stimulants have different pharmacologic mechanisms that may affect treatment effectiveness. The guideline suggests considering long-acting amphetamine formulations for cocaine use disorder and long-acting MPH for amphetamine-type StUD, with additional consideration for co-occurring ADHD. These substance-specific recommendations are consistent with stimulant subtype being a clinically plausible treatment-effect modifier.

Against this background, the structure of the available evidence becomes important. Four trials involved cocaine and 2 involved amphetamine as the focus of the StUD. MPH was evaluated in both groups, whereas MAS was evaluated only in cocaine-related trials.¹ The authors explicitly considered stimulant type a potential effect modifier, but their transitivity discussion focused mainly on its clustering with study location and setting. They argued that treatment-seeking status, confirmed diagnoses, and concomitant cognitive behavioral therapy supported the plausibility of network comparison.¹ These similarities do not address whether patients with cocaine-versus amphetamine-focused StUD are sufficiently exchangeable with respect to relative pharmacotherapy effects.

Oliva et al¹ provide a useful synthesis of a limited evidence base. However, because MAS was evaluated only in cocaine trials, its relative ranking against MPH is difficult to disentangle from possible differences related to stimulant subtype. Treatment rankings across the broader StUD category should therefore be interpreted with caution. Future trials should better distinguish cocaine use disorder from amphetamine-type stimulant use disorder when comparing pharmacotherapies.

Article Information

Published Online: November 11, 2026. https://doi.org/10.4088/JCP.26lr16713
© 2026 Physicians Postgraduate Press, Inc.
J Clin Psychiatry 2026;87(4):26lr16713
To Cite: Yen MW, Shan JC. Stimulant subtype and  transitivity in pharmacotherapy rankings for co-occurring  attention-deficit/hyperactivity disorder and stimulant use  disorder.J Clin Psychiatry. 2026;87(4):26lr16713
Author Affiliations: Department of Psychiatry, Cathay  General Hospital, Taipei, Taiwan (Yen, Shan); Department of Psychiatry, National Taiwan University Hospital and  College of Medicine, National Taiwan University, Taipei,  Taiwan (Shan); School of Medicine, National Tsing Hua  University, Hsinchu, Taiwan (Shan).
Corresponding Author: Jia-Chi Shan, MD, MHS,  Department of Psychiatry, Cathay General Hospital, No.  280, Sec. 4, Ren’ai Road, Da’an District, Taipei, Taiwan  ([email protected]).
Financial Disclosure: Dr Yen has no financial or other  relationships to disclose. Dr Shan has received lecture  honoraria from Center Laboratories, Eisai Taiwan, Hoan  Pharmaceuticals, Janssen, Otsuka Pharmaceutical, Servier, Synmosa Biopharma, and Yei-Chuan International  Trading Co., Ltd.
Funding/Support: None.
Use of AI-Assisted Technologies in the Writing Process:  In the writing of this manuscript, the authors used ChatGPT  (GPT-5.6 Sol, OpenAI) and DeepSeek (DeepSeek-V4.1-Flash, DeepSeek) to improve readability and language  during manuscript preparation. The authors reviewed and  verified the content and take full responsibility for the  content of the publication.