Response to Hall <i>et al</i>.: Prescription psychostimulants for amphetamine‐type stimulant use disorder ‐ acknowledging challenges but not giving up on its potential cost‐effectiveness
Bibliographic record
Abstract
We appreciate the comments by Hall et al. [1] on our meta-analysis [2]. They have raised some very legitimate concerns related to the development of new treatments for amphetamine-type stimulant (ATS) use disorder (ATSUD). Challenges pertaining to the feasibility of trialing psychostimulants for ATSUD, to the differences between the tentative stimulant agonist therapy and established opioid agonist therapy (OAT), and to the certainty of the evidence through the pooling of results from studies with small sample sizes were already mentioned in our meta-analysis and shared by our group of authors. Hall et al. [1] have also criticized the justification for further trials of high-dose stimulants, mainly because of the small effect size observed for craving and the lack of any effect on other outcomes in the main analysis. However, they ignored the statistically significant results of the ATS use by urinalysis in the sensitivity analysis and the increase of the risk reduction of ATS use from a small (11%) to a moderate effect (29%) when including the only study [3] with high-dose methylphenidate (180 mg/day) in the subgroup analysis by medication dosage. While this significant signal is based on a single study conducted in an attention deficit hyperactivity disorder (ADHD)-only population, it brings the urge to more endeavors on trialing high-dose prescription psychostimulants, especially in the context of a disorder for which few, if any, interventions have proven very efficacious to date. We completely agree on the concerns with the challenges related to conducting trials with high-dose psychostimulants, both in terms of feasibility and the risk–benefit ratio. That is precisely why we advocated for an acceleration of the research effort in this field and the use of strategies to improve retention while mitigating risks, such as psychostimulant formulations with longer duration of action, and combination with psychosocial interventions [4]. The upcoming research can also elaborate on not-well-studied patient-reported outcomes, especially quality of life, rather than only abstinence-based outcomes, while also testing new supervision strategies that may be more cost-effective. In conclusion, we are on the same page with Hall et al. [1] regarding the challenges that come with trialing high-dose psychostimulants for ATSUD, such as the feasibility and safety of the intervention and the need for adequate power and higher retention rates. However, we believe that further high-quality trials of psychostimulants should not be discouraged, as psychostimulants possess one of the only signals of efficacy among well-studied medications for the treatment of ATSUD. Whether or not these efforts will result in the provision of effective management of ATSUD as does OAT for opioid use disorder is not known. However, given the burden of ATSUD for those who live with such disorders, their family and loved ones as well as society, the positive signal highlighted by our meta-analysis, even if it comes with challenges and potential concerns, merits further exploration and rigorous assessment. Heidar Sharafi: Conceptualization (equal); writing—original draft (equal); writing—review and editing (equal). Didier Jutras-Aswad: Conceptualization (equal); writing—original draft (equal); writing—review and editing (equal). Not applicable. D.J.A. receives study material from Cardiol Therapeutics for a clinical trial funded by the Quebec Ministry of Health and Social Services and holds a clinical scientist career award from Fonds de Recherche du Québec (FRQS).
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".