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- Page navigation anchor for RE: Critical Examination of Incorporating prescription psychostimulants into the continuum of care for people with stimulant use disorder in CanadaRE: Critical Examination of Incorporating prescription psychostimulants into the continuum of care for people with stimulant use disorder in Canada
We thank Morin et al for their response. We agree that implementation studies are needed to continue to build real world protocols for the provision of prescription psychostimulants (PPs) to people with stimulant use disorder.
Morin et al. reference a study by Tatangelo et al., which makes an important contribution to the literature on PPs and provides data from a real-world setting (1). The study matched cases and controls on age, sex, and index date of prescribed stimulant. When making direct comparisons, it is important that selection of controls considers characteristics that might be associated with the outcome of interest (2). It is reasonable to assume that baseline cocaine use will be associated with the outcome of urine positive for cocaine, and thus is unclear why attempts have not been made to balance baseline cocaine use indicators between cases and controls (31% vs 20% of urine tests positive for cocaine at baseline).
It does not appear that the study design or presented results allow for “increases” in cocaine consumption to be directly compared between cases and controls as Morin et al reference. The only model that includes both cases and controls, and baseline and follow-up data found “no statistical difference in cocaine positive urine tests before and after prescription”. The observed “statistically significant increase in cocaine-positive urine tests” was found in analyses conducted with follow-up data only, where pre-prescription differe...
Show MoreCompeting Interests: Scott MacDonald reports serving as the treasurer (unpaid) for the Safe Community Save Lives Project, a nonprofit organization. Heather Palis has received a Canadian Institutes for Health Research award, a University of British Columbia Institute of Mental Health Marshall Fellowship and a Michael Smith Health Research British Columbia Trainee Award.References
- Tatangelo M, Tahsin F, Morin KA, Marsh DC. Association of prescribed oral stimulants on cocaine use among patients enrolled in opioid agonist treatment: A retrospective longitudinal cohort study. Front Psychiatry. 2022;13:107469
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- Tardelli VS, Bisaga A, Arcadepani FB, Gerra G, Levin FR, Fidalgo TM. Prescription psychostimulants for the treatment of stimulant use disorder: a systematic review and meta-analysis. Psychopharmacology (Berl). 237. Germany2020. p. 2233-55.
- Kiluk BD, Fitzmaurice GM, Strain EC, Weiss RD. What defines a clinically meaningful outcome in the treatment of substance use disorders: reductions in direct consequences of drug use or improvement in overall functioning? Addiction. 2019;114(1):9-15.
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- Page navigation anchor for RE: Incorporating prescription psychostimulants into the continuum of care for people with stimulant use disorder in CanadaRE: Incorporating prescription psychostimulants into the continuum of care for people with stimulant use disorder in Canada
We thank Elefante et al for their response. We acknowledge the point made regarding the distinction between studies on cocaine (CUD) vs. methamphetamine use disorder (MUD). The lack of conclusions regarding effectiveness of PPs for MUD is driven primarily by the small number of studies on prescribed psychostimulants (PPs) for MUD at the time of the review (1). Evidence is growing, for example, a population-level Swedish nationwide cohort recently found that lisdexamphetamine was associated decreased risk of hospitalization and all-cause mortality for people with MUD (2).
It is important to note that distinguishing between CUD and MUD might be challenging in practice, where people may or may not fit the clinical diagnosis for one or both given changing patterns of stimulant use based on preference, cost, and availability (3). Furthermore, PP preferences may not map directly onto patterns of unregulated stimulant use, suggesting that the suitability of PPs to particular patients may be more complex than considering current CUD or MUD diagnosis (4).
Regarding adverse events (AEs), we have not characterised PPs as "not associated with AEs”, but note, as stated directly in the cited review that PPs have not been “associated with serious adverse events (SAEs)” (5). Furthermore, recent reviews have justified exclusion of safety data because prior reviews found “no medication and placebo difference in dropouts due to any AEs, cardiovascular events, or SAEs”(1)....
Show MoreCompeting Interests: Scott MacDonald reports serving as the treasurer (unpaid) for the Safe Community Save Lives Project, a nonprofit organization. Heather Palis has received a Canadian Institutes for Health Research award, a University of British Columbia Institute of Mental Health Marshall Fellowship and a Michael Smith Health Research British Columbia Trainee Award.References
- Tardelli VS, Bisaga A, Arcadepani FB, Gerra G, Levin FR, Fidalgo TM. Prescription psychostimulants for the treatment of stimulant use disorder: a systematic review and meta-analysis. Psychopharmacology (Berl). 237. Germany2020. p. 2233-55.
- Heikkinen M, Taipale H, Tanskanen A, Mittendorfer-Rutz E, Lähteenvuo M, Tiihonen J. Association of Pharmacological Treatments and Hospitalization and Death in Individuals With Amphetamine Use Disorders in a Swedish Nationwide Cohort of 13 965 Patients. JA
- Papamihali K, Collins D, Karamouzian M, Purssell R, Graham B, Buxton J. Crystal methamphetamine use in British Columbia, Canada: A cross-sectional study of people who access harm reduction services. PLoS One. 2021;16(5):e0252090.
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- Page navigation anchor for RE: The Need for Objective Evaluation Before Incorporating Prescription Stimulants into the Continuum of Care for Stimulant Use Disorders in CanadaRE: The Need for Objective Evaluation Before Incorporating Prescription Stimulants into the Continuum of Care for Stimulant Use Disorders in Canada
We thank Bahji et al for their comment and provide our response below.
The authors note that Tardelli et al. concluded evidence to support prescription psychostimulants (PPs) “is lacking”. We find this statement to be misleading, given Tardelli et al’s conclusions “PPs, particularly prescription amphetamines given in robust doses, have a clinically significant beneficial effect to promote abstinence in the treatment of individuals with PSUD, specifically the population with cocaine use disorder” (1).
While the evidence to support PPs has not reached the same level as evidence supporting medications for other substance use disorders (SUDs), such as opioid agonist treatment (OAT) for opioid use disorder (OUD), the level of evidence available for OAT does not need to represent the benchmark for action on PP implementation.
Despite a plethora of evidence from clinical trials to support OAT, logistical and political barriers have continued to limit OAT access in Canada (2). Furthermore, the lack of applicability of clinical trial data to real world settings is often used to discount or limit implementation of medications for OAT (e.g. injectable OAT), and there is no reason to expect this same barrier will not apply to PP implementation efforts. Prescribers and patients have the expertise to jointly monitor medication effects and discontinue PPs if the risks are deemed to outweigh the benefits.
Regarding the risk of psychosis for people using meth...
Show MoreCompeting Interests: Scott MacDonald reports serving as the treasurer (unpaid) for the Safe Community Save Lives Project, a nonprofit organization. Heather Palis has received a Canadian Institutes for Health Research award, a University of British Columbia Institute of Mental Health Marshall Fellowship and a Michael Smith Health Research British Columbia Trainee Award.References
- Tardelli VS, Bisaga A, Arcadepani FB, Gerra G, Levin FR, Fidalgo TM. Prescription psychostimulants for the treatment of stimulant use disorder: a systematic review and meta-analysis. Psychopharmacology (Berl). 237. Germany2020. p. 2233-55.
- Pijl EM, Alraja A, Duff E, Cooke C, Dash S, Nayak N, et al. Barriers and facilitators to opioid agonist therapy in rural and remote communities in Canada: an integrative review. Subst Abuse Treat Prev Policy. 2022;17(1):62.
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- Stowe MJ, Calvey T, Scheibein F, Arya S, Saad NA, Shirasaka T, et al. Access to Healthcare and Harm Reduction Services During the COVID-19 Pandemic for People Who Use Drugs. J Addict Med. 2020;14(6):e287-e9.
- Page navigation anchor for RE: The Need for Objective Evaluation Before Incorporating Prescription Stimulants into the Continuum of Care for Stimulant Use Disorders in CanadaRE: The Need for Objective Evaluation Before Incorporating Prescription Stimulants into the Continuum of Care for Stimulant Use Disorders in Canada
Palis and MacDonald advocate for expanded utilization of prescribed psychostimulants as a treatment option within the care continuum for individuals with stimulant use disorders. While addressing the drug overdose crisis is imperative, the evidence supporting their proposal is limited, and their argument does not adequately address the potential risks.
Unlike substitution therapies for opioid use disorders, the effectiveness of prescribed psychostimulants for stimulant use disorders is uncertain. Most reviews and meta-analyses, including Tardelli et al.'s (2020) study, concluded that evidence supporting pharmacological interventions for these disorders is lacking and the benefits of prescribed stimulants in treating stimulant use disorders are not well-established (1,2).
Prescribed stimulants carry substantial risks, particularly for individuals using methamphetamines, where the risk of psychosis is high (3). The potential to reduce cravings for illicit stimulants remains inconclusive, contradicting neurobiological evidence (4).While prescribed stimulants might have a role for some select individuals with opioid and stimulant use disorders (without a history of psychosis), broader integration lacks evidence (5). Rigorous clinical trials assessing factors like adherence, substance use patterns, retention, cravings, and overdoses, are essential before widespread implementation. Comprehensive services should accompany prescribing, including housing,...
Show MoreCompeting Interests: Dr. Bahji’s work was supported by CIHR and Calgary Health Trust research grants. NIDA grant R21-DA-043949 and a CIHR Project Grant partly support Dr. George’s work. Dr. Danilewitz reports personal fees from the industry for advisory board/speaker fees/consultation/education grants from Eisai Ltd, Otsuka, Lundbeck, Winterlight Labs and the Ontario Brain Institute. He receives a stipend from the Canadian Psychiatric Association for administrative work and has received support for academic meeting attendance and presentations. Dr. George is a consultant to Frutarom, Aelis and Roche, Principal Editor of the journal Neuropsychopharmacology (NPP) and Chair of the Scientific Advisory Committee of the Canadian Centre for Substance Use and Addiction (CCSA). The remaining authors have no conflicts of interest to disclose.References
- Tardelli VS, Bisaga A, Arcadepani FB, Gerra G, Levin FR, Fidalgo TM. Prescription psychostimulants for the treatment of stimulant use disorder: a systematic review and meta-analysis. Psychopharmacology (Berl). 2020 Aug;237(8):2233–55.
- Ronsley C, Nolan S, Knight R, Hayashi K, Klimas J, Walley A, et al. Treatment of stimulant use disorder: A systematic review of reviews. PLOS ONE. 2020 Jun 18;15(6):e0234809.
- Crockford DN, Meunier S, Ghosh SM. Methamphetamine-Induced Psychosis: A Clinician’s Guide. Can J Addict. 2019 Dec;10(4):5.
- Siefried KJ, Acheson LS, Lintzeris N, Ezard N. Pharmacological Treatment of Methamphetamine/Amphetamine Dependence: A Systematic Review. CNS Drugs. 2020 Apr 1;34(4):337–65.
- Palis H, Xavier C, Dobrer S, Desai R, Sedgemore K olt, Scow M, et al. Concurrent use of opioids and stimulants and risk of fatal overdose: A cohort study. BMC Public Health. 2022 Nov 15;22(1):2084.
- Page navigation anchor for RE: Incorporating prescription psychostimulants into the continuum of care for people with stimulant use disorder in CanadaRE: Incorporating prescription psychostimulants into the continuum of care for people with stimulant use disorder in Canada
We thank Drs. Palis and MacDonald for their commentary on incorporating prescription psychostimulants (PPS) into the continuum of care for people with stimulant use disorder (StUD).1 While the evidence is still evolving, PPs remain promising agents for the pharmacologic treatment of StUD. However, this piece raises some issues that warrant further discussion, particularly concerning treating patients with significant psychiatric co-morbidities.
First, the authors cite a meta-analysis by Tardelli et al., which concludes PPs are a safe and effective treatment for StUD.4 However, it should be noted that StUD is a broad category, and the outcomes described in those with cocaine use disorder (CUD) and methamphetamine use disorder (MUD) differ. Although the potential for effectiveness in treating MUD is not excluded, the findings by Tardelli et al. primarily stem from studies focusing on CUD, and the generalizability of those results to MUD remains an important research question.
Second, the authors characterize PPs among people with StUD as "not associated with adverse events." However, based on available studies involving a general population, PPs appear to carry a risk of psychosis. A large registry study established a baseline risk for inducing psychosis of approximately 1 in 660.2 This risk may be small but significantly increases for those who have previously developed psychosis following a prescription. Cressman et al. found that reinitiating PP tr...
Show MoreCompeting Interests: None declared.References
- 1. 1. Palis H, MacDonald S. Incorporating prescription psychostimulants into the continuum of care for people with stimulant use disorder in Canada. CMAJ. 2023 Jul 17;195(27):E934-E935.
- 2. 2. Moran LV, Ongur D, Hsu J, Castro VM, Perlis RH, Schneeweiss S. Psychosis with Methylphenidate or Amphetamine in Patients with ADHD. N Engl J Med. 2019 Mar 21;380(12):1128-1138.
- 3. 3. Cressman AM, Macdonald EM, Huang A, Gomes T, Paterson MJ, Kurdyak PA, Mamdani MM, Juurlink DN; Canadian Drug Safety and Effectiveness Research Network. Prescription Stimulant Use and Hospitalization for Psychosis or Mania: A Population-Based Study.
- 4. 4. Tardelli VS, Bisaga A, Arcadepani FB, Gerra G, Levin FR, Fidalgo TM. Prescription psychostimulants for the treatment of stimulant use disorder: a systematic review and meta-analysis. Psychopharmacology (Berl). 2020 Aug;237(8):2233-2255.
- 5. 5. Starzer MSK, Nordentoft M, Hjorthøj C. Rates and Predictors of Conversion to Schizophrenia or Bipolar Disorder Following Substance-Induced Psychosis. Am J Psychiatry. 2018 Apr 1;175(4):343-350.
- Page navigation anchor for RE: Critical Examination of Incorporating prescription psychostimulants into the continuum of care for people with stimulant use disorder in CanadaRE: Critical Examination of Incorporating prescription psychostimulants into the continuum of care for people with stimulant use disorder in Canada
Palis and McDonald (1) present evidence from a systematic review claiming that prescription psychostimulants are not associated with serious adverse events in patents with stimulant use disorders. While this systematic review offers valuable insights, it may not be sufficient to draw conclusions about the safety and efficacy of prescribed psychostimulants in real-world settings. It is crucial to assess whether the results can be generalized to broader populations, particularly considering the complexities and variability in stimulant use disorder cases.
In our retrospective cohort study of 30,227 individuals (2) we observed that the use of oral stimulant prescriptions to treat cocaine use did not yield clinically significant benefits among Opioid Agonist Therapy (OAT) patients in a real-world setting. In fact, patients who received prescriptions for oral stimulants showed an increase in cocaine consumption both before and after treatment compared to patients without an oral stimulant prescription. It is possible that the lack of impact on cocaine use may be attributed to the potential need for higher doses of psychostimulants to yield more significant effects, which, in turn, increases the risk of adverse effects, including heart attacks and strokes.
We want to add two important factors missing from the discussion in Palis and MacDonald’s article to consider. First, the existing literature does not provide clear guidance on the appropriate duration of oral st...
Show MoreCompeting Interests: None declared.References
- Palis H, MacDonald S. Incorporating prescription psychostimulants into the continuum of care for people with stimulant use disorder in Canada. CMAJ 2023;195(27):E934-E5, doi: 10.1503/cmaj.230266
- Tardelli VS, Bisaga A, Arcadepani FB, et al. Prescription psychostimulants for the treatment of stimulant use disorder: a systematic review and meta-analysis. Psychopharmacology. 2020;237(8):2233-55, doi: 10.1007/s00213-020-05563-3
- Tatangelo M, Tahsin F, et al. Association of prescribed oral stimulants on cocaine use among patients enrolled in opioid agonist treatment: A retrospective longitudinal cohort study. Front Psychiatry. 2022;13:1074691, doi: 10.3389/fpsyt.2022.1074691