RESIDENT: Cardiovascular Risk and Prognostic Factors in Psychostimulant Therapy in the Treatment of ADHD, A Systematic Review

Abstract

Introduction: The use of psychostimulant medications, including methylphenidates and amphetamines, is the cornerstone of attention-deficit/hyperactivity disorder (ADHD) treatment (1). While their efficacy in reducing ADHD symptoms is well-demonstrated, concerns about their cardiovascular safety, particularly during long-term use, remain a topic of significant clinical interest (2,3). For instance, psychostimulants are known to increase heart rate by 3–10 beats/min or blood pressure by 3–8 mm Hg (4). However, evidence suggests that while short-term cardiovascular effects are relatively mild and reversible upon discontinuation, the long-term implications are less clear (5). While various systematic reviews exist implicating psychostimulants with cardiovascular diseases, few summarize predictors associated with such adverse outcomes. Aim: In individuals treated with psychostimulants for ADHD, are there any risk or prognostic factors which predict mortality or incidence of cardiovascular disease? Methods: MEDLINE, EMBASE, and PubMed will be searched for studies investigating any risk factors and prognostic factor (i.e. sex, age, comorbidity). Studies will be included if they met the following criteria: 1) observational or comparative study, 2) investigate psychostimulant use in patients with ADHD, 3) measure mortality and/or incidence of cardiovascular disease (e.g., acute myocardial infraction, out-of-hospital cardiac arrest), and 4) stratify outcomes based on baseline characteristics (e.g., male v. female). Quality and bias will be assessed using the Newcastle-Ottawa Scale for nonrandomized studies, and Risk-of-Bias 2 (RoB-2) tool for randomized studies.

Learning Objectives

1. Understand the cardiovascular effects of psychostimulant medications; 
2. Evaluate risk and prognostic factors between psychostimulant therapy and cardiovascular outcomes; and
3. Consider the long-term implications of psychostimulant therapy in ADHD treatment.

Literature References

Canadian ADHD Practice Guidelines [Internet]. Toronto; 2020. Available from: www.caddra.ca

2. Holt A, Strange JE, Rasmussen PV, Nouhravesh N, Nielsen SK, Sindet-Pedersen C, et al. Long-Term Cardiovascular Risk Associated With Treatment of Attention-Deficit/Hyperactivity Disorder in Adults. J Am Coll Cardiol [Internet]. 2024 May [cited 2025 Jan 15];83(19):1870–82. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0735109724066075

3. Zhang L, Li L, Andell P, Garcia-Argibay M, Quinn PD, D’Onofrio BM, et al. Attention-Deficit/Hyperactivity Disorder Medications and Long-Term Risk of Cardiovascular Diseases. JAMA Psychiatry. 2024 Feb 7;81(2):178–87.

4. Fay TB, Alpert MA. Cardiovascular Effects of Drugs Used to Treat Attention-Deficit/Hyperactivity Disorder Part 2. Cardiol Rev [Internet]. 2019 Jul 1;27(4):173–8. Available from: https://journals.lww.com/00045415-201907000-00002

5. Martinez-Raga J, Knecht C, Szerman N, Martinez MI. Risk of Serious Cardiovascular Problems with Medications for Attention-Deficit Hyperactivity Disorder. CNS Drugs [Internet]. 2013 Jan 17;27(1):15–30. Available from: http://link.springer.com/10.1007/s40263-012-0019-9