Comparative cardiovascular side effects of medications for attention-deficit/hyperactivity disorder in children, adolescents and adults: protocol for a systematic review and network meta-analysis

BMJ Open. 2022 Sep 26;12(9):e062748. doi: 10.1136/bmjopen-2022-062748.


Introduction: Pharmacotherapy is an important component of the multimodal treatment of attention-deficit/hyperactivity disorder (ADHD). Cardiovascular safety of medications for ADHD is of concern from a clinical and public health standpoint. We aim to conduct a network meta-analysis (NMA) comparing the effects of available medications for ADHD on blood pressure (diastolic and systolic), heart rate and ECG parameters over the short-term and long-term treatment.

Methods and analysis: Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines for protocols and NMAs will be followed. We will include parallel group or cross-over randomised controlled trials (RCTs) conducted in patients with a primary diagnosis of ADHD (no age limits). We will search an extensive number of electronic databases (including MEDLINE, CINAHL, CENTRAL, EMBASE, ERIC, PsycINFO, OpenGrey, Web of Science) from their inception and contact study authors/drug manufacturers to gather relevant unpublished information. No language restrictions will be applied. The main outcomes (assessed at 12 weeks, 26 weeks and 52 weeks) will be: (1) change in diastolic and systolic blood pressure (mm Hg); (2) change in heart rate, measured in beats/min; (3) change in any available ECG parameters. We will conduct random effects of NMA using standardised mean differences with 95% CIs for continuous outcomes and ORs with 95% CIs for dichotomous outcomes. We will use the Cochrane risk of bias tool-version 2 to assess the risk of bias of included RCTs and the Confidence In Network Meta-Analysis tool to evaluate the confidence of evidence contributing to each network estimate. Sensitivity analyses will investigate effects at different dose regimens.

Ethics and dissemination: No institutional review board approval will be necessary. The results of this systematic review and meta-analysis will be presented at national and international conferences and published in peer-reviewed journals.

Prospero registration number: CRD42021295352.

Keywords: Adult psychiatry; Child & adolescent psychiatry; PAEDIATRICS.

MeSH terms

  • Adolescent
  • Adult
  • Attention Deficit Disorder with Hyperactivity* / chemically induced
  • Attention Deficit Disorder with Hyperactivity* / drug therapy
  • Central Nervous System Stimulants* / adverse effects
  • Child
  • Cross-Over Studies
  • Humans
  • Meta-Analysis as Topic
  • Methylphenidate* / therapeutic use
  • Network Meta-Analysis
  • Systematic Reviews as Topic


  • Central Nervous System Stimulants
  • Methylphenidate