BackgroundDespite recommendations, documentation of indication on prescriptions and inpatient medication orders is not routinely practised. There has been a recent systematic review of indication documentation for antimicrobials, but not for interventions relating to indication documentation for medication more broadly. Our aims were to 1) identify, describe and synthesise the literature relating to effectiveness of interventions aimed at improving indication documentation and/or indication-based prescribing in both primary and secondary healthcare; 2) synthesise participant perspectives to identify barriers and facilitators to these interventions; and 3) make recommendations for both practice and research.MethodsA systematic literature search was conducted using Medline, Embase and CINAHL using two search concepts: electronic prescribing systems, and indication documentation and/or indication-based prescribing. Qualitative, quantitative and mixed-methods studies were included; outcome measures and results were extracted to produce a narrative synthesis. Quality appraisal by two independent reviewers was undertaken using the Mixed Methods Appraisal Tool.ResultsWe identified 21 studies evaluating interventions to aid indication documentation. Indication documentation was either via free-text, selection from a list, or by use of pre-defined indication-based order sentences for individual medications. For a number of outcomes, there was a mostly positive impact, including appropriateness of the medication order (6 of 8 studies), rates of prescribing error (2/2) and some less commonly reported clinical (2/4) and workflow-related outcomes (2/3). There was a less favourable impact on accuracy of indication documentation and rates of medication use, highlighting some unintended consequences that may occur when implementing new interventions. Participant insights from prescribers and other healthcare professionals complemented quantitative study results, highlighting both facilitators and barriers to indication documentation and the associated interventions. For example, barriers included long drop-down lists and the need to use workarounds to navigate approval systems due to time or knowledge constraints. Facilitating factors included the perceived benefits of indication documentation on communication among the healthcare team and with the patient.ConclusionIndication documentation has the potential to improve appropriate prescribing and reduce prescribing errors. However, further benefits to the prescriber, multidisciplinary team and patient may only be realised by developing methods of indication documentation that integrate more efficiently with prescriber workflows.PROSPERO registration numberCRD42021278495.