SynthesisCNS drugs2026
Tolerance and Tachyphylaxis to Medications for Attention-Deficit/Hyperactivity Disorder (ADHD): A Systematic Review of Empirical Studies.
Synthesis in CNS drugs, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
4 authors.
Funding
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Abstract
BACKGROUND AND
objectiveIndividuals with attention-deficit/hyperactivity disorder, their families and clinicians may report worsening symptoms despite compliant use of medication, suggesting potential tolerance, but evidence remains conflicting. Some studies have also suggested tachyphylaxis, or acute tolerance, though research is limited. We conducted the first systematic review of empirical studies focussing on tolerance/tachyphylaxis to attention-deficit/hyperactivity disorder medication to clarify their potential clinical relevance.
methodsAs registered on PROSPERO (CRD42024594759), we searched PubMed, OVID (including PsychInfo and MEDLINE) and Web of Knowledge up to 1 September, 2024, and assessed the risk of bias using National Institutes of Health quality assessment tools.
resultsThe identified 17 studies were either interventional or observational, and varied greatly in design and duration. Four investigated tachyphylaxis, nine tolerance to the subjective and behavioural effects, and four tolerance to cardiovascular effects. We found preliminary evidence of tachyphylaxis to the affective or behavioural effects of stimulants, as well as tolerance to the subjective effects of d-amphetamine, such as drug liking and excitation, in neurotypical volunteers in the short term. Conversely, there was little or no evidence for tolerance to the therapeutic or cardiovascular effects of attention-deficit/hyperactivity disorder medication in clinical settings in the longer term. Quality was rated as low in most studies because of small sample sizes and methodological limitations.
conclusionsOverall, these results do not support the hypothesis that tolerance commonly develops to the therapeutic effects of attention-deficit/hyperactivity disorder medication, although robustly designed longitudinal studies are needed to provide more conclusive evidence. Clinicians may consider other potential explanations for reduced therapeutic effects over time, including natural fluctuations of symptoms, limited compliance, life events and co-occurrent mental health conditions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.