Drug discontinuation effects are part of the pharmacology of a drug
Open accessAbstract
Most reviews of drug withdrawal effects focus on drugs of potential abuse such as opioids, benzodiazepines, etc. Abrupt discontinuation of many other drugs used in medicine cause withdrawal syndromes, some of which can be fatal. Discontinuation of a number of cardiovascular drugs can increase risk of cardiovascular events above that of people not taking these drugs. These include β-adrenergic receptor antagonists, aspirin, HMG-CoA reductase inhibitors (statins), and heparin. Rebound hypertension occurs after abrupt cessation of many antihypertensive drugs. The possibility of discontinuation syndromes has usually been neglected until adverse clinical events force them to be noticed. Attention to the possibility of drug discontinuation effects is an important part of drug safety evaluation.
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Dose reduction intervals are better guided by the time needed for neuroadaptations to resolve rather than drug elimination.
“Although the half-lives of these drugs (most less than 24 hours, with some exceptions including commonly prescribed drugs like diazepam and clonazepam) may suggest that dose reductions could be made every few days, dose reduction intervals are better guided by the time needed for neuroadaptations to resolve rather than drug elimination (Reidenberg, 2011).”
From Pharmacological principles for safe benzodiazepine and Z-drug dose reduction (2026) · cites this paper as Reidenberg, 2011
The Drug Discontinuation Syndromes and Withdrawal Syndromes sections say that biological adaptation can persist after a drug is eliminated, producing withdrawal effects. The Conclusion recommends tapering rather than abrupt discontinuation. The paper does not explicitly say that intervals between dose reductions should be set by the time needed for adaptations to resolve rather than by drug elimination. (LLM, conf=0.86)
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References 49 · Cited by 82
- Authors
- Reidenberg, M. M.
- Affiliations
- Weill Cornell Medicine (US)
- Corresponding author
- Reidenberg, Marcus M.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 339
- Issue
- 2
- Pages
- 324-328
- ISSN
- 0022-3565 (ISSN-L)
- PMC
- PMC3200000
- OpenAlex
- W2170880546
- Cited by
- 82
- References
- 49
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 6 · 2023: 6 · 2022: 11 · 2021: 9 · 2020: 6 · 2019: 7 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 2 · 2013: 6 · 2012: 2
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (RR024996)
- Agency for Healthcare Research and Quality (U18HS016075, 5U18-HS016075)
- National Center for Research Resources (UL1RR024996)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- drug withdrawal syndrome, rebound hypertension, beta-blockers, aspirin, statins, heparin, drug safety assessment, antihypertensive drugs
- MeSH terms
- Adrenergic beta-Antagonists, Antihypertensive Agents, Aspirin, Awards and Prizes, Cardiovascular Agents, Humans, Substance Withdrawal Syndrome, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Drug-Related Side Effects and Adverse Reactions
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