The DOI matches its Crossref record; 100 of the 100 references it cites were found in a registry or an index.
Antidepressant Discontinuation Syndromes: Clinical Relevance, Prevention and Management
Abstract
Discontinuation symptoms are recognised with tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs) and miscellaneous antidepressants. A wide variety of symptoms have been described, differing somewhat between antidepressant classes, and several symptom clusters or discontinuation syndromes appear to exist. A common feature is onset within a few days of stopping the antidepressant or, less commonly, reducing the dosage. Discontinuation syndromes are clinically relevant as they are common, can cause significant morbidity, can be misdiagnosed leading to inappropriate treatment and can adversely effect future antidepressant compliance. Preventative strategies include tapering antidepressants prior to stoppage and educating patients and healthcare professionals to ensure that antidepressants are taken consistently and not stopped abruptly. Most reactions are mild and short-lived and require no treatment other than patient reassurance. Severe cases can be treated symptomatically or the antidepressant can be reinstated before being gradually withdrawn. Reinstatement usually leads to symptom resolution within 24 hours. Some individuals require very conservative tapering schedules to prevent the re-emergence of symptoms. With SSRIs and venlafaxine another strategy to consider is switching to fluoxetine, which may suppress the discontinuation symptoms, but which has little tendency to cause such symptoms itself. Neonatal discontinuation symptoms can follow maternal use of antidepressants during pregnancy and possibly breast feeding. The patient and doctor must take this into consideration when making prescribing decisions. Discontinuation symptoms have received little systematic study with the result that most of the recommendations made here are based on anecdotal data or expert opinion. Research is needed to provide a firm evidence base for future recommendations.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In addition, it has been suggested that gradual discontinuation can reduce both rebound insomnia [84, 85] and rebound anxiety [1].”
From Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications (2020) · cites this paper as [84]
In the citing paper
“It is now suspected that antidepressant withdrawal syndrome is more common and severe than earlier presumed, affecting roughly 30–50% of those who attempt to stop their treatment.12,13,23,24”
From Protracted withdrawal syndrome after stopping antidepressants: a descriptive quantitative analysis of consumer narratives from a large internet forum (2020) · cites this paper as [24]
In the citing paper
“With new-generation antidepressants, it has been widely observed that risk of withdrawal emerges after the drugs have been taken for 1 to 2 months.24,39”
From Protracted withdrawal syndrome after stopping antidepressants: a descriptive quantitative analysis of consumer narratives from a large internet forum (2020) · cites this paper as [24]
In the citing paper
“We now have increasing evidence for postwithdrawal disorders with SSRI long-term use [6,15,16,26,37] .”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [15]
In the citing paper
“Persistent postwithdrawal disorders have been described with different classes of CNS drugs (e.g.protracted insomnia for alcohol and benzodiazepine withdrawal [10,36] and major depression/dysphoria for cocaine and amphetamine withdrawal [10,23] ), and even more so with specific drugs (e.g.quetiapine and paroxetine) within a drug class [6,15,16,33] .”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [15]
In the citing paper
“Data from controlled trials [15,20,29] , case reports [16] , and online patient reports [26] show that paroxetine is most likely to be associated with new withdrawal symptoms, and fluoxetine the least.”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [15]
In the citing paper
“Rebound anxiety [2,14] and rebound panic [15] were then reported with abrupt benzodiazepine discontinuation [9] .”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [15]
In the citing paper
“According to most studies [1,15,16,20,29] , even with gradual tapering, withdrawal symptoms still occur.”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [15]
In the citing paper
“They may resemble rebound symptoms being more severe than the original symptoms, but these disorders persist at least 6 weeks in contrast to rebound symptoms and [6,15,16,26,37] .”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [15]
In the citing paper
“Given the evidence for the high risk of disabling withdrawal with paroxetine”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [15]
In the citing paper
“thought to be related to noradrenergic and cholinergic supersensitivity [15,35]”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [15]
In the citing paper
“Persistent postwithdrawal panic disorder [15,38] has been shown to occur following withdrawal of paroxetine, and paroxetine has also been associated with other postwithdrawal disorders [6,15,16] .”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [15]
Citations
Cites
Birth Outcomes in Pregnant Women Taking Fluoxetine
Chambers, C., Johnson, K. A., Dick, L. M., Felix, R. J., & Jones, K. L. (1996) · New England Journal of Medicine · doi:10.1056/nejm199610033351402 · Cited by 735
Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial
Rosenbaum, J. F., Fava, M., Hoog, S. L., Ascroft, R. C., & Krebs, W. B. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00126-7 · Cited by 574
Priest, R. G., Vize, C., Roberts, A., Roberts, M., & Tylee, A. (1996) · BMJ · doi:10.1136/bmj.313.7061.858 · Cited by 385
Serotonin Reuptake Inhibitor Withdrawal
Coupland, N. J., Bell, C. J., & Potokar, J. P. (1996) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-199610000-00003 · Cited by 303
(1993) · American Journal of Psychiatry · doi:10.1176/ajp.150.10.1485 · Cited by 263
Paroxetine in the Treatment of Panic Disorder a Randomised, Double-Blind, Placebo-Controlled Study
Oehrberg, S., Christiansen, P. E., Behnke, K., Borup, A. L., Severin, B., Soegaard, J., Calberg, H., Judge, R., Ohrstrom, J. K., & Manniche, P. M. (1995) · British Journal of Psychiatry · doi:10.1192/bjp.167.3.374 · Cited by 261
Pharmacologic Treatment of Depression During Pregnancy
Wisner, K. L. (1999) · JAMA · doi:10.1001/jama.282.13.1264 · Cited by 250
Emergence of Adverse Events Following Discontinuation of Treatment With Extended-Release Venlafaxine
D, M. F. M., Mulroy, R., Alpert, J. E., Nierenberg, A. A., & Rosenbaum, J. F. (1997) · American Journal of Psychiatry · doi:10.1176/ajp.154.12.1760 · Cited by 198
Withdrawal syndromes associated with antipsychotic drugs
Gárdos, G., Jo, C., & Tarsy, D. (1978) · American Journal of Psychiatry · doi:10.1176/ajp.135.11.1321 · Cited by 192
Michelson, D., Fava, M., Amsterdam, J., Apter, J., Londborg, P., Tamura, R., & Tepner, R. G. (2000) · British Journal of Psychiatry · doi:10.1192/bjp.176.4.363 · Cited by 181
Research works printed but not linked: 25
- Ceccherini-Nelli, 1993, Am J Psychiatry, 150, 165
- Diamond, 1989, Psychopharmacol Bull, 25, 209
- Law, 1981, Am J Psychiatry, 118, 647
- Geller, 1987, J Clin Psychopharmacol, 7, 252
- Liskin, 1984, J Clin Psychopharmacol, 5, 46
- Halle, 1993, J Psychiatry Neurosci, 18, 49
- Einbinder, 1995, Am J Psychiatry, 152, 1253
- Black, 1993, J Clin Psychiatry, 54, 146
- Louie, 1996, Am J Psychiatry, 153, 1652
- Schatzberg, 1997, J Clin Psychiatry, 58, 5
- DArcy, 1993, Int Pharm J, 7, 140
- Stoukides, 1991, Am J Psychiatry, 148, 1263
- Kasantikul, 1995, J Med Assoc Thai, 78, 53
- Parker, 1998, Aust N Z J Psychiatry, 32, 292
- Agelink, 1997, Am J Psychiatry, 154, 1473
- Wolfe, 1997, Am Fam Physician, 56, 452
- 1996, Aust Adverse Drug Reactions Bull Nov, 15, 3
- Frost, 1995, Am J Psychiatry, 152, 810
- Stem, 1980, J Clin Psychiat, 41, 66
- Mander, 1998, Lancet, 339, 15
- Rosenblatt, 1996, Curr Affect Illness, 15, 8
- Phillips, 1995, Am J Psychiatry, 152, 645
- Eggermont, 1972, Acta Paediatr Belg, 26, 197
- 1997, Austral Adverse Drug Reactions Bull Nov, 16, 14
- Dahl, 1997, Br J Psychiatry, 171, 91
Cited by
Sorted by citations
Adverse Effects of Atypical Antipsychotics
Haddad, P. M., & Sharma, S. G. (2007) · CNS Drugs · doi:10.2165/00023210-200721110-00004 · Cited by 468
Self-citationDavies, J., & Read, J. (2019) · Addictive Behaviors · doi:10.1016/j.addbeh.2018.08.027 · Cited by 387
Walter, H. J., Bukstein, O. G., Abright, A. R., Keable, H., Ramtekkar, U., Ripperger-Suhler, J., & Rockhill, C. (2020) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2020.05.005 · Cited by 335
Efficacy and Tolerability of Desvenlafaxine Succinate Treatment for Menopausal Vasomotor Symptoms
Speroff, L., Gass, M. L. S., Constantine, G. D., & Olivier, S. (2008) · Obstetrics and Gynecology · doi:10.1097/01.aog.0000297371.89129.b3 · Cited by 333
Maternal Selective Serotonin Reuptake Inhibitor Use During Pregnancy and Newborn Neurobehavior
Zeskind, P. S., & Stephens, L. E. (2004) · PEDIATRICS · doi:10.1542/peds.113.2.368 · Cited by 279
Metadata
- Authors
- Haddad, P. M.
- Corresponding author
- Haddad, Peter M.
- ORCID
- Haddad, Peter M.
- Venue
- Drug Safety
- Published
- 2001
- Volume
- 24
- Issue
- 3
- Pages
- 183-197
- ISSN
- 0114-5916 (ISSN-L)
- OpenAlex
- W1593032895
- Cited by
- 214
- References
- 99
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 7 · 2023: 5 · 2022: 10 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 9 · 2017: 8 · 2016: 7 · 2015: 10 · 2014: 7 · 2013: 24 · 2012: 4
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Safety (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- antidepressant discontinuation syndrome, antidepressant withdrawal symptoms, selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, antidepressant tapering, fluoxetine, venlafaxine, breastfeeding
- MeSH terms
- Animals, Antidepressive Agents, Antidepressive Agents, Tricyclic, Humans, Monoamine Oxidase Inhibitors, Patient Compliance, Substance Withdrawal Syndrome, Syndrome, Selective Serotonin Reuptake Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review