Antidepressant Withdrawal Syndromes: Listening to the Patient and Taking It Slow

As the article by Badre et al made clear, the issue of antidepressant withdrawal syndromes is undergoing renewed scrutiny by patients, psychiatrists, and other prescribing clinicians. In this article, we aim to put this issue into the broader context of risk-benefit assessment, provide updated findings on the likely frequency and severity of these syndromes, and offer guidance to clinicians on how best to recognize and manage problems arising from the discontinuation of antidepressant medications. Our recommendations are based on a targeted review of the literature and on our respective experiences as a psychopharmacology consultant (R.W.P.) and psychiatric clinician-researcher (J.F.H.). We also comment on certain aspects of the Badre et al article that we find problematic and offer some personal reflections. We recognize the disparate terminology prevalent in the published literature and will use the term antidepressant withdrawal/discontinuation symptoms (AWDS) for this discussion.

Background Issues

AWDS are nothing new to the field of psychiatry, although they are increasingly recognized as potentially serious and long-lasting in a minority of patients. Among the earliest reports of AWDS was that of Anderson and Kristiansen (1959), who noted withdrawal symptoms following discontinuation of the tricyclic antidepressant, imipramine.¹ One of the earliest (1998) reports to reach a wide US audience was that of Rosenbaum et al, who wrote that “abrupt interruption of antidepressant therapy for [5 to 8] days was associated with the emergence of new somatic and psychological symptoms in patients treated with paroxetine and to a lesser degree sertraline, with few symptoms seen with fluoxetine.”²

As Badre et al correctly note, discontinuation symptoms—often termed withdrawal symptoms—are complex and multiform, potentially involving neurological, systemic, and psychological phenomena. Although data are incomplete and sometimes contradictory, risk factors for AWDS appear to include, among others, the use of antidepressants with a short half-life (eg, paroxetine, venlafaxine); high doses; drugs with prominent anticholinergic effects and no active metabolites (eg, paroxetine); and rapid tapering (< 1-2 months) or sudden discontinuation of the drug.³ Although a long duration of exposure to an antidepressant is often listed as a risk factor, this has not been definitively proven, according to several meta-analyses.

The frequency and severity of AWDS remain a source of uncertainty and controversy, with widely divergent numbers found in the literature. A 2019 meta-analysis reported that more than half (56%) of individuals attempting to stop taking antidepressants experienced withdrawal effects, with nearly half of those reporting severe symptoms.⁴ This translates to approximately 25% of all individuals in the study who attempted withdrawal experiencing severe symptoms.⁴ However, these findings were likely inflated due to selection bias associated with the inclusion of online surveys. Henssler et al performed the first meta-analytic assessment of the incidence of antidepressant discontinuation symptoms and of placebo effects. Their study found that—considering nonspecific (placebo) effects—the incidence of antidepressant discontinuation symptoms was approximately 15%, affecting 1 in 6 to 7 patients who discontinue their medication.⁵ About 1 in 35 patients (roughly 3%) were found to have severe antidepressant discontinuation symptoms.⁵ Antidepressant agents differed substantially in the risk of inducing AWDS; within the selective serotonin reuptake inhibitor/selective serotonin-norepinephrine reuptake inhibitor group, discontinuation symptoms were most frequently observed and most severe with desvenlafaxine, venlafaxine, and paroxetine.

Critics of this study have argued, among other concerns, that the inclusion of studies with a relatively short duration (average of about 25 weeks) likely underestimated the frequency and severity of withdrawal effects.⁶ However, as indicated earlier, 3 meta-analyses did not find a statistically significant association between withdrawal symptoms and treatment duration, concluding that the current evidence was inconclusive. Moreover, the evidence regarding AWDS after long-term exposure remains limited and methodologically weak.⁷

It is noteworthy that approximately 17% of patients (about 1 in 6) report at least 1 discontinuation-like symptom after stopping a placebo.⁵ Indeed, as many as 44% of patients discontinuing a placebo will report discontinuation-like symptoms based on the Discontinuation Emergent Signs and Symptoms scale.⁸ Evidence suggests that these symptoms occur either by chance—independently of the treatment—or are the product of the nocebo effect⁹; this is the “mirror image” of the placebo effect, triggered by the expectation that the inert treatment the patient is receiving will have negative effects.⁹ Due to the impact of nonspecific and nocebo effects as well as the low specificity of our currently available diagnostic instruments, it appears that only about half of the reported antidepressant withdrawal symptoms are in fact attributable to the antidepressant itself.⁹

And although it is correct to say that antidepressants can induce homeostatic changes resulting in withdrawal symptoms during discontinuation—as can β-blockers and anticonvulsants—it is incorrect to link antidepressants with addiction, as some have claimed. (Badre et al did not make this assertion.) Antidepressant withdrawal does not produce the characteristic physiological responses seen in, for example, barbiturate, opiate, or alcohol withdrawal (eg, diaphoresis, tachycardia, myoclonus, seizures, and persistent drug craving).¹⁰ Furthermore, whereas antidepressant discontinuation can produce physiological and vegetative withdrawal symptoms, antidepressant use manifests none of the key features of genuine addiction (eg, drug craving, losing control of drug intake, spending excessive time getting and using the drug, neglecting personal responsibilities, and giving up social activities because of drug misuse). And, unlike with genuinely addictive drugs, true tolerance to antidepressants (ie, requiring higher and higher doses over time to achieve the same effect) has not been demonstrated.¹¹

There is also controversy regarding the usual duration of AWDS. Earlier descriptions (2006) held that AWDS usually lasted “about 2 weeks” and “generally do not persist beyond 3 weeks.”¹⁰ More recent reports make it clear that although “most cases are mild and last no more than 8 weeks…some cases can be severe, and symptoms can last for a year or more.”¹²

Finally, as Badre et al correctly observed, there is concern regarding the ability of clinicians to distinguish AWDS from relapse or recurrence of the underlying depressive disorder for which an antidepressant was prescribed (more on this point in the next section).

Comments on Badre et al article

Although we appreciate the cautionary statements from Badre and colleagues, we wish to raise some concerns about several claims in their article, which appear in quotes:

• “Antidepressant withdrawal reactions…are now understood to be potentially more common, complex, severe, and long-lasting than previously acknowledged in clinical guidelines.…”

Response: We generally agree, but we would caution that there are very few, if any, randomized, controlled studies using extended antidepressant tapering periods (ie, over 2 or more months). The current evidence suggests that AWDS are highly dependent on the specific antidepressant agent and that when considering all antidepressants used, severe AWDS will affect only a small subgroup of patients. In line with currently available evidence, our own experience suggests that for the vast majority of patients, gradual tapering of antidepressant agents over 2 to 4 months does not lead to prolonged or severe withdrawal symptoms. That said, patients taking high doses of short half-life agents such as paroxetine or venlafaxine may require significantly longer tapering periods.

• “A significant clinical concept is persistent [postwithdrawal] disorders (PPWD). While some symptoms are acute (lasting < 6 weeks), a subset of patients experiences symptoms, including severe anxiety and depression, that last for months or even years after cessation.”

Response: This claim is based mainly on subjective reports and patient-generated narratives. We do not mean to minimize the intense distress often experienced by individuals who report such persistent symptoms after cessation of antidepressants, particularly persistent sexual dysfunction.¹³ However, the actual etiology, frequency, and duration of PPWD are not known. Moreover, the role of psychosocial factors, rather than true biological withdrawal, has not been ruled out as a contributing factor in some PPWD cases. Even those clinicians highlighting the reality of PPWD acknowledge that, “only large prospective cohort studies with systematic assessment of symptoms will be able to answer these fundamental questions.”¹⁴ Although hyperbolic tapering (ie, incorporating very small subtherapeutic doses into the final stages of tapering) as described by Badre et al may be necessary for difficult cases, many patients, in our experience, can be successfully tapered off their antidepressant via gradual, individualized, proportional dose-reduction strategies (eg, 40 mg to 35 mg to 30 mg to 25 mg to 20 mg to 15 mg over 2-4 months). This approach is guided primarily by the patient’s comfort level and the passage of time. We are not aware of any controlled studies comparing hyperbolic tapering to such a patient-centered approach. To be clear, we wholeheartedly agree with Badre et al that clinicians need to “go slow and be patient,” and that—for many patients—a “cut and hold” approach “is a common and effective strategy.”

• Regarding “…interpreting an expected physiological withdrawal syndrome as an illness recurrence. This common diagnostic error results in the reinstatement of medication, trapping patients in a cycle of long-term use based on a misunderstanding of their symptoms….When a patient stops an antidepressant and experiences depression 2 months later, the reflexive diagnosis is ‘relapse.’”

Response: We are not aware of any published studies demonstrating that such a putative diagnostic error is common in psychiatric practice or that psychiatrists react in a reflexive manner to the appearance of discontinuation symptoms. On the contrary, in our experience, psychiatrists have long recognized important differences in the manifestation of relapse, recurrence, and physiological withdrawal (Table).¹⁵

Indeed, in a personal communication to the author (R.W.P.) on December 5, 2025, mood disorder expert Roger S. McIntyre, MD, FRCPC, wrote, “A relapse or recurrence is defined by symptom intensification on a symptom measurement tool like the MADRS [Montgomery-Åsberg Depression Rating Scale] or the HAMD-17 [17-item Hamilton Depression Rating Scale], and/or the need for hospitalization, and/or the emergence of safety concerns like suicidality. This is quite different from the somatic distress that a relatively small percentage of people would experience after treatment discontinuation. The notion that the discontinuation phenomenology is being interpreted as a relapse—stacking the cards in favor of the antidepressant—rests on the assumption that the investigators are unable to distinguish the phenomenon of discontinuation from relapse criteria. That seems a bit of a stretch, as I am not aware of any evidence that the antidepressant discontinuation syndrome is itself consistently correlated with symptom intensification on a clinician-reported outcome measure of depression.”

Furthermore, we regard the phrase, “trapping patients in a cycle of long-term use” as inappropriate. In our experience, with proper informed consent and judicious discussion of risks and benefits, most patients do not feel trapped by long-term use of antidepressants. On the contrary—and often, despite adverse effects—many patients feel appreciative for their improved quality of life.¹⁶

• “Do Not Reflexively Diagnose Recurrence: When a patient who has reduced or stopped a dose presents with new or worsening symptoms, withdrawal should be the primary differential diagnosis.”

Response: This advice requires careful qualification. If the “new or worsening symptoms” occur within a month or so of reducing or stopping the antidepressant, withdrawal is certainly a plausible consideration. But if the symptoms first appear 2 to 6 months after stopping, relapse of the original depression is much more likely. (After 6 months, recurrence is likely—see Table). We know of no recognized physiological mechanism that would produce a genuine withdrawal syndrome de novo, with onset after (roughly) the first month of drug discontinuation. One possible exception is the delayed onset of mild, self-limited AWDS, emerging approximately 6 weeks after the abrupt discontinuation of the very long half-life agent fluoxetine.¹⁷

• “Plan the Exit Strategy: Discuss the process for eventually stopping [the antidepressant] at the first appointment, as is commonly recommended for benzodiazepines.”

Response: Although eventually stopping antidepressant treatment may be appropriate after remission (and the treatment continuation phase) of a first major depressive episode, this strategy may not be in the best interest of patients with recurrent (3 or more) episodes of severe, incapacitating major depression (see Footnote). For many patients, clinically severe depression is a recurring or chronic and severely disabling disease. The World Health Organization has clearly stated, “Depression is the leading cause of ill health and disability worldwide.”¹⁸ Furthermore, both the American Psychiatric Association and the UK's National Institute for Health and Care Excellence recommend maintenance antidepressant treatment for 2 years or longer, sometimes indefinitely, for individuals with multiple prior episodes or severe episodes.^19,20

Of course, the possibility of eventually discontinuing antidepressant treatment can always be discussed with the patient without presenting it during the first appointment as an expected course of action. The informed consent process must also clarify that time-limited pharmacological treatment is not a cure for depression, which usually merits some form of talk therapy.

Finally, conflating the issue of eventually stopping antidepressant treatment (“exit strategy”) with benzodiazepine discontinuation represents a pharmacological category mistake. These are 2 entirely different classes of agents with entirely different pharmacodynamic properties and very different patterns of withdrawal effects; for example, as noted in an article on the Clear Behavioral Health website, “…Quitting benzos cold turkey can cause convulsions, seizures, psychosis, paranoia, mood swings, mania, and death”—outcomes rarely if ever seen with sudden discontinuation of antidepressant treatment.²¹

Concluding Thoughts

There is much we still do not know about the AWDS phenomenon. Unfortunately, many studies of AWDS did not involve structured assessments using validated tools for the detection of withdrawal symptoms.²² On the one hand, survey-based studies may be biased in favor of high rates and severity of AWDS, as respondents who have had bad experiences with discontinuation are more likely to report symptoms than respondents selected at random. On the other hand, studies based mainly on very short periods of exposure to antidepressants may understate the frequency and severity of AWDS. This issue is far from settled.⁷

To be clear, we want to acknowledge that whatever the usual frequency and duration of AWDS, some patients may experience severe and prolonged withdrawal symptoms that greatly interfere with activities of daily living, vocational function, and quality of life. These facts were not sufficiently emphasized in early clinical guidelines. Nevertheless, in our experience, most problems with antidepressant discontinuation can be averted by slow, careful, individualized tapering, often over several months, and—all other things being equal—by avoiding short half-life agents (eg, paroxetine and venlafaxine) in the first place. Hyperbolic tapering may be necessary in some cases, as discussed by Badre et al. And although we favor conservative use of antidepressants—generally limited to moderate to severe cases of major depressive disorder—we also believe that these medications improve the quality of life for many patients with severe, recurrent depression, who may benefit from long-term (> 2 years) use. As always, informed consent as an ongoing process remains the cornerstone of responsible medical care.

Dr Henssler is a psychiatrist and psychotherapist. He is a senior physician, researcher, and lecturer as well as the head of the Evidence-Based Mental Health Research Group at Charité University Hospital in Berlin, Germany.

Dr Pies is professor emeritus of psychiatry and a lecturer on bioethics and humanities at SUNY Upstate Medical University in Syracuse, New York; a clinical professor of psychiatry at Tufts University School of Medicine in Boston, Massachusetts; and editor in chief emeritus of Psychiatric Times (2007-2010). Dr Pies is the author of several books, including several textbooks on psychopharmacology. A collection of his works can be found on Amazon.

Acknowledgments: The authors wish to thank Roger S. McIntyre, MD, FRCPC, for his helpful comments on some aspects of this article. However, the views expressed here are solely those of the authors.

Footnote: The authors are well aware of the methodological shortcomings of antidepressant relapse prevention trials, including the limitations of enriched design studies. The latter select patients who have already shown a positive response (eg, to an open-label treatment phase) before randomly assigning them in a double-blind phase, often for a randomized withdrawal trial to test long-term maintenance, creating a study population “enriched” for responders. We acknowledge that in some cases, this type of study may lead to withdrawal symptoms and overestimate drug efficacy.²³ Nonetheless, it is a logical error to infer from such methodological limitations that, therefore, no patients with severe, recurrent depression will benefit from long-term maintenance on an antidepressant. The shortcomings of enriched design studies are methodological criticisms of how efficacy is scientifically proven, not definitive proof that the medication itself is ineffective in real-world clinical practice.

References

1. Andersen H, Kristiansen ES. Tofranil-treatment of endogenous depressions. Acta Psychiatr Scand. 1959;34(4):387-397.

2. Rosenbaum JF, Fava M, Hoog SL, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry. 1998;44(2):77-87.

3. Pies RW, Osser DN. Sorting out the antidepressant “withdrawal” controversy. Psychiatric Times. March 11, 2019. https://www.psychiatrictimes.com/view/sorting-out-antidepressant-withdrawal-controversy

4. Davies J, Read J. A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: are guidelines evidence-based? Addict Behav. 2019;97:111-121.

5. Henssler J, Schmidt Y, Schmidt U, et al. Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis. Lancet Psychiatry. 2024;11(7):526-535.

6. Moncrieff J, Hobday H, Sørensen A, et al. Evidence on antidepressant withdrawal: an appraisal and reanalysis of a recent systematic review. Psychol Med. 2025;55:e191.

7. Baethge C, Bschor T, Henssler J. Double counting, double standards. Psychol Med. 2025;55:e329.

8. Stein DJ, Ahokas AA, de Bodinat C. Efficacy of agomelatine in generalized anxiety disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol. 2008;28(5):561-566.

9. Expectations contribute to symptoms following discontinuation of antidepressants. News release. Charité and University Hospital Cologne. June 6, 2024. Accessed January 5, 2025. https://www.charite.de/en/service/press_reports/artikel/detail/antidepressants_new_data_on_prevalence_of_discontinuation_symptoms

10. Shelton RC. The nature of the discontinuation syndrome associated with antidepressant drugs. J Clin Psychiatry. 2006;67(suppl 4):3-7.

11. Henssler J, Heinz A, Brandt L, Bschor T. Antidepressant withdrawal and rebound phenomena. Dtsch Arztebl Int. 2019;116(20):355-361.

12. Antidepressant discontinuation syndrome. Cleveland Clinic. Updated August 30, 2023. Accessed January 5, 2025. https://my.clevelandclinic.org/health/diseases/25218-antidepressant-discontinuation-syndrome

13. Healy D. Post-SSRI sexual dysfunction & other enduring sexual dysfunctions. Epidemiol Psychiatr Sci. 2019;29:e55.

14. Hengartner MP, Schulthess L, Sorensen A, Framer A. Protracted withdrawal syndrome after stopping antidepressants: a descriptive quantitative analysis of consumer narratives from a large internet forum. Ther Adv Psychopharmacol. 2020:10:2045125320980573.

15. Shelton RC. Steps following attainment of remission: discontinuation of antidepressant therapy. Prim Care Companion J Clin Psychiatry. 2001;3(4):168-174.

16. Pies RW. Antidepressants, the Hamilton Depression Rating Scale conundrum, and quality of life. J Clin Psychopharmacol. 2020;40(4):339-341.

17. Zajecka J, Fawcett J, Amsterdam J, et al. Safety of abrupt discontinuation of fluoxetine: a randomized, placebo-controlled study. J Clin Psychopharmacol. 1998;18(3):193-197.

18. “Depression: let’s talk” says WHO, as depression tops list of causes of ill health. News release. World Health Organization. March 30, 2017. Accessed January 5, 2025. https://www.who.int/news/item/30-03-2017--depression-let-s-talk-says-who-as-depression-tops-list-of-causes-of-ill-health

19. Practice Guideline for the Treatment of Patients With Major Depressive Disorder. 3rd ed. American Psychiatric Association; 2010. Accessed January 8, 2026. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf

20. Depression in adults: treatment and management. National Institute for Health and Care Excellence. June 29, 2022. Accessed January 5, 2025. https://www.nice.org.uk/guidance/ng222

21. The dangers of benzo detox and Xanax withdrawal. Clear Behavioral Health. January 2, 2023. Accessed January 5, 2025. https://clearbehavioralhealth.com/the-dangers-of-benzo-detox-and-withdrawal/

22. Psych News Special Report: antidepressant withdrawal with Dr. Bryan Shapiro. American Psychiatric Association. September 22, 2025. Accessed January 5, 2025. https://www.psychiatry.org/psychiatrists/education/podcasts/medical-mind/2025/psych-news-special-report-antidepressant-withdrawa

23. Ghaemi SN, Selker HP. Maintenance efficacy designs in psychiatry: randomized discontinuation trials — enriched but not better. J Clin Transl Sci. 2017;1(3):198-204.