Exiting Antidepressants: A Needed Spotlight on Withdrawal

For decades, the conversation around antidepressants has focused on efficacy. Now, a growing body of evidence, much of it originating from patients, is forcing a reevaluation of what happens when it is time to stop. Antidepressant withdrawal reactions are now understood to be potentially more common, complex, severe, and long-lasting than previously acknowledged in clinical guidelines.

A central concern for clinicians has been the overlap between withdrawal symptoms and a recurrence of the original symptoms. This ambiguity has historically led to 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. Here are highlights of a recent review we wrote, a clinically focused overview of the evidence and best practices for safe deprescribing.¹

Antidepressant Discontinuation

Antidepressant use in the United States has tripled over 30 years.² It is not just more patients, but longer treatment. The median duration of use is now 5 years,³ with 60% of patients taking them for 2 or more years.⁴ The trend persists despite a weakening scientific foundation, including the 2023 systematic review reiterating the poor evidence for the "serotonin hypothesis" of depression.⁵ In parallel, the psychiatric view of depression shifted from that of a time-limited, episodic disorder to a "common, chronic, and disabling disease."⁶ This framing encouraged earlier and longer-term pharmacological treatment, creating a practice environment where initiating medication is routine, but clear, safe guidance on stopping has been lacking.

Discontinuation can trigger a complex, multisystemic syndrome. Clinicians must be familiar with its broad constellation of symptoms to avoid misdiagnosis, and keep in mind that patients may feel and report integrated psychobiological experiences, not discrete symptoms.

• Neurologic: Dizziness, vertigo, headache, "brain zaps" (electric shock sensations), tinnitus, paresthesia, brain fog or cognitive dysfunction, and akathisia.
• Systemic: Flu-like symptoms, nausea, chills, and gastrointestinal distress.
• Psychological: New-onset or worsening anxiety, irritability, emotional blunting, spontaneous tearfulness, sleep disturbance, fatigue, and concentration difficulties.

A significant clinical concept is persistent postwithdrawal disorders.⁷ While some symptoms are acute (lasting less than 6 weeks), a subset of patients experiences symptoms, including severe anxiety and depression, that last for months or even years after cessation. When a patient stops an antidepressant and experiences depression 2 months later, the reflexive diagnosis is "relapse." The alternative hypothesis, that the patient is experiencing a protracted iatrogenic withdrawal syndrome, is rarely considered.

The belief that long-term maintenance therapy with antidepressants is essential to prevent recurrence is built on a foundation of relapse prevention trials that are methodologically flawed. In these trials, patients who respond to an antidepressant are randomly assigned to either continue the drug or be switched to a placebo. The placebo group is frequently discontinued abruptly or tapered rapidly.⁸ Unsurprisingly, this group experiences high rates of distress, which the study then codes as "relapse." These studies do not prove that maintenance therapy prevents recurrence. They support that (1) abruptly stopping an antidepressant causes adverse symptoms, and (2) those adverse symptoms are routinely labeled as relapse. This flawed evidence has distorted our understanding of long-term use and created a significant barrier to safe deprescribing.

As patients felt their severe withdrawal experiences were dismissed, they formed online peer-support groups.⁹ These communities were among the first to identify the flaw in standard tapering and to develop a solution based on pharmacology.

It is hypothesized that the traditional, linear taper (eg, 20 mg → 15 mg → 10 mg → 5 mg → STOP) is suboptimal because the relationship between antidepressant dose and its effect on the serotonin transporter is not linear but hyperbolic. This means that a dose drop from 20 mg to 15 mg has a much smaller effect on brain receptor occupancy than one from 5 mg to 0. This could explain why so many patients "fail" their taper at the very end.

Hyperbolic tapering attempts to correct this. It involves making progressively smaller dose reductions as the total dose gets lower, aiming for a smoother, more linear reduction in biologic effect, not in milligrams.

• In practice: A taper might look like: 20 mg → 15 mg → 10 mg → 7.5 mg → 5 mg → 4 mg → 3 mg → 2.5 mg → 2 mg → 1.6 mg → 1.2 mg → 0.9 mg → 0.6 mg → 0.4 mg → 0.2 mg → 0.1 mg → STOP
• Implications: This method often requires doses not commonly manufactured by pharmaceutical companies, requiring patients to manage dose reductions themselves by crushing tablets, counting capsule beads, using compounding pharmacies, or resorting to liquid formulations.

This patient-derived method is now endorsed by the UK's Royal College of Psychiatrists,¹⁰ and detailed in the 2024 Maudsley Deprescribing Guidelines.¹¹

Given the state of the evidence, new clinical recommendations are needed. Clinicians should consider that severe, and sometimes protracted, withdrawal can occur. Here are common sense recommendations.

1. Before Initiating Treatment (Informed Consent)

• Explicitly warn about discontinuation: This is the core of informed consent. Patients must be told before starting that the drug can cause physical dependence and that stopping can be difficult and cause severe, prolonged symptoms for some individuals.
• Plan the exit strategy: Discuss the process for eventually stopping at the first appointment, as is commonly recommended for benzodiazepines.

2. Implementing Best Practices for Tapering

• Promote shared decision-making: Tapering must be a collaborative process guided by the patient's experience to find a tolerable rate of reduction.
• Avoid abrupt discontinuation: Unless there is an urgent, life-threatening medical necessity, avoid stopping an antidepressant abruptly.
• Consider hyperbolic tapering: Taper by progressively smaller, "hyperbolic" dose reductions. Be prepared for this to take months or even years.
• Go slow and be patient: A "cut and hold" approach (making a small reduction, then holding at that dose for weeks or months to stabilize) is a common and effective strategy.
• Validate the patient's experience: Validate that their symptoms (brain zaps, emotional lability, etc) are recognized, real, and common.

3. Responding Thoughtfully to Withdrawal Symptoms

• 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.
• Screen for withdrawal: Actively inquire about common physical withdrawal symptoms (dizziness, flu-like feelings, brain zaps, palpitations) rather than just mood symptoms.
• Pause, don't reverse: If withdrawal is intolerable, pause the taper and stabilize on the last well-tolerated dose.
• Document accurately: Document emerging symptoms as "antidepressant withdrawal" rather than "relapse of depression" to guide future, more cautious tapering attempts.
• Provide psychosocial support: Tapering can be a frightening and isolating process. Regular follow-up, active listening, and counseling are essential.

Concluding Thoughts

The clinical understanding of antidepressant withdrawal is undergoing a paradigm shift. The long-held belief that withdrawal is mild, brief, and rare is being replaced by a more accurate picture of a syndrome that can be complex, severe, and protracted. By prioritizing true informed consent, embracing conservative hyperbolic tapering, and learning to distinguish iatrogenic withdrawal from illness recurrence, clinicians can prevent harm and better support their patients through every phase of treatment, including considering nonpharmacological intervention in every instance.

Modern psychiatric practice often struggles within the confines of short, pharmacologically focused visits. In this constrained paradigm, the field has leaned too heavily on the perceived safety of antidepressants to justify their widespread use. The promotion of measurement-based care has further complicated this by encouraging reliance on rapid depression scales; these tools frequently misinterpret any distress, including withdrawal as a relapse of depression. It is time we acknowledge the reality of withdrawal. This means prioritizing genuine informed consent before the first prescription is written and learning to distinguish discontinuation symptoms from recurrence of the original problem. Ultimately, we must commit to supporting patients through the difficult process of exiting the very medications prescribed to help them.

Dr Badre is a clinical and forensic psychiatrist in San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr Badre can be reached at his website, BadreMD.com. His upcoming textbook of psychiatry is available on Amazon. Dr Cohen is a professor of social welfare and associate dean at the University of California, Los Angeles Luskin School of Public Affairs. Ms Strassle was formerly an assistant chief counsel at the Office of the Chief Counsel for the US Food and Drug Administration.

References

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10. Stopping antidepressants. Royal College of Psychiatrists. March 2024. Accessed December 15, 2025. https://www.rcpsych.ac.uk/mental-health/treatments-and-wellbeing/stopping-antidepressants

11. Horowitz M, Taylor D. The Maudsley Deprescribing Guidelines: Antidepressants, Benzodiazepines, Gabapentinoids, and Z-Drugs. Wiley; 2024.