In the evolving landscape of psychiatric care, deprescribing is emerging as a core competency. Last May at the 2025 American Psychiatric Association (APA) conference, I heard Christopher Aiken, MD; Nassir Ghaemi, MD; and a panel discussion led by Ronald Winchel, MD mention deprescribing in passing. Tetyana Rocks, Ph.D and colleagues presented a course titled Redefining mental health care: Integrating diet, lifestyle, and deprescribing in professional practice.
Next year’s 2026 APA conference promises to offer more presentations specifically about deprescribing, by psychiatry leaders Donovan Maust, MD; John Kane, MD; Anita Clayton, MD; and others.
In early February, Stephen Stahl, MD, PhD, an internationally recognized educator in psychiatry with specific expertise in psychopharmacology, and co-author Jeffrey Strawn, MD published Stahl’s Deprescriber’s Guide. In it, they present deprescribing not as the antithesis of prescribing but a deliberate, patient-centered intervention.
I interviewed Drs. Stahl and Strawn about their new book via email.
“We’ve long focused on how to start medications, but much less on how to stop them or how to change course when a treatment has been successful, stopped helping, or created new problems….”
Strawn & StahlFrom the Prescriber’s Guide to the Deprescriber’s Guide
Dr. Stahl shaped the contemporary psychopharmacology treatment paradigm with his 1996 book Essential psychopharmacology: Neuroscientific basis and clinical applications. That book is now in its 5th edition. A related book,Stahl’s Essential Psychopharmacology: Prescriber’s Guide is in its eighth edition.
In 2000, he founded the Neuroscience Education Institute (NEI) to provide continuing medical education (CME) about psychopharmacology. Currently, he is NEI’s chairman and Editor-in-Chief of the journal CNS Spectrum.
Recently, Dr. Stahl estimated that his many publications have sold more than 2 million copies worldwide (the number of psychiatrists globally is less than 500,000).
His publications and speaking have made an internationally recognized educator in psychiatry with specific expertise in psychopharmacology. He is also an Adjunct Professor of Psychiatry at the University of California, San Diego and an Honorary Fellow in Psychiatry at the University of Cambridge.
Jeffrey R. Strawn, MD, a professor of Psychiatry at the University of Cincinnati College of Medicine, is a Distinguished Fellow of the American Academy of Child & Adolescent Psychiatry and has authored numerous peer-reviewed publications and textbooks on psychopharmacology and psychotherapy.
“Deprescribing is finally being recognized as a core competency….”
Strawn & StahlHe directs the Anxiety Disorders Research Program, where his work focuses on the treatment of anxiety and depressive disorders in children and adults.
In our correspondence, Drs. Stahl and Strawn, looking beyond psychopharmacology’s historical emphasis on initiating medications while often overlooking strategies for discontinuing them, envision deprescribing becoming normalized, with enhanced guidelines, and shared decision-making, transforming it into routine clinical practice.
They highlighted critical gaps in deprescribing research that future studies must bridge, including comparative trials of tapering methods like linear, prolonged, and hyperbolic strategies tailored to individual factors such as treatment duration and patient history. They call for longer-term investigations to better differentiate withdrawal symptoms from relapse. Ultimately, they anticipate the trajectory of deprescribing shifting from debating its merits to refining its application.
Stahl and Strawn respond to my questions
Badre: Deprescribing is gaining significant attention, with developments of guidelines and prominent discussions at the 2025 APA conference. How would you characterize the current role of deprescribing in psychiatry, and where do you see it heading in the next few years?
Strawn & Stahl: Deprescribing is finally being recognized as a core competency, not an ideological movement. As we write in the Deprescriber’s Guide, deprescribing isn’t simply the reverse of prescribing. Instead, it’s a strategic and patient-centered process that requires as much judgment and pharmacology as starting a medication.
“Ideally, deprescribing becomes what it should be: routine clinical maintenance, not a movement.”
Strawn & StahlWe’ve long focused on how to start medications, but much less on how to stop them or how to change course when a treatment has been successful, stopped helping, or created new problems (e.g., tolerability concerns). That doesn’t make deprescribing anti-medication; it makes it part of good medicine.
Looking ahead, we think deprescribing will become more normalized and less politicized. We’ll see clearer, medication-specific guidance, better integration of shared decision-making, and more realistic research that reflects how long people actually stay on medications. Ideally, deprescribing becomes what it should be: routine clinical maintenance, not a movement.
Badre: Could you share some of the core principles behind your approach to deprescribing? I am particularly interested in your thoughts on the scientific basis and practical application of hyperbolic tapering.
Strawn & Stahl: Our basic principle is that stopping a medication is a clinical intervention. It deserves planning, monitoring, and follow-up, just like starting one. In practice, that means individualizing how tapering or discontinuation is performed based on the initial condition being treated, the patient’s history, the duration of treatment, the reason for initial treatment, prior discontinuation experiences, and psychological factors.
Hyperbolic tapering has been proposed and there’s an interesting pharmacologic rationale for it, and clinically it may make sense in some situations. However, the approaches rely on occupancy at a single receptor, whereas many of our medications affect multiple receptors. For example, in discontinuing, would the hyperbolic discontinuation be based on 5-HT2A, D2 or H1?
“The goal isn’t to taper as slowly as possible or taper based on one single receptor, it’s to taper as slowly as necessary for that patient.”
Strawn & StahlThe goal isn’t to taper as slowly as possible or taper based on one single receptor, it’s to taper as slowly as necessary for that patient.
Badre: Many clinicians are concerned about the risks of deprescribing, such as relapse or withdrawal. How do you address these concerns, and what does the evidence say about the range of patient outcomes?
Strawn & Stahl: When we talk with patients and clinicians about deprescribing, we usually start with a simple statement: two things can be true at once. Some patients experience real discontinuation symptoms. And many patients relapse when an effective medication is stopped, not because the drug harmed them, but because the underlying illness returns. Most of the confusion, and much of the polarization in this area, comes from collapsing those two phenomena into one.
Withdrawal itself is heterogeneous. Its severity varies widely among patients and medications, and much of the controversy reflects differences in how it is measured.
“…we try to keep colleagues out of two equally unhelpful traps. One is the reflexive minimization of withdrawal. The other is the opposite, assuming withdrawal is inevitable, severe, and prolonged for most patients.”
Strawn & StahlSome studies rely on structured symptom checklists over short time frame whereas others depend on retrospective self-report. For example, a recent JAMA Psychiatry meta-analysis using the Discontinuation-Emergent Signs and Symptoms (DESS) framework found that, on average, the number of discontinuation symptoms in the first week after stopping antidepressants fell below thresholds typically considered clinically significant, and did not show an association between discontinuation and worsening mood (Kalfas et al., 2025).
That suggests that depressive symptoms emerging later in the course are more likely to reflect relapse rather than withdrawal per se. At the same time, real-world survey data tell a complementary story. Among patients with longer antidepressant exposure, a subset report more intense and more persistent symptoms during discontinuation. These studies are careful to acknowledge their limitations (e.g., selection bias, recall effects, lack of placebo control), but they remind us that withdrawal is not imaginary, nor is it uniform.
Clinically, in the Deprescriber’s Guide, we try to keep colleagues out of two equally unhelpful traps. One is the reflexive minimization of withdrawal. The other is the opposite, assuming withdrawal is inevitable, severe, and prolonged for most patients. Neither position is supported by the evidence, and neither serves patients well.
Relapse, on the other hand, is a well-established risk in many conditions and is often misattributed to withdrawal. Discontinuation trials repeatedly show that stopping an effective medication increases relapse risk, and that risk is not static. That is to say that it depends on how long the patient has been well. As we discuss in the Deprescriber’s Guide, a double-blind discontinuation study in generalized anxiety disorder demonstrated that patients treated with venlafaxine ER for 12 months before tapering had substantially lower relapse rates than those treated for only 6 months (32% versus 54%) (Rickels et al., 2010). Findings like this address myths in our field.
Deprescribing is neither inherently virtuous nor inherently dangerous. It is a risk–to-benefit decision, that must consider diagnosis, duration of stability, prior course of illness, patient preferences, and the real sometimes competing risks of relapse and withdrawal (Stimpfl et al., 2025). The goal is not to stop medication, but to stop thoughtlessly continuing or thoughtlessly stopping it.
Badre: A key clinical challenge is distinguishing between withdrawal phenomena and a relapse of the underlying condition.
“ In practice, we focus on timing, symptom pattern, and trajectory. Symptoms that emerge quickly after dose reduction, fluctuate within a day, or include features the patient never had before are more suggestive of discontinuation effects.”
Strawn & StahlWhat is your framework for navigating this diagnostic gray area?
Strawn & Stahl: In practice, we focus on timing, symptom pattern, and trajectory. Symptoms that emerge quickly after dose reduction, fluctuate within a day, or include features the patient never had before are more suggestive of discontinuation effects.
Symptoms that resemble the original illness and persist or worsen over time raise more concern for relapse.
We also rely heavily on measurement-based care and functional outcomes, not just symptom descriptions. Sometimes the only way to clarify the picture is to pause the taper, slow it down, or briefly reinstate a dose and observe what happens. That’s not a setback, it’s diagnostic information.
Badre: Psychiatric care has shifted from primarily short-term interventions to frequent long-term maintenance. How does deprescribing fit into this modern context, and what role should it play in routine practice?
Strawn & Stahl: Psychiatry now treats many conditions as long-term or recurrent, and often appropriately so. Deprescribing doesn’t oppose that model. It gives clinicians a structured way to ask whether the current medication, dose, and combination still make sense for the patient in front of them.
“Despite growing clinical interest, practice has moved faster than evidence, and the next phase of the field needs to be driven by data that reflect how patients actually discontinue medications in real-world settings.”
Strawn & StahlDeprescribing, as we note regularly in the Deprescriber’s Guide, is already happening, often without clinician involvement. Patients stop medications on their own because of side effects, cost, or uncertainty. One of the strongest arguments for deprescribing is that it allows us to guide a process that would otherwise be unmanaged.
Badre: Looking forward, what are the most critical unanswered questions in deprescribing research that future studies should aim to address?
Strawn & Stahl: Despite growing clinical interest, practice has moved faster than evidence, and the next phase of the field needs to be driven by data that reflect how patients actually discontinue medications in real-world settings.
A central unanswered question is who benefits from which tapering strategy. Linear, prolonged, and hyperbolic tapers are widely used, yet we lack head-to-head trials that consider important clinical phenomena (e.g., dose, duration of exposure, prior withdrawal history, age and comorbidity).
Another major gap is more precise differentiation between withdrawal and relapse. Many trials assess discontinuation effects over short intervals and rely on brief symptom checklists, which may capture early physical symptoms but miss later affective or functional changes. As highlighted in a recent meta-analysis (Kalfas et al., 2025), mood worsening after antidepressant discontinuation does not consistently parallel early withdrawal signals, suggesting that relapse and withdrawal are often conflated. Studies with longer follow-up, repeated measurement, and placebo-controlled discontinuation designs are needed.
We, as a field, also lack evidence on how to communicate about deprescribing without creating nocebo effects. Transparency is essential, but how risk is framed likely influences symptom experience.
Taken together, the future of deprescribing research is not about deciding whether deprescribing is good or bad, but about determining how to do it well for the right patient, at the right time, and in the right way.
Nicolas Badre, MD is a clinical and forensic psychiatrist in San Diego and an advisor to the Psychotropic Deprescribing Council. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care at various institutions, including USD Department of Counseling & School of Law, NMCSD Psychiatry, and FHCSD Psychiatry. His psychiatry textbook, Essential Psychopathology & Its Treatment, 5th Edition, can be pre-ordered on Amazon. His website is BadreMD.com.
Mark Horowitz
Stahl and Strawn disparage deprescribing as a ‘movement’ while ignoring how Stahl’s own texts helped create overprescribing and clinician indifference to withdrawal issues. They overlook that hundreds of thousands now seek safer tapering advice online because standard care has caused harm.
The interview and the book they are promoting defend the status quo, insisting long-standing prescribing practices remain sound despite mounting evidence to the contrary. Almost every chapter promotes long-term maintenance of medications through highly misleading interpretations of discontinuation or ‘relapse-prevention’ trials. These trials typically stop drugs rapidly, misclassify withdrawal as relapse, and thereby inflate the apparent protective effect of staying on medication. The co-authors’claim that relapse may be ‘misattributed to withdrawal’ reverses the actual problem – most trials do not measure withdrawal at all.
To justify long-term use, they misrepresent Rickels (2010) by citing absolute differences while ignoring relative risk. After 12 months, the relapse rate in those who discontinue falls compared with 6 months (32 percent vs 54 percent), but the matched maintenance arm also improves (7 percent vs 12 percent), likely because early relapsers have already dropped out. The relative risk is similar at both time points (actually slightly more at 12 months – risk ratio of 5.3 vs 4.8), supporting shorter rather than longer treatment. The data align with evidence that withdrawal risk increases with duration of exposure, not with claims that antidepressants become more effective over time.
They downplay withdrawal by relying on meta-analyses such as Kalfas, which focused primarily on short-term users and therefore miss the severe, persistent withdrawal more common in longer-term patients. This is akin to crashing a car at 5 miles per hour and declaring high-speed driving safe.
Their claims that depressed mood is more likely relapse than withdrawal rely on studies that did not closely examine this question. Studies like Rosenbaum (1998) that did carefully examine this issue in a double-blinded fashion show high rates of withdrawal being mislabelled as relapse when depression scales are used for evaluation.
Their deprescribing guidance is equally problematic. Despite mounting empirical evidence and patient experience showing that gradual, hyperbolic tapering over months or years reduces harm, the book repeats outdated advice: reduce over a few weeks to the smallest tablet or capsule, then stop. This is precisely what is most likely to induce severe and protracted withdrawal. As psychopharmacologist David Taylor and I demonstrated in The Maudsley Deprescribing Guidelines, dropping from the smallest tablet to zero is a neurochemical cliff edge. Taper-specific small doses are needed to soften the descent.
Stahl’s and Strawn’s misunderstanding of hyperbolic tapering is striking. The law of mass action applies across serotonergic, dopaminergic, cholinergic and histaminergic systems, meaning rational tapers for all such drugs must be hyperbolic. Failure to grasp this principle leads directly to harmful recommendations for rapid tapers.
In several chapters they advise adding further psychiatric drugs – antipsychotics, pregabalin, mood stabilisers, z-drugs, more antidepressants – if patients struggle with rapid tapers. This fuels prescribing cascades;patients can end up on unwarranted multiple medications as a direct consequence of this unwise approach to tapering.
Finally, their description of withdrawal symptoms reveals limited familiarity. They state symptoms ‘fluctuate within a day’, which they can – but they may also last weeks or months, and may be delayed. Their suggestion that persistent symptoms indicate relapse ignores that persistence and worsening are hallmark features of withdrawal.
Their call for more studies delays needed action, and updated international guidance already renders their book outdated. If this book proves as influential as Stahl’s previous texts, it will perpetuate harmful practices with serious consequences for patients.
Mark Horowitz
Physician
London
Sam Hall
Stahl’s Deprescriber’s Guide claims to provide structured guidance for the deprescribing of psychotropic medications. In practice, however, aspects of its recommendations raise serious concerns about patient safety.
The tapering strategies outlined in the text, including suggestions such as stopping at half the lowest tablet dose, risk oversimplifying the complex, non linear neurobiological effects of dose reduction. These effects are well documented in pharmacological research. PET imaging studies have demonstrated a hyperbolic relationship between SSRI dose and serotonin transporter (SERT) occupancy. For example, the PET study by Jeffrey H. Meyer and colleagues (2004) demonstrated that even relatively small doses of SSRIs occupy a large proportion of serotonin transporters. This means that reductions at lower doses can produce disproportionately large neurobiological changes.
This non linear pharmacology underpins the rationale for hyperbolic tapering strategies reflected in The Maudsley Deprescribing Guidelines. Simplified tapering schedules that rely on large percentage reductions at lower doses risk destabilising patients whose nervous systems have undergone significant neuroadaptation following long term drug exposure.
In my experience as a patient, following conventional tapering advice resulted in severe and prolonged withdrawal symptoms. These symptoms were frequently misinterpreted as relapse or the emergence of new psychiatric pathology. The result was further prescribing and a cascade of iatrogenic polypharmacy.
The guide does not sufficiently distinguish withdrawal syndromes from relapse, nor does it adequately emphasise the need for highly individualised tapering strategies for long term users. Frameworks that default to standardised deprescribing schedules risk repeating the same institutional blind spots that have historically contributed to patient harm.
Another concern is the drug centric framing of withdrawal management. In clinical practice, withdrawal related destabilisation is often addressed through switching, substitution or augmentation strategies. Rather than facilitating true deprescribing, this can lead to additional layers of pharmacological intervention.
This was my experience. During antidepressant withdrawal, I was prescribed 25 mg of Quetiapine for insomnia. Despite later attempts at an extremely cautious micro taper, I have been unable to discontinue the drug due to the destabilisation created by prior antidepressant switches and withdrawal.
In this context, “deprescribing” risks becoming a process of medication substitution or symptom masking rather than a genuine shift toward stabilisation and minimal pharmacological intervention.
Finally, it is also relevant that Stephen M. Stahl has longstanding financial relationships with pharmaceutical companies. While such relationships are common in academic psychopharmacology, they nonetheless raise legitimate questions about potential bias toward drug centred frameworks of treatment and discontinuation.
Existing resources, including The Maudsley Deprescribing Guidelines, already provide pharmacologically informed, patient centred strategies that emphasise gradual tapering and safety. Any new guidance in this area should clearly improve upon these principles rather than risk perpetuating harm under the guise of deprescribing.
Mismanaged deprescribing can be profoundly disabling, life altering and, in some cases, life threatening. Layering additional drugs on top of withdrawal often compounds the harm. Effective deprescribing requires caution, humility and genuine respect for lived experience, qualities that should be foundational to any credible clinical framework.
References:
Meyer, J. H., Wilson, A. A., Sagrati, S., Hussey, D., Carella, A., Potter, W. Z., Ginovart, N., Spencer, E. P., Cheok, A., & Houle, S. (2004).
Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: An [11C]DASB positron emission tomography study. American Journal of Psychiatry, 161(5), 826–835.
Richard Johnson
This book has already received a range of reviews, both favorable and critical, many from clinicians who either intend to incorporate it into practice or who disagree with its approach. I am not a doctor, scientist, therapist, or healthcare professional. I write solely from the perspective of 32 years of lived experience as a psychiatric patient.
During that time I have been prescribed 17 psychiatric medications and at least 29 additional medications used to manage their adverse effects. I experienced severe complications from psychotropic drugs including type 2 diabetes, metabolic syndrome, 100 pounds of weight gain, cardiac and thyroid issues, vision problems, circadian rhythm disruption, akathisia, tremors, cognitive impairment, and more. At one point I was admitted to the ICU after inpatient medication changes caused life-threatening metabolic, cardiac, and gastrointestinal symptoms. At the time these issues were attributed to dysfunction in various body systems. Looking back, it is clear they were the result of polypharmacy gone terribly wrong. Since discontinuing one medication and tapering another, many of these problems have improved or resolved.
The book does contain positive elements. The authors acknowledge that medications may outlast their usefulness and that deprescribing is an essential part of mental health care. They emphasize that how medications are tapered is just as important as how they are initiated, and that abrupt discontinuation can have serious consequences that are preventable through proper tapering strategies. They also highlight the importance of shared decision-making and recognize the value of patient lived experience in informing ethical prescribing and deprescribing practices. As someone who has experienced multiple provider-directed rapid tapers, abrupt withdrawals, and medication swaps, I am encouraged to see these issues addressed in a clinical text.
However, the book still contains serious concerns. It often fails to clearly distinguish withdrawal from relapse and gives little attention to protracted withdrawal syndromes. Taper recommendations are frequently linear and overly rapid compared with real-world patient experiences. Withdrawal management often involves adding additional medications, increasing the risk of further polypharmacy. The concept of neurological kindling from repeated medication changes is absent. Finally, medications are ranked by withdrawal severity despite strong evidence that individual physiology and medication history are far more predictive.
This book is a start in the right direction but a poor one at best and as such I recommend staying away from it. In its current form it is more of a potential danger to the patient than anything else. There are better references available for safe deprescribing.
R Johnson
USN Retired
Amanda McBarron
Dr. Stephen Stahl and Dr. Jeffrey Strawn deserve recognition for acknowledging the importance of deprescribing and the need for rigorous research in this area, an important shift in psychiatric discourse. However, their deprescribing guide ultimately fails to align with emerging pharmacodynamic evidence and lived clinical outcomes. By characterizing protracted withdrawal as “theoretical and controversial”, insufficiently distinguishing withdrawal from relapse phenomena, endorsing linear tapering strategies that do not align with transporter and receptor occupancy principles, and asserting that antidepressants and related agents do not produce physiological dependence, the text risks perpetuating the very harms deprescribing efforts are intended to mitigate.
The relapse versus withdrawal framework presented in the guidelines oversimplifies complex discontinuation phenomena by suggesting that symptoms emerging weeks to a month after discontinuation are more likely attributable to relapse than withdrawal. However, mounting clinical observations and patient reports document withdrawal symptoms that may be delayed, fluctuating, or protracted. The categorical attribution of anxiety, depression, panic attacks, restlessness, dizziness, ect to relapse, particularly following discontinuation of agents such as alprazolam, fails to adequately consider that these symptoms are also well-recognized features of withdrawal syndromes.
Recommended benzodiazepine tapering schedules are linear in design, may proceed at rates faster than many patients can physiologically tolerate, and conclude at doses that may still represent substantial receptor occupancy. This approach does not reflect the non-linear pharmacodynamic relationship between dose reduction and receptor binding, nor does it address the growing body of evidence and patient reports supporting hyperbolic tapering strategies.
Similar pharmacodynamic concerns arise in the discussion of fluoxetine. The suggestion that fluoxetine “self-tapers” due to its long half-life and is unlikely to produce withdrawal syndromes creates a false sense of safety. Serotonin transporter occupancy remains substantial even at very low doses, smaller than clinically marketed. Stahl and Strawn recommend discontinuation at 20 mg, without even tapering to the lowest marketed dose. This represents a significant reduction in transporter binding and severely underestimates the potential for withdrawal phenomena.
Lastly, the text distinguishes benzodiazepines as capable of producing physiological dependence, yet does not extend this framework to antidepressants, mood stabilizers, stimulants, or other psychotropics, despite similar neuroadaptive mechanisms underlying chronic receptor modulation. This selective acknowledgment creates an inconsistent model of dependence across drug classes.
Deprescribing is a necessary evolution in psychiatric practice. Yet, if implemented without full recognition of dependence mechanisms and withdrawal complexity, it risks replicating the very iatrogenic harms it seeks to correct. Patient safety depends on aligning tapering guidance with pharmacological principles, true informed consent, and real-world discontinuation outcomes. Overall, current psychotropic medication research relies heavily on short-term trials and narrowly defined populations that do not reflect real-world use, comorbidity, or long-term exposure. This limits generalizability to patients undergoing discontinuation from extended treatment. Future deprescribing research should prioritize long-term outcomes, complex polypharmacy, clearer distinctions between withdrawal and relapse phenomena, and systematic study of protracted withdrawal syndromes so evidence better reflects clinical realities.
Amanda McBarron RN-BSN, APRN, FNP-BC
Massachusetts
Daniel Cohrs
While I was encouraged to see Stahl publish a resource on deprescribing—given the much-needed attention he can bring to this underinvestigated area of psychiatry—both The Deprescriber’s Guide and this interview raised important concerns. He cites a recent JAMA Psychiatry (Kalfas et al. 2025) meta-analysis reporting a lack of “clinically significant” withdrawal effects within the first week after discontinuation as evidence that “depressive symptoms emerging later in the course are more likely to reflect relapse rather than withdrawal per se” However, the average treatment duration in these studies was only 12 weeks.
It is well established that withdrawal risk is relatively low with treatment under six months but increases substantially with longer exposure, particularly after years of use (Horowitz, Framer, Hengartner, Sørensen, & Taylor, 2023). As a result, the absence of findings in Kalfas et al. is unsurprising and largely uninformative.
Earlier work by Rosenbaum et al. demonstrated rapid onset of depressive symptoms following discontinuation, coinciding with high rates of somatic withdrawal symptoms, and rapid resolution with reinstatement—both occurring within approximately one week (Rosenbaum, Fava, Hoog, Ascroft, & Krebs, 1998). This pattern is inconsistent with relapse, which would be expected to show a broader distribution in time to onset and slower resolution. Similarly, antidepressant maintenance trials such as PREVENT (Kocsis et al. 2007) demonstrate rapid symptom emergence after discontinuation, suggesting that a proportion of cases labeled as relapse likely reflect withdrawal.
Of greater concern are the tapering protocols in Stahl’s guide, which do not extend below minimum therapeutic doses for serotonin reuptake inhibitors (SRIs). Minimum therapeutic doses produce approximately 80% serotonin transporter (SERT) occupancy, helping explain why many patients experience withdrawal when discontinuing at this dose (Sørensen, Ruhé, & Munkholm, 2022). While high occupancy may be required for therapeutic effects, it is not required for biological activity. Chronic SRI use induces many neuroadaptative changes (Artigas 2013) (Dankoski, Agster, Fox, Moy, & Wightman, 2014), and for many patients, tapering to subtherapeutic doses is necessary to gradually reverse these changes and minimize withdrawal. Ignoring all of this risks withdrawal unnecessarily for many patients.
References
Artigas, F. (2013). Serotonin receptors involved in antidepressant effects. Pharmacology & Therapeutics, 137(1), 119–131.
Benmansour, S., Owens, W. A., Cecchi, M., Morilak, D. A., & Frazer, A. (2002). Serotonin clearance in vivo is altered to a greater extent by antidepressant-induced downregulation of the serotonin transporter than by acute blockade of this transporter. The Journal of Neuroscience, 22(15), 6766–6772.
Dankoski, E. C., Agster, K. L., Fox, M. E., Moy, S. S., & Wightman, R. M. (2014). Facilitation of serotonin signaling by SSRIs is attenuated by social isolation. Neuropsychopharmacology, 39(13), 2928–2937.
Horowitz, M. A., Framer, A., Hengartner, M. P., Sørensen, A., & Taylor, D. (2023). Estimating Risk of Antidepressant Withdrawal from a Review of Published Data. CNS Drugs, 37(2), 143–157.
Kalfas, M., Tsapekos, D., Butler, M., McCutcheon, R. A., Pillinger, T., Strawbridge, R., Bhat, B. B., et al. (2025). Incidence and Nature of Antidepressant Discontinuation Symptoms: A Systematic Review and Meta-Analysis. JAMA psychiatry, 82(9), 896–904.
Kocsis, J. H., Thase, M. E., Trivedi, M. H., Shelton, R. C., Kornstein, S. G., Nemeroff, C. B., Friedman, E. S., et al. (2007). Prevention of recurrent episodes of depression with venlafaxine ER in a 1-year maintenance phase from the PREVENT Study. The Journal of Clinical Psychiatry, 68(7), 1014–1023.
Quentin, E., Belmer, A., & Maroteaux, L. (2018). Somatodendritic regulation of raphe serotonin neurons: a key to antidepressant action. Frontiers in Neuroscience, 12, 982.
Rosenbaum, J. F., Fava, M., Hoog, S. L., Ascroft, R. C., & Krebs, W. B. (1998). Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biological Psychiatry, 44(2), 77–87.
Sørensen, A., Ruhé, H. G., & Munkholm, K. (2022). The relationship between dose and serotonin transporter occupancy of antidepressants: a systematic review. Molecular Psychiatry, 27(1), 192–201.
Daniel Cohrs, MD
California
Nick Nowak
We have developed a medical culture with a well-defined and accessible on-ramp to pharmacotherapy for both clinicians and patients, yet comparatively limited structure around deprescribing. That imbalance warrants critical attention.
Educational resources such as those authored by Dr. Stephen M. Stahl are advancing the field by providing clinicians with shared language and neurobiological frameworks. They also help legitimize an increasingly important clinical priority: reducing medication burden when it is safe, appropriate, and aligned with patient goals.
As a pharmacist, my focus is therapeutic optimization, not indefinite continuation. The aim is to achieve the lowest effective dose for the shortest necessary duration, based on individualized care. Deprescribing is not a departure from evidence-based care; it represents a progression toward precision medicine. It reflects a disciplined effort to match treatment intensity to evolving clinical needs over time.
Historically, symptom-suppression models have emphasized medication initiation without equivalent attention to structured discontinuation. In complex neuropsychiatric conditions, this has contributed to polypharmacy and prolonged exposure without clearly defined exit strategies. The future of tapering must be patient-centered, behavioral health–led, and clinician-supported. Thoughtful deprescribing requires prospective planning, patient education, longitudinal monitoring, and respect for neuroadaptive physiology; it cannot be reduced to abrupt dose reductions or informal guidance.
Tapering should be recognized as a core clinical competency across primary care, psychiatry, and specialty practice. We invest substantial training in starting medications; we must apply comparable rigor to stopping them.
A meaningful gap persists between emerging deprescribing research and real-world prescribing behavior. Closing this gap will require standardized frameworks, interdisciplinary collaboration, and integration of taper planning into routine care.
If durable outcomes are the objective, tapering must be incorporated into the standard of care from the moment pharmacotherapy is initiated, not addressed only when complications arise.
Nick Nowak, PharmD, BCPS
Asheville, North Carolina