Easy to start hard to stop: our approach to mitigate antidepressant withdrawal

 

I am beyond happy and extremely grateful for my recent teams victory of the ACCP clinical research challenge. Beyond our win I care far more about the real problem we sought to address.

This project started with my own passion for psychiatry, including the complexities of not only psychopharmacologic modalities of care, but the nuances I'm doing it right. Like a growing number of people, especially young adults, I was once prescribed antidepressants. When the time came to discontinue them under my provider’s guidance, I faced severe withdrawal symptoms that lasted for months. It was one of the most painful experiences of my life, and, critically, I’m far from alone.

Antidepressants remain among the most commonly prescribed drug classes worldwide, a trend that continues to rise, especially among younger populations. In many cases, these medications are life changing. When initiated with thoughtful intent, they offer meaningful relief to individuals navigating some of the most difficult periods of their lives.

Our pharmacological advances, from the early days of imipramine and iproniazid to the generally well-tolerated SSRIs, are nothing short of remarkable. But even miracles can cast shadows.

We’ve become a society increasingly reliant on these agents. Antidepressants, often started in moments of crisis, are now being used chronically, far beyond their originally studied durations. While initial trials spanned just six weeks, most guidelines suggest use for 6–18 months. Yet many patients remain on them for years, even decades.

This isn't just a clinical concern, it's largely a humanistic one. These medications are not without trade-offs: emotional blunting (40-60%), sexual dysfunction (73%), and other side effects can profoundly impact a person's ability to connect, build relationships, and live fully. And perhaps most concerning of all: these drugs are notoriously difficult to discontinue.

That’s the exact challenge my team sought to address in our winning proposal for the 2025 ACCP Clinical Research Challenge.

Discontinuing antidepressants is extremely difficult. Withdrawal symptoms occur in the majority of patients attempting to stop, with average rates around 56% with some report as high as 86%. More than half of subjects report these symptoms as severe. Symptoms of withdrawal include dizziness, insomnia, agitation, anxiety, flu-like symptoms, and in some cases, even suicidality. And this occurs not just with abrupt discontinuation but also with standard tapering over 2 to 4 weeks.

This is due to the unique pharmacologic principles of the serotonin transporter, and the dose response effects of agents (SSRIs) that block it. In short, even small changes can have large effects, especially at lower doses. There is significant neurobiological adaptation and tolerance that occurs as individuals remain on antidepressants over time, with the brain adjusting to artificially sustained serotonergic enhancement.

As a society, we seem to easily understand the fact when it comes to caffeine and caffeine headaches, however the same does not seem to hold true as it comes to other drugs that affect our brains.

Our team developed Structured Proportional Tapering (SPT) to address this gap. This pharmacist-led protocol reduces antidepressant doses by 10 percent of the previous dose every two weeks, resulting in a gradual, exponential taper that aligns with the neurobiology of SSRI withdrawal. Pharmacists provide dosing support, education, and individualized monitoring using commercially available liquid formulations. This approach offers a scalable and patient-centered model that addresses both the clinical and human challenges of antidepressant discontinuation.

I'd like to thank my fellow teammates Sami Gangji and Hailey Joo in addition to our advisor Dr. Nicole Asal and the very generous Dr. Aisling Caffrey