Antidepressant Withdrawal: A Brief History

Antidepressant Withdrawal

A Brief History

The newest generation of antidepressant medications was heralded as a breakthrough in depression treatment when Prozac was introduced in 1988. As a drug, Prozac was seen as safer and more effective than the tricyclic antidepressants which had higher risks for toxicity in overdose. While excitement for the drug reached a fever pitch, a problem started to emerge: discontinuation frequently caused concerning side effects.

Antidepressant withdrawal is a controversial topic. Even before the introduction of selective serotonergic reuptake inhibitors (SSRIs) like Prozac and Paxil, the older tricyclic antidepressants were being recognized for having withdrawal symptoms that could be severe in a subset of patients (Garner 1993).

For the SSRIs, concerns over the challenges around discontinuation began to mount as a significant percentage of patients reported withdrawal symptoms. When patients stopped their antidepressant, it wasn’t unusual for them to experience worsening depression and anxiety, paresthesias (tingling and burning sensations), fatigue and sleep or gastrointestinal issues (Coupland 1996).

Antidepressant Withdrawal or Discontinuation Syndrome?

As providers started to recognize the problem, the published research—almost all of which was sponsored by the pharmaceutical industry—started to downplay the phenomenon by using the term “discontinuation syndrome” over withdrawal. Studies from authors with financial relationships to Eli Lilly, the manufacturer of Prozac, published numerous studies minimizing withdrawal symptoms, claiming they were rare and that they only lasted a few weeks (Haddad 1998). Some authors even blamed patients for having discontinuation symptoms, claiming that if they had only taken their medication consistently they would have avoided any problems (Kaplan 1997).

However, as the research continued, it became clear that withdrawal was a real phenomenon that could have devastating effects. Focusing on double blind trials, a review from 2019 found that around 56% of patients discontinuing antidepressant medications experienced withdrawal (Davies 2019). Of those experiencing withdrawal, studies suggest that just under half describe their symptoms as severe (Davies 2019).

Recent Controversy Around Antidepressant Withdrawal Research

More recently, arguments have resurfaced about the actual incidence rate and severity of withdrawal symptoms. A meta-analysis from 2024 in Lancet claimed that withdrawal was only present in 15% of patients discontinuing medications with under 3% having severe symptoms (Henssler 2024). For anyone that has worked with patients discontinuing antidepressants, these numbers seem strikingly low. It’s worth noting that the authors only included short-term studies that were mostly sponsored by the pharmaceutical industry. In addition, the methodology for identifying withdrawal symptoms in patients in the included studies were wide ranging, with one of the larger studies not even listing a methodology for how patients with withdrawal were identified. For these reasons, the analysis could easily have underinflated the real-world incidence.

The study rekindled a firestorm around antidepressant withdrawal with researchers arguing about the quality of the data used to calculate withdrawal incidence. Even if the lower incidence rates are correct, it still would mean that there are potentially around one million individuals in the United States who will struggle with severe withdrawal symptoms if or when they decide to stop their antidepressant medication.

Treatment for Antidepressant Withdrawal

Regardless of the exact incidence of antidepressant withdrawal, there are valid concerns for patients who want to discontinue these medications or have tried and failed to discontinue them previously due to the severity of withdrawal. Generally, slow tapering is recommended, but may still not be enough to mitigate symptoms. The research suggests that slow tapering with small decreases in medication per step that is tailored to the individual has the best chance of reducing withdrawal (van Os 2023).

From clinical experience, other factors that commonly worsen withdrawal include nutrient deficiencies. Similar to depression itself, individuals with more severe withdrawal may have deficiencies in vitamin D, magnesium, vitamin B12, folate, zinc, omega-3s and amino acids. Identifying and treating these deficiencies before medication tapering can be very useful for decreasing symptoms. For a more complete discussion, see my book on functional medicine for antidepressant withdrawal.

Conclusion

Antidepressant withdrawal is a common phenomenon that can significantly affect a patient’s treatment progress and mental health. While the incidence and severity of withdrawal have often been downplayed, a significant percentage of patients experience withdrawal when stopping antidepressant medications. Tapering these medications slowly, to tolerance, can reduce the symptoms. In addition, before starting a taper, checking patients for common nutritional deficiencies and fully correcting them can help to reduce the severity of withdrawal.