For decades, patients and clinicians alike have been wrestling with a conundrum as old antidepressants themselves. How do you safely stop taking the drugs? Or wean a patient off of them? And is there any way to avoid (or at least mitigate) the risks of severe withdrawal symptoms?
Now, a new meta-analysis suggests that maybe all that hand-wringing might have been for nothing. The new research, appearing in JAMA Psychiatry, analyzed data from nearly 18,000 participants in 50 randomized clinical trials (RCTs) to better understand the incidence and severity of antidepressant discontinuation symptoms.
And what did they find? Now quote what they expected to find. Sure, the patients who stopped taking antidepressants experienced saw their symptoms flare up, more so than those who stayed on medication or discontinued a placebo, However, on average, they endured just one additional symptom than the control group, and the severity remained below the threshold for a clinically significant discontinuation syndrome.
“Our work should reassure the public because we replicated other findings, from high-quality studies, and have highlighted the clinical symptoms to look out for. Despite previous concern about stopping antidepressants, our work finds that most people do not experience severe withdrawal, in terms of additional symptoms,” lead author and Imperial College London Senior Clinical Lecturer Sameer Jauhar, PhD, added. “Importantly, depression relapse was not linked to antidepressant withdrawal in these studies, suggesting that if this does occur, people will need to see their health professional to rule out a recurrence of their depressive illness.”
Mild – Yet Obvious – Symptoms
The researchers reviewed trials using both standardized rating scales (most notably the Discontinuation-Emergent Signs and Symptoms (DESS) scale) and reports of individual adverse events. Their goal was to provide a clearer picture of what people can expect after stopping antidepressants.
After one week of discontinuation, the participants who quit their meds reported an average of one additional symptom on the DESS compared to those who either kept taking their antidepressants or stopped taking a placebo. The patients complained of dizziness, nausea, vertigo, and nervousness the most. Dizziness stood out as the most common symptom, affecting about 6% of participants who dropped their meds.
Despite these symptoms, the mean DESS score remained well below the threshold for a clinically significant discontinuation syndrome. Perhaps most importantly, the researchers discovered no link between antidepressant discontinuation and a deterioration of depression itself. That, the authors suggest, implies that emerging mood symptoms post-treatment are more likely to signal a true relapse of depression, rather than actual withdrawal.
“While uncommon, our study highlights that there could be a sub-group of people who develop more severe withdrawal symptoms than the wider population of antidepressant users,” Michail Kalfas, of the Institute of Psychiatry, Psychology & Neuroscience at King’s College London, said. “Our focus must now turn to look at the pharmacological basis for this reaction, and ask whether it relates to the way they metabolize these drugs.”
Different Drugs Sparked Different Reactions
The researchers also found that some antidepressants seemed more likely to trigger discontinuation symptoms than others. Some drugs, such as desvenlafaxine and duloxetine, boasted higher rates of symptoms after discontinuation. On the other, drugs like vortioxetine showed little to no difference from placebo in terms of individual symptoms.
Venlafaxine had the highest rate of dizziness upon withdrawal, plaguing 17.5% of patients.
Finally, it’s worth noting that how patients approached discontinuation (whether abrupt or tapered) made little difference to – at least short-term – symptom severity. Most of the studies used only brief tapering periods, though, which leaves some lingering questions about whether longer, more gradual tapers might make more of a difference.
Reframing the Discontinuation Conversation
This new research fills in some gaps in what we know about antidepressant discontinuation. Media coverage and a handful of earlier studies have painted a dark picture of withdrawal symptoms. It’s a narrative that has probably discouraged some people from leaving their antidepressants behind when it’s appropriate.
But these findings suggest that, for most patients, the actual incidence and severity of discontinuation symptoms – especially in placebo-controlled settings – aren’t as bad as we thought.
That doesn’t mean discontinuation is a risk-free endeavor. The researchers caution that dizziness, nausea, and anxiety-like symptoms are real and should be monitored. But they also warn against overemphasizing withdrawal effects in ways that could worsen symptoms through expectation alone—a well-documented nocebo phenomenon.
Critically, the study confirms that we should never approach antidepressant discontinuation casually. While withdrawal symptoms are usually mild, depression relapse remains a substantial risk, especially right after discontinuation. Careful monitoring and thoughtful decision-making remain integral to a successful transition.
The Takeaway
For clinicians and patients alike, this study informs a more grounded perspective on weaning patients off of antidepressants. Discontinuation symptoms remain a risk of the process, but on average, they’re relatively modest and less likely to become clinically significant, in most cases. But, we shouldn’t discount the risk of depression relapse.
The findings also challenge assumptions around the need for prolonged tapering regimens.
But, until more research clarifies things, it’s clear that antidepressant discontinuation requires careful planning. But we can take solace knowing that the specter of debilitating withdrawal might not be as bad as we once thought.
Further Reading
Understanding and Managing Withdrawal Syndromes After Discontinuation of Antidepressant Drugs
Why Antidepressants May Take Weeks to Show Benefits
Study Tackles the Mystery of Brain Zaps in Antidepressant Withdrawal
