By Maryanne Demasi at Brownstone dot org.

When a major study appears in JAMA Psychiatry - a high-profile journal that shapes headlines and clinical decisions - its findings carry weight.

So when Kalfas and colleagues released what they billed as the most comprehensive analysis of antidepressant withdrawal to date, it drew immediate attention.

The study concluded that symptoms were generally "mild," short-lived, and possibly amplified by nocebo effects - positioning itself as the last word on the subject.

The authors mobilised a rapid media campaign to shape the public narrative, with the Science Media Centre issuing expert commentary to "reassure both patients and prescribers" that most withdrawal symptoms were "not clinically significant."

But for grassroots advocates who've spent years exposing the realities of withdrawal, the study felt like a gut punch. They argue it presents a dangerously misleading picture - one that could entrench outdated practices and delay long-overdue reform.

"The idea that withdrawal is rare or mild is a manufactured consensus based on industry-aligned data," said Morgan Stewart of the advocacy group Antidepressant Coalition for Education. "This is a misleading analysis of antidepressant withdrawal."

A Flawed Foundation

Kalfas et al. conducted a systematic review and meta-analysis - methods widely regarded as the gold standard in evidence-based medicine. It examined 50 studies involving more than 17,000 patients.

But these reviews are only as reliable as the data they include. If the underlying studies are biased or poorly designed, the result is what critics call "Garbage in, garbage out."

That's exactly what happened here.

Most antidepressant trials last just a few weeks or months, even though many people take these drugs for years. In the US, for example, half of all antidepressant users have been on them for more than five years. Short-term trials are of little relevance to this population.

Worse, many trials enrolled patients already taking antidepressants - then abruptly withdrew them before randomisation. As a result, those assigned to placebo experienced withdrawal symptoms that blurred the difference between treatment and control groups, artificially minimising the harms.

This sleight of hand isn't new. It exploits a structural weakness of placebo-controlled trials, which are ill-equipped to capture the real-world challenges of stopping antidepressants.

Kalfas et al. found that people who stopped antidepressants reported, on average, only one more symptom than those who stayed on treatment or placebo. But the study didn't assess symptom severity and followed patients for just two weeks.

That's not long enough. Many patients report that symptoms don't emerge until after that timeframe, so the study simply fails to reflect what happens in real life.

To make matters worse, most of the included trials were industry-funded and commonly used medications such as paroxetine, or escitalopram, which is known for causing severe withdrawals.

What Patients Experience - And Why Doctors Misinterpret It

In 2024, Danish physician Peter Gøtzsche and I conducted our own systematic review, published in the International Journal of Risk & Safety in Medicine. We examined interventions used to help patients taper off antidepressants.

We found success rates ranging from 9% to 80%, with a median of just 50%. Many participants described their symptoms as "severe."

Crucially, our meta-regression showed that longer tapering durations significantly increased the chances of success.

Yet doctors often mistake withdrawal symptoms - like anxiety, insomnia, dizziness, or low mood - for relapse. Patients are told their depression has returned, and the drug is reinstated.

In reality, these symptoms are often physiological responses to withdrawal. But too often, patients are gaslit by a system that refuses to acknowledge the problem.

https://blog.maryannedemasi.com/p/quitting-antidepressants-can-be-tricky

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