There has long been a mismatch in antidepressant research: Many people take the drugs for years, while most randomized trials last just six to 12 weeks.

A recent clinical review published in the Australian Journal of General Practice has brought that gap into sharper focus. The authors re-examined the studies used to justify long-term antidepressant treatment, arguing that important limitations make the evidence for years-long treatment less certain.

The review examined both short-term trials and longer-term studies, the latter focused mainly on preventing depression relapse.

“There is no robust evidence for long-term use of these drugs because of the flaws with these long-term studies,” Dr. Mark Horowitz, the review’s corresponding author and associate professor in psychiatry at Adelaide University, as well as the lead clinician in the National Psychiatric Deprescribing Clinic within the National Health Service in the UK, told The Epoch Times via email.

His primary argument is that the longer-term trials—studies in which some people stay on antidepressants while others stop—can mistake withdrawal symptoms for a return of depression. 

Not all psychiatrists agree with that assessment. Dr. Awais Aftab, a psychiatrist at Case Western Reserve University, told The Epoch Times via email that Horowitz’s review correctly highlights genuine uncertainty in the existing evidence. But he said the review takes a skeptical stance toward that uncertainty.

For patients, however, the practical challenge of deciding how to balance a medication’s ongoing benefits against its potential downsides—is real.

When Studies Last Months but Treatment Lasts Years

Nearly one in six U.S. adults report currently taking antidepressants, prescribed for depression, anxiety, obsessive-compulsive disorder, and other conditions. They typically stay on them for two to five years. Yet most antidepressant research comes from randomized controlled trials lasting only months.

Besides, while those studies consistently show that antidepressants perform better than placebo on average, the difference is modest: Across trials, antidepressants improve depression scores by about two points more than placebo on a 52-point scale. Even among people with severe depression, the difference antidepressants make is about three points.

Short-term trials cannot show what happens when people continue antidepressants for years. They cannot capture delayed benefits, long-term side effects, or what happens when people try to stop treatment.

“Many people remain on these drugs for years or even decades,” Horowitz said. “That means we actually know much less about their long-term effects than many people assume.”

Relapse or Withdrawal?

One of the main sources of evidence for long-term antidepressant treatment comes from studies known as relapse-prevention trials. These studies typically recruit people who have improved on antidepressants for a year or more and are randomly assigned either to continue taking the medication or to taper off it over several weeks.

These studies consistently find that people who continue taking antidepressants are less likely to be diagnosed with a relapse than those who stop treatment.

However, the review states that the design creates a central problem: Stopping antidepressants can trigger withdrawal symptoms—including low mood, anxiety, and insomnia—that resemble depression returning. If those symptoms develop after discontinuation, it can be difficult for researchers to determine whether they reflect withdrawal, relapse, or both.

“Withdrawal symptoms and relapse often look remarkably similar,” Horowitz said. That means some of the apparent benefit of continuing treatment may reflect the prevention of withdrawal. 

Researchers generally agree on what these studies found. The debate is about what those findings mean.

The Landmark Study

Much of the debate centers on the landmark ANTLER study, a UK trial that concluded people who continued antidepressants were less likely to relapse over one year than those who discontinued treatment—39 percent and 56 percent, respectively. 

Seventy percent of the participants had been on an antidepressant for more than three years.

The study has been widely cited as evidence that continuing antidepressants lowers the risk of relapse. However, Horowitz and his co-authors argue that the ANTLER and similar studies overestimate the benefits because they did not distinguish withdrawal symptoms from relapse.

Withdrawal symptoms can look much like depression returning. Horowitz compared the problem to studying smoking by asking smokers to either keep smoking or quit abruptly, then concluding that smoking prevents anxiety because those who quit became irritable, sleepless, and unfocused. 

“When people stopping antidepressants become anxious, sleepless, or emotionally distressed, we have to be careful not to automatically assume this represents the return of a psychiatric disorder,” Horowitz said.

He argued the overlap creates a challenge both for researchers and for clinicians treating patients because many withdrawal symptoms are also symptoms used to diagnose depression and anxiety.

“We know this because they occur to people even without underlying mental health issues,” he said, pointing to people given antidepressants for pain, menopause, and even in healthy volunteers. “Those are many of the same symptoms clinicians use to diagnose depression or anxiety disorders in the first place.”

However, Glyn Lewis, one of the lead investigators of the ANTLER study, disagreed. 

While he acknowledged that stopping antidepressants can temporarily increase symptoms of depression or anxiety, he said that is different from relapsing. 

In the case of ANTLER, relapse was defined using internationally accepted diagnostic criteria for depression.

“If withdrawal symptoms were to explain these findings, one would have to expect withdrawal to lead to a syndrome identical to the internationally agreed definition of depression,” Lewis told The Epoch Times. “It is unlikely that discontinuation would lead to someone experiencing a depressive disorder meeting diagnostic criteria.”

Dr. Mark Olfson, a professor of epidemiology and psychiatry at Columbia University, told The Epoch Times it is unlikely to be a withdrawal symptom because the difference between the groups persisted throughout long-term follow-up—not just in the weeks immediately after tapering.

Deciding Whether to Stop Antidepressants

The debate over relapse-prevention studies is only one part of the decision about long-term antidepressant treatment. Patients and clinicians must also weigh whether a medication continues to provide meaningful benefits against any side effects or other downsides that may emerge over time.

The review points to a growing body of evidence linking long-term antidepressant use with adverse effects including sexual dysfunction, emotional blunting, weight gain, sleep problems, and possible cognitive effects. 

Because antidepressants affect multiple chemical signaling systems throughout the body, different medications can produce different side effects in different people—and those side effects can build the longer someone remains on treatment.

An analysis published in The Lancet compared 30 antidepressants, highlighting substantial differences in the types and frequency of side effects across medications. 

The one point psychiatrists agree on is that long-term treatment should be reassessed periodically rather than continued automatically.

“A prescription should not become a default setting that continues simply because nobody has stopped to ask whether it remains necessary,” Horowitz said. He recommended that treatment should be reviewed periodically—ideally every six months—to discuss whether the medication is still providing meaningful benefit.

Antidepressants should not be stopped abruptly. If a patient decides to stop treatment, tapering should generally be gradual and individualized. Slowing the taper when symptoms emerge may help clinicians determine whether those symptoms represent withdrawal—which often improves with time—or depression returning, which may require a different treatment approach, Horowitz said.

But there is little good evidence that routinely tapering patients off antidepressants improves outcomes, Aftab said. The available evidence does not resolve every question about the risks and benefits of continuing or stopping treatment, he added, so “clinicians and patients have to operate under uncertainty and should aim to personalize treatment in a collaborative manner as much as possible.”

“The goal is not to persuade everyone to stop antidepressants, nor to persuade everyone to stay on them,” Horowitz said, “but to ensure that patients are making genuinely informed choices based on the best available evidence.”