1 in 6 People Who Stop Antidepressants Have Withdrawal Symptoms

Key Takeaways

• A meta-analysis of nearly 80 studies showed that many people who stop taking antidepressants experience withdrawal symptoms.
• Some of these symptoms, like "brain zaps," can be quite distressing.
• People discontinuing antidepressants should consult closely with their provider to minimize the risk of withdrawal symptoms.

A new study estimates that about 15 percent of people who stop taking antidepressants will experience withdrawal symptoms like dizziness, headaches, nausea, insomnia, irritability, and even electric-shock like sensations sometimes called "brain zaps."

Research published this week in The Lancet Psychiatry highlighted that in 1 out of 35 people coming off antidepressants , these symptoms are likely to be severe.

"Like all medications, antidepressants present important benefits, but also carry risks, including discontinuation symptoms, which are also common among a variety of general medications, like drugs for high blood pressure or mild painkillers," says study author Christopher Baethge, MD , a researcher in the department of psychiatry and psychotherapy at University Hospital Cologne in Germany. "Our findings can inform clinicians and patients about the probable extent of antidepressant discontinuation symptoms without causing undue alarm."

Some Antidepressants Are More Likely to Cause Withdrawal Symptoms

The severity and frequency of withdrawal symptoms depends on the type of medication that people were taking, according to the analysis.

Stopping imipramine (Tofranil), paroxetine (Paxil and Seroxat), desvenlafaxine (Pristiq), and venlafaxine (Effexor) and were associated with more severe withdrawal symptoms compared with other antidepressants. Withdrawal symptoms were more frequent for those stopping desvenlafaxine, venlafaxine, imipramine, or escitalopram (Lexapro).

Fluoxetine (Prozac) and sertraline (Zoloft), on the other hand, had the lowest rates of discontinuation symptoms.

"There really is a difference with the different types of medications," says Lisa Fortuna, MD , chair of the department of psychiatry and neuroscience at the University of California in Riverside, adding that this often has to do with how quickly our bodies metabolize specific drugs.

"The ones that leave your system more quickly are always likely to cause more side effects," she says.

The study indicates that symptoms typically occur within a few days after stopping a medication and are usually temporary - but they can last up to several weeks or months in some cases.

The Extent of the Problem May Be Smaller Than Previously Thought

While these latest findings confirm that withdrawal symptoms may affect a significant number of people, they also suggest that these side effects may occur less frequently than past studies have suggested.

Previous research has estimated that over half of people quitting antidepressants experience withdrawal symptoms, and that among that group, half experience severe symptoms.

Dr. Baethge and his collaborators noted that these earlier estimates were largely based on observational studies that cannot reliably determine cause and effect.

He and his team pointed out that well-conducted randomized controlled trials (where half of trial participants are offered a placebo, or dummy pill, and the other half get the medication) can more accurately distinguish between symptoms directly caused by the medication and "nonspecific" symptoms that might be due to other factors.

With the aim of getting a more comprehensive and precise view of the problem, researchers conducted an analysis of 79 trials including over 21,000 people. A total of 16,532 were discontinuing antidepressants, while 4,470 were stopping a placebo. Participants were 45 years old on average, and nearly three-quarters were women. The majority of the studies included were randomized controlled trials.

"One of the powerful things about a meta-analysis like this is that it's pulling data from multiple studies to come to a conclusion," says Dr. Fortuna, who was not involved in the research. "You gain a lot from multiple studies and not just one."

Antidepressant Withdrawal Symptoms May Not Always Be Due to the Drug Itself

Before taking the results from placebo participants into account, study authors had found that about 1 in 3 patients overall had withdrawal symptoms.

When looking specifically at the outcomes from the randomized controlled trials, however, they discovered that about 17 percent of those who stopped taking a placebo drug also experienced withdrawal symptoms.

"I was surprised at the high incidence of antidepressant discontinuation symptoms among patients going off placebo," says Baethge. The results suggested that about half of all symptoms experienced in those stopping antidepressants may be related to factors other than the drugs themselves.

Coming Up With a Plan When Going Off an Antidepressant

For Beth Salcedo, MD, medical director of the Ross Center mental health practice in Washington, DC, and past president of the Anxiety and Depression Association of America , this paper validates what psychiatrists know well and what so many people experience.

"The study emphasizes how important it is to have a plan for a slow tapering [gradually reducing doses] and close contact with the clinician prescribing the medication," says Dr. Salcedo, who was not involved in the study. "It should remind all of those prescribing these meditations that monitoring is warranted."

She emphasizes that tapering can reduce the likelihood of withdrawal effects, including jarring symptoms like brain zaps.

"Brain zaps are also very common during withdrawal and not at all dangerous, but can be both scary and disturbing," says Salcedo. "This is why a thorough discussion of what to expect during the taper is necessary, and warning about abrupt discontinuation should be a conversation at the start of treatment."

Fortuna further advises that knowing the effects of discontinuation may also help people who have trouble adhering to their medications.

"There can be similar negative effects from not taking medications consistently," she says. "It can be really scary if you don't know what to expect, so it's really important to have good communication with your doctor."

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Sources

1. Hennsler J et al. Incidence of Antidepressant Discontinuation Symptoms: A Systematic Review and Meta-Analysis. The Lancet Psychiatry . June 5, 2024.
2. Davies J et al. A Systematic Review Into the Incidence, Severity and Duration of Antidepressant Withdrawal Effects: Are Guidelines Evidence-Based? Addictive Behaviors . October 2019.