Antidepressants: New study sheds light on withdrawal symptoms

Around one in six people who stop antidepressants will experience withdrawal symptoms as a direct result of the medicine – lower than previous estimates, according to the largest study of its kind.

A new analysis published in The Lancet Psychiatry of randomised controlled trials found 15% of patients will experience one or more discontinuation symptoms that are directly caused by stopping the drugs, while around 2-3% will suffer severe symptoms.

Previous research has suggested much higher rates of withdrawal symptoms, with 56% of all patients affected, though experts have said this figure is not robust.

In 2022/23, 86 million antidepressants were prescribed to an estimated 8.6 million patients in England, NHS figures show.

In the new research, the most commonly used antidepressants in the UK were found to have the lowest rates of withdrawal symptoms throughout the study.

Stopping antidepressants can lead to various symptoms or none at all.

The most frequently reported are dizziness, headache, nausea, insomnia and irritability.

Discontinuation symptoms typically occur within a few days, and the new study found they lasted from 1·5 to 196 days.

Researchers in Germany looked at a range of antidepressants for the work, which included data for 21,000 patients involved in 79 pieces of research.

Most (72%) of those included were women and the average age was 45.

From a list of 11 separate antidepressants, citalopram, sertraline and fluoxetine – which are the most commonly used in the UK – had the lowest chances of suffering withdrawal symptoms.

According to researchers, fluoxetine, for example, takes longer to leave the body and may account for fewer withdrawal effects.

However, venlafaxine, which is also used in the UK, was second highest for people experiencing symptoms.

Glyn Lewis, professor of epidemiological psychiatry at the University College London Division of Psychiatry, told the PA news agency: “The commonest antidepressants used in the UK are sertraline, citalopram and fluoxetine – and these are all antidepressants with a lower risk of discontinuation symptoms.

“However, venlafaxine is also used relatively commonly though, as a second line antidepressant in those who haven’t responded to the first one.

“Venlafaxine does appear to lead to more discontinuation symptoms when stopped and as a result doctors will tend to advise a longer tapering period when people stop using venlafaxine.

“There is also a slow release form of venlafaxine that will reduce the possibility of discontinuation symptoms.”

In a linked editorial, Prof Lewis and his colleague Dr Gemma Lewis said many of the studies in the new overall analysis were small, “often using antidepressants not commonly used now, and studying people who had not taken the antidepressants for a very long time”.

But they added: “Despite these limitations, the results here are a substantial improvement on anything that has been published before.”

Dr Jonathan Henssler, from Charite – Universitatsmedizin Berlin, an author on the study, said: “There is strong evidence that antidepressants can be effective for many people who are experiencing a depressive disorder, either alone, or alongside other treatments such as psychotherapy.

“However, they do not work for everyone, and some patients may experience unpleasant side effects. In patients who have recovered with the help of antidepressants, the decision from doctors and patients may be to stop taking them in time.

“Therefore, it’s important both doctors and patients have an accurate, evidence-based picture of what might happen when patients stop taking antidepressants.

“It’s important to note that antidepression discontinuation symptoms are not due to antidepressants being addictive.

“There is a crucial need for all patients stopping antidepressants to be counselled, monitored and supported by healthcare professionals.

“However, our findings, which consolidate data from a large number of studies, should also provide reassurance that rates of discontinuation symptoms are not as high as some previous single studies and reviews have suggested.”

The research found stopping taking imipramine, paroxetine and venlafaxine was associated with a higher risk of severe symptoms compared with other antidepressants.

Dr Sameer Jauhar, consultant psychiatrist at King’s College London, said previous estimates of withdrawal symptoms have been high.

He added: “This new, thorough review and meta-analysis indicates rates are much lower, and also occur in people coming off placebo, as opposed to antidepressants.

“When accounting for placebo, the rates of withdrawal symptoms are around 14%, and 2% for severe withdrawal.

“It should be acknowledged that this only pertains to those taking part in trials, though this is the best evidence we have.

“Clinically, doctors will still need to have conversations about stopping medications and doing this safely, though it will be gratifying to know rates of withdrawal are nowhere near as high as reported.

“This work is a salutary lesson, as some people may have been dissuaded from taking a potentially effective treatment, based on poor quality evidence that did not conform diligently to the scientific method.

“Science does correct itself, and the authors are to be congratulated on this work.”

The NHS website says people who wish to come off antidepressants should speak to their doctor, who will probably recommend coming off them gradually over several weeks.

Professor Oliver Howes, chairman of the psychopharmacology committee at the Royal College of Psychiatrists, said: “Antidepressants are a clinically recommended treatment, and they are effective at reducing the symptoms of moderate to severe depression, particularly when used in combination with talking therapies.

“It is important patients discuss their treatment options with a qualified practitioner, including their benefits, risks and side-effects…

“If someone chooses to stop taking their antidepressants, their doctor should help them to do so slowly and in a controlled manner that limits the impact of any potential withdrawal symptoms.”