Results from largest review of its kind on antidepressant withdrawal symptoms

(Press-News.org) The largest review of ‘gold standard’ antidepressant withdrawal studies to date has identified the type and incidence of symptoms experienced by people discontinuing antidepressants, finding most people do not experience severe withdrawal.

In a systematic review and meta-analysis of previous randomised controlled trials relating to antidepressant withdrawal, a team of researchers led by Imperial College London and King’s College London concluded that, while participants who stopped antidepressants did experience an average of one more symptom than those who continued or were taking placebos, this was not enough to be judged as significant.

The most common symptoms were dizziness, nausea, vertigo and nervousness. Importantly, depression was not a symptom of withdrawal from antidepressants, and was more likely to reflect illness recurrence.

Researchers at Imperial College London, King’s College London, UCL and UK collaborators say their study provides much needed, clearer guidance for clinicians, patients and policymakers.

Dr Sameer Jauhar, lead author, at Imperial College London, said: “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. 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.”

Clinical academics from around the UK worked collaboratively to conduct the largest and most rigorous analysis of randomised controlled trials in antidepressant withdrawal, examining data from 50 trials across multiple conditions. The data involved a total of 17,828 participants, with an average age of 44 years, of whom 70% were female.  Two meta-analyses were conducted, one of the trials that used a standardised measure known as the Discontinuation Emergent Signs and Symptoms scale (DESS), and the other of the trials that used various other scales.

Across antidepressants, irrespective of type taken, the number of extra symptoms generally equated to one more symptom on the 43-symptom item scale. In placebo-controlled randomised controlled trials, the most common symptoms across antidepressants were dizziness (7.5% vs 1.8%), nausea (4.1% vs 1.5%), vertigo (2.7% vs 0.4%) and nervousness (3% vs 0.8%).

Experiencing just one symptom is below the 4 or more cutoff for clinically important discontinuation syndrome. 

The nature, and rates, of different symptoms varied between antidepressants, and some symptoms were also seen with placebo. This helped to clarify which symptoms were likely to be illness recurring, such as the participant relapsing into depression.

The data involved different types of antidepressants, including the serotonin-norepinephrine reuptake inhibitors (SNRIs) venlafaxine and duloxetine; the selective serotonin reuptake inhibitors escitalopram, sertraline and paroxetine; agomelatine, which is a melatonin receptor agonist and selective serotonin receptor antagonist; and vortioxetine, which inhibits the reuptake of serotonin as well as partial agonist and antagonist effects on various serotonin receptors.

The most symptoms were seen with discontinuance of venlafaxine, where approximately 20% of people suffered from dizziness, compared to 1.8% taking placebo. With vortioxetine, fewer than one extra symptom was seen on the standardised discontinuation scale. No extra symptoms were seen with agomelatine.

Adding non-placebo controlled studies increased these rates slightly; dizziness (11.8%, nightmares 8.1%, nervousness 7.6%, nausea 5.8%).

Relapse of depression was not seen in those withdrawing from antidepressants, even in people with existing depression.

The review included studies with different discontinuation regimes, but in the majority of studies (44), people either discontinued abruptly or tapered over 1 week.

Michail Kalfas, of the Institute of Psychiatry, Psychology & Neuroscience at King’s College London, said: "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. Our focus must now turn to look at the pharmacological basis for this reaction, and ask whether it relates to the way they metabolise these drugs.”

In terms of study limitations, 38 of the trials followed people up for up to two weeks post-discontinuation (the time period one would expect most discontinuation symptoms to occur), so researchers say this limits long-term conclusions. However, they note that findings from the 2021 UCL-led ANTLER trial involving long-term antidepressant users - which was included in this review – suggested severe withdrawal is infrequent, even after prolonged use.

The study follows recent concerns about the effects of stopping antidepressants, as well as various guidance changes on their prescribing. This current meta-analysis helps resolve the debate by showing that withdrawal is a real and drug-specific phenomenon, though not an inevitable outcome.

Professor Allan Young, Head of Psychiatry at the Department of Brain Sciences at Imperial College London, said: “Depression and anxiety are common conditions and antidepressant treatments are effective and generally quite well tolerated.  However, concerns have been raised about the after-effects of stopping these treatments and this is something that has affected patients and clinicians.  Changes of guidance may also have impacted the use of these treatments. Now, this cutting-edge review clarifies the scientific evidence and should reassure all parties about the use, and discontinuation, of these treatments.  Official guidance should now be changed to reflect the evidence.”

Incidence and Nature of Antidepressant Discontinuation Symptoms, A Systematic Review and Meta-analysis by Michail Kalfas, Sameer Jauhar et al is published in JAMA Psychiatry on 9th July 2025. DOI: 10.1001/jamapsychiatry.2025.1362.

The authors will present their findings and discuss the clinical implications in a briefing hosted by the Science Media Centre online on Tuesday 8th July at 10.30am UK time. For an invitation, please contact Freya Robb, Science Media Centre: freya@sciencemediacentre.org

 

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For more information or an interview with the authors, please contact:

Samantha Rey

Media Officer (Medicine)

Imperial College London

Tel: +44 (0)20 020 7594 1507

E-mail: s.rey@imperial.ac.uk / Medicine.media@imperial.ac.uk
Out of hours duty media officer: +44(0) 7803 886 248

 

This press release uses a labelling system developed by the Academy of Medical Sciences to improve the communication of evidence. For more information, please see: http://www.sciencemediacentre.org/wp-content/uploads/2018/01/AMS-press-release-labelling-system-GUIDANCE.pdf

 

NOTES TO EDITORS:

 

About Imperial College London
 

We are Imperial – a world-leading university for science, technology, engineering, medicine and business (STEMB), where scientific imagination leads to world-changing impact.   

As a global top ten university in London, we use science to try to understand more of the universe and improve the lives of more people in it. Across our nine campuses and throughout our Imperial Global network, our 22,000 students, 8,000 staff, and partners work together on scientific discovery, innovation and entrepreneurship. Their work navigates some of the world’s toughest challenges in global health, climate change, AI, business leadership and more.  

Founded in 1907, Imperial’s future builds on a distinguished past, having pioneered penicillin, holography and fibre optics. Today, Imperial combines exceptional teaching, world-class facilities and a habit of interdisciplinary practice to unlock scientific imagination.  

https://www.imperial.ac.uk/

 

About King’s College London and the Institute of Psychiatry, Psychology & Neuroscience

 

King’s College London is amongst the top 35 universities in the world and top 10 in Europe (THE World University Rankings 2023), and one of England’s oldest and most prestigious universities. With an outstanding reputation for world-class teaching and cutting-edge research, King’s maintained its sixth position for ‘research power’ in the UK (2021 Research Excellence Framework).  

King's has more than 33,000 students (including more than 12,800 postgraduates) from some 150 countries worldwide, and some 8,500 staff. The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s is a leading centre for mental health and neuroscience research in Europe. It produces more highly cited outputs (top 1% citations) on psychiatry and mental health than any other centre (SciVal 2021), and on this metric has risen from 16th (2014) to 4th (2021) in the world for highly cited neuroscience outputs. In the 2021 Research Excellence Framework (REF), 90% of research at the IoPPN was deemed ‘world leading’ or ‘internationally excellent’ (3* and 4*). World-leading research from the IoPPN has made, and continues to make, an impact on how we understand, prevent and treat mental illness, neurological conditions, and other conditions that affect the brain.

www.kcl.ac.uk/ioppn | Follow @KingsIoPPN on Twitter, Instagram, Facebook and LinkedIn 


 

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