King's College London

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.

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.

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 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 9^th July 2025. DOI: 10.1001/jamapsychiatry.2025.1362.