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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, including colleagues at the University of Oxford, 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 say their study, published in the journal JAMA Psychiatry, provides much needed, clearer guidance for clinicians, patients and policymakers.
Clinical academics from around the UK, including Associate Professor Robert McCutcheon and Professor Phil Cowen from Oxford's Department of Psychiatry, 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.
Associate Professor McCutcheon, Wellcome Clinical Research Career Development Fellow at the Department of Psychiatry at Oxford, said:
This analysis found that people discontinuing antidepressants experienced more withdrawal symptoms than those continuing treatment or receiving placebo. However, the number and severity of symptoms varied substantially between medications, and in most cases, it seems that withdrawal symptoms are manageable for patients. Further research is needed to understand long-term effects, especially in people treated for extended periods."
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.
- Read comments from Professor Michael Browning and Associate Professor Susannah Murphy on this study in the New Scientist.