At least 15% of people who stop taking antidepressants will suffer from withdrawal symptoms, suggests a recent analysis, which found dizziness, headache and nausea among the common symptoms occurring more frequently with some medications than others.
The researchers in Germany analysed data in 79 studies involving 21 000 patients and found that nearly one in seven people experienced one or more withdrawal symptoms that were directly caused by coming off antidepressants, while about 3% experienced severe symptoms.
Most common, according to the findings published in The Lancet Psychiatry, were irritability, dizziness, headache, nausea and insomnia.
These symptoms typically occur within a few days, and can last from a couple of days to more than six months.
The authors also compared the types of medication taken, finding citalopram, sertraline and fluoxetine – the most commonly used antidepressants in the UK – had the lowest risks of symptoms, reports The Guardian.
But stopping taking imipramine (Tofranil), paroxetine (Paxil or Seroxat) and desvenlafaxine (Pristiq) was associated with a higher risk of severe symptoms.
Dr Jonathan Henssler, from Charité-Universitätsmedizin Berlin, one of the co-authors of the study, said that while antidepressants can be effective for many people, they do not work for everyone. Whatever the reason for coming off the medication, doctors and patients need an accurate, evidence-based picture of what might happen, he added.
“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,” he said.
Some critics questioned the findings, as about half the studies involved patients who had been taking antidepressants for three months or less.
But Christopher Baethge, co-author of the research and professor of psychiatry at the University of Cologne, said that although patients normally need to take antidepressants for several weeks before a risk of withdrawal symptoms can be expected, the prevalence of symptoms did not increase with longer use: “In our sample of studies, we found no increased risk of discontinuation symptoms among patients taking antidepressants for a longer period of time than three months.”
A previous analysis had suggested that as many as 56% of patients experienced withdrawal symptoms when stopping antidepressants, but that has been criticised as not robust.
Dr Sameer Jauhar, a consultant psychiatrist at King’s College London, said although the research looked only at patients taking part in trials, it was “the best evidence we have” and it was “gratifying to know rates of withdrawal are nowhere near as high as reported”.
The researchers identified some limitations of their study, in particular the possibility of the recurrence of depression after medication was stopped being interpreted as withdrawal symptoms.
They also noted that only seven antidepressants were investigated in three or more studies, and that no studies had been found on several widely used antidepressants such as mirtazapine, bupropion or amitriptyline.
Study details
Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis
Jonathan Henssler, Yannick Schmidt, Christopher Baethge et al.
Published in The Lancet Psychiatry on 5 June 2024
Summary
Background
Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms has not been quantified. An estimate of antidepressant discontinuation symptoms incidence could inform patients and clinicians in the discontinuation of treatment, and provide useful information to researchers in antidepressant treatments. We aimed to assess the incidence of antidepressant discontinuation symptoms in patients discontinuing both antidepressants and placebo in the published literature.
Methods
We systematically searched Medline, EMBASE, and CENTRAL from database inception until Oct 13, 2022 for randomised controlled trials (RCTs), other controlled trials, and observational studies assessing the incidence of antidepressant discontinuation symptoms. To be included, studies must have investigated cessation or tapering of an established antidepressant drug (excluding antipsychotics, lithium, or thyroxine) or placebo in participants with any mental, behavioural, or neurodevelopmental disorder. We excluded studies in neonates, and those using antidepressants for physical conditions such as pain syndromes due to organic disease. After study selection, summary data extraction, and risk of bias evaluation, data were pooled in random-effects meta-analyses. The main outcome was the incidence of antidepressant discontinuation symptoms after discontinuation of antidepressants or placebo. We also analysed the incidence of severe discontinuation symptoms. Sensitivity and meta-regression analyses tested a selection of methodological variables.
Findings
From 6095 articles screened, 79 studies (44 RCTs and 35 observational studies) covering 21 002 patients were selected (72% female, 28% male, mean age 45 years [range 19·6–64·5]). Data on ethnicity were not consistently reported. 16 532 patients discontinued from an antidepressant, and 4470 patients discontinued from placebo. Incidence of at least one antidepressant discontinuation symptom was 0·31 (95% CI 0·27–0·35) in 62 study groups after discontinuation of antidepressants, and 0·17 (0·14–0·21) in 22 study groups after discontinuation of placebo. Between antidepressant and placebo groups of included RCTs, the summary difference in incidence was 0·08 [0·04–0·12]. The incidence of severe antidepressant discontinuation symptoms after discontinuation of an antidepressant was 0·028 (0·014–0·057) compared with 0·006 (0·002–0·013) after discontinuation of placebo. Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms. Heterogeneity of results was substantial.
Interpretation
Considering non-specific effects, as evidenced in placebo groups, the incidence of antidepressant discontinuation symptoms is approximately 15%, affecting one in six to seven patients who discontinue their medication. Subgroup analyses and heterogeneity figures point to factors not accounted for by diagnosis, medication, or trial-related characteristics, and might indicate subjective factors on the part of investigators, patients, or both. Residual or re-emerging psychopathology needs to be considered when interpreting the results, but our findings can inform clinicians and patients about the probable extent of antidepressant discontinuation symptoms without causing undue alarm.
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