Antidepressant discontinuation syndrome occurs in 15% of cases

Evan Walker
Evan Walker TheMediTary.Com |
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New research confirms that one in every six to seven people who get off antidepressants experience withdrawal symptoms. Image credit: Carolin Voelker/Getty Images.
  • A systematic review and meta-analysis has demonstrated that approximately 15% of individuals experience withdrawal symptoms, such as dizziness, headache, nausea, insomnia and irritability, when discontinuing antidepressants.
  • Severe symptoms were noted in about 3% of cases, with a higher risk linked to certain medications like imipramine, paroxetine and desvenlafaxine.
  • Despite these findings, the study underscores the importance of evidence-based guidance for patients and healthcare professionals to manage the discontinuation process effectively, highlighting that these symptoms are not due to addiction and can be mitigated with proper support.

According to a systematic review and meta-analysis recently published in The Lancet Psychiatry, there is a 15% chance — or roughly one in six to seven people — of experiencing discontinuation symptoms, also known as withdrawal symptoms, when stopping antidepressants.

The analysis also found that severe discontinuation symptoms, which might cause patients to drop out of a study or resume taking antidepressants, occurred in about 3% — or one in 35 — of those who stopped the medication.

The researchers emphasize that there is strong evidence supporting the effectiveness of antidepressants for many individuals with depressive disorders, either alone or in combination with other treatments like psychotherapy.

However, these medications do not work for everyone and can cause unpleasant side effects for some patients.

For those who have recovered with the aid of antidepressants, doctors and patients may decide to discontinue their use over time. Therefore, it is important for both doctors and patients to have a clear, evidence-based understanding of what might occur when antidepressants are stopped.

The aim of this study was to review all available evidence to determine the likely incidence of discontinuation symptoms directly caused by stopping antidepressants, the probable incidence of severe symptoms and the differences between various types of antidepressants.

The researchers conducted a review and meta-analysis of 79 trials (44 RCTs and 35 observational studies), which included data from 21,002 individuals — 16,532 discontinuing antidepressants and 4,470 discontinuing from placebo.

The average age of the participants was 45 years, with 72% being women.

The analysis revealed that 31% of individuals who stopped taking an antidepressant experienced at least one symptom, such as dizziness, headache, nausea, insomnia or irritability.

Severe symptoms occurred in about 3%, or one in 35 people. Stopping imipramine (Tofranil), paroxetine (Paxil or Seroxat), and venlafaxine (Effexor)/ desvenlafaxine (Pristiq) was associated with a higher risk of severe symptoms compared to other antidepressants.

In randomised controlled trials, 17% of participants experienced discontinuation-like symptoms when stopping a placebo, suggesting that approximately half of the symptoms in those stopping antidepressants might be due to negative expectations — the so-called nocebo effect — or nonspecific symptoms that could occur in the general population.

David Merrill, MD, PhD, a geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center at Providence Saint John’s Health Center in Santa Monica, CA, also not involved in the study, similarly noted that this is an important topic to cover.

“It’s helpful to be able to tell patients that discontinuation symptoms are possible but not inevitable, and even less likely to be severe. So if stopping a drug becomes an issue, they should let their doctor know so they can help figure out what to do,” Merrill said.

“It’s often possible to lessen discontinuation symptoms by temporarily resuming the discontinued drug and the re-attempting the process of stopping the medication. Ideally, the second time stopping can be done more gradually over a longer period of time to lessen or prevent side effects from re-emerging.”

– David Merrill, MD, PhD

De Quevedo added that “awareness of withdrawal symptoms is crucial for understanding the safety and effectiveness of antidepressants, as well as recognizing that these symptoms, if they occur, are a normal part of the process.”

“This understanding can help reduce the stigma surrounding mental Health treatment and encourage more individuals to seek help when needed,” he said.

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