Depression Guidelines Fall Short in Characterizing Withdrawal

Current depression guidelines offer incomplete guidance for clinicians to identify antidepressant withdrawal, based on data from a review of 21 guidelines.

Previous research suggests that approximately half of patients who discontinue or decrease dosage of antidepressants experience withdrawal symptoms, wrote Anders Sørensen, MD, of Copenhagen University Hospital, and colleagues. These symptoms are diverse and may include flulike symptoms, fatigue, anxiety, and sensations of electric shock, they noted. Most withdrawal effects last for a few weeks, but some persist for months or years, sometimes described as persistent postwithdrawal disorder, they added.

“Symptoms of withdrawal and depression overlap considerably but constitute two fundamentally different clinical conditions, which makes it important to distinguish between the two,” the researchers emphasized.

In a study published in the Journal of Affective Disorders, the researchers identified 21 clinical practice guidelines (CPGs) for depression published between 1998 and 2022. The guidelines were published in the United Kingdom, the United States, Canada, Australia, Singapore, Ireland, and New Zealand. They compared descriptions of withdrawal from antidepressants and calculated the proportion of CPGs with different information.

Overall, 15 of the 21 studies in the review (71%) noted that antidepressants are associated with withdrawal symptoms, but less than half (43%) used the term “withdrawal symptoms,” or similar. Of the nine guidelines that mentioned withdrawal symptoms, five used the term interchangeably with “discontinuation symptoms” and six used the term “discontinuation symptoms” only when discussing antidepressant withdrawal. In addition, six CPGs specifically stated that patients who stop antidepressants can experience withdrawal symptoms, and five stated that these symptoms also can occur in patients who are reducing or tapering their doses.

The type of withdrawal symptoms was mentioned in 10 CPGs, and the other 11 had no information on potential withdrawal symptoms, the researchers noted. Of the CPGs that mentioned symptoms specifically associated with withdrawal, the number of potential symptoms ranged from 4 to 39.

“None of the CPGs provided an exhaustive list of the potential withdrawal symptoms identified in the research literature,” the researchers wrote in their discussion.

Only four of the guidelines (19%) mentioned the overlap in symptoms between withdrawal from antidepressants and depression relapse, and only one provided guidance on distinguishing between the two conditions. Most of the symptoms of withdrawal, when described, were characterized as mild, brief, or self-limiting, the researchers noted.

“Being in withdrawal is a fundamentally different clinical situation than experiencing relapse, requiring two distinctly different treatment approaches,” the researchers emphasized. “Withdrawal reactions that are more severe and longer lasting than currently defined in the CPGs could risk getting misinterpreted as relapse, potentially leading to resumed unnecessary long-term antidepressant treatment in some patients,” they added.

The findings were limited by several factors including the inclusion only of guidelines from English-speaking countries, which may limit generalizability, the researchers noted. Other potential limitations include the subjective judgments involved in creating different guidelines, they said.

However, the results support the need for improved CPGs that help clinicians distinguish potential withdrawal reactions from depression relapse, and the need for more research on optimal dose reduction strategies for antidepressants, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

This article originally appeared on, part of the Medscape Professional Network.

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