Bologna, Italy—Despite their widespread use in medical practice, the antidepressant drugs selective serotonin reuptake inhibitors (SSRI) and serotonin-noradrenaline reuptake inhibitors (SNRI) have been reported to produce withdrawal symptoms after reduction or discontinuation.

An article in the journal Psychotherapy & Psychosomatics sought to identify the occurrence, frequency, and features of withdrawal symptoms after SNRI discontinuation.

“Such a review appears to be important in view of the fact that SNRI are increasingly prescribed and usually considered the first choice in the treatment of mood and anxiety disorders, both for their efficacy and for their presumed high levels of safety and tolerability. They are also employed in clinical conditions such as chronic pain, functional medical disorders, and menopausal symptoms,” according to the study.

To provide more information, a group of researchers from two Italian universities, as well as the State University of New York Buffalo and Pennsylvania State University conducted a systematic review of the literature. The study team searched electronic databases PubMed, the Cochrane Library, Web of Science, and MEDLINE from the inception of each database to June 2017.

Ultimately, the researchers found that 61 English-language reports met the criteria for inclusion—22 double-blind randomized, controlled trials, six studies where patients were treated in an open fashion and then randomized to a double-blind controlled phase, eight open trials, one prospective naturalistic study, one retrospective study, and 23 case reports.

Based on those reports, they determined that withdrawal symptoms occurred after discontinuation of any type of SNRI, although the rate of symptoms appeared to be higher with venlafaxine. Results indicate that symptoms typically occurred within a few days from discontinuation and lasted a few weeks, also with gradual tapering. The study also found evidence of late onset and/or a longer persistence of disturbances.

“Clinicians need to add SNRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with other types of psychotropic drugs,” study authors write. “The results of this study challenge the use of SNRI as first-line treatment for mood and anxiety disorders.”

Lead author Giovanni A. Fava, MD of the University of Bologna, Italy, and the University at Buffalo, NY, pointed out, “This type of antidepressant drugs is widely used with the wrong assumption that they do not cause dependence and problems upon discontinuation. We should be more cautious in prescribing them and be aware of the problems that ensue when you stop them.”

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