What is Serotonin Withdrawal Syndrome?

Serotonin withdrawal syndrome or discontinuation syndrome describes a number of symptoms that may occur when patients stop taking selective serotonin reuptake inhibitors (SSRIs) or selective serotonin norepinephrine reuptake inhibitors (SNRIs). The syndrome occurs in about 20% of patients who, for at least five weeks, use medicines, like fluvoxamine (Luvox®), paroxetine (Paxil®), venlafaxine and desvenlafaxine (Effexor® and Pristiq®), and setraline (Zoloft®), and then abruptly discontinue treatment. The syndrome stands in contrast to what doctors once thought and advocated to their patients: SSRIs and SNRIs created no trouble in discontinuation. By the mid-1990s, the reports of a variety of physical and emotional symptoms in some patients who stopped taking these medications were too significant to ignore, and the medical community has had to readjust how it talks about antidepressants that prevent serotonin reuptake and how it deals with discontinuation recommendations.

The symptoms of serotonin withdrawal syndrome are varied, and diagnosis is made if people exhibit one or more symptoms upon withdrawal. They can include headache, extreme tiredness, nausea and/or vomiting, and difficulty sleeping. Some patients experience trouble walking, have pronounced dizziness, or feel lightheaded. Sometimes the disorder feels like a bad case of stomach flu with chills, fever, vomiting, and diarrhea. Patients have also reported pins and needles sensations or what is called a “brain zap,” which feels like an electric charge that suddenly occurs in the head. There are other possible results of discontinuation, such as a sense of strong anxiety or depression, increased dreaming, a sense that nothing is real, agitated feelings, or suicidality.

Since some of these symptoms are also present in depression or anxiety conditions, it may be difficult to distinguish whether withdrawal is the specific problem or is creating a reemergence of the illness the antidepressant was treating. Generally, serotonin withdrawal syndrome occurs very quickly after medications are discontinued, so the symptoms are linked directly to it. Nevertheless, an appearance of strong anxiety, depression, or suicidality should always indicate that patients speak with their doctors, and patients are furthermore advised to never discontinue an SSRI/SNRI “cold turkey.”

One of the best ways to avoid serotonin withdrawal syndrome is to taper off an antidepressant, instead of stopping it quickly. Resuming taking an SSRI can also stop symptoms, which, in some patients, can last for several months or more. If patients are interested in stopping one of these medications, even if only to switch to a different type, it is in their interest to have a slow tapering plan in place. This reduces risk of manifesting discontinuation symptoms.

Patients shouldn’t necessarily choose a drug by if its discontinuation may cause serotonin withdrawal syndrome. They can inquire from doctors about the drugs that have the greatest likelihood of these effects, but patients still can’t determine if they’ll be among the 20% of SSRI/SNRI users who experience them. Choice of antidepressant is better based on its effectiveness in the individual, and not on whether tapering off the drug will be required.