SSRI Discontinuation Syndrome

By: Shannon Tellier, PharmD Candidate c/o 2013

Antidepressant discontinuation syndrome has been reported in all categories of antidepressants after an abrupt interruption of therapy.1  Symptoms usually occur within a few days of stopping or reducing the dosage of the antidepressant, and rarely occur with therapy of less than five weeks.1  If left untreated, most symptoms self-resolve within one day and three weeks.1  It is difficult to determine the incidence of discontinuation symptoms due to underreporting, but selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome may be as high as 40%.2

Many pathological hypotheses exist for this discontinuation syndrome, but a definite explanation remains unknown.  Since long-term use of SSRIs results in a down regulation of postsynaptic serotonin receptors, these receptors may remain in their hypoactive state for days to weeks.3  There is also a concern of a temporary absence of serotonin in the synapse after a sudden withdrawal of an SSRI.3  A combination of down-regulated receptors and absence of serotonin may be responsible for SSRI discontinuation syndrome.3  All SSRIs may cause a discontinuation syndrome, but it is more prevalent with paroxetine due to its short half-life (and less likely, if ever, with fluoxetine due to its long half-life).3

Recognition of symptoms of antidepressant discontinuation syndrome is important for both the patient and health care provider.1,3  The FINISH mnemonic (Flu-like symptoms, Insomnia, Nausea, Imbalance, Sensory Disturbances, Hyperarousal) is used to remember these symptoms.3  The most common symptoms for SSRI discontinuation include dizziness, nausea, lethargy and headache.1

To prevent the symptoms of discontinuation syndrome, a healthcare provider-supervised tapering over six to eight weeks is recommended.3  There are no validated recommendations, but SSRIs should be tapered slowly (agent-specifically) due to their varying half-lives and active metabolites.3  If the patient starts experiencing discontinuation syndrome, the full dose of antidepressant can be restarted and very slowly tapered again.3  Another option is to provide fluoxetine, which is “self-tapering” due to its long half-life and active metabolite.2  In mild to moderate cases of discontinuation syndrome, the patient can be treated symptomatically.1  For example, a patient can be prescribed a short course of benzodiazepines for insomnia.1  In general, the patient should be reassured that these symptoms are benign and will subside within one day to three weeks.1

Education about antidepressant discontinuation syndrome for patients and healthcare providers is essential to prevent misdiagnosis (particularly when an antidepressant is discontinued or switched to another agent).  Often, discontinuation symptoms, such as fatigue, appetite changes, insomnia, and cognitive problems may be mistaken as a depressive relapse.3  It should be explained to the patient that relapses occur two to three weeks after stopping an antidepressant, and discontinuation syndrome can occur in little as a few hours after missing a dose.3  In addition, patients who are nonadherent to their antidepressants may experience discontinuation syndrome, and believe that their treatment regimen is ineffective.3  Switching antidepressants may also result in discontinuation syndrome from stopping the first agent.3  Patients may associate these symptoms as adverse effects from the new antidepressant, leading to more therapy changes.3  Therefore, it is important for the health care provider to be aware of antidepressant discontinuation syndrome to prevent misdiagnosis and unnecessary therapy changes.

As mentioned previously, increased professional awareness allows for the early recognition of antidepressant discontinuation syndrome, and can prevent misdiagnosis or unnecessary therapy changes.  Patients should not to abruptly stop an antidepressant, and ought to taper slowly (under supervision of their health care provider).  The patient should also be reassured that antidepressants are not addictive, and that these symptoms are not life threatening and will resolve in a couple of weeks.1,3


  1. Haddad P.  Antidepressant Discontinuation Syndromes: Clinical Relevance, Prevention, and Management.  Drug Saf 2001;24(3):183-197.
  2. Cole SA, Christensen JF, Raju Cole M, et al.  Chapter 22.  Depression.  In: Feldman MD, Christensen JF, eds.  Behavioral Medicine: A Guide for Clinical Practice.  Third ed.  New York: McGraw-Hill; 2008.  Accessed Oct 30, 2012.
  3. Warner CH, Bobo W, Warner C, et al.  Antidepressant Discontinuation Syndrome.  Am Fam Physician 2006;74(3):449-56.
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