Tapering Down, Reducing or Stopping Use of Serotonin Reuptake Inhibitor Antidepressants

"Patients stopping serotonin reuptake inhibitor (SRI) antidepressants are susceptible to SRI withdrawal, a constellation of somatic and cognitive-emotional symptoms usually occurring within 24–48 hours of stopping or reducing dosages. The syndrome may follow a protracted course and is often associated with substantial morbidity and functional impairment.1,2 Systematic reviews have reported the incidence of antidepressant withdrawal to be 33%–56%, based on short-term studies.3,4

"In recent years, the high rates of SRI withdrawal despite ostensibly gradual taper protocols have been explained by positron emission technology (PET) radioligand neuroimaging data. These studies show that about 80% occupancy of the serotonin transporter (SERT) occurs at minimum therapeutic doses of SRI antidepressants, with considerable occupancy even at subtherapeutic doses, as represented by a hyperbolic curve (Table 1).5–7 To avoid precipitous changes in SERT occupancy, which are thought to induce neurobiological instability, dosage reductions should respect this hyperbolic relationship. Progressively lower subtherapeutic doses must be incorporated into an SRI taper to maximally attenuate the risk of withdrawal symptoms.5–9"