Newer Antidepressants and the Discontinuation Syndrome

Data on discontinuation phenomena associated with serotonin selective reuptake inhibitors(SSRIs) are derived primarily from (1) published case reports, (2) data bases of adverse drug reactionsthat have been spontaneously reported to national monitoring bureaus, and (3) clinical studies of drugdiscontinuation. Some of the symptoms seen on SSRI discontinuation, such as nausea, lethargy, insomnia,and headache, are similar to those reported with tricyclic discontinuation. However, SSRIdiscontinuation is also associated with novel symptom clusters, including problems with balance, sensoryabnormalities, and possibly aggressive and impulsive behavior. Although generally mild andshort-lived, discontinuation symptoms can be severe and chronic and have a major impact on thepatient’s lifestyle. The incidence of discontinuation symptoms varies widely among the differentSSRIs; the highest rate is seen with paroxetine. The variation in incidence might be explained by thedifferent pharmacokinetic and pharmacodynamic profiles of the SSRIs.