Background: Withdrawal symptoms on selective serotonin reuptake inhibitor (SSRI) discontinuation have raised clinical attention increasingly. However, delirium is rarely reported in the SSRI discontinuation syndrome.

Case: We report a case of delirium developing after fluoxetine discontinuation in a 65-year-old female patient with major depressive disorder. She experienced psychotic depression with limited response to treatment of fluoxetine 40 mg/d and quetiapine 100 mg/d for 3 months. After admission, we tapered fluoxetine gradually in 5 days because of its limited effect. However, delirious pictures developed 2 days after we stopped fluoxetine. Three days later, we added back fluoxetine 10 mg/d. Her delirious features gradually improved, and the clinical presentation turned into previous psychotic depression state. We gradually increased the medication to fluoxetine 60 mg/d and olanzapine 20 mg/d in the following 3 weeks. Her psychotic symptoms decreased, and there has been no delirious picture noted thereafter.

Conclusions: Delirium associated with fluoxetine discontinuation is a much rarer complication in SSRI discontinuation syndrome. The symptoms of SSRI discontinuation syndrome may be attributable to a rapid decrease in serotonin availability. In general, the shorter the half-life of any medication, the greater the likelihood patients will experience discontinuation symptoms. Genetic vulnerability might be a potential factor to explain that SSRI discontinuation syndrome also occurred rapidly in people taking long–half-life fluoxetine. The genetic polymorphisms of both pharmacokinetic and pharmacodynamic pathways might be potentially associated with SSRI discontinuation syndrome.