Selective Serotonin Reuptake Inhibitor Toxicity

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants. Other clinical indications for SSRI use include anxiety disorders, obsessive-compulsive disorder, panic disorders, and eating disorders. Compared to their predecessors, the monoamine oxidase inhibitors and tricyclic antidepressants, SSRIs are associated with fewer toxic effects. Individual SSRIs differ from each other regarding structure and pharmacokinetics but, as a group, they act by potentiating the action of serotonin. SSRIs are less cardiotoxic than many first-generation antidepressants, but there is still evidence that they inhibit sodium, calcium, and potassium ion channels at concentrations near therapeutic levels. Citalopram and escitalopram are known to cause QTc prolongation. There also have been reports of atrial fibrillation and bradycardia related to fluoxetine use. Adverse effects of SSRIs are vague and nonspecific but include hyponatremia, anorgasmia, sedation, stimulation, and gastric irritation. Seizures are uncommon but have been reported; Isbister et al. reported a seizure incidence of 1.9%. They may also inhibit platelet secretion, aggregation, and plug formation. Patients with adverse effects from SSRIs will present with a range of symptoms, and some researchers have advocated for the term “serotonin toxicity” rather than “serotonin syndrome” to highlight that this condition is a spectrum of symptoms rather than a single clinical entity. In patients with mild symptoms, the benefit they receive from the prescribed SSRI may outweigh the negative side effects.