Selective serotonin reuptake inhibitor

Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.

SSRIs primarily work by blocking serotonin reabsorption (reuptake) via the serotonin transporter, leading to gradual changes in brain signaling and receptor regulation, with some also interacting with sigma-1 receptors, particularly fluvoxamine, which may contribute to cognitive effects. Marketed SSRIs include six main antidepressants—citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline—and dapoxetine, which is indicated for premature ejaculation. Fluoxetine has been approved for veterinary use in the treatment of canine separation anxiety.

SSRIs are the most widely prescribed antidepressants in many countries. In adults, they are recommended as a first-line treatment for moderate to severe depression, while for mild depression non-drug treatments are preferred unless the patient chooses medication. SSRIs have modest benefits over placebo, with uncertain clinical significance, and may produce a substantial drug-specific response in only a minority of patients. There is no consistent evidence linking depression to low serotonin levels, and long-term use may reduce serotonin concentrations. Fifty years after their introduction, SSRIs remain widely used for depression, though their effectiveness, mechanisms, and role in medicalizing normal life remain debated.

Their effectiveness, especially for mild to moderate depression, remains debated due to mixed research findings and concerns about bias, placebo effects, and adverse outcomes. SSRIs can cause a range of side effects, including movement disorders like akathisia and various forms of sexual dysfunction—such as anorgasmia, erectile dysfunction, and reduced libido—with some effects potentially persisting long after discontinuation (post-SSRI sexual dysfunction). SSRIs pose drug interaction risks by potentially causing serotonin syndrome, reducing efficacy with NSAIDs, and altering drug metabolism through CYP450 enzyme inhibition. SSRIs are safer in overdose than tricyclics but can still cause severe toxicity in large or combined doses. Stopping SSRIs abruptly can cause withdrawal symptoms, so tapering, especially from paroxetine, is recommended, with fluoxetine causing fewer issues.