Selective serotonin reuptake inhibitor

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Selective serotonin reuptake inhibitor
Drug class
Serotonin, the neurotransmitter that is involved in the mechanism of action of SSRIs
Class identifiers
Synonyms	Serotonin-specific reuptake inhibitors, serotonergic antidepressants[1]
Use	Major depressive disorder, anxiety disorders
ATC code	N06AB
Biological target	Serotonin transporter
Clinical data
Drugs.com	Drug Classes
Consumer Reports	Best Buy Drugs
External links
MeSH	D017367
Legal status
In Wikidata

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.^[2] 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.

Positive antidepressant trial results are much more likely to be published than negative ones, and many meta-analyses have conflicts of interest due to pharmaceutical industry involvement, often downplaying potential risks. While warnings about antidepressants possibly causing suicidal thoughts were added after years of debate, the evidence has remained controversial, with some experts questioning the strength of the link even after regulatory actions.