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 psychiatric 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. A 2018 meta analysis of 21 antidepressants showed that all antidepressants (including SSRIs) were more effective than placebo in adults with major depressive disorder.
Medical uses The main indication for SSRIs is major depressive disorder; however, they are frequently prescribed for anxiety disorders, such as social anxiety disorder, generalized anxiety disorder, panic disorder, obsessive–compulsive disorder, eating disorders, chronic pain, and, in some cases, for post-traumatic stress disorder. They are also frequently used to treat depersonalization disorder, although with varying results.
Depression
In adults In 2022, the UK National Institute for Health and Care Excellence (NICE) recommended that antidepressants be offered as a first-line treatment for moderate to severe depression, but for mild depression, non-drug interventions are preferred unless the patient chooses medication. They recommended that antidepressants should not be routinely offered for mild depression and should generally be used only if non-drug treatments fail or the patient prefers medication. In a 2018 review, all 21 studied antidepressants were more effective than placebo for major depressive disorder. The commonly used definition of antidepressant "response" as a 50% symptom reduction dichotomizes continuous data, which methodologists note can inflate effect sizes, exaggerate drug–placebo differences, and may not reliably indicate clinical significance. A large FDA trial analysis found that SSRIs and other antidepressants produced only modest average benefits over placebo, with about 15% of patients experiencing a substantial drug-specific response. SSRIs and other antidepressants may have average treatment effects that fall below the minimal important difference on common depression outcome measures, leaving their clinical significance in acute moderate-to-severe depression uncertain. There is no consistent evidence that depression is caused by lowered serotonin activity or concentrations, with some data suggesting that long-term antidepressant use may reduce serotonin levels.
In children The NICE Guideline recommends that SSRIs should not be used to treat depression in children and young people, except for fluoxetine, which may be considered for moderate to severe depression when psychological therapies alone are insufficient. In the United States, they are approved for use in pediatric patients; however, individuals under 25 years of age should be closely monitored for an increased risk of suicidality, as indicated by the FDA black box warning. SSRIs have the best outcomes when combined with cognitive-behavioral therapy. Their benefits are modest and tolerability varies. The benefits may be clinically unimportant and there are uncertain effects on suicide risk.
Social anxiety disorder SSRIs show some evidence of effectiveness for social anxiety disorder, including reducing relapse and disability, but the overall quality of evidence is low to moderate and tolerability is slightly lower than placebo.
Post-traumatic stress disorder Two SSRIs are FDA-approved for PTSD: paroxetine and sertraline. The 2023 VA/DoD guideline for PTSD recommends the SSRIs sertraline and paroxetine as first-line pharmacological treatments when trauma-focused therapy is unavailable or not preferred; evidence for other SSRIs is insufficient, and medications are recommended to be tailored to each patient's individual needs. A 2022 Cochrane review found that SSRIs improve PTSD symptoms in 58% of patients compared with 35% on placebo (RR 0.66) and are considered first-line treatment.
Generalized anxiety disorder SSRIs are recommended by the National Institute for Health and Care Excellence (NICE) for the treatment of generalized anxiety disorder (GAD) in adults who have not responded to initial interventions such as education, self-help strategies, or psychological therapies. SSRIs are more effective than placebo for treating GAD with similar overall acceptability, though they increase dropout due to adverse effects.
Obsessive–compulsive disorder In Canada, SSRIs are a first-line treatment of adult obsessive–compulsive disorder (OCD). In the UK, they are first-line treatment only with moderate to severe functional impairment and as second-line treatment for those with mild impairment, though, as of early 2019, this recommendation is being reviewed. SSRIs are more effective than placebo for reducing OCD symptoms and global severity in children and adolescents, and combining them with exposure therapy is probably more effective than using an SSRI alone.
Panic disorder SSRIs are approved to treat panic disorder. SSRIs may be more effective than placebo in reducing panic disorder symptoms, but they are associated with a higher risk of adverse effects and may be less well tolerated.
… excerpt ends here. Continue reading the full article.
