Major
Established
Description
Combining two SSRIs is generally contraindicated due to markedly elevated serotonin syndrome risk and no additional therapeutic benefit.
Mechanism
Both agents inhibit SERT-mediated serotonin reuptake; concurrent use produces additive serotonin accumulation in central synapses.
Clinical Significance
Dual SSRI therapy provides no clinical advantage over monotherapy and substantially raises serotonin toxicity risk.
Management
Avoid concurrent use; when switching SSRIs, allow an appropriate washout period (5 half-lives of the discontinued drug).