fluoxetine + mirtazapine

Fluoxetine + mirtazapine is a combination of two antidepressant medications used off-label for the treatment of major depressive disorder, particularly in cases where monotherapy has not achieved remission. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that increases synaptic serotonin by inhibiting its reuptake into presynaptic neurons. Mirtazapine is an atypical tetracyclic antidepressant that enhances noradrenergic and serotonergic neurotransmission primarily through antagonism of central presynaptic alpha-2 adrenergic inhibitory autoreceptors and heteroreceptors, as well as antagonism at certain serotonin receptors (notably 5-HT2 and 5-HT3). The rationale for combining these agents is to target multiple neurotransmitter systems to potentially increase efficacy in treatment-resistant depression. However, this combination carries an increased risk of serotonin syndrome and should be used with caution under specialist supervision[1][5][2][3].