selective serotonin reuptake inhibitor + serotonin-norepinephrine reuptake inhibitor + tricyclic antidepressant

A combination of three antidepressant drug classes: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs). This combination is used in treatment-resistant depression and is designed to simultaneously increase serotonin and norepinephrine neurotransmission, and in the case of TCAs, often modulate additional neurotransmitter systems. SSRIs selectively block the serotonin transporter, SNRIs block both serotonin and norepinephrine transporters, and TCAs primarily block both serotonin and norepinephrine transporters but also affect histamine, muscarinic cholinergic, and adrenergic receptors. Such combinations are rarely recommended for routine use due to increased risk of adverse effects, including serotonin syndrome and cardiac toxicity. This regimen is typically considered only in severe, refractory cases and often requires specialist oversight[1][3][5][7].