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This combination therapy refers to the adjunctive treatment regimens evaluated in a Phase 4 investigator-initiated clinical trial led by Mark A. Frye at UCLA. The study investigated whether the addition of either liothyronine (triiodothyronine/T3) or pindolol to the selective serotonin reuptake inhibitor (SSRI) citalopram could accelerate the onset of therapeutic response in patients with major depressive disorder (MDD). Citalopram works by inhibiting the serotonin transporter (SERT), increasing synaptic serotonin levels. Pindolol, a beta-blocker with 5-HT1A receptor antagonist properties, is used to block presynaptic autoreceptors that normally inhibit serotonin release, while liothyronine acts as a thyroid hormone receptor agonist to enhance the overall antidepressant effect. The trial was designed to address the typical 4-6 week delay in SSRI efficacy by utilizing these augmentation strategies.
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