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Nortriptyline + lithium is a combination therapy used primarily in the management of major depressive disorder, particularly for patients who are resistant to standard antidepressant treatments or as continuation therapy following electroconvulsive therapy (ECT). Nortriptyline is a tricyclic antidepressant that increases the activity of serotonin and norepinephrine in the brain by inhibiting their reuptake. Lithium is a mood stabilizer with complex mechanisms, including modulation of dopaminergic, glutamatergic, and GABAergic neurotransmission; inhibition of inositol monophosphatase signaling; alteration of catecholamine and serotonin metabolism; effects on neural plasticity via glycogen synthetase kinase-3β and other kinases; downregulation of certain serotonin receptors; increased synthesis of norepinephrine and serotonin. The combination has been shown to reduce relapse rates after ECT more effectively than either agent alone[2][3][4][5][6][8].
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