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Treatment of intraoperative hypotension in a patient on chronic tricyclic antidepressant therapy(TCA) is contro-versial. Evidence based guidelines for the management of psychotropic drugs during perioperative period are lacking. We present a patient who was subjected to bilateral total knee replacement under combined spinal epidural anaesthe-sia. She developed refractory hypotension after release of tourniquet and responded only to large dosage of norepi-nephrine along with acid base correction. We believe that chronic TCA therapy led to depleted catecholamine re-serves and down regulation of its receptors. Release of tourniquet led to metabolic acidosis and subsequently in-creased free clomipramine concentration in blood leading to severe refractory hypotension.