Imipramine effect on hypothalamic-pituitary-adrenal axis response to hypoglycemia

Six control subjects underwent an insulin tolerance test before and after the administration of therapeutic doses of imipramine hydrochloride for 10 days to investigate effects of tricyclic antidepressants on hypothalamic-pituitary-adrenal axis response to hypoglycemia. The mean steady-state tricyclic blood level was 141 (SD = 66) ng/ml. Baseline levels of glucose, cortisol, and adrenocorticotropic hormone (ACTH) were not affected by the administration of imipramine. After administration of imipramine for 10 days, subjects uniformly had a significantly lower glucose nadir than before its administration (before imipramine: mean = 32 mg/dl; SD = 5; after imipramine: mean = 24 mg/dl; SD = 6). There was no difference in ACTH or cortisol response before and after the administration of imipramine. These findings suggest that imipramine hydrochloride increases sensitivity to the hypoglycemic effects of insulin, but does not alter the counterregulatory response of ACTH and cortisol.