Hormonal Imipramine

Mitsushima D, Hei DL, Terasawa E GABA is an inhibitory neurotransmitter restricting the release of luteinizing hormone-releasing hormone before the onset of puberty. Proc Natl Acad Sci USA 91 395-399, 1994 Miura N, Nakata N, Tanaka Y, et al Improving effects of FG-7080 a serotonin reuptake inhibitor on scopolamine-induced performance deficits of memory tasks in rats. Jpn J Pharmacol 62 203-206, 1993 Mizuta T, Segawa T Chronic effects of imipramine and lithium on 5-HT receptor subtypes in rat frontal cortex, hippocampus and choroid plexus quantitative receptor autoradiographic analysis. Jpn J Pharmacol 50 315-326, 1989... 

Prange AJ, Wilson 1C, Rabon AM, et al Enhancement of imipramine antidepressant activity by thyroid hormone. Am J Psychiatry 126 457-468, 1969... 

Prange AJ Jr, Wilson 1C, Breese GR, et al Hormonal alteration of imipramine response a review, in Hormones Behavior and Psychopathology. Edited by Sachar EJ. New York, Raven, 1976, p 41... 

Spurious hyperthyroidism occurred in a child taking thyroid hormone and imipramine for enuresis (89). The ability of thyroid hormone to increase receptor sensitivity to catecholamines has long been known, and has been used to enhance the clinical response in some refractory patients, especially women. 

The Division of Drug Experience of the US Department of Health and Welfare issued a note on five cases of the syndrome of inappropriate antidiuretic hormone secretion and drugs to which it has been attributed (1137). All involved drugs with a tricyclic structure one patient was taking imipramine, three carbamazepine, and the others the closely related muscle relaxant cyclobenz-aprine. The dosage of imipramine was 50 mg/day for 3 weeks and the patient was a 72-year-old woman. Other cases have been reported, involving amitriptyline (1137), imipramine, and protriptyline (SEDA-17,17). 

It has since been assumed that this is the therapeutic action of tricyclic antidepressants, which are sometimes referred to as monoamine reuptake inhibitors or MARIs. However the exact significance of this reuptake process is unknown, especially as the tricyclic antidepressants have numerous other actions and influence, directly or indirectly, almost all neurotransmitters, many neuropeptides and most hormones (Khan 1999). Further studies of reuptake by heart muscle preparations showed that chlorpromazine was a stronger reuptake inhibitor than imipramine and not all the tricyclic antidepressants had this action (Lahti Maickel 1971). In addition, it has not been possible to demonstrate that reuptake inhibition is actually correlated with increased availability or activity of noradrenalin or serotonin. In fact most evidence suggests that tricyclic drugs reduce levels of noradrenalin (Frazer Mendels 1977 Heydorn, Frazer, Mendels 1980 Schildkraut, Winokur, Applegate 1970). 

Tricyclic antidepressants increase the release of endogenous antidiuretic hormone and can therefore potentiate the antidiuretic effect of desmopressin. A hyponatremic convulsion occurred in a child who was given desmopressin and imipramine (171). 

The antidepressant response to imipramine, amitriptyline and possibly other tricyclics can be accelerated by the use of thyroid hormones. However, isolated cases of paroxysmal atrial tachycardia, thyrotoxicosis and hypothyroidism have occurred on concurrent use. 

Wilson IC, Prange AJ, McClane TK, Rabon AM, Lipton MA. Thyroid-hormone enhancement of imipramine in nonretarded depressions. NEnglJMed (1970) 282, 1063-7,... 

A preliminary clinical paper reported that high doses of L-tryptophan produced an antidepressive response similar to that elicited by imipramine.48 imipramine caused a decrease in the rate of disappearance of norepinephrine from the rat brain after a single intraperitoneal dose, but not after long-term administration by this route. This result may explain the delayed onset of action of the tricyclic antidepressives, and suggests that thyroid hormone or pharmacological agents that increase the turnover of norepinephrine in the brain, if... 

SUMMARY - The enhancement of the speed and efficacy of imipramine by the addition of thyroid hormone to the treatment program represents a promising develofanent in the control of depression. The apparent clinical failure of many new structures that exhibited high activity in one or more animal test procedures is indicative of the poor correlation between animal models and the complex nature of human depression. Biochemical, neuropharmacological and human pharmacological studies may yield new clues to the discovery of more effective, rapidacting, and less toxic antidepressives than those that are now available. 

Differences in the effects of acute and chronic treatment with imipramine and protriptyline on central NE metabolism in the rat have been observed. The turnover of NE was decreased after acute administration but increased during chronic administration of these drugs. The increase in NE turnover occurred sooner when thyroxine was administered with imipramine. It is suggested that these observations may help to explain the delayed onset of clinical antidepressive effects and the accelerating and enhancing effects of thyroid hormone on the clinical effects of imipramine. It has been suggested that thyroxine may exert some of its... 

An interaction between oestrogens and imipramine has been previously reported (41 ). Another observation has been that women respond less well than men to antidepressants in general. In studying this possibility it was found that 50 mg of ethinyloestra-diol worsened the antidepressant effect of imipramine in women (42 -). To study the basis of this sex-linked interaction further the authors gave methyltestosterone and imipramine to 5 men with primary unipolar depression. Four of these men developed a paranoid reaction which disappeared when the hormone was withdrawn. The mechanism of the interaction is unexplained. 

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