ORAL CONTRACEPTIVES AND DEPRESSION

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In 1967 2 correspondents pointed out the possible association of depression with the taking of oral contraceptives and later the same year Daly et al. suggested some possible reasons for this. I should like to suggest a further possible explanation for the precipitation or aggravation of depression in certain women taking oral contraceptives. Dewhurst has postulated that a dysfunction of tryptophan metabolism is implicated in the onset of certain types of depression and it has also been suggested that one of the mechanisms involved is a shift of tryptophan metabolism from the serotonin pathway to the kynurenine pathway. Price et al. have shown that the use of steoid hormones for ovulation control results in a disturbance of tryptophan metabolism along the kynurenine pathway. Similar disturbances occur during pregnancy just before menstruation and with the administration of cortisone. Since cortisone oral contraceptives and pregnancy all have in common the possibility of precipitating severe depression in susceptible patients and are also known to upset tryptophan metabolism then if tryptophan metabolism is shown to be associated with control of mood it would be more credible that these effects are mediated in some way through an upset of tryptophan metabolism than to believe that this is just mere coincidence. The fact that progestogens given alone do not cause this disturbance of tryptophan metabolism and are also reported not to cause depression would lend weight to this view whereas the disturbance of tryptophan metabolism by hydrocortisone pyrollase oral contraceptives (and presumably pregnancy and menstruation) apparently create a functional deficiency of pyridoxine for the disturbance of tryptophan metabolism along the kynurenine pathway is corrected by giving supplementary pyridoxine. Apparently the steroid hormones have the effect of loosening the binding of some pyridoxine to its enzyme. Since the decarboxylation of tryptophan to trypatamine and serotonia is also dependent on pyridoxine it would be interesting to know whether giving supplemental pyridoxine would protect patients on oral contraceptives from becoming depressed. In this regard one patient in her 4th month of pregnancy had her symptoms of depression and irritability completely resolved 5 days after starting on pyridoxine 50 mg daily. Similarly another young woman who became extremely irritable and difficult to live with during the 2nd 1/2 of her menstrual cycle cased to have these episodes soon after starting on pyridoxine. These are only straws in the wind but it does seem that the matter merits further investigation.(Full text)