Imipramine oestrogens

There is evidence that oestrogens can sometimes reduce the effects of imipramine, yet at the same time paradoxically cause imipramine toxicity. The general clinical importance of this interaction has yet to be evaluated. 

Among the possible reasons for these effects are that the oestrogens increase the bioavailability of imipramine, or inhibit its metabolism. ... 

These interactions are inadequately established. There is no obvious reason for avoiding concurrent use, but it would seem reasonable to be alert for any evidence of toxicity and/or lack of response to tricyclic antidepressant treatment in those taking oestrogens in any form. One study suggested that the imipramine dosage should be reduced by about one-third. More study is needed. 

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 Four of these men developed a paranoid reaction which disappeared when the hormone was withdrawn.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. 

The following case-report by Khurana (127CR) also suggests that there is an interaction between imipramine and oestrogens ... 

A 32-year-old woman taking 2.5 mg conjugated oestrogen and 100 mg imipramine daily showed symptoms of lethargy, depersonalization, and occasional tremors. The oestrogen dose was increased to 5 mg and then to 7.5 mg daily, but her condition became worse. She was taken to hospital with extreme lethargy, nausea, constant headache and low normal blood pressure. A complete withdrawal of oestrogen, then replacement with a dose of only 0.625 Mg resulted in a dramatic subsidence of symptoms. 

---