Tranylcypromine was originally developed as an analogue of amphetamine.[1] Although it was first synthesized in 1948,[3] its MAOI action was not discovered until 1959. Precisely because tranylcypromine was not, like isoniazid and iproniazid, a hydrazine derivative, its clinical interest increased enormously, as it was thought that it might have a more acceptable therapeutic index than previous MAOIs.[4]
The drug was introduced by Smith, Kline & French in the United Kingdom in 1960 and approval in the United States soon followed in 1961.[5] It was withdrawn from the market in February 1964 due to a number of patient deaths involving hypertensive crises with intracranial bleeding. However, it was reintroduced later that year with more limited indications and specific warnings of the risks.[6]
Clinical use
Despite their well-established efficacy, indications for monoamine oxidase inhibitors are currently very limited, due to their significant potential for adverse effects, many interactions, and the availability of newer and safer (although not necessarily more efficacious) antidepressants.[2] Tranylcypromine is indicated primarily for the treatment of major depressive disorder, and can also be used in the management of various mood and anxiety disorders, typically as a last resort after conventional antidepressants have been tried without success.
Effectiveness
Tranylcypromine is highly effective in the treatment of anergic depression in comparison to placebo.[7] In comparison to imipramine, tranylcypromine has been shown to be more effective in anergic bipolar depression, and results in fewer patients leaving treatment.[8] As contrasted with alprazolam, carbamazepine, and trifluoperazine, only tranylcypromine was effective in increasing the favorability of patients' self-evaluations in the treatment of women with borderline personality disorder.[9] Tranylcypromine has shown substantial effectiveness in treatment-resistant depression, with,[10][11] or, at unusually high dosages, without,[12] lithium. However, at normal dosages, tranylcypromine proved no more effective than venlafaxine and mirtazapine in treatment-resistant depression, and was associated with worse side effects.[13]