David Wallace was a pretty well renowned American writer. He suffered greatly from depression, and was treated with Phenelzine for about 20 years. Towards the end of that period, he started noticing some issues with it, and decided to try an alternative...nothing worked, and the depression returned. He switched back to Phenelzine, only to find it had lost its effectiveness. Not only was the depression resistant to all treatment, but it got worse and worse, until finally he committed suicide. A horror story.
So the question is, how could a depressive illness be resistant to so many scientifically approved treatments? Even more importantly, how could a drug like Phenelzine suddenly lose its effectiveness?
I think I have an answer. It has been shown that Phenelzine also inhibits the function of Vitamin B6, which is crucial for serotonin, dopamine and GABA synthesis. This inhibition becomes more pronounced over time. So it makes sense to think that his taking Phenelzine had caused some kind of long-lasting deficit in utilising Vitamin B6. The answer is simple: supplement with the vitamin, but I don't think Wallace knew that until it was too late.