Phenelzine didn't work, should I ask my psychiatrist to give Parnate a shot?

Yes, I'd say try it. It's markedly different to phenelzine in its make-up and effects. All MAOIs are not equal!

Worst case you can move on to ECT afterwards, if you choose.

At least then you'll have chalked up Parnate as something you tried that didn't work.

I think it depends on how one looks at it. Your psychiatrist is partly right in that it is less likely to work. However, I've heard the occasional bad story about ECT and I think you should be given the chance to try Parnate anyway first for that reason. Just my non-professional opinion though...

“If you don’t respond to Phenelzine, you won’t respond to Parnate.” Jesus Murphy, does he use that line of reasoning when he prescribes other medications in his practice? If he genuinely believes that, then he has no excuse to be practicing as a psychiatrist and only has a surface level understanding of pharmacology and how medications work in general. Please, do not take his aforementioned comment as having any credibility or intuitive knowledge, because he’s simply dead wrong at the expense of your treatment.

That aside, for now, allow me to explain why trialing Parnate even after failure to respond to Nardil is incredibly important to your treatment. The two medications are not the same, and by this, I mean the metabolites of each medication causes different and clear distinctive changes, which is why assuming they’re the same based on his surface level understanding completely undermines and render his statement as wrong and terribly misleading.

These metabolites impact the response in such a way that there is no endpoint similarity beyond the fact that they both inhibit Monoamine Oxidase (hence the title of MAOI) — and there’s distinct evidence that the therapeutic response is certainly not just caused by inhibiting that enzyme.

Think of it like this: inhibiting or stopping the enzyme from functioning opens the gate for the medication’s metabolites to have a much greater impact. That’s not to say that there are aren’t fundamental changes in inhibiting MAO alone, but the metabolites are essentially where the magic begins to happen and why there are different responses from Nardil/Phenelzine to Parnate/Tranylcypromine.

Now, Nardil’s metabolites and the specificity for what it’s assumed to work primarily for social anxiety and depression, is due to it inhibiting the MAO enzyme, but where it gains ground for social anxiety is due to the fact that its metabolites inhibit GABA Transimase (GABA T) and Alanine Transimase (ALA T), which subsequently increases the alanine and GABA levels in the brain which causes decreased anxiety in its response.

Then we get to Parnate, which again, inhibits the MAO enzyme, while its metabolites and overall function is indicated for the most severe forms of depression, concerning efficiency for the ‘Anergic’ symptom profile (i.e. more severe ‘biological’ depression). The metabolites render it also as a supplementary Norepinephrine Reuptake Inhibitor at doses of 40mg+ where people begin to see a lot of improvement, and likely increases in a more potent manner, trace neurotransmitters like Phenylethylamine (endogenous amphetamine) than what Nardil is able to produce. People tend to consider Parnate as being more dopaminergic and Nardil as more serotonergic, which oversimplifies things; nonetheless, it shows that patients see two different responses to them.

I’ve been on both and I’m currently on Nardil 60mg and was on Parnate before. Due to insurance and Express Scripts constantly messing up, I had to switch to Nardil since it was crazy cheap to buy out of pocket when they messed my order up. In terms of efficiency and differences, Parnate is by far more effective and potent from my experience, being that it handles my depression incredibly fast as opposed to Nardil, which took a longer amount of time, but still doesn’t reach quite far enough as Parnate does with minimizing depression. I’d say I was in complete remission on Parnate, and less on Nardil, unless it gives out like you experienced. With Parnate, I never had any periods where the depression returned as I do with Nardil.

The last important thing that’s crucial to understand, which your doctor seems to completely miss, is that in order for ECT to be a practical option, you HAVE to have a medication that can manage you in the long-term! It is an adjunctive treatment that can’t produce remission or be used daily like a medication to manage depression, as it would be impossible to receive ECT sessions daily or weekly, and from that point, it is substituted as an additional treatment for times when the medication doesn’t manage your depression effectively enough that it causes non-functional symptoms (catatonia) or suicidal thoughts with intent to attempt.

I know from experience. Before trying Parnate, I was told if I failed to respond to ECT then they would trial a MAOI, and at 21 years old (now 23) they conducted sessions that didn’t do anything but cause transient memory issues even after it was over — the entire event was a hazy dream. But at the same time, they didn’t have me on any medication that decreased my symptoms entering it and even refused trying a MAOI afterwards. Afterwards, the doctor refused to trial a MAOI despite discussing it, and I took control and found a doctor that would and I was prescribed Parnate and hit full remission of my symptoms within 3 weeks.

Considering your situation, I see no logical pathway by undergoing ECT without first trialing Parnate up to 60mg, 80mg, and even 120mg, which can be accomplished as fast as you can manage the hypotensive response. I could take my full dose of 60mg after I was forced to withdraw cold turkey (insurance halfway killed me, go figure) and it only caused orthostatic hypotension that was managed by postural changes from sitting to standing.

If that doesn’t work, you can augment it with a stimulant or dopamine reuptake inhibitor like Methylphenidate which is what they did in early reports when the medication first began use for those who didn’t respond fully, and ended up in remission after adding a stimulant or methylphenidate on. You can even use Lithium, Lamictal, and a true NRI like Nortriptyline which makes it safer to tyramine/food interactions (which is a joke how overstated it is), but you’d likely need to find a psychiatrist willing to look at resources which can be found and provided on here to show its safety for adding a stimulant or Methylphenidate, like I’m having to present to a neurologist this month.

I apologize for the wall of text, but I feel that this is clearly an important issue that needs to be addressed so you can have a clear picture on why your psychiatrist is wrong as all the data points to, and for you to know your options that stand a much higher chance for you to hit remission. If you have any questions, please feel free to ask!

Marplan ftw (if you're can afford it and live in the US). Nardil was up & down all the time for me. Marplan makes me feel like myself.