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Comment by hnpolicestate | Hacker News Reader

"There is a very large group of people for whom they do not work"

- many people are unwilling to wait the proper amount of time "4-6 weeks" for efficacy to manifest *especially* when for the first 2-3 weeks you many times feel much worse than baseline.

First month on Effexor made me feel miserable. More anxious but much, much more irritable and depressed. Then one day a month in I'm sitting at my desk and I suddenly feel high as a kite lol. Melting bliss.

That feeling too fades and then you just feel better than baseline until you build tolerance to current dose. Raise, rinse and repeat.

Better than having to be near an exit whenever inside a structure!

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Depending on the population and methodology, anywhere from 10-30% of people diagnosed with major depressive disorder are considered to have "treatment-resistant" depression, which usually means they've failed to respond to at least two antidepressants despite adequate compliance (exact definitions vary as this is not a separate diagnosis) [1].

[1] https://www.hopkinsmedicine.org/health/conditions-and-diseas...

Doctors I've talked to have said it's 4 to 6 weeks to reach a baseline, where the medication reaches a steady level in the blood and receptor changes in the brain reach a new equilibrium, but even up to 2+ months for the real effect to kick in.

Those 4-6 weeks are when your brain is adapting to an ever increasing serum level of antidepressants, and it takes about ~2 weeks for serotonin receptors to downregulate in response. That time can be very uncomfortable, specifically because SSRIs indirectly activate 5HT2C, leading to dysphoria, anxiety, etc, before the receptor is sufficiently downregulated.

tl;dr: it can take longer than 4-6 weeks for efficacy to manifest

This is what I've heard from those I know that take anti depressants - the time that is suggested before you would be able to look back and say: "I'm doing much better than four weeks ago", is a bit daunting.

First and foremost because you take them at a point in your life where you're, well, depressed (used as a blanket term here). So patiently waiting for the effect to manifest is a burden in itself, in addition to hoping it works and not being sure if you're experiencing a placebo or actual effect.

But what scares me more, personally, is that it takes such a long time to get on and ween off. It seems to fundamentally change something in the human body or brain. As opposed to e.g. amphetamines, and benzos, which may have long lasting effects from prolonged use, but otherwise appear to be pretty straight forward.

Having never needed antidepressants, I'm curious if others who have taken them, worried about this before or afterwards?

At least in my experience, going off traditional SSRIs wasn't fun, but after it's out of your blood and you wait your ~2 weeks for what is essentially serotonin withdrawal to subside, there weren't any lasting effects.

I've experienced worse withdrawals from other drugs, but I've read that some people do get PAWS-like symptoms from SSRI, and especially SNRI, withdrawal.

> benzos

A friend working in rehab said benzos are very difficult to end taking - because of the way one gets addicted to em.

Yep, benzos work great for treating stuff like occasional anxiety attacks or sleep issue, but taking them regularly is never a good idea.

Benzos (and alcohol) withdrawal can both be deadly if not tapered. They are not to be fucked around with.

Well I was talking about how fast they have a noticable effect on people. Not about wether or not someone should take them, nor if they are addictive and to what degree. So I don't see the point in your reply, to be honest.

In my body, a Benzodiazepine cessation causes a drop of the blood pressure to around 70/30 for a few days. Kept me in bed.

Interesting that you talk about Effexor. Effexor was the one drug that “worked” for me.

But over time, my thinking and behavior became more and more erratic. I became highly unstable, doing bizarre and unsafe things I never would have considered prior to Effexor. So I needed to come off. Ok, then I had to endure a month of brain shivers, where moving my head made the world stutter like there was a strobe light. After getting through that, I developed dystonia, which lasted for the next fifteen years.

This is why I said that the statement needed clarification. Everyone that had them work for them thinks “they work”. Bullshit. They worked _for you_.

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