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Comment by jotm | Hacker News Reader

I hope they work for some, but for me, SSRI's are frankly, trash. All the downsides with none of the upsides.

The only thing that worked was Imipramine, and I can't get it anymore because it's "old" and "not recommended".

The newer focus on psychedelics and drugs usually used for recreational purposes seems more encouraging.

If you're anti-depressant resistant, I'd recommend you try Gabapentin, a seemingly overlooked drug that works wonders for anxiety and depression. Quick tolerance buildup, do not give in and try to go over ~2g/day.

The somewhat similar Phenibut also works, but it's a direct GABA agonist with terrible withdrawal symptoms and an extremely fast tolerance buildup.

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> I hope they work for some, but for me, SSRI's are frankly, trash. All the downsides with none of the upsides.

They absolutely work for many people. Unfortunately, many people deprive themselves of SSRI trials because they read too many negative anecdotes online. If you're seriously depressed for an extended period of time, it's worth a trial of an SSRI medication. If it doesn't work, just taper off and be done with it. At least you'll know.

> The only thing that worked was Imipramine, and I can't get it anymore because it's "old" and "not recommended".

That's bizarre. Imipramine is still widely prescribed with over a million prescriptions per year in the United States alone. If it works for you and your doctor is withholding it for some reason, please see a different doctor ASAP.

Given your strange and definitely not-normal experience with the medical system, can I suggest that you refrain from giving advice to others? I'm sorry you've had a negative experience with SSRIs and doctors, but it's extremely important that you not dissuade others from seeking proper medical treatment.

> If you're anti-depressant resistant, I'd recommend you try Gabapentin, a seemingly overlooked drug that works wonders for anxiety and depression. Quick tolerance buildup, do not give in and try to go over ~2g/day.

I recommend against Gabapentin as a first-line or even a second-line treatment. "Quick tolerance buildup" is not compatible with long term treatment stability. Gabapentin can be prescribed in limited circumstances for anxiety, but it's not a good first choice solution.

> The somewhat similar Phenibut also works, but it's a direct GABA agonist with terrible withdrawal symptoms and an extremely fast tolerance buildup.

Please don't recommend Phenibut. It's not an antidepressant. It's highly addictive and has severe rebound and withdrawal symptoms. Drugs that make you temporarily feel good should not be confused with antidepressant drugs.

SSRI's work barely better than placebo because the serotonin theory of depression is dead. They would never be invented today.

>Please don't recommend Phenibut. It's not an antidepressant. It's highly addictive and has severe rebound and withdrawal symptoms. Drugs that make you temporarily feel good should not be confused with antidepressant drugs.

This kinda sounds like drugs like clonazepam or lorazepam. They're also very addictive, and are not antidepressants at all, however they are anti-anxiety drugs and they work very quickly. And anxiety and depression seem to go hand-in-hand for many sufferers, so they do seem to really help some people, at least initially.

I think a big problem is the medical establishment really doesn't have a good handle on what depression really is (biologically) or how to treat it.

> This kinda sounds like drugs like clonazepam or lorazepam. They're also very addictive, and are not antidepressants at all, however they are anti-anxiety drugs and they work very quickly. And anxiety and depression seem to go hand-in-hand for many sufferers, so they do seem to really help some people, at least initially.

Phenibut works through similar pathways as those drugs. A lot of people overestimate their understanding of Phenibut by reducing it to a simple GABA-B agonist, but at the high doses that people take for euphoric effects it's actually doing a lot more.

> I think a big problem is the medical establishment really doesn't have a good handle on what depression really is (biologically) or how to treat it.

We can always improve, yes, but the standard treatment protocols (therapy, lifestyle changes, therapy + medication) are actually quite decent if you find a provider who cares enough to work with you. Many people find a lot of relief through standard practices. Unfortunately, many people don't have the resources or patience for therapy, and they won't tolerate any side effects from medication (which tend to diminish over time). A lot of those cases are the most vocally negative about depression treatment and "big pharma", skewing the overall perception. Many of the SSRI and therapy success stories don't go broadcasting their depression stories to the world. They just quietly go back to their lives.

Of course, it's worth trying anything.

I did say they didn't work for me. Sertraline and fluoxetine specifically.

Anyone suffering should go to a doctor and try some medication. It's better than giving up thinking nothing will work (which is a symptom of depression!).

> They absolutely work for many people. Unfortunately, many people deprive themselves of SSRI trials because they read too many negative anecdotes online. If you're seriously depressed for an extended period of time, it's worth a trial of an SSRI medication. If it doesn't work, just taper off and be done with it. At least you'll know.

SSRI's do not work. Linked elsewhere in this thread: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/

> The serotonin theory is as close as any theory in the history of science to having been proved wrong. Instead of curing depression, popular antidepressants may induce a biological vulnerability making people more likely to become depressed in the future.

Serotonin being the key driver of depression is as wrong as complex carbs being the healthiest macronutrient.

A newer meta analysis from 2018 says they do work: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889788/

> We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo

Anecdotally, SSRIs do work for some people, and it can be life changing.

I've got you beat; neither SSRIs nor gabapentin nor any other of a variety of on- and off-label meds worked for me.

Despite that I don't think it's a good idea to recommend or disrecommend any specific drug; it is very much a biochemical roll of the dice as to whether a med will work on a given individual and the odds aren't even particularly good. My suggestion to the depressed is to try as many as you can withstand to increase your odds of finding something that works, with the understanding you might be among the unlucky ones that nothing works on.

>Despite that I don't think it's a good idea to recommend or disrecommend any specific drug; it is very much a biochemical roll of the dice as to whether a med will work on a given individual and the odds aren't even particularly good.

Since many drugs seem to affect different people differently, it seems we really need to work on understanding how drugs affect people differently based on their genetics. This is similar to, for instance, how some people think cilantro tastes like soap, because of a gene mutation. I think there isn't nearly enough attention being paid to this, and it's making the field of psychiatry look like various drugs are no better than placebo, when it's much more likely that some drugs work great for some people, but terribly or not at all for others, so right now it's a crap-shoot when instead we should be figuring out what will actually work for certain people based on their genetics instead of shooting in the dark.

> The somewhat similar Phenibut also works, but it's a direct GABA agonist with terrible withdrawal symptoms and an extremely fast tolerance buildup

Some antidepressants can have terrible withdrawal symptoms too - I went through the worst couple of weeks of my life after tapering off dosulpine, and I know someone else who had it rough after tapering off a tricyclic.

> Some antidepressants can have terrible withdrawal symptoms too - I went through the worst couple of weeks of my life after tapering off dosulpine, and I know someone else who had it rough after tapering off a tricyclic.

Apples and oranges. Not all withdrawals are equally bad.

Savvy healthcare providers will switch you to Fluoxetine, which has an extremely long half-life, and then taper the Fluoxetine.

Phenibut's withdrawal symptoms are on another level entirely, especially when people take abuse-level dosages to feel temporary euphoria: https://www.reddit.com/r/quittingphenibut/

Dosulpine, and tricyclics, have SNRI effects, rather than SSRI effects, so I don't think fluoxetine would work here.

In my case, I had only been taking it for a few weeks, and tapered off slowly until I was only taking a quarter of a pill - I was not prepared for what ensued.

You are right though, not everyone experiences the same things with these kinds of medicines - presumably it all comes done to genetics.

But I think it's worth mentioning that SNRIs and SSRIs can have awful side effects, especially since this often seems to be downplayed or even downright ignored by doctors (mine didn't even mention it as a possibility, and had even told me it was OK to stop without tapering).

If you can’t get “the only thing that worked,” then you need a new doctor. It’s irresponsible and borderline malpractice to take someone off a medication that works simply because it’s “old” or “not recommended,” unless the reason it’s no longer recommended is because of previously unknown side effects.

It sounds like you found what you need in gabapentin, so I’m glad for that, but I would have gotten a new doctor in your situation instead.

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