Hacker News Board Hacker News, browsed like a classic message board
Live data from Hacker News

Comparative efficacy and acceptability of 21 antidepressant drugs

thelancet.com

Post reply on HN
Print view View original

61–70 of 113 posts

Re: Comparative efficacy and acceptability of 21 antidepressant drugs

#61

Post by ComputerGuru »

ggm wrote: post #45
meowface wrote: post #41

Earlier quoted context omitted.

Few drugs solely act to agonize or antagonize a single type of receptor in a single part of the brain. Many of these compounds do a lot of different things, some big and some small. Anti-depressants have very complex mechanisms of action which we don't fully understand, and may not understand for a long time. They are a rough and imprecise solution to what for some is an otherwise intractable and potentially fatal pr…

I grossly oversimplified what he said, and he's a trained clinical psychologist. The underlying point is exactly what you said: Anti-depressants have very complex mechanisms of action which we don't fully understand, and may not understand for a long time. That they work is good. That they work about as well as CBT does, poses questions which as you observe goes to: Obviously therapy and other techniques should be at…

With no disrespect intended to your friend, a trained clinical psychologist wouldn’t necessarily know the underlying mechanism of these drugs. The split between medical psychiatry and clinical psychology is real.

Re: Comparative efficacy and acceptability of 21 antidepressant drugs

#62

Post by soundwave106 »

tyu100 wrote: post #55
evincarofautumn wrote: post #25

Earlier quoted context omitted.

Likewise, if storebought doesn’t do the trick, some people (myself and my partner included) have better luck with the recreational variety—mushrooms were the thing that kicked me in the psychological ass and started me on the path to recovery from alcoholism (which was partly self-medicating for anxiety). To be clear, this is absolutely not something I’d recommend lightly. Taking (who knows how strong) mushrooms or L…

This study, along with long-accepted clinical practice and the generic cheapness of most anti-depressants now, and the effectiveness of CBT/therapy if it's available to you, means you should really avoid self-medicating for major depression. Why take risks with your health when there are lots of safe, cheap and efficacious treatments that can be monitored by your doctor?

The poster asked for "access to psychedelics (and analogues) in a safe, professional setting", which ideally (if the treatment is one that indeed works and isn't placebo) would be one that is monitored by your doctor. I agree that self-medication is not idea.

The issue here I think is that most current anti-depressants are currently of the SSRI / SNRI / tri-cyclic class. These treatments work great for some people, but do not work for everyone.

In one case (ketamine), this particular hallucinogenic drug has emerged as a candidate for anti-depression therapy (at least in mechanism) that works quite a bit different than the above (acts on glutamate). Non-hallucinogenic glutamatergic anti-depression drugs are being developed as a result, but as one is well aware, this takes time. Until one of these drugs emerges (rapastinel seems furthest along at this time), off-label ketamine clinics do exist where you can take the drug with some degree of clinical supervision.

I have not seen too much on the serotonin agonist hallucinogens in the past relieving depression, but Googling, there does seem to be a newish article on psilocybin (https://www.nature.com/articles/s41598-017-13282-7) that suggests it does offer a possible interesting anti-depression mechanism too. Possibly more exploration is needed here to confirm whether it works well (or not) and, if so, how.

I don't think we've even come close to exploring all routes to resolving depression, so I think exploring as many routes as possible is a good path. (And I do think scientists are doing this -- the parent article was for instance the first time I've heard of a melatonin receptor agonist as an anti-depressant candidate! https://en.wikipedia.org/wiki/Agomelatine )

Re: Comparative efficacy and acceptability of 21 antidepressant drugs

#63

Post by markroseman »

kqr wrote: post #39
icantdrive55 wrote: post #12

Earlier quoted context omitted.

I am obviously confused, as usual. I'm not used to reading these studies. I'm looking at the study. I'm looking at the #3 graph under Tables and Functions Tab. It says amitriptyline is the best drug? Isn't that an older drug, or am I misreading the chart?

"Best" is a complicated concept. Yes, amitriptyline has the greatest efficacy, i.e. response rate in a clinical setting. It may still have poor effectiveness (how well it works in the real world) because it belongs to a class of medications which, if you use them, you have to exclude many types of common foods from your diet. It also has less safety margins in terms of overdosing than many modern alternatives. And th…

Amitriptyline is a tricyclic; it's MAOI's that require a special (low-tyramine) diet.

Re: Comparative efficacy and acceptability of 21 antidepressant drugs

#64

Post by ComputerGuru »

projektfu wrote: post #60
imperio59 wrote: post #35

Horrible side effects, no tests for diagnosis, no actual cures (have you heard of these drugs actually curing depression? No. Once you get on them you are basically on them for life...)... I think this "Science" of psychiatry has a long ways to go to actually get repeatable, scientifically proven results.

Yes, cures happen all the time. I'm an anecdote, but I was cured of depression using venlafaxine. Talk therapy was used at various times but it was not effective. I no longer take venlafaxine and I am not depressed. I will say that getting "off" of venlafaxine is troublesome and must be pursued gradually and slowly because the withdrawal is severe. Once I was cured it took about 9 months to go drug free.

I take venlafaxine for migraines and and of the many drugs I’ve tried, absolutely nothing compares to the withdrawal symptoms for venlafaxine. They start 12 hours after missing a dose and doctors have no official designation for them, besides being insanely nasty.

Please for the love of all that is holy, if you are on venlafaxine and want to switch to something else: titrate. Not all doctors know about the withdrawal problems with venlafaxine. They are horrendous.

Re: Comparative efficacy and acceptability of 21 antidepressant drugs

#65

Post by markroseman »

ggm wrote: post #6

A professional I know in the field (who repudiates drugs for CBT, and so is probably biassed, but still...) says that the lack of clarity over how an antagonist and a suppressant can both be claimed to operate on the same underlying problem and have adherents, points to bad understanding of what actually causes the problem.

Depression and other mental illnesses are defined by a set of symptoms. Suggesting one particular cause is being disingenuous. Having said that, the whole notion of "too much" or "too little" of something like serotonin is a gross oversimplification, at best useful as a metaphor to explain things to people at a very high level.

If you want to take it a step further, think about what's causing communication via neurotransmitters to be slowed or sped up (not enough available? not being released? not being picked up by receptor?), the fact that there are multiple receptors for each neurotransmitter which drugs may or may not manipulate, the fact that there are multiple neurotransmitters (which end up affecting different areas of the brain and hence different symptoms, though some symptoms are influenced by multiple neurotransmitters), and that putting all these things together to result in the right balance of communication (not quantity of chemicals) in the brain, it would be a surprise if there weren't multiple different approaches for the "same" problem.

Re: Comparative efficacy and acceptability of 21 antidepressant drugs

#66

Post by Jaruzel »

projektfu wrote: post #60
imperio59 wrote: post #35

Horrible side effects, no tests for diagnosis, no actual cures (have you heard of these drugs actually curing depression? No. Once you get on them you are basically on them for life...)... I think this "Science" of psychiatry has a long ways to go to actually get repeatable, scientifically proven results.

Yes, cures happen all the time. I'm an anecdote, but I was cured of depression using venlafaxine. Talk therapy was used at various times but it was not effective. I no longer take venlafaxine and I am not depressed. I will say that getting "off" of venlafaxine is troublesome and must be pursued gradually and slowly because the withdrawal is severe. Once I was cured it took about 9 months to go drug free.

I'm on Venlafaxine (300mg/day). Previously I tried Amitriptyline, and Citalopram, both of which did not suit me, so I pulled myself off them... each time the depression and anxiety returned.

Although I am fairly happy on Venlafaxine (it stopped me killing myself, so that's a plus), I'd like to get off it at some point as the side affects are quite annoying. Can I ask you how you feel you were 'cured' and are there any resources I can look at? Thanks.

Re: Comparative efficacy and acceptability of 21 antidepressant drugs

#67

Post by Jaruzel »

aianus wrote: post #49
gliese1337 wrote: post #15

As another person who is on antidepressants, and tried going off them for a while: well, duh. Yeah, I know, anecdotes aren't data, and I'm glad this is being verified by more reliable statistical methods, but this is not news to the many of us who might be dead or worse if someone hadn't said "you are sick--go see a doctor" and if that doctor hadn't said "you need medication--let's see if this works". Without antidep…

> it's amazing what you can do when you actually have enough neurotransmitters in your brain Anything except having an orgasm, in my case.

Seconded. They don't actually warn you about the emotional impact of not being able to orgasm, and the added stresses it can add to a relationship. :(

Re: Comparative efficacy and acceptability of 21 antidepressant drugs

#68

Post by jernfrost »

comex wrote: post #20

The problem with studies of antidepressants is that they're almost all based on short-term, fixed-length treatment courses. After all, you can't do a double blind trial that lasts years on end; it would be unethical to give someone a placebo for that long, when antidepressants are believed to work better. Yet (AFAIK) people who go on antidepressants typically stay on them for years, so the studies are reviewing a fai…

The feedback loop is definitely a major component. It is why I've frequently entertained the thought of doing drugs. Simply because I feel a need for something to help me get started down the right path. Exercise, eat better, see friends, actually complete stuff properly at work etc.

Depression has a tendency to put you in a state where you are just barely holding on to life and doing anything extra each day to improve your condition seems like an insurmountable obstacle.

Re: Comparative efficacy and acceptability of 21 antidepressant drugs

#69

Post by hmhrex »

jdietrich wrote: post #34
amputect wrote: post #8

I think that the United States is getting better about dealing with mental health, but we still have a long way to go. This is a little soap-boxy and anecdotal, and I apologize if it's inappropriate here. If I hadn't gotten a prescription for Prozac I probably would have killed myself by now. And I definitely would have destroyed my marriage and most of my important friendships. That's not an over-dramatization, it's…

>If I hadn't gotten a prescription for Prozac I probably would have killed myself by now. The majority of people with depression just get better of their own accord, for no obvious reason. The NNT for most antidepressants is ~7, meaning you need to give them to about seven patients for one patient to see a clinically-significant improvement. The evidence suggests that there's no significant relationship between SSRI…

This is the main reason I stayed away from medication for 12 years. That is until 3 weeks ago.

I decided late 2017, after a major depressive episode, that I needed to get help after 12 years of dealing with this depression. I kept thinking that I had a handle on it, and then it coming back weeks, months or years later.

I read The Depression Cure (https://www.amazon.com/Depression-Cure-6-Step-Program-withou...) about 5 years ago, and it helped for awhile, but it started to worsen again, and after awhile, getting the right diet, exercise and sleep seemed impossible because of the depression and anxiety.

I started therapy about 3 months ago, and finally agreed to try medication. I started taking Zoloft 3 weeks ago, and the side effects are downright awful. I made it through the first 3 weeks though, and I'm starting to feel a lot better.

Zoloft might not end up being the right medication for me, and there might be a better one, but my goal is to find something that takes 10%-20% of the depression and anxiety symptoms away so that I can start my path to curing this beast with the methods Dr. Iliardi outlines in The Depression Cure. Once I'm at a point where I'm better, I'm going to try and ween off the medication and try to live a healthy, great life without SSRIs.

Re: Comparative efficacy and acceptability of 21 antidepressant drugs

#70

Post by markroseman »

aianus wrote: post #58
tyu100 wrote: post #55

Earlier quoted context omitted.

This study, along with long-accepted clinical practice and the generic cheapness of most anti-depressants now, and the effectiveness of CBT/therapy if it's available to you, means you should really avoid self-medicating for major depression. Why take risks with your health when there are lots of safe, cheap and efficacious treatments that can be monitored by your doctor?

Psychiatrists have a three month waiting list here in Canada and therapy is $100/h.

Three months in some places. Here in Victoria, unless you're in crisis, it's actually almost impossible for most people to get in to see a psychiatrist, and if you can, the waiting list is well over a year.
Post reply on HN