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 the honest truth just based on the direction my life was heading without them.
If you can't make your own neurotransmitters, store bought are fine. I'm not writing this to say "RARGH YOU MUST USE THESE DRUGS", but I absolutely am writing it to say "hey, this worked for me and got me out of a really dark and bad place". If you are reading this from a dark and bad place, please know that you're not alone. You have a lot of options, and I promise that if you take that first step, things can get better.
>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 use and suicide risk except for young people, for whom SSRIs may actually increase the risk of suicidal behaviours and self-harm.
>If you can't make your own neurotransmitters, store bought are fine.
There is no evidence whatsoever that people with depression are "deficient" in neurotransmitters. We don't really understand the mechanism of action of any antidepressant. Plenty of drugs that have no effect whatsoever on serotonin are equally effective as SSRIs.
Antidepressants can be useful for some patients, but they aren't miracle drugs - they aren't even particularly good drugs. If you're depressed then you should certainly consider pharmacological treatment, but you should regard it as only one tool among many. Talking therapy is equally effective and the combination of drugs and talk therapy is more effective than either alone. You might need to try several different drugs before you find one that works for you and has tolerable side-effects, especially if you have been depressed for some time or have comorbid conditions. If your depressive symptoms are relatively mild, you should probably look at lifestyle interventions like diet, exercise, sleep hygiene and self-help before considering drug treatment.
As someone in the very same boat, I appreciate and can relate to the line you have to walk. My life was positively changed by going on Prozac in a way that I didn't think was possible. After years and years of trying any way of dealing with depression that didn't involve medication, I was absolutely at a dangerous place. Most of my reasoning was that I didn't really believe in the efficiency of medication, and even if so, I didn't think I was actually someone with depression, just that I had been, since i was a kid, putting myself into constant situations that caused severe anxiety and depression. It didn't all work at once, and I had a lot of weird steps between starting and being in a state that I would now consider "my normal self that I never knew I actually was", but it's been an overall life changing experience.
That being said, I understand that medication, or even the same medications, can't work for some people in the way they did with me. It's difficult to explain the position of "I know medication doesn't always work and isn't always an answer, but sometimes it is an answer that I would hate to be missed out on".
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 LSD isn’t exactly the most precise or reliable way to go about it, and there are attendant risks.
I just hope in the future there’s more access to psychedelics (and analogues) in a safe, professional setting, because they’ve been shown to be another potentially useful tool in the antidepressant/anxiolytic/self-care kit.
I'd like to expand a bit and reiterate that not everyone who suffers from depression has primary depression with no discernable cause. Most seriously depressed people in my experience have various situational causes (physical health, financial, social etc) and the depression is a side effect of those and not the main issue. Without tackling the root cause, drugs usually just cover, drag out, and add issues, yet the mental health system mostly uses these drugs as a blunt instrument and fail to address the cause. In the right circumstance, and right conditions, they CAN enable someone to get out of a rut and take actions they wouldn't have without so they do have a place after someone with unexplainable depression who has tried less invasive and risky options like lifestyle changes.
I am not encouraging people not to try medication if they feel it is a good option, simply asking people to realize A. It's not a cure without a plan to fix the cause and B. Not to follow the common victim blaming that often occurs when these simple "fixes" don't work for people (OP isn't doing that and I don't intend to sound as if I am saying so...in fact they made it clear it's not a magical fix suited for all) Drugs are a tool, not a cure, and need to be wielded responsibly and properly. Sadly I don't believe that happens a lot of the time.
> If you are reading this from a dark and bad place, please know that you're not alone. You have a lot of options, and I promise that if you take that first step, things can get better.
I really think they need to have some sort required of "Life Skills" class in high school. In which they teach you how to get help, how to ask for help, how to share your feelings with friends in a safe way. And your options if you do get into a deep dark way. Based on personal evidence, almost every adult gets depressed in some way and many don't know how to get help or deal with it in a healthy way.
I didn't learn any of that till my 30s. I nearly committed suicide multiple times. Our current society and the toxic religious one i grew up in taught me that a man needs to be strong and doesn't need to rely on others. Pray to God and just pull yourself up by your bootstraps mentality.
It's amazing how helpful it is to know that you are loved and cared for. And people want to help you. You just have to ask for it.
Attitudes towards mental health in the US and the west in general are quite frustrating, and I hope they are improving. On the right there seems to be a tendency to deny nuanced views of mental illness from economic, religious, or simply conservative cultural motivations, or to push sedative (using this term metaphorically) medication as a panacea. On the left there are many influenced by the (understandable but deeply destructive) anti-psychiatry movements who both affirm mental illness and deny proper care. It is quite frustrating to see someone talk about their own "undiagnosed mental illness" while citing Foucault to disparage people you care about for seeking psychiatric methods that, as you described, saved their lives.
>"We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression."
Wikipedia defines treatment resistant depression as "cases of major depressive disorder that do not respond adequately to appropriate courses of at least two antidepressants."
Maybe I'm unfamiliar with study methodology, but doesn't this undermine the study's conclusion? It's essentially stating that forms of deppresesion that respond well to antidepressants respond well to antidepressants.
SSRIs are generally indicated for what's called mild/moderate depression, the most common form, not for the serious conditions that you highlighted.
There were some older meta-studies that called into question their general efficacy vs. placebo even for mild/moderate depression but this new meta-study (with the additional previously unpublished data from their initial approval trials) looks like it has finally settled the matter.
Reading this paper I'm amazed at the increased efficacy of some of the newer SSRI's despite not having a novel mechanism of action. This is similar to how effective some of the newer statins are at lowering LDL cholesterol despite the drug class being around for decades.
edit: It looks like I'm a bit out-of-date in my knowledge but the general point still stands. DSM V has a definition of 'major depressive disorder' which seems to have replaced the old mild/moderate categorization and this study looked at all anti-depressants that treat this type of depression, not just SSRIs.
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.
I basically agree with your friend, but I'm pro-drugs for pepole who find them helpful. I very strongly suspect that the underlying "problem", like with cancer, is actually an enormous variety of problems that cluster into vaguely similar symptom groups. I am absolutely not an expert here, this is a layperson's opinion, but it's really hard to imagine that there's just one specific cause that we're treating. I think that's why different drug classes vary so wildly in effectiveness from person to person, there's a ton of underlying confounding variables that we simply don't understand.
But what we do know is that anti-depressants can be a powerful tool for helping people who aren't responsive to other types of treatment. Even if it takes some effort to figure out which one is the best fit for the underlying disorder, that's better than nothing.
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 problem.
Obviously therapy and other techniques should be attempted before drug prescription, but your friend is grossly oversimplifying how these drugs work and how psychiatrists portray how they work.
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.
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 fairly artificial use case. It's like the handful of controlled trials that attempt to compare programming languages, which by necessity ask participants to solve short, fixed programming exercises, even though that bears little resemblance to the process of real software development.
In the case of antidepressants - on one hand, there are some reasons to expect short-term interventions to be the best-case scenario in terms of evaluating benefit, such as the greater risk of side effects with long-term use, and drug tolerance effects. On the other hand, I suspect (but don't have data to prove) that placebos are much less effective in the long term. People think the placebo effect is in part a reaction to the social experience of interacting with a doctor, getting personal attention and concern for whatever condition is supposedly being treated. To the extent this is true, the novelty of the experience is probably a large factor, and over the long term you'd expect a reversion to the mean. So even if antidepressants are less effective in the long term than the short term, they might be more compelling as a treatment option, because the alternative (placebo) loses even more of its effectiveness.
Edit: Another factor is that the effects of reduced depression may take a long time to be fully apparent. Depression tends to work in feedback loops: as an oversimplified example, you feel bad about yourself, so you lose motivation to take care of your life, so you start neglecting essential tasks, the consequences of which make you feel even worse about yourself. And lifting yourself out of depression is the same thing in reverse. So if an antidepressant has the effect of reducing your susceptibility to depression - i.e. under the same life circumstances, you wouldn't lose quite as much motivation, or see things quite as darkly - then even a small change might tip the balance and let you stay at equilibrium in a more functional state of mind. But before you can reach that equilibrium, you have to go through a long process of getting your life back in order and regaining self-confidence.
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.
Reading through the paper it seems like all the statistics are presented as Odds Raios vs placebo. But I couldn't find the actual efficacy of placebo. Did I miss it or does someone know?
Something being twice as effective as a placebo is great when the placebo effect helps 30% of patients, not so much when it's 3%
placebo rates would be something in the 15-40% remission rate range, in small RCTs. it varies more than you would think from one trial to another. antidepressant efficacy would be something like 20-45%. recovery rates are usually higher in smaller trials, and lower in bigger trials, partly because people get more high-touch service in smaller academic studies
"In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19–1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51–0·84)."
"For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43–0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates."
It appears that agomelatine[1] and vortioxetine[2] are effective and well-tolerated. Good to know.
[1] https://en.wikipedia.org/wiki/Agomelatine : "...avoids the weight gain, sexual dysfunction, and severe withdrawal associated with the most commonly used classes of antidepressants..."
[2] https://en.wikipedia.org/wiki/Vortioxetine : "...Incidence of sexual dysfunction is higher in patients taking vortioxetine than in people taking placebos but appears to be lower than in people taking most other antidepressants..."
However, agomelatine was not approved in the US due to clinical trials not showing effectiveness (withdrawn by the drug company after phase III), although regular melatonin is super easily available here and I've heard some people say it helps. For a good analysis it is important to get access to unpublished studies submitted to the FDA. I don't have links but I think there are a couple that have done that.
Edit: Looks like they did include some unpublished studies at least.
This analysis look at effects over 8 weeks. The first four weeks on antidepressants you're feeling terrible due to onset side effects (on top of your depression). Once that settles, you feel better. But there is no way to tell if you feel objectively better than before the medication started.
> "But there is no way to tell if you feel objectively better than before the medication started."
Would you elaborate at what you mean here? Two reads I have are either (a) you're getting at whether feelings like this are subjective, which is true definitionally but seems to me to be uninteresting, or (b) assessment tools (such as the Beck inventory) are imprecise, which is also true, but can still provide some basis for comparison. Or something else that I'm missing?
That said, I would like to see a longer time scale to see if the changes are maintained.
Statistically, rating scales typically used in these studies have been validated as showing effect, and clinical interviews can pick up a lot of things. That said, it's normally hard for you to be able to look back eight weeks and subjectively compare how you feel then and now. Usually it's not the person being treated, but those around them (family etc.), who notice the improvements first.
PSA: The first thing to realize is that psychiatrists, and regular practitioners, have no clue what will work for you.
In my case, it took 8+ years of trying, giving up, and trying again. E.g., Prozac didn't affect me at all, but the doctor never suggested increasing the initial dose. Paxil didn't work, Lexapro kinda worked, and now on the maximum dose of Effexor.
The biggest difference makers were the doctors perfectly willing to help me find a solution. Keep trying to find one like this, and don't give up.
This applies to everything in life. Just because an expert tells you it'll work, doesn't mean it will. Balance the possible negative effects against the possible gains, and once you have learned how it affects yourself, make your own decision.
(Unless trying something creates a condition that cannot be reverted, e.g. death)
Close enough to accurate. The better ones can apply useful heuristics (symptom matching, family response, etc.) as well as more sophisticated management of dose, side effects, etc. to converge on the solution much faster, but at this point, there's definitely still trial and error involved.
Yeah, with me it took a few tries as well. My doctor tried me on a few, before giving up and referring me to a specialist, who basically said that none of the doses I had been given so far were very high, so why don't we just increase the one you are on now. It worked.
I knew a lot of other grad students, myself included, who would throw anything with meta-analysis in the introduction in the trash. You cannot deal with controls across completely different studies in meaningful ways.
I'm also hesitant about anything that tries to claim things definitively without question. Science is about continually questioning your axioms. Without doubt[1] there is no progress.
As someone who has been on various anti-depressants, I will say that some of them "worked" .. but the side effects were quite high. Working only lasted the first few weeks with several different SSRIs. Eventually the side effects ended up being worse than the treatment.
I found the most effective thing for me was simply a really good therapist. She did try to recommend drugs to me again after I had quit, but she did respect my wishes to not be on them. I feel that having someone who really showed me my options and truly helped examine negative thinking patterns helped a lot more than the drugs ever did.
That being said, I know people who say they'd be in serious trouble or dead without SSRIs. It's a tough line to talk about. I personally would rather not ever be on them again. Dulling the pain for me also meant dulling life.
There are trade offs and we need to talk about them and have full discussions on the consequences of mind alternating drugs. When things are written into pure absolutes, it is a means of killing real discussion and dialogue.
Hopefully you and those other grad students will have learned more by the time you finish your degree. A proper meta analysis does consider the differences in controls across studies, and can be extremely useful in understanding why different studies got different results and identify bad studies. Not only do they help gain a better understanding of results, but they help find ways to better design future studies.
>I knew a lot of other grad students, myself included, who would throw anything with meta-analysis in the introduction in the trash. You cannot deal with controls across completely different studies in meaningful ways.
You probably need to rethink this. Meta-analysis can be quite stable and valid.
> Dulling the pain for me also meant dulling life.
I've heard quite a few people say similar things (including my therapist), but it's such a sharp contrast to my own experience. There are indeed very good reasons not to use these drugs (I currently don't and it's costing me dearly), but "dulling" is not a word that would ever come to my mind if I tried to describe the experience of being on them. The years I was medicating are actually the brightest patch of my adult life.
Well, I guess such differences are to be expected when we don't know what depression is and why these drugs work.
Glad that worked for you. Having seen many psychotropics poorly chosen/prescribed, your experience is certainly not uncommon, though far from universal.
Best thing would be understanding that different solutions are right for different people, and we get in trouble by generalizing (whether it's about meds, therapy, nutrition, exercise, etc.). One illness, many root causes, many different presentations, and the appropriate solution depends on a multitude of variables.
I was worried as to the source of this study and the people who are claiming this "puts to rest the controversy of antidepressant drugs".
It's all psychologists who naturally benefit greatly from a public perception that medication is effective. If I had seen quotes from psychologists saying "This is better than therapy - I'm stopping therapy and giving them drugs" then I would be on the bandwagon with the rest.
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 the science has a long way to go, but you're ridiculously generalizing. Some people stay on antidepressants long term, but most don't. Many psychotropics are used only short term. I think your test/cure paradigm is a bit of a "red herring"... maybe it would be nice if it were the case, but symptom (and impact) based diagnosis plus subjective improvement to symptoms, functioning and quality of life still counts to people actually suffering, as well as their families.
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.
So it should probably be noted that given these are powerful psychotropic drugs so it's difficult to control for them with a placebo and we don't really know their longitudinal effects. Also proper diet, exercise, yoga, or meditation can all help with mood and depression but you can't patent that shit. This isn't to say the drugs have no value but the bar to use them should be high.
I don't think that researches like this make sense at all. Each depression is unique in it's pathogenesis, there are no drugs that work for everyone. For example, a depression caused by a chronic desease or the one with deep roots in your childhood - a true research needs to evaluate all 21 drugs in each situation.
Is this not an insanely low bar? How can we take this paper seriously? We are talking about brain alchemy and more than 80% of the trials under consideration have a moderate to high risk of bias?!
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 antidepressants, my best case scenario is being an unemployed grad-school drop-out. With anti-depressants... well, it's amazing what you can do when you actually have enough neurotransmitters in your brain!
> well, it's amazing what you can do when you actually have enough neurotransmitters in your brain!
This notion of chemical imbalance in the brain is wrong/misleading by the way.[0]
> The fact that two efficacious classes of medications exert opposing effects on serotonin levels raises questions concerning a simplistic chemical imbalance model.
I would love to have someone explain this study in a simple way, with simple percentages.
For example, what is the efficacy of, say Prozac, compared to placebo?
"In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89–2·41) for amitriptyline and 1·37 (1·16–1·63) for reboxetine."
This says all antidepressants work between what percentage?
And in another post, someone mentioned the newer antidepressants were better that the older ones. What percentage better?
(And yes--I need to brush up on my statistics. I've taken a few of these drugs. I used to know how to read a simple study, and stopped because the results were so depressing. I am throughly confused with this study, and the charts. Then again, I'm not feeling great.)
- how well would harmless placebo pills work in their place?
I currently believe that there needs to be a safe, placebo-like option for people without severe illnesses. For those who are severe (and can tolerate side effects as serious as suicidality), it still seems to be a good idea to prescribe them.
How would that work? Do placebos work even if people know they're placebos? Could doctors just start prescribing a placebo called Fauxzac and it would work some of the time?
amputect|8 years ago
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 the honest truth just based on the direction my life was heading without them.
If you can't make your own neurotransmitters, store bought are fine. I'm not writing this to say "RARGH YOU MUST USE THESE DRUGS", but I absolutely am writing it to say "hey, this worked for me and got me out of a really dark and bad place". If you are reading this from a dark and bad place, please know that you're not alone. You have a lot of options, and I promise that if you take that first step, things can get better.
jdietrich|8 years ago
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 use and suicide risk except for young people, for whom SSRIs may actually increase the risk of suicidal behaviours and self-harm.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353604/
>If you can't make your own neurotransmitters, store bought are fine.
There is no evidence whatsoever that people with depression are "deficient" in neurotransmitters. We don't really understand the mechanism of action of any antidepressant. Plenty of drugs that have no effect whatsoever on serotonin are equally effective as SSRIs.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471964/
Antidepressants can be useful for some patients, but they aren't miracle drugs - they aren't even particularly good drugs. If you're depressed then you should certainly consider pharmacological treatment, but you should regard it as only one tool among many. Talking therapy is equally effective and the combination of drugs and talk therapy is more effective than either alone. You might need to try several different drugs before you find one that works for you and has tolerable side-effects, especially if you have been depressed for some time or have comorbid conditions. If your depressive symptoms are relatively mild, you should probably look at lifestyle interventions like diet, exercise, sleep hygiene and self-help before considering drug treatment.
https://www.nice.org.uk/guidance/cg90
publicfig|8 years ago
That being said, I understand that medication, or even the same medications, can't work for some people in the way they did with me. It's difficult to explain the position of "I know medication doesn't always work and isn't always an answer, but sometimes it is an answer that I would hate to be missed out on".
evincarofautumn|8 years ago
I just hope in the future there’s more access to psychedelics (and analogues) in a safe, professional setting, because they’ve been shown to be another potentially useful tool in the antidepressant/anxiolytic/self-care kit.
hestipod|8 years ago
I am not encouraging people not to try medication if they feel it is a good option, simply asking people to realize A. It's not a cure without a plan to fix the cause and B. Not to follow the common victim blaming that often occurs when these simple "fixes" don't work for people (OP isn't doing that and I don't intend to sound as if I am saying so...in fact they made it clear it's not a magical fix suited for all) Drugs are a tool, not a cure, and need to be wielded responsibly and properly. Sadly I don't believe that happens a lot of the time.
analogmemory|8 years ago
I really think they need to have some sort required of "Life Skills" class in high school. In which they teach you how to get help, how to ask for help, how to share your feelings with friends in a safe way. And your options if you do get into a deep dark way. Based on personal evidence, almost every adult gets depressed in some way and many don't know how to get help or deal with it in a healthy way.
I didn't learn any of that till my 30s. I nearly committed suicide multiple times. Our current society and the toxic religious one i grew up in taught me that a man needs to be strong and doesn't need to rely on others. Pray to God and just pull yourself up by your bootstraps mentality.
It's amazing how helpful it is to know that you are loved and cared for. And people want to help you. You just have to ask for it.
anticnstrctv|8 years ago
alex_hitchins|8 years ago
imperio59|8 years ago
Also would you say the drug cured you? Are you able to function without taking it now?
harbie|8 years ago
Wikipedia defines treatment resistant depression as "cases of major depressive disorder that do not respond adequately to appropriate courses of at least two antidepressants."
Maybe I'm unfamiliar with study methodology, but doesn't this undermine the study's conclusion? It's essentially stating that forms of deppresesion that respond well to antidepressants respond well to antidepressants.
tyu100|8 years ago
There were some older meta-studies that called into question their general efficacy vs. placebo even for mild/moderate depression but this new meta-study (with the additional previously unpublished data from their initial approval trials) looks like it has finally settled the matter.
Reading this paper I'm amazed at the increased efficacy of some of the newer SSRI's despite not having a novel mechanism of action. This is similar to how effective some of the newer statins are at lowering LDL cholesterol despite the drug class being around for decades.
edit: It looks like I'm a bit out-of-date in my knowledge but the general point still stands. DSM V has a definition of 'major depressive disorder' which seems to have replaced the old mild/moderate categorization and this study looked at all anti-depressants that treat this type of depression, not just SSRIs.
alz|8 years ago
unknown|8 years ago
[deleted]
ggm|8 years ago
amputect|8 years ago
But what we do know is that anti-depressants can be a powerful tool for helping people who aren't responsive to other types of treatment. Even if it takes some effort to figure out which one is the best fit for the underlying disorder, that's better than nothing.
JamesBarney|8 years ago
And as little as we know about how drugs work we know less about how CBT works.
meowface|8 years ago
Obviously therapy and other techniques should be attempted before drug prescription, but your friend is grossly oversimplifying how these drugs work and how psychiatrists portray how they work.
markroseman|8 years ago
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.
raducu|8 years ago
Do you mean agonist-antagonist mechanism of action of some drugs that treat the same condition?
As far as I know different drugs can work on serotonin/dopamine/norepinephrine but in different parts of the brain and produce different results.
comex|8 years ago
In the case of antidepressants - on one hand, there are some reasons to expect short-term interventions to be the best-case scenario in terms of evaluating benefit, such as the greater risk of side effects with long-term use, and drug tolerance effects. On the other hand, I suspect (but don't have data to prove) that placebos are much less effective in the long term. People think the placebo effect is in part a reaction to the social experience of interacting with a doctor, getting personal attention and concern for whatever condition is supposedly being treated. To the extent this is true, the novelty of the experience is probably a large factor, and over the long term you'd expect a reversion to the mean. So even if antidepressants are less effective in the long term than the short term, they might be more compelling as a treatment option, because the alternative (placebo) loses even more of its effectiveness.
Edit: Another factor is that the effects of reduced depression may take a long time to be fully apparent. Depression tends to work in feedback loops: as an oversimplified example, you feel bad about yourself, so you lose motivation to take care of your life, so you start neglecting essential tasks, the consequences of which make you feel even worse about yourself. And lifting yourself out of depression is the same thing in reverse. So if an antidepressant has the effect of reducing your susceptibility to depression - i.e. under the same life circumstances, you wouldn't lose quite as much motivation, or see things quite as darkly - then even a small change might tip the balance and let you stay at equilibrium in a more functional state of mind. But before you can reach that equilibrium, you have to go through a long process of getting your life back in order and regaining self-confidence.
jernfrost|8 years ago
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.
gehwartzen|8 years ago
Something being twice as effective as a placebo is great when the placebo effect helps 30% of patients, not so much when it's 3%
itschekkers|8 years ago
random_throw|8 years ago
"In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19–1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51–0·84)."
fernly|8 years ago
"For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43–0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates."
It appears that agomelatine[1] and vortioxetine[2] are effective and well-tolerated. Good to know.
[1] https://en.wikipedia.org/wiki/Agomelatine : "...avoids the weight gain, sexual dysfunction, and severe withdrawal associated with the most commonly used classes of antidepressants..."
[2] https://en.wikipedia.org/wiki/Vortioxetine : "...Incidence of sexual dysfunction is higher in patients taking vortioxetine than in people taking placebos but appears to be lower than in people taking most other antidepressants..."
joveian|8 years ago
Edit: Looks like they did include some unpublished studies at least.
askvictor|8 years ago
grzm|8 years ago
Would you elaborate at what you mean here? Two reads I have are either (a) you're getting at whether feelings like this are subjective, which is true definitionally but seems to me to be uninteresting, or (b) assessment tools (such as the Beck inventory) are imprecise, which is also true, but can still provide some basis for comparison. Or something else that I'm missing?
That said, I would like to see a longer time scale to see if the changes are maintained.
markroseman|8 years ago
jkmcf|8 years ago
In my case, it took 8+ years of trying, giving up, and trying again. E.g., Prozac didn't affect me at all, but the doctor never suggested increasing the initial dose. Paxil didn't work, Lexapro kinda worked, and now on the maximum dose of Effexor.
The biggest difference makers were the doctors perfectly willing to help me find a solution. Keep trying to find one like this, and don't give up.
tinymollusk|8 years ago
(Unless trying something creates a condition that cannot be reverted, e.g. death)
markroseman|8 years ago
mnw21cam|8 years ago
djsumdog|8 years ago
I knew a lot of other grad students, myself included, who would throw anything with meta-analysis in the introduction in the trash. You cannot deal with controls across completely different studies in meaningful ways.
I'm also hesitant about anything that tries to claim things definitively without question. Science is about continually questioning your axioms. Without doubt[1] there is no progress.
As someone who has been on various anti-depressants, I will say that some of them "worked" .. but the side effects were quite high. Working only lasted the first few weeks with several different SSRIs. Eventually the side effects ended up being worse than the treatment.
I found the most effective thing for me was simply a really good therapist. She did try to recommend drugs to me again after I had quit, but she did respect my wishes to not be on them. I feel that having someone who really showed me my options and truly helped examine negative thinking patterns helped a lot more than the drugs ever did.
That being said, I know people who say they'd be in serious trouble or dead without SSRIs. It's a tough line to talk about. I personally would rather not ever be on them again. Dulling the pain for me also meant dulling life.
There are trade offs and we need to talk about them and have full discussions on the consequences of mind alternating drugs. When things are written into pure absolutes, it is a means of killing real discussion and dialogue.
[1]: https://khanism.org/science/doubt/
tallanvor|8 years ago
sjg007|8 years ago
You probably need to rethink this. Meta-analysis can be quite stable and valid.
entropyneur|8 years ago
I've heard quite a few people say similar things (including my therapist), but it's such a sharp contrast to my own experience. There are indeed very good reasons not to use these drugs (I currently don't and it's costing me dearly), but "dulling" is not a word that would ever come to my mind if I tried to describe the experience of being on them. The years I was medicating are actually the brightest patch of my adult life.
Well, I guess such differences are to be expected when we don't know what depression is and why these drugs work.
markroseman|8 years ago
Best thing would be understanding that different solutions are right for different people, and we get in trouble by generalizing (whether it's about meds, therapy, nutrition, exercise, etc.). One illness, many root causes, many different presentations, and the appropriate solution depends on a multitude of variables.
SpikeDad|8 years ago
It's all psychologists who naturally benefit greatly from a public perception that medication is effective. If I had seen quotes from psychologists saying "This is better than therapy - I'm stopping therapy and giving them drugs" then I would be on the bandwagon with the rest.
imperio59|8 years ago
I think this "Science" of psychiatry has a long ways to go to actually get repeatable, scientifically proven results.
markroseman|8 years ago
projektfu|8 years ago
siliconc0w|8 years ago
dmitripopov|8 years ago
alz|8 years ago
alz|8 years ago
alz|8 years ago
gliese1337|8 years ago
Without antidepressants, my best case scenario is being an unemployed grad-school drop-out. With anti-depressants... well, it's amazing what you can do when you actually have enough neurotransmitters in your brain!
lawl|8 years ago
This notion of chemical imbalance in the brain is wrong/misleading by the way.[0]
> The fact that two efficacious classes of medications exert opposing effects on serotonin levels raises questions concerning a simplistic chemical imbalance model.
[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522609/
aianus|8 years ago
Anything except having an orgasm, in my case.
icantdrive55|8 years ago
https://www.students4bestevidence.net/a-beginners-guide-to-i...
I would love to have someone explain this study in a simple way, with simple percentages.
For example, what is the efficacy of, say Prozac, compared to placebo?
"In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89–2·41) for amitriptyline and 1·37 (1·16–1·63) for reboxetine."
This says all antidepressants work between what percentage?
And in another post, someone mentioned the newer antidepressants were better that the older ones. What percentage better?
(And yes--I need to brush up on my statistics. I've taken a few of these drugs. I used to know how to read a simple study, and stopped because the results were so depressing. I am throughly confused with this study, and the charts. Then again, I'm not feeling great.)
smt88|8 years ago
- how serious are the side effects?
- how well would harmless placebo pills work in their place?
I currently believe that there needs to be a safe, placebo-like option for people without severe illnesses. For those who are severe (and can tolerate side effects as serious as suicidality), it still seems to be a good idea to prescribe them.
tlrobinson|8 years ago
How would that work? Do placebos work even if people know they're placebos? Could doctors just start prescribing a placebo called Fauxzac and it would work some of the time?
icantdrive55|8 years ago
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