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.
I agree with all of this, and I can’t help but ask: when did we start ignoring people’s environment and their circumstances? I have tens of thousands of dollars of student loan debt (my monthly payment is basically a mortgage payment) and I’m not particularly satisfied at work. Is it any wonder I find it impossible to get out of bed? Now, I try to be careful because, sure, perhaps the depression was already there and is just making my life complicated, but that seems less likely. I KNOW I’m not happy at work; I KNOW my debt burden makes me feel trapped and helpless. Look at Harlow’s monkeys. Turns out putting creatures in helpless, depressing environments makes them feel helpless and depressed. If seeing your friend get blown up by a roadside bomb can give you PTSD, couldn’t falling wages, no social safety net, stressful news media, crushing debt, and poor job mobility make you depressed?
a) We're a highly medicalized society with very weak institutions for providing informal psychosocial care and support.
b) Saturation marketing of psychiatric medication has caused the general public to grossly over-estimate their efficacy, even in countries where direct-to-consumer marketing is banned.
c) The wholesale price of a generic sertraline pill is about 4¢, so it's cheap enough to dole out like candy.
d) Medicalizing unhappiness is politically convenient.
If you're depressed, you go to your doctor. That's the message you've been told for decades, it's how our society is set up. In another culture, you might speak to your priest or a village elder. It's undoubtedly a net positive that we've got access to some kind of evidence-based psychiatric care, but a lot of the other structures that people used to rely on for psychosocial care have crumbled. We're less likely to know our neighbours. We have fewer close friends. Our employment is more impersonal and precarious. We're less likely to go to church. If we do go to church, it may well be a megachurch with a congregation of hundreds rather than a close-knit community church.
Doling out pills is the absolute cheapest treatment option, even if some proportion of those pills are expensive proprietary drugs. It's orders of magnitude cheaper than psychotherapy and immeasurably cheaper than building a more humane society. Your doctor can't prescribe a good friend, a sympathetic partner or a better job.
It suits your employer if you conceptualize your misery as the symptom of a "neurotransmitter deficiency" rather than a symptom of your crappy job. You probably won't be as productive, but at least you won't go on strike or burn down your office. It suits the government equally well if you see misery as a personal rather than societal problem.
Some people are just depressed for no discernible reason. Lots of people are being diagnosed with depression when they're just struggling with a shit set of circumstances that would make anyone miserable. The medical model helps some number of people in both camps. Society needs to do a better job of helping people live healthy and fulfilled lives.
We're not ignoring their environment. But unfortunately, most of the time drugs are quicker and easier for the prescribers, and therefore cheaper and more available for the patient, than extended psychotherapy, etc.
If the underlying problem is a psychosocial stressor, the meds won't fix that, though they might help you control the symptoms long enough that they give you the opportunity/resilience to address the stressor. And sometimes, while maybe not ideal, just controlling the symptoms is enough even for the long term.
"We" absolutely are ignoring their environment in the USA at least. People cannot even access healthcare here without additional, significant financial stress and burden. My entire family and the strong majority of my region and a general majority overall oppose the policies and systems that would give someone like me a life and future. Even seeing how it's gone for me my family refuses to support social systems and offer help to those in need. It's "stealing my money" to them and ruined our relationships seeing how selfish they are turning their back on me AND society.
I know the causes of my issues, there are at a minimum mitigations available but I can't BUY them because everything here is a business and competition and someone else took me out of the race by taking lots of money to end my capacity to compete (poor medical intervention) and I was left holding all the additional baggage with no help. I have friends who suffered catastrophes living in countries who don't think social systems are evil, and they had the tools to heal as much as possible and improve their lives and be able to contribute to the whole again. I wasn't afforded that opportunity and it's been a constant downhill slide.
Pardon the tone and it is not directed at you, it just infuriates me that American society ignores such important things and once someone is not able to WIN in the Thunderdome they are cast aside and/or expected to live with little to nothing and even more needs, while it continues focusing on pushing what are in my view largely ineffective, but very profitable "interventions". I find the predilection for painting over damage in this country over restoring/shoring up someone's foundation to be maddening.
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.
For the more severe anxiety disorders, the proof of efficacy above placebo is much better than what we have for depression. People don't get better by taking placebos for their OCD. For anyone experiencing anxiety problems, I highly recommend finding a competent therapist who knows CBT. For anxiety that constantly interferes with daily life, medication may be appropriate.
For me the SSRIs completely wiped out my OCD to the point where I sometimes forget that I have problems with anxiety. Depression is downright benign compared to how bad the situation can get with other psychiatric disorders. Unfortunately the demand for competent medical professionals far outstrips what is available.
I do agree that SSRIs are over-prescribed for minor depression problems, but let's not demonize a whole class of medications which are highly useful for more serious psychiatric issues.
Some people need it because their brains is just plain imbalanced, I get that. For some, that imbalance can be fixed with lots of work, however for some, it can't. I'm _hoping_ to be able to fix mine, but I'm willing to work with a doctor to figure out if that's possible.
I wish you the best. Definitely don’t be afraid to discuss alternatives with your doctor if you’re not happy with Zoloft...sometimes it takes a few tries before you find whaat works best for you.
Thanks for the reminder. I'm trying to tough out a month, because side effects tend to wear off within 3-4 weeks, and review with my doctor and therapist then.
Assuming that efficacy is randomly distributed, you're left with some very frustrating math. You'd need to try five drugs to have a better than 50/50 chance of getting a positive outcome. After seven drugs, there's still a 34% chance that none of them have worked. After fifteen drugs, there's still about a 10% chance that nothing has worked. I expect that most patients will give up on drug treatment well before that point.
I don't want to be overly negative about antidepressant drugs - they're a useful treatment for many patients - but I do feel that the popular perception of their efficacy is far greater than the reality. Many people seem to feel extremely disheartened when antidepressant drugs don't work for them, often believing that there must be something uniquely wrong with them. The language of psychiatry doesn't help, describing these people as "treatment-resistant" rather than "people we don't know how to treat".
If you try antidepressant drugs and they don't seem to do anything, don't keep taking them just because you think you're supposed to. Speak to your doctor about alternative drug and non-drug treatments. If you have access, try a range of psychotherapies. If your symptoms are relatively mild, look at lifestyle interventions. If your symptoms are particularly severe and/or chronic, give some serious thought to rTMS or ECT.
i agree with your points, but 50% is already good i think.
it is less than anyone might spontaneously guess, but it is still good, considering that you will try a couple of other things in addition, like cognitive therapy.
So getting some good months long treatment by a doctor can lead to (lets say) 70% curation rate. It then becomes sad if people choose to stay away from doctors and I just commented to not discourage possible ill persons.
You probably just wanted to stress that such pills are far away from doing guaranteed miracles and you are right.
> 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.
Which is fine, as long as they stay alive long enough for natural changes to occur. If a prescription gives only hope, that could be enough to keep people strong enough to battle through another day, week, month, year.
>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.
The paper says:
"However, in children and adolescents, there appears to be a bit of increased risk of suicidal ideations and attempts, but not of completed suicides."
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.
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 )
One issue worth mentioning is that psychiatrists are one of the hardest specialists to find that participate in health insurance. This is only anecdotal in my area, but many that take insurance have multiple month waiting periods for new patients. Or you can pay $200 to see one on your dime.
It's not the cost of the medication that's the problem. It's access to the professional to prescribe the medication that drives people to self-medicate, IMHO.
Ditto. Also, at least for state-provided health insurance, there seem to be quite a few that accept it but aren't on the state's registry for some reason, so it's worth calling and asking.
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.
I generally agree—I guess I just mean I wish there were a safer/tested way to take advantage of other serotonergics, after the first line of defense fails, for those who are less cavalier than I am about their neurochemistry.
Also in my case it wasn’t depression, so I can’t really speak to that, but SSRIs are also prescribed for anxiety disorders. I chose not to go on them when they were offered because I didn’t feel that the side effects were worth it, and they weren’t the correct treatment anyway because at the time I was mainly anxious due to alcohol withdrawal. (I’m lucky I didn’t have a seizure!)
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.
Jordan Peterson talks about this in one of his lectures. I can't look it up now but if you google "Jordan Peterson antidepressant" you should find something
> 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.
The anti-psychiatry folks are extreme enough that they deny mental illness altogether, though many other "psychiatric survivor" communities do not deny, and often celebrate "lived experience", but are critical of psychiatric treatments.
>"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.
> 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.
There are huge differences in the mechanism of action, quantitatively speaking, even within a class of antidepressants. As a particularly striking example, you're allowed to call your drug an SNRI as long as it has any detectable N effect at all -- even if the N effect is too small to practically make any sort of difference, and the drug is practically an SSRI.
Right, so since a common problem with anti-depressants are the varied side effects of different classes (insomnia, weight loss/gain, sexual dysfunction, etc.. and etc..) a big part of going on an anti-depressant is you and your doctor finding a drug and a dose that shows both efficacy and a tolerable side effect profile.
This study generalizes this process by discussing both efficacy (how well the drug helps with depression) and the tolerability of the treatment, as measured by how long people tend to stay on the drug (the site is down right now so I forget the actual term used). Once the paper is accessible again have a look at some of the graphs that chart both of these measures. Generally, the drugs in the upper-right quadrants are better, showing both good efficacy and tolerability.
It's important to remember that these drugs are ranked in term of efficacy vs placebo at reaching a specific outcome threshold (greater than 50% reduction in depressive symptoms). So best in terms of efficacy just means the highest ranked has the best statistical chance of working. It does not mean that it works x% better than another drug (i.e. Drug A reduces symptoms 60% and Drug B only 50%. It also means that the drug ranked #1 might not work for you at all; the "best" for you could be drug ranked #16.
This is basically a ranking to use in when trying drugs to statistically maximize your chance of finding one that works.
"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 then there's also the odd fact that earlier trials of antidepressants show better effect than recent ones -- even for the same treatment and all else held equal. We don't know why.
Basically, the foods you need to avoid are any that might cause constipation, because Amitriptyline kind of does that for you already. The parent post was possibly confusing Amitriptyline with a different drug.
It is very weird to be mixing two different antidepressants. Depending on what your other antidepressant is, it could be dangerous. Were your two medications prescribed by the same doctor, and if not, have the two doctors talked to each other? A very simplistic view is that some antidepressants cause the body to make more serotonin, and others prevent the body from destroying serotonin as quickly. Doing one is fine, but doing both at the same time can lead to serotonin syndrome.
Amitriptyline does have higher risk from overdose than SSRIs, but has much gentler withdrawal symptoms.
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.
Yes, but we need professionals to be more overt we are groping in the dark I think.
The recent news about why ketamine works is a very specific aha moment, they showed a focussed impact on a brain functional element which seems to re-stim negative ideation and so blocking it relieves a cycle and then permits some kind of reset. Layman's analogies.
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.
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 attempted before drug prescription
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.
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.
I am a layman so probably use words inadvisably. Some drugs supress effects in the brain, some enhance. Yet both are seen to be deployed to try and treat depression. This is a very confusing signal. If the condition can present from either too much or not enough of something, what diagnostic determines which to try? What evidence do we have, of a mechanism to determine which except for "suck it and see"
I see, my intuition is that the brain is like a very complex analog amplifying station with different types of transistors, capacitors, resistors, whatever.
Drug A decreases 100ohm resistor values to 50 in a noise filter stage and "fixes" your problem with the radio.
Drug B has same 100ohm -> 50ohm effect, but in a different section of the radio and doesn't work.
Drug C increases the speaker resistance from 5ohm -> 10ohm and "fixes" your problem because you simply cannot hear the noise.
Drug D increases the microphone resistance from 5ohm -> 10ohm and the noise simply is not picked up.
Drugs A and B work the same way, drug C and D work the same way, but opposite to how drugs A and B work and they all provide the same net effect as far as I'm concerned.
This is a good analogy, because there are a lot of different biochemical pathways that can play roles in mental health. To add add to that, here's a good image of 4 of the ways a drug can effect activity at certain sites (not mental health specific, general pharmacology principles): https://commons.wikimedia.org/wiki/File:Inverse_agonist_3.sv...
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..."
I didn't read the paper but going off your comment and the parent - escitalopram was in both lists, whereas vortioxetine wasn't. http://en.wikipedia.org/wiki/Escitalopram
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.
In any case, looking back that 8 weeks and comparing to now, _after you've just been through 4 weeks of hell_, you'll report that you're feeling a lot better, even if you've only returned to the same level you were before starting the meds.
Are there studies that use family/etc as the basis for their data? That would be a lot more valuable, as long as they also include a control.
The studies also need to look a lot longer than 8-12 weeks, partly due to the onset side effects, but also as a lot of depression is caused by a stress event that passes and resolves in a few months. It is interesting that a placebo has a positive effect (not as large as the meds); I wonder if they measured the effect of no treatment at all.
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.
If you have a medical disease, you talk about finding a cure... For aids, cancer, diabetes... The research is headed towards cures.
Funny enough that all the PR and talk from Pharma companies on these psychiatric drugs is all about treatment, and "living"and "coping"with symptoms... No cures, just selling you pills that don't actually work to cure your problem, just masks the symptoms or distracts you with side effects that are worse than your original issue (like obesity, loss of sexual function, etc...)
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.
I felt that I was not depressed anymore and I started working with my psychiatrist to reduce dosage until I was on the minimum dose. Then I stopped when I was feeling particularly good and kept a bottle of 5-HTP on hand. I'm not sure if that was necessary or not.
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.
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.
Well, yeah, there is that. I am somewhat fortunate to be the sort of person who doesn't care too much about that, but it can definitely be a sucky tradeoff for many people.
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?
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.