To provide one additional anecdote: I came off escitalopram with no taper after taking it for about five years (10mg). I got brain zaps for a while, got very irritated at times, but largely was fine after a few weeks. Not downplaying the withdrawal effects for some people, but they’re not as catastrophic as this article suggests for many (perhaps most).
And overall I’m very glad I took it! It got me through a rough patch, and seems (in combination with therapy, and some life changes) to have rewired me a little. Symptoms I had for a decade prior have not returned. And I’m not sure I could have made those life changes without it.
It can be catastrophic if one is managing family life, kids, taking them to and from activities on top of one’s own work. Then come misc stresses like tax returns, some expensive home repair, etc. Also dealing with depression without the anti-depressant. Switching mental health medication is no fun.
I am glad your experience was tolerable but it’s a whole arc and everyone’s tolerance + circumstances are unique which makes it all the more challenging (even for doctors).
Withdrawal effects, like the beneficial effects, are highly individual. I had no withdrawal effects from escitalopram after being on it for a couple of years but I know people who’ve had the issues described in the article.
It's been years since, but I too had brain zaps coming off of it. It took a few months for those to go away.
I tried to describe it to my doctor and he seemed like he never heard of it before and sort of look at me like I was crazy, or at least that is what I sensed. But I ended up researching online and found it was a thing that happens.
Interesting is your doctor a general practitioner or a psychiatrist? A psychiatrist definitely knows about this stuff. GPs in my experience know almost nothing about anything beyond what seems like a script they operate from.
What seems most broken is that medicine apparently didn't have a great way to predict which group you’d fall into, or much of a plan for the people who had a really bad time stopping. Also, RIP the anti-spider benefits
Good news, exposure therapy is quite effective for arachnophobia and is the first-line treatment. SSRIs do not have the same level of supporting evidence, and the effects are not as durable.
> SSRIs do not have the same level of supporting evidence, and the effects are not as durable.
To the extent that we can measure depression, SSRIs have been widely proven in gold standard phase III clinical trials to help with the treatment of major depression. What exactly is supposed to be lacking in the supported evidence?
Thanks, yeah, but if I’m honest I don’t really care enough to go through with it. I almost did once, years ago, the London Zoo have a programme.
I mentioned it though as one of the most stark changes I noticed after getting on an SSRI was pretty much immediately losing my fear of spiders. It was the first sign I had that showed it was doing something.
I used to literally, on occasion, launch my phone across the room if I was scrolling and came across a spider (sometimes drenching myself with coffee or whatever in the process!) and then one day, shortly after getting on it, I stumbled across some awful tarantula video or something and I just stared at it like “huh, why am I not freaking out”.
Same experience early this year but I did halve the dosage to 5mg for a month, which was of near zero difference. But the full withdrawal? Oh man it is no joke.
Sure seems like it to me, but my doctor seemed bemused when I mentioned it to him and I don't think they're routinely prescribed for them. I reckon if I'd have paired the SSRI with some exposure therapy, it would have cured me of it long-term. I do have an additional phobia however (I'd rather not say which) and it didn't make any impact on that at all, so YMMV.
Worth noting as well that I had no expectation of any changes to my arachnophobia going in. It didn't even cross my mind.
Though this article concentrates on the SSRIs, other meds like the SNRIs can have a similar or even worse withdrawal effect. We didn't call it "Side Effexor" for nothing.
People legitimately need these drugs, including in the short term. The problem for acute stressors once they resolve is how to get them back off.
For something prescribed to get someone through a temporary crisis, "how and when do we get you back off this safely?" should probably be discussed at the beginning, not years later when the patient decides to stop.
> Though this article concentrates on the SSRIs, other meds like the SNRIs can have a similar or even worse withdrawal effect.
And don't even get me started on tricyclics or MAOIs... no, seriously, don't get me started on them! The current generation of first-line antidepressants (SSRIs/SNRIs) might as well be free compared to the old school crazy pills.
It's probably less "modern antidepressants are uniquely bad" and more "we got much better at starting people on safer drugs than we did at figuring out how to stop them"
Much of medicine (especially mental health related) is rather primitive. We are literally reverse engineering discoveries that seem to work on some other animals, and then figuring out how (to the best of our limited ability).
I liken SSRIs to carpet bombing - also their mechanism to increase seratonin in the brain is by making something else not use it (reuptake inhibition). We’re guessing that other thing isn’t a big deal. But who knows. Serotonin is produced in the gut and it controls melatonin, which controls our sleep. It’s all connected in a bizarre way.
It's like inserting objects into the body's event loop and hoping it produces the desired effects as it circulates, only to find that everything reacts to the event, not just the parts we want.
Only slightly related, but can anyone ELI5 why Bupropion XL is not the universal first line treatment for depression and is hardly used at all in Europe?
It has fewer side effects vs. SSRIs, can be safely used as a long term medication (which many people do with SSRIs even though it can have negative effects), and doesn't have the same horrible withdrawal symptoms (although you still need to taper).
Well this would be an improvement over my former NHS GP practice deciding the best way for me to come off antidepressants was immediately stopping them without renewing the prescription or even discussing it with me! I think they just forgot to renew the prescription.
"Prolonged" is not a long time either. You can be ensnared after just a couple weeks. And even a safe taper is still pretty hellish.
I had to wean off Klonopin, prescribed for a bout of COVID induced insomnia. Only on it for a month and it took a microgram taper and nine months to get off of completely. Had to go slow because the original recommended rate was wayyyyy too spicy for my central nervous system. Even at the slow rate I was going it was difficult to make it through life. Most doctors are unaware of how to deprescribe this shit safely.
I forget exactly which antidepressant I was on, but when i finally stopped taking it, i was instructed to reduce dosage by half a pill every two weeks.
Anecdotally, that was not anywhere close to slow enough. I had panic attacks almost every day while I was reducing the dosage. Those weeks were hell. I couldn’t think straight. I honestly don’t remember much of what occurred during that time, because the withdrawal took over my life. The pills were too tiny to split into fourths easily, but I wish I had done something to reduce dosage in smaller increments or over a longer time period.
It makes me strongly reconsider ever taking any antidepressants ever again. They didn’t tell me when I started taking them that the withdrawal would be so terrible. Those months were easily some the worst of my life.
I've taken antidepressants for years (20 mg prozac) and have sometimes tapered off them, restarting later. I can barely tell that I'm taking them, I feel 100% like myself on--and off of--them. I know they do something because when talking about difficult traumas with my therapist, if I'm not taking flouoxetine I will get choked up to the point I can't speak. That's the only difference I can perceive. My dose is not a "happy pill", it simply smooths out some extreme lows. Tapering off (a few weeks of 50% exponential declines) I've done because it's recommended, but again, I've never noticed any affect on mood before, during, or after.
after a number of years, a small dose of lithium (300mg) was recommended by a psychiatrist who stood apart (at least in that respect), and it was magic at mood stabilization, I never before even realized that I experienced hypomania (and I took it for anxiety), I just thought I was "bold".
(Lithium is not a drug, it's an element, taken as a metallic salt. It occurs naturally in the water in various parts of the world, and those populations have been studied and suffer lower rates of mental illness. My shrink said his recommendation was based in conjunction with the prozac I was taking, i.e. a known correlation. Bipolar II is a different mental condition than bipolar I, and somewhat slippery/loosely defined)
The extreme anecdotal stories people report online as in this forum strike me, an experienced but likewise only an anecdotal user, as more an artifact of underlying emotional distress rather than a result of the drugs.
I just wanted to contribute a different voice to this topic.
I should add, I do have "extra money" and am able to pay extremely qualified and expensive doctors, an option that is not available to everyone, including those with full public health services.
TLDR: Rate is individualized and determined by the patient's tolerance. If symptoms appear, maintain or increase dose to stabilize, then try reducing again later. Use liquid medication for more granular dosing.
Doctors aren't "finally learning" how to manage withdrawals. This is essentially the common sense algorithm, and I'm pretty annoyed that they wrote this whole ass article just for that.
They work so well for some they are miracle drugs, and for others they do nothing or have negative effects. This is typical. We still don’t fully understand why or even why they work at all.
My parents tried seeking out help for me when I was about 10 years old, but they got cold feet, and I believe that they were unwilling to accept any responsibility or blame for what was going on at home. So when I reached the age of majority, they fully funded therapist and psychiatrist sessions for me, and they foisted Prozac upon me, starting around 1991.
I began taking Prozac and suddenly exhibited a remarkable improvement in my mood and affect. These improvements were largely because I was getting attention, I was getting "weekly pep talks" from a professional, and at long last, there were names I could affix to those extremely troublesome spirits that tormented me night and day.
But the doctors, having a practice in the Children's Hospital, didn't see fit to warn me not to drink alcohol, especially not to excess, and I was simply reaching that age where this was happening frequently. So, the mixture of SSRI plus ethanol was really disastrous for me and my loved ones.
I cycled through all kinds of meds, and clinicians tried finding some other stuff to medicate, like maybe hypothyroidism, and I really hated the medication, and I got hospitalized and discharged with a cocktail of at least 5 prescriptions all at once. I suffered really awful adverse side effects. But it wasn't realistic to stop. I kept cycling through new and different drugs. Every time it was new and different, and I had more complaints, and I stopped again and again. I had all the "brain zaps" especially Zappy Zoloft, and more hospitals and more upheavals in life.
I've finally reached a point where I can steadfastly refuse any medication, up to the point where inpatient treatment is done. I am 100% off drugs, and I feel great about that. I tend to inform my providers that I have "a Lithium deficiency" because bipolar isn't real: it's merely a cluster of highly-subjective "symptoms" and behaviors, under an ever-widening umbrella, and the bottom line is that they just want to put Lithium Carbonate on the checklist of "subject is treating this thing" and then once I'm taking enough of it, they can heap on more and more drugs on top. And Lithium is one of those where they grab you for a monthly blood test, to "trust, but verify" as the Soviets would say.
So I am pleased that SSRIs and their ilk are far, far behind me. I inwardly chuckle or sigh wistfully when I hear another patient extolling the virtues of ECT or Ketamine or something. How wonderful for you to be dependent on quacks and pseudoscience. Read any Wikipedia page for these drugs.
They are fairy tales.
I am a practicing Roman Catholic: I don't need to believe in fairy tales from foreigners and infidels who distribute condoms and wear white coats.
I think exercise, sunlight, good sleep and diet, and good social relationships are all more effective than SSRIs. But anyone who's had bad depression knows how hard those things are to maintain if you're depressed. SSRIs make some portion of people functional enough where they can at least build a healthy life. But definitely not everyone, and they are definitely not "the cure"
> I felt no different before, during or after them.
SSRI onset is slow, which is one of the common problems with treatment.
In studies where they survey both the patient and their family members, the family members actually start noticing improvements before the patient. Onset is slow and it takes a long time for patients to realize the positive effects.
Ideally they’re prescribed along with other lifestyle changes like your walks. It doesn’t have to be an either-or. A lot of patients get offended when doctors suggest things like walking because they think it indicates the doctor is telling them to “just walk it off” which doesn’t go well.
It’s not surprising you didn’t feel anything noticeable after a few weeks. It’s also unfortunate, but not too surprising, that your doctor wasn’t informed enough to communicate these things. Some doctors are great about setting expectations and following up. Others write a prescription and send patients off to fill it without the necessary context.
The other problem with SSRI treatment is that individually they are only barely better than placebo. They're among the worst classes of drugs as far as NNT, effect size or remission rate (individually! STAR-D treatment algorithm works for the vast majority of people)
Especially in acute cases, I think they should be replaced or augmented by something stylistically in the direction of esketamine. 6-8 weeks per medication trial is an absolute eternity, especially since some minority of major depressive episodes resolve spontaneously after a few months to a year.
> The other problem with SSRI treatment is that individually they are only barely better than placebo. They're among the worst classes of drugs as far as NNT,
These numbers are really misunderstood when taken out of context.
Which sounds terrible if you know nothing about NNT. But when you learn that Tylenol has an NNT of almost 5 and even a powerful drug like Xanax has an NNT of 4, you realize that NNT is a difficult measure of drug efficacy.
> Especially in acute cases, I think they should be replaced or augmented by something stylistically in the direction of esketamine. 6-8 weeks per medication trial is an absolute eternity
Ketamine and esketamine are used a lot to begin therapy. They’re not good long-term options though, so they’re best used to start treatment as a bridge to SSRI efficacy.
> SSRIs have an NNT around 7, depending on the study you look at [...] Which sounds terrible if you know nothing about NNT. But when you learn that Tylenol has an NNT of almost 5 and even a powerful drug like Xanax has an NNT of 4, you realize that NNT is a difficult measure of drug efficacy
This kind of comparison is utterly meaningless (like saying a Cohen's d of 0.3 is large for phenomena X, so if we see 0.4 in phenomena Y, it is large in Y), and is why NNT is basically deceptive for antidepressants.
What qualifies as an effective "treatment" has to be anchored to a minimal important difference, and this is what antidepressants really don't clearly have, on average. I.e. saying the NNT of SSRIs is around 7 is not really practically interpretable, because they tend not to base NNTs here on the amount of patients that actually experienced a clinically meaningful change, they just count the number that exceed some arbitrary (usually purely statistical) threshold.
Okay, so we set aside NNT, even though their NNH is also quite low, and that's highly relevant, what about effect size and remission rate? This feels a bit like cherrypicking. And you'll note I said "augmented", as well, if somebody is going through the treatment algorithm with SSRIs, by all means, that's the bridge to stability for somebody on a longer term course.
But many people don't need anything more than acute treatment, so what about them?
> what about effect size and remission rate? This feels a bit like cherrypicking
Trying to pull out NNT feels like cherry picking because it sounds really bad to people who don’t know how other drugs look on this measure.
If your point is that it would be better if we had better drugs then I agree.
I think trying to imply that SSRIs are barely a step above useless is not helpful, though. Statistics like NNT and remission rates do not capture incremental improvements that these medications can make for people who need all the help they can get. Even if it doesn’t cause complete remission by itself it can be very helpful.
> If your point is that it would be better if we had better drugs then I agree.
My point is that there are other interventions which do have an effect size over the perceptual threshold. Exercise is a big one, but there are lots - sleep deprivation, intensive therapy, the esketamine class, TMS, ECT in extremis, (nature exposure and other seeming woo like that need study but are promising) are all significantly better than handing someone an SSRI. And many of those don't have the withdrawal symptom and side effects under treatment that SSRIs do. People are, in aggregate, being harmed by SSRIs displacing things that work right now, and also displacing the urgency of new drug development in the space.
The gap is that, in an acute treatment setting, people are being handed a drug that cannot be effective for at least a week or two, up to 6-8 weeks, instead of drugs that work in hours or days.
+1 on therapeutic ketamine. Got me out of a bad spot, and felt better long after it was over. You can get it by mail in the US from Mindbloom, who offered excellent care despite being remote in my case.
Lexapro, noted in the article, was literally life changing for me. I felt better within 3d and I notice severe issues if I miss ~3d of doses in a row, even though the half-life should support ~7d without according to my physician.
That said, yes; walking is the best medicine for me.
Best way to manage the withdrawal would be to dramatically reduce them being prescribed in the first place.
The linked article says they have "small to moderate effectiveness", but this is being far too generous. The correct way to measure drug effectiveness is if the treatment meets the standard of a minimal important difference. I.e. you measure depression on various rating scales, like the 17-point HAM-D, and research suggests a minimal important difference (i.e. one patients and clinicians can actually notice) needs to be about 3-5 points. But the average effects of almost all antidepressants do not meet these thresholds, i.e. the effect actually appears practically invisible. [1]
Then you'll get waffling like "oh, but it really has a big effect for some people", but, well, no, we've looked at that too, and the placebo groups get just as miraculous "big effects", i.e. evidence supporting the idea "they really help some people" is also largely lacking [2-3]. All the other attempted saves ("oh, but eventually you find one that works for you") are also not really well supported either [4].
Like, maybe they really help some people, but it is far, far less clear than most assume, and should be balanced with concerns like withdrawal and serious side effects like emotional blunting and sexual dysfunction.
EDIT: And just to be clear to anyone doing a drive-by downvote thinking this is about recent asinine US politics, it emphatically isn't. There are serious methodological concerns here that desperately need to be communicated to the public.
> Best way to manage the withdrawal would be to dramatically reduce them being prescribed in the first place.
No, that will just hurt more people up front for longer. The truth is antidepressants have a larger effect on mental health than actually gets reported because of how improvements are measured. If you look at a patient who doesn't get out of bed, is in trouble at work/school for performance, doesn't spend social time with friends, etc, and 6 months after starting an SSRI they're indistinguishable from other people but still have other issues, we call that a "mild impact" because they self-report other problems.
The truth is we took someone from being passively suicidal to functioning normally, and we fail to look at the self-reported problems, we just report them. The self reported problems tend to change from "I don't care about anything" to "I'm unhappy at my job" or "I'm stressed at how much I have to do with work and my kids and home." These are actually major improvements, the patient has gone from being actually clinically depressed to significant improvement but continued unhappiness with life circumstances as opposed to unhappiness with life in general.
Antidepressants are amazing, we need to improve therapists and how they deal with medicated patients. Too many therapists dismiss meds and too many psychiatrists dismiss therapy. I've been in this space for a long time now, healthcare IT in the mental/behavioral health space. We're engaged in a long erm research study to help demonstrate the value of a tightly integrated therapy/psych team and more advanced treatments and when you get everyone in the room pulling in the same direction patient outcomes are amazing.
One actual issue that antidepressants face is that they're not the only treatment, but many doctors are reluctant to move to TMS or esketamine, despite the amaing success rates they have with patients who have not had success with two or more drugs. If two drugs failed you, the third has a 14% chance of helping. The 4th is single digits. But you pivot to TMS and you see 60-80 percent improvement rates. Esketamine is close too.
ADs aren't the problem, it's that we don't take mental health as serious as we take physical health.
> You look at a patient who doesn't get out of bed, is in trouble at work/school for performance, doesn't spend social time with friends, etc, and 6 months after starting an SSRI they're indistinguishable from other people but still have other issues, we call that a "mild impact" because they self-report other problems.
This really lines up with what I've seen anecdotally. My partner literally doesn't remember how bad things were before he took antidepressants because depression impacted his ability to form memories. He self reports that antidepressants had a mild impact, but from an outside perspective nearly everything about his life changed.
> But you pivot to TMS and you see 60-80 percent improvement rates. Esketamine is close too.
I have received both rTMS and esketamine and the providers themselves told me they saw roughly a 30-40% response rate (not remission, that's even lower!). Upon researching the topic myself, I found that the meta analysis usually agreed with this 30% figure, but recent research papers mark eskatamine even lower. Both treatments can be miraculous for a few select people and it makes a good headline, but it's a total failure for the majority of people.
I agree with you that those treatments should be easier to access, though.
> Too many therapists dismiss meds and too many psychiatrists dismiss therapy.
This is the only factually true statement in your entire comment.
The problem with the entire argument that you're making is that the natural rate of remission in uncomplicated major depressive episodes is very close to the rate that SSRIs create, individually, and very close in terms of timing. If you do something more like STAR-D you see higher rates, but that also takes so long that many people naturally remit.
> The truth is antidepressants have a larger effect on mental health than actually gets reported because of how improvements are measured.
The truth is actually exactly the opposite, and I provided very high-quality evidence demonstrating this to be the case. You have nothing but bald assertions.
Well I think that we do not know enough about genesis of depression and other mental issues. So this is just symptomatic therapy. And as such it should be prescribed only for very short terms. Analogy: how would you perceive someone who prescribed his febrile patient paracetamol for 10 years just because it works? And in his defense he/she claims that febrile condition has well known metabolic chain and that paracetamol lowers fever mainly by interrupting the COX → PGE₂ part of the fever pathway in the brain.
So did you take them and have a bad time? Because they definitely work for me and I doubt a placebo could have such a large effect on the 48 hour stomach pains I used to get alongside my frequent panic attacks.
I find it funny that people complain about emotional blunting when that is the entire purpose of the drug. I would prefer not to live on the razors edge ever again. I’ve had chronic anxiety and depression ever since I was a child, though.
For some people the emotional blunting is desirable, especially as you said, if the problem is chronic anxiety. But for many other people, their depression is defined by a lack of positive affect and anhedonia, meaning that emotional blunting is literally making things worse.
Depression is highly heterogenous, and I am glad the medication helped you.
SSRIs have much more clinical evidence of efficacy for addressing anxiety disorders vs a placebo than depression. The effect size is ~0.7 vs 0.2 in meta studies.
Totally agree, they really shouldn't be called antidepressants at all. Important to add tho that for many with depression they have comorbid anxiety and often the anxiety is harder to tolerate than depression, so removal of anxiety symptoms can be hugely beneficial.
Also, IME they are dosed completely wrong. So many people seem to be on very low doses, which has no improvement on placebo in the studies I've read.
Whereas, higher doses are _hugely_ better than placebo, especially for anxiety.
What's worse is a lot/most studies on SSRIs in general often don't adjust for dose. Which seems like an enormous oversight to me.
> I find it funny that people complain about emotional blunting when that is the entire purpose of the drug.
The ideal would be to blunt the negatives but not the positives. The effect of some of the older antidepressants can be to blunt both, across the board.
Some of the newer atypical antidepressants can address depression without making everything flat.
On an academic level, we have reined in much of the excess enthusiasm in antidepressants that was courtesy of 90s-era pharmaceutical reps and ad men, but I don't think this revision ever occurred in the cultural consciousness at large.
See also: The Serotonin Theory of Depression: a Systematic Umbrella Review of the Evidence (2022). It's worth reading the introduction and results in full, but here are two important quotes (footnote markers removed):
> Our comprehensive review of the major strands of research on
serotonin shows there is no convincing evidence that depression
is associated with, or caused by, lower serotonin concentrations or
activity. Most studies found no evidence of reduced serotonin
activity in people with depression compared to people without,
and methods to reduce serotonin availability using tryptophan
depletion do not consistently lower mood in volunteers. High
quality, well-powered genetic studies effectively exclude an
association between genotypes related to the serotonin system
and depression, including a proposed interaction with stress.
> The chemical imbalance theory of depression is still put forward
by professionals, and the serotonin theory, in particular, has
formed the basis of a considerable research effort over the last few
decades. The general public widely believes that depression
has been convincingly demonstrated to be the result of serotonin
or other chemical abnormalities, and this belief shapes
how people understand their moods, leading to a pessimistic
outlook on the outcome of depression and negative expectancies
about the possibility of self-regulation of mood. The idea
that depression is the result of a chemical imbalance also
influences decisions about whether to take or continue anti-depressant medication and may discourage people from dis-continuing treatment, potentially leading to lifelong dependence
on these drugs.
Personally, I both agree that SSRI antidepressants were likely overprescribed early on, and disagree with the notion that the chemical imbalance theory is unsupported. N = 1, they can absolutely work. It took a few to find one that really did, hence I am certain it is not a placebo effect.
The idea that simple serotonin deficiency is the whole entirety of all depressions is 100% discredited and completely incoherent in the face of current evidence, but yes, for sure it remains clear and plausible that some forms or aspects of depression involve a serotonin deficiency.
However, tianeptine is serotonin reuptake enhancer and also can help with depression, so any simple deficiency hypothesis also doesn't look good either.
Broadly, the "chemical imbalance" theory, left vague and unspecified, is still basically sane (though not specific enough to be super useful).
The "chemical imbalance" theory is objectively wrong, but still useful in that it conveys the fact that mental disorders have physical causes. It's a purposeful simplification.
Many people take SSRIs and other medications because they believe the serotonin imbalance theory to be the modern scientific consensus. A doctor would be fired and ostracized for using the four humours, but can prescribe life-altering medication after five minutes to correct chemical imbalance, a theory which has never had much support within the scientific community.
Indeed, a rebuttal [1] to that paper starts with:
> Moncrieff et al. report in a review of reviews that depression is not generally linked with serotonin deficiency. This is hardly news to neuropharmacologists, which Moncrieff et al. tacitly admits, as they justify their review by citing examples of laity and general practitioners believing depression is caused by a “chemical imbalance”, i.e., in serotonin. For instance, already in 1986 did Depue and Spoont point out that serotonin deficiency may not be a general cause of depression or other psychiatric illness. Further, that increasing extracellular serotonin—e.g., with selective serotonin reuptake inhibitors (SSRIs)—treats depression does not mean decreased serotonin causes depression.
I have a lot of trust in the science of medicine, but almost none in healthcare. It seems like the research is totally divorced from the medieval treatments I see doctors give all the time. "This is hardly news to neuropharmacologists" vs "laity and general practitioners believe ..." indeed.
Yup, I would agree. The meta-research / methodological research and awareness here is really quite impressive, even though its conclusions are a bit grim and not well-known.
A good book on this is Mind Fixers: Psychiatry's Troubled Search for the Biology of Mental Illness. Describing the history of how many of these classes of drugs came about is pretty eye opening, I would say the book is pretty nuanced in its conclusions.
Because the 1 in 10 stat I find seems a bit low, at least in my circle, and those are the ones who are open about it.
And the people I know have been on them approximately a decade. What baffles me is that a fair number of them triggered their own depressive episodes, and likely did need therapy and something at the time - but have all long since move past those "moments".
"As effective as placebo" does not mean worthless. As you point out, placebo antidepressants are fairly effective.
It's a terrible bind. Patients want a pill to fix things, but if they know it's just a sugar pill, it doesn't work. It has to have active ingredients that might work. That's why there's little desire to change the status quo on antidepressants much. Anyone who reads the medical literature knows they're statistically underwhelming, but the experienced reality is that they help people a lot.
Talking therapies, CBT, exercise are all good alternatives but they take time and effort that a depressed person might not be able to manage. An antidepressant prescription they can get in 15 minutes.
> As you point out, placebo antidepressants are fairly effective.
This is a misunderstanding of concepts like regression to the mean, and also the active placebo elements involved.
> but the experienced reality is that they help people a lot
And the evidence is that the reality people think they are experiencing is wrong, i.e, they are improving and factually experiencing improvement, but misattributing the cause to the drug.
> "As effective as placebo" does not mean worthless
In one sense of worthless, perhaps, but since drugs have larger costs relative to placebo, well, we can argue they are worse than worseless in another.
Better instead to talk about cost-benefit tradeoffs, number-needed-to-treat vs number-needed-to-harm and etc though, and try to get better at prescribing more carefully to those they clearly benefit.
It’s unethical to prescribe a patient a placebo in a way that suggests that what they are receiving is scientifically proven.
In a clinical trial setting, you can prescribe a placebo, because the patient is fully aware and clearly consenting to the fact that they may receive a placebo. Lying to a patient, in a clinical setting, from a position of authority, is a completely different matter. The informed consent would be completely absent, the patient’s ability to make informed choices about their own healthcare would be undermined and withheld, and the provider would be deriving financial benefit from the patient and / or through insurance claims for what amounts to a scam.
The patient, who would be seeking a treatment from a trusted expert, would believe that they are receiving proven treatments in exchange for their time, patience, money, reduced quality of life due to side effects, and opportunity costs in terms of not going to a different provider or trying something else, but in reality their provider would be misleading them. Some patients would even die as a result of taking a particular placebo and depending on it—either because of side effects or due to the lack of effectiveness—when they tragically would have been better off trying a different approach or medication. How could a patient possibly give informed consent in such a scenario, for one thing? How could they meaningfully compare treatment options and make their own informed choices when the advice they receive includes lies?
Alas, some providers believe in placebo effects so much more strongly than their patients’ right to autonomy that when faced with complaints of side effects, they will just lie more and more to their patients in hopes that the side effects will go away, but that’s really just more gaslighting to people who are already in difficult situations.
What's your opinion of the claim that antidepressants have small impact on people with mild to moderate depression, but significantly more impact on people with severe depression [1]?
I ask as a nonexpert because this is a view I've read a few times from people I trust more than most, and I know two people who suffered from severe depression who credited SSRIs for getting them through.
Honestly, every time I look into if the "treatment by severity effect" is clearly established, I feel I come away only able to shrug. It is at least plausible, but hasn't been clearly established or refuted.
What does seem clear to me is that the whole cost-benefit considerations change in favor of anti-depressants when the depression is severe. I wouldn't say anti-depressants should be first-line treatments for ordinary depression, but for severe depression, I think they are a very reasonable first-line option.
Sure, they still might not help, but the costs / harms don't seem so bad compared to the potential costs / harms of leaving the severe major depression untreated, and the other options look all pretty terrible here too.
My anecdotal experience going on and off Paxil is that it does work for me, and no matter how badly I want to live Rx-free, I consistently devolve into a moody mess without them.
Agreed. They have to be significantly helping at least some, but we can't say who these people are for certain yet, or how many there really are.
And yes, in some cases, no other options are possible, so even if the evidence is pretty dismal for their effectiveness, they are still broadly safe enough to definitely be worth a try. They probably just shouldn't be the first-line approach.
> I’m not trying to discount mental health, I just think there are better solutions than drugs to fix your state of mind.
Find one that's as effective on the general population.
I mean, sure, perhaps lifestyle changes are better. Can you get a higher percentage to change them and improve people's lives than we currently can with drugs?
As a top performer in school, I definitely think (and still point out), that you can get fantastically high results in SAT/GRE without paying any test prep service. I and many of my peers did it. There are better solutions than paying those services. But how many who don't pay do as well as those who do? I can tell them how to study as much as I can, but the reality is that statistically, people who attend will do better than if they don't.
From a medical standpoint, telling people to change how they live and think has a fairly low success rate. The best options usually don't work on the masses.
I don’t get why people are so negative about drugs. They’re just a medical treatment, with pluses and minuses. If they help and they’re not too costly then what’s the big deal? Half the population is addicted to caffeine and nobody cares. A huge number of people need medical intervention for other things and we don’t get this quasi moralistic opposition to them.
Agreed. The problem is largely that the pluses of antidepressants have been quite significantly overstated, and the minuses have been understated, meaning the cost-benefit equation is unfortunately quite different than what the general public assumes.
We don't want to get rid of them, we just need to recalibrate prescribing, and also to properly assess cessation at intervals more frequently than we have been.
Yeah, I’m open to the idea that their effectiveness may have been overestimated and they’re overprescribed as a result. But this “I can’t believe we’ve normalized antidepressants” “there are better solutions than drugs” stuff is just moralizing.
I suppose it can be moralizing, and probably is in the parent comment.
For me I still feel the surprise because I've followed the evidence carefully for well over a decade, and the methodological problems and lack of evidence for meaningful effectiveness have always been clear. I.e. it is clear standardized effect sizes are meaningless, and you need to determine important differences, as this is just basic science, but only a tiny handful of papers ever bothered.
So it feels very much like "how can we have normalized something so incredibly scientifically shaky", i.e. for me the moralizing is not "drugs are bad, how are we normalizing drugs" it is "how can an entire medical field and society so recklessly adopt something so obviously weakly supported". I.e. my dismay is more about the weak epistemic standards of society than it is about drugs.
To provide one additional anecdote: I came off escitalopram with no taper after taking it for about five years (10mg). I got brain zaps for a while, got very irritated at times, but largely was fine after a few weeks. Not downplaying the withdrawal effects for some people, but they’re not as catastrophic as this article suggests for many (perhaps most).
And overall I’m very glad I took it! It got me through a rough patch, and seems (in combination with therapy, and some life changes) to have rewired me a little. Symptoms I had for a decade prior have not returned. And I’m not sure I could have made those life changes without it.
Sadly my arachnophobia came back though. Oh well.
It can be catastrophic if one is managing family life, kids, taking them to and from activities on top of one’s own work. Then come misc stresses like tax returns, some expensive home repair, etc. Also dealing with depression without the anti-depressant. Switching mental health medication is no fun.
I am glad your experience was tolerable but it’s a whole arc and everyone’s tolerance + circumstances are unique which makes it all the more challenging (even for doctors).
Withdrawal effects, like the beneficial effects, are highly individual. I had no withdrawal effects from escitalopram after being on it for a couple of years but I know people who’ve had the issues described in the article.
This isn’t a one size fits all area of medicine.
It's been years since, but I too had brain zaps coming off of it. It took a few months for those to go away.
I tried to describe it to my doctor and he seemed like he never heard of it before and sort of look at me like I was crazy, or at least that is what I sensed. But I ended up researching online and found it was a thing that happens.
Interesting is your doctor a general practitioner or a psychiatrist? A psychiatrist definitely knows about this stuff. GPs in my experience know almost nothing about anything beyond what seems like a script they operate from.
You are assuming a lot about the competency of some specific doctor who knows where in the world...
What seems most broken is that medicine apparently didn't have a great way to predict which group you’d fall into, or much of a plan for the people who had a really bad time stopping. Also, RIP the anti-spider benefits
Good news, exposure therapy is quite effective for arachnophobia and is the first-line treatment. SSRIs do not have the same level of supporting evidence, and the effects are not as durable.
> SSRIs do not have the same level of supporting evidence, and the effects are not as durable.
To the extent that we can measure depression, SSRIs have been widely proven in gold standard phase III clinical trials to help with the treatment of major depression. What exactly is supposed to be lacking in the supported evidence?
Thanks, yeah, but if I’m honest I don’t really care enough to go through with it. I almost did once, years ago, the London Zoo have a programme.
I mentioned it though as one of the most stark changes I noticed after getting on an SSRI was pretty much immediately losing my fear of spiders. It was the first sign I had that showed it was doing something.
I used to literally, on occasion, launch my phone across the room if I was scrolling and came across a spider (sometimes drenching myself with coffee or whatever in the process!) and then one day, shortly after getting on it, I stumbled across some awful tarantula video or something and I just stared at it like “huh, why am I not freaking out”.
Same experience early this year but I did halve the dosage to 5mg for a month, which was of near zero difference. But the full withdrawal? Oh man it is no joke.
Is it possible for phobias to be treated with antidepressants or other medications? I need to look into this
Sure seems like it to me, but my doctor seemed bemused when I mentioned it to him and I don't think they're routinely prescribed for them. I reckon if I'd have paired the SSRI with some exposure therapy, it would have cured me of it long-term. I do have an additional phobia however (I'd rather not say which) and it didn't make any impact on that at all, so YMMV.
Worth noting as well that I had no expectation of any changes to my arachnophobia going in. It didn't even cross my mind.
Exposure seems to be the best way out.
I tried to come off Trintellix. 4 weeks was fine. 5th week immense thoughts of doom. Had to take Xanax to bridge it kicking in again.
Though this article concentrates on the SSRIs, other meds like the SNRIs can have a similar or even worse withdrawal effect. We didn't call it "Side Effexor" for nothing.
People legitimately need these drugs, including in the short term. The problem for acute stressors once they resolve is how to get them back off.
For something prescribed to get someone through a temporary crisis, "how and when do we get you back off this safely?" should probably be discussed at the beginning, not years later when the patient decides to stop.
> Though this article concentrates on the SSRIs, other meds like the SNRIs can have a similar or even worse withdrawal effect.
And don't even get me started on tricyclics or MAOIs... no, seriously, don't get me started on them! The current generation of first-line antidepressants (SSRIs/SNRIs) might as well be free compared to the old school crazy pills.
It's probably less "modern antidepressants are uniquely bad" and more "we got much better at starting people on safer drugs than we did at figuring out how to stop them"
Much of medicine (especially mental health related) is rather primitive. We are literally reverse engineering discoveries that seem to work on some other animals, and then figuring out how (to the best of our limited ability).
I liken SSRIs to carpet bombing - also their mechanism to increase seratonin in the brain is by making something else not use it (reuptake inhibition). We’re guessing that other thing isn’t a big deal. But who knows. Serotonin is produced in the gut and it controls melatonin, which controls our sleep. It’s all connected in a bizarre way.
> I liken SSRIs to carpet bombing
It's like inserting objects into the body's event loop and hoping it produces the desired effects as it circulates, only to find that everything reacts to the event, not just the parts we want.
https://news.ycombinator.com/item?id=37029912
> school crazy
Yep, that’s how I associate SSRIs.
Only slightly related, but can anyone ELI5 why Bupropion XL is not the universal first line treatment for depression and is hardly used at all in Europe?
It has fewer side effects vs. SSRIs, can be safely used as a long term medication (which many people do with SSRIs even though it can have negative effects), and doesn't have the same horrible withdrawal symptoms (although you still need to taper).
Anxiety is a common comorbidity in depression patients and buprioprion can dramatically raise anxiety levels
It is a second-line treatment for a reason. Great when it works. Harmful when it does not.
It has a long and scary list of side effects, good if it works for you
[delayed]
My doctor tried me on Bupropion for ADHD and I think it caused my BorderlinePD to get much worse, so definitely YMMV.
Well this would be an improvement over my former NHS GP practice deciding the best way for me to come off antidepressants was immediately stopping them without renewing the prescription or even discussing it with me! I think they just forgot to renew the prescription.
SSRIs not Benzodiazepines. Withdrawals from the later can be life-threatening if you abruptly stop after prolonged use.
"Prolonged" is not a long time either. You can be ensnared after just a couple weeks. And even a safe taper is still pretty hellish.
I had to wean off Klonopin, prescribed for a bout of COVID induced insomnia. Only on it for a month and it took a microgram taper and nine months to get off of completely. Had to go slow because the original recommended rate was wayyyyy too spicy for my central nervous system. Even at the slow rate I was going it was difficult to make it through life. Most doctors are unaware of how to deprescribe this shit safely.
I forget exactly which antidepressant I was on, but when i finally stopped taking it, i was instructed to reduce dosage by half a pill every two weeks.
Anecdotally, that was not anywhere close to slow enough. I had panic attacks almost every day while I was reducing the dosage. Those weeks were hell. I couldn’t think straight. I honestly don’t remember much of what occurred during that time, because the withdrawal took over my life. The pills were too tiny to split into fourths easily, but I wish I had done something to reduce dosage in smaller increments or over a longer time period.
It makes me strongly reconsider ever taking any antidepressants ever again. They didn’t tell me when I started taking them that the withdrawal would be so terrible. Those months were easily some the worst of my life.
I've taken antidepressants for years (20 mg prozac) and have sometimes tapered off them, restarting later. I can barely tell that I'm taking them, I feel 100% like myself on--and off of--them. I know they do something because when talking about difficult traumas with my therapist, if I'm not taking flouoxetine I will get choked up to the point I can't speak. That's the only difference I can perceive. My dose is not a "happy pill", it simply smooths out some extreme lows. Tapering off (a few weeks of 50% exponential declines) I've done because it's recommended, but again, I've never noticed any affect on mood before, during, or after.
after a number of years, a small dose of lithium (300mg) was recommended by a psychiatrist who stood apart (at least in that respect), and it was magic at mood stabilization, I never before even realized that I experienced hypomania (and I took it for anxiety), I just thought I was "bold".
(Lithium is not a drug, it's an element, taken as a metallic salt. It occurs naturally in the water in various parts of the world, and those populations have been studied and suffer lower rates of mental illness. My shrink said his recommendation was based in conjunction with the prozac I was taking, i.e. a known correlation. Bipolar II is a different mental condition than bipolar I, and somewhat slippery/loosely defined)
The extreme anecdotal stories people report online as in this forum strike me, an experienced but likewise only an anecdotal user, as more an artifact of underlying emotional distress rather than a result of the drugs.
I just wanted to contribute a different voice to this topic.
I should add, I do have "extra money" and am able to pay extremely qualified and expensive doctors, an option that is not available to everyone, including those with full public health services.
TLDR: Rate is individualized and determined by the patient's tolerance. If symptoms appear, maintain or increase dose to stabilize, then try reducing again later. Use liquid medication for more granular dosing.
Doctors aren't "finally learning" how to manage withdrawals. This is essentially the common sense algorithm, and I'm pretty annoyed that they wrote this whole ass article just for that.
SSRIs and SNRIs just didn't work very well for me. If they had an positive effect at all, it wasn't enough to rise above the proverbial noise.
Coming off of them wasn't too bad though. I got the brain zaps, but those were easy to cope with.
More than anything the whole experience was a waste of money, and what finally fixed my problems was retirement and a greater attention to my health.
Have you looked into mirtazapine (tetra cyclic), vortioxetine (serotonin modulator) or atomoxetine (SNDRI). Atomoxetine has been a god send for me.
They work so well for some they are miracle drugs, and for others they do nothing or have negative effects. This is typical. We still don’t fully understand why or even why they work at all.
My parents tried seeking out help for me when I was about 10 years old, but they got cold feet, and I believe that they were unwilling to accept any responsibility or blame for what was going on at home. So when I reached the age of majority, they fully funded therapist and psychiatrist sessions for me, and they foisted Prozac upon me, starting around 1991.
I began taking Prozac and suddenly exhibited a remarkable improvement in my mood and affect. These improvements were largely because I was getting attention, I was getting "weekly pep talks" from a professional, and at long last, there were names I could affix to those extremely troublesome spirits that tormented me night and day.
But the doctors, having a practice in the Children's Hospital, didn't see fit to warn me not to drink alcohol, especially not to excess, and I was simply reaching that age where this was happening frequently. So, the mixture of SSRI plus ethanol was really disastrous for me and my loved ones.
I cycled through all kinds of meds, and clinicians tried finding some other stuff to medicate, like maybe hypothyroidism, and I really hated the medication, and I got hospitalized and discharged with a cocktail of at least 5 prescriptions all at once. I suffered really awful adverse side effects. But it wasn't realistic to stop. I kept cycling through new and different drugs. Every time it was new and different, and I had more complaints, and I stopped again and again. I had all the "brain zaps" especially Zappy Zoloft, and more hospitals and more upheavals in life.
I've finally reached a point where I can steadfastly refuse any medication, up to the point where inpatient treatment is done. I am 100% off drugs, and I feel great about that. I tend to inform my providers that I have "a Lithium deficiency" because bipolar isn't real: it's merely a cluster of highly-subjective "symptoms" and behaviors, under an ever-widening umbrella, and the bottom line is that they just want to put Lithium Carbonate on the checklist of "subject is treating this thing" and then once I'm taking enough of it, they can heap on more and more drugs on top. And Lithium is one of those where they grab you for a monthly blood test, to "trust, but verify" as the Soviets would say.
So I am pleased that SSRIs and their ilk are far, far behind me. I inwardly chuckle or sigh wistfully when I hear another patient extolling the virtues of ECT or Ketamine or something. How wonderful for you to be dependent on quacks and pseudoscience. Read any Wikipedia page for these drugs.
They are fairy tales.
I am a practicing Roman Catholic: I don't need to believe in fairy tales from foreigners and infidels who distribute condoms and wear white coats.
Thank you for your attention to this matter!
Thank you for coming to my TED Talk.
When I was diagnosed with depression - amongst other things - my doctor prescribed SSRIs with a caveat that they might or might not work.
After a few weeks I was tapered off them.
I felt no different before, during or after them.
What helped was 3 daily walks around the park, around 9km per day after each meal.
Anecdotal but it is what it is. Right now I have bigger problems than just depression.
I think exercise, sunlight, good sleep and diet, and good social relationships are all more effective than SSRIs. But anyone who's had bad depression knows how hard those things are to maintain if you're depressed. SSRIs make some portion of people functional enough where they can at least build a healthy life. But definitely not everyone, and they are definitely not "the cure"
> After a few weeks I was tapered off them.
> I felt no different before, during or after them.
SSRI onset is slow, which is one of the common problems with treatment.
In studies where they survey both the patient and their family members, the family members actually start noticing improvements before the patient. Onset is slow and it takes a long time for patients to realize the positive effects.
Ideally they’re prescribed along with other lifestyle changes like your walks. It doesn’t have to be an either-or. A lot of patients get offended when doctors suggest things like walking because they think it indicates the doctor is telling them to “just walk it off” which doesn’t go well.
It’s not surprising you didn’t feel anything noticeable after a few weeks. It’s also unfortunate, but not too surprising, that your doctor wasn’t informed enough to communicate these things. Some doctors are great about setting expectations and following up. Others write a prescription and send patients off to fill it without the necessary context.
The other problem with SSRI treatment is that individually they are only barely better than placebo. They're among the worst classes of drugs as far as NNT, effect size or remission rate (individually! STAR-D treatment algorithm works for the vast majority of people)
Especially in acute cases, I think they should be replaced or augmented by something stylistically in the direction of esketamine. 6-8 weeks per medication trial is an absolute eternity, especially since some minority of major depressive episodes resolve spontaneously after a few months to a year.
> The other problem with SSRI treatment is that individually they are only barely better than placebo. They're among the worst classes of drugs as far as NNT,
These numbers are really misunderstood when taken out of context.
SSRIs have an NNT around 7, depending on the study you look at (random Google result https://pubmed.ncbi.nlm.nih.gov/19588448/ as an example )
Which sounds terrible if you know nothing about NNT. But when you learn that Tylenol has an NNT of almost 5 and even a powerful drug like Xanax has an NNT of 4, you realize that NNT is a difficult measure of drug efficacy.
> Especially in acute cases, I think they should be replaced or augmented by something stylistically in the direction of esketamine. 6-8 weeks per medication trial is an absolute eternity
Ketamine and esketamine are used a lot to begin therapy. They’re not good long-term options though, so they’re best used to start treatment as a bridge to SSRI efficacy.
> SSRIs have an NNT around 7, depending on the study you look at [...] Which sounds terrible if you know nothing about NNT. But when you learn that Tylenol has an NNT of almost 5 and even a powerful drug like Xanax has an NNT of 4, you realize that NNT is a difficult measure of drug efficacy
This kind of comparison is utterly meaningless (like saying a Cohen's d of 0.3 is large for phenomena X, so if we see 0.4 in phenomena Y, it is large in Y), and is why NNT is basically deceptive for antidepressants.
What qualifies as an effective "treatment" has to be anchored to a minimal important difference, and this is what antidepressants really don't clearly have, on average. I.e. saying the NNT of SSRIs is around 7 is not really practically interpretable, because they tend not to base NNTs here on the amount of patients that actually experienced a clinically meaningful change, they just count the number that exceed some arbitrary (usually purely statistical) threshold.
Okay, so we set aside NNT, even though their NNH is also quite low, and that's highly relevant, what about effect size and remission rate? This feels a bit like cherrypicking. And you'll note I said "augmented", as well, if somebody is going through the treatment algorithm with SSRIs, by all means, that's the bridge to stability for somebody on a longer term course.
But many people don't need anything more than acute treatment, so what about them?
> what about effect size and remission rate? This feels a bit like cherrypicking
Trying to pull out NNT feels like cherry picking because it sounds really bad to people who don’t know how other drugs look on this measure.
If your point is that it would be better if we had better drugs then I agree.
I think trying to imply that SSRIs are barely a step above useless is not helpful, though. Statistics like NNT and remission rates do not capture incremental improvements that these medications can make for people who need all the help they can get. Even if it doesn’t cause complete remission by itself it can be very helpful.
> If your point is that it would be better if we had better drugs then I agree.
My point is that there are other interventions which do have an effect size over the perceptual threshold. Exercise is a big one, but there are lots - sleep deprivation, intensive therapy, the esketamine class, TMS, ECT in extremis, (nature exposure and other seeming woo like that need study but are promising) are all significantly better than handing someone an SSRI. And many of those don't have the withdrawal symptom and side effects under treatment that SSRIs do. People are, in aggregate, being harmed by SSRIs displacing things that work right now, and also displacing the urgency of new drug development in the space.
The gap is that, in an acute treatment setting, people are being handed a drug that cannot be effective for at least a week or two, up to 6-8 weeks, instead of drugs that work in hours or days.
+1 on therapeutic ketamine. Got me out of a bad spot, and felt better long after it was over. You can get it by mail in the US from Mindbloom, who offered excellent care despite being remote in my case.
Lexapro, noted in the article, was literally life changing for me. I felt better within 3d and I notice severe issues if I miss ~3d of doses in a row, even though the half-life should support ~7d without according to my physician.
That said, yes; walking is the best medicine for me.
I start getting effects the same day if I miss my morning dose, but like you, it was life changing (in a good way) for me.
I've got two friends who didn't benefit from it, so it isn't a miracle cure for everyone, sadly.
Best way to manage the withdrawal would be to dramatically reduce them being prescribed in the first place.
The linked article says they have "small to moderate effectiveness", but this is being far too generous. The correct way to measure drug effectiveness is if the treatment meets the standard of a minimal important difference. I.e. you measure depression on various rating scales, like the 17-point HAM-D, and research suggests a minimal important difference (i.e. one patients and clinicians can actually notice) needs to be about 3-5 points. But the average effects of almost all antidepressants do not meet these thresholds, i.e. the effect actually appears practically invisible. [1]
Then you'll get waffling like "oh, but it really has a big effect for some people", but, well, no, we've looked at that too, and the placebo groups get just as miraculous "big effects", i.e. evidence supporting the idea "they really help some people" is also largely lacking [2-3]. All the other attempted saves ("oh, but eventually you find one that works for you") are also not really well supported either [4].
Like, maybe they really help some people, but it is far, far less clear than most assume, and should be balanced with concerns like withdrawal and serious side effects like emotional blunting and sexual dysfunction.
EDIT: And just to be clear to anyone doing a drive-by downvote thinking this is about recent asinine US politics, it emphatically isn't. There are serious methodological concerns here that desperately need to be communicated to the public.
[1] https://pubmed.ncbi.nlm.nih.gov/33593736/
[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC7451660/
[3] https://pubmed.ncbi.nlm.nih.gov/33175895/
[4] https://pmc.ncbi.nlm.nih.gov/articles/PMC11844611/
> Best way to manage the withdrawal would be to dramatically reduce them being prescribed in the first place.
No, that will just hurt more people up front for longer. The truth is antidepressants have a larger effect on mental health than actually gets reported because of how improvements are measured. If you look at a patient who doesn't get out of bed, is in trouble at work/school for performance, doesn't spend social time with friends, etc, and 6 months after starting an SSRI they're indistinguishable from other people but still have other issues, we call that a "mild impact" because they self-report other problems.
The truth is we took someone from being passively suicidal to functioning normally, and we fail to look at the self-reported problems, we just report them. The self reported problems tend to change from "I don't care about anything" to "I'm unhappy at my job" or "I'm stressed at how much I have to do with work and my kids and home." These are actually major improvements, the patient has gone from being actually clinically depressed to significant improvement but continued unhappiness with life circumstances as opposed to unhappiness with life in general.
Antidepressants are amazing, we need to improve therapists and how they deal with medicated patients. Too many therapists dismiss meds and too many psychiatrists dismiss therapy. I've been in this space for a long time now, healthcare IT in the mental/behavioral health space. We're engaged in a long erm research study to help demonstrate the value of a tightly integrated therapy/psych team and more advanced treatments and when you get everyone in the room pulling in the same direction patient outcomes are amazing.
One actual issue that antidepressants face is that they're not the only treatment, but many doctors are reluctant to move to TMS or esketamine, despite the amaing success rates they have with patients who have not had success with two or more drugs. If two drugs failed you, the third has a 14% chance of helping. The 4th is single digits. But you pivot to TMS and you see 60-80 percent improvement rates. Esketamine is close too.
ADs aren't the problem, it's that we don't take mental health as serious as we take physical health.
> You look at a patient who doesn't get out of bed, is in trouble at work/school for performance, doesn't spend social time with friends, etc, and 6 months after starting an SSRI they're indistinguishable from other people but still have other issues, we call that a "mild impact" because they self-report other problems.
This really lines up with what I've seen anecdotally. My partner literally doesn't remember how bad things were before he took antidepressants because depression impacted his ability to form memories. He self reports that antidepressants had a mild impact, but from an outside perspective nearly everything about his life changed.
> But you pivot to TMS and you see 60-80 percent improvement rates. Esketamine is close too.
I have received both rTMS and esketamine and the providers themselves told me they saw roughly a 30-40% response rate (not remission, that's even lower!). Upon researching the topic myself, I found that the meta analysis usually agreed with this 30% figure, but recent research papers mark eskatamine even lower. Both treatments can be miraculous for a few select people and it makes a good headline, but it's a total failure for the majority of people.
I agree with you that those treatments should be easier to access, though.
> Too many therapists dismiss meds and too many psychiatrists dismiss therapy.
This is the only factually true statement in your entire comment.
The problem with the entire argument that you're making is that the natural rate of remission in uncomplicated major depressive episodes is very close to the rate that SSRIs create, individually, and very close in terms of timing. If you do something more like STAR-D you see higher rates, but that also takes so long that many people naturally remit.
> The truth is antidepressants have a larger effect on mental health than actually gets reported because of how improvements are measured.
The truth is actually exactly the opposite, and I provided very high-quality evidence demonstrating this to be the case. You have nothing but bald assertions.
Well I think that we do not know enough about genesis of depression and other mental issues. So this is just symptomatic therapy. And as such it should be prescribed only for very short terms. Analogy: how would you perceive someone who prescribed his febrile patient paracetamol for 10 years just because it works? And in his defense he/she claims that febrile condition has well known metabolic chain and that paracetamol lowers fever mainly by interrupting the COX → PGE₂ part of the fever pathway in the brain.
So did you take them and have a bad time? Because they definitely work for me and I doubt a placebo could have such a large effect on the 48 hour stomach pains I used to get alongside my frequent panic attacks.
I find it funny that people complain about emotional blunting when that is the entire purpose of the drug. I would prefer not to live on the razors edge ever again. I’ve had chronic anxiety and depression ever since I was a child, though.
For some people the emotional blunting is desirable, especially as you said, if the problem is chronic anxiety. But for many other people, their depression is defined by a lack of positive affect and anhedonia, meaning that emotional blunting is literally making things worse.
Depression is highly heterogenous, and I am glad the medication helped you.
SSRIs have much more clinical evidence of efficacy for addressing anxiety disorders vs a placebo than depression. The effect size is ~0.7 vs 0.2 in meta studies.
Totally agree, they really shouldn't be called antidepressants at all. Important to add tho that for many with depression they have comorbid anxiety and often the anxiety is harder to tolerate than depression, so removal of anxiety symptoms can be hugely beneficial.
Also, IME they are dosed completely wrong. So many people seem to be on very low doses, which has no improvement on placebo in the studies I've read.
Whereas, higher doses are _hugely_ better than placebo, especially for anxiety.
What's worse is a lot/most studies on SSRIs in general often don't adjust for dose. Which seems like an enormous oversight to me.
> I find it funny that people complain about emotional blunting when that is the entire purpose of the drug.
The ideal would be to blunt the negatives but not the positives. The effect of some of the older antidepressants can be to blunt both, across the board.
Some of the newer atypical antidepressants can address depression without making everything flat.
On an academic level, we have reined in much of the excess enthusiasm in antidepressants that was courtesy of 90s-era pharmaceutical reps and ad men, but I don't think this revision ever occurred in the cultural consciousness at large.
See also: The Serotonin Theory of Depression: a Systematic Umbrella Review of the Evidence (2022). It's worth reading the introduction and results in full, but here are two important quotes (footnote markers removed):
> Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity. Most studies found no evidence of reduced serotonin activity in people with depression compared to people without, and methods to reduce serotonin availability using tryptophan depletion do not consistently lower mood in volunteers. High quality, well-powered genetic studies effectively exclude an association between genotypes related to the serotonin system and depression, including a proposed interaction with stress.
> The chemical imbalance theory of depression is still put forward by professionals, and the serotonin theory, in particular, has formed the basis of a considerable research effort over the last few decades. The general public widely believes that depression has been convincingly demonstrated to be the result of serotonin or other chemical abnormalities, and this belief shapes how people understand their moods, leading to a pessimistic outlook on the outcome of depression and negative expectancies about the possibility of self-regulation of mood. The idea that depression is the result of a chemical imbalance also influences decisions about whether to take or continue anti-depressant medication and may discourage people from dis-continuing treatment, potentially leading to lifelong dependence on these drugs.
https://www.nature.com/articles/s41380-022-01661-0
The conclusions in that were not universally accepted, and some critiques were rather damning:
https://www.kcl.ac.uk/news/a-response-to-the-serotonin-theor...
Personally, I both agree that SSRI antidepressants were likely overprescribed early on, and disagree with the notion that the chemical imbalance theory is unsupported. N = 1, they can absolutely work. It took a few to find one that really did, hence I am certain it is not a placebo effect.
The idea that simple serotonin deficiency is the whole entirety of all depressions is 100% discredited and completely incoherent in the face of current evidence, but yes, for sure it remains clear and plausible that some forms or aspects of depression involve a serotonin deficiency.
However, tianeptine is serotonin reuptake enhancer and also can help with depression, so any simple deficiency hypothesis also doesn't look good either.
Broadly, the "chemical imbalance" theory, left vague and unspecified, is still basically sane (though not specific enough to be super useful).
The "chemical imbalance" theory is objectively wrong, but still useful in that it conveys the fact that mental disorders have physical causes. It's a purposeful simplification.
Many people take SSRIs and other medications because they believe the serotonin imbalance theory to be the modern scientific consensus. A doctor would be fired and ostracized for using the four humours, but can prescribe life-altering medication after five minutes to correct chemical imbalance, a theory which has never had much support within the scientific community.
Indeed, a rebuttal [1] to that paper starts with:
> Moncrieff et al. report in a review of reviews that depression is not generally linked with serotonin deficiency. This is hardly news to neuropharmacologists, which Moncrieff et al. tacitly admits, as they justify their review by citing examples of laity and general practitioners believing depression is caused by a “chemical imbalance”, i.e., in serotonin. For instance, already in 1986 did Depue and Spoont point out that serotonin deficiency may not be a general cause of depression or other psychiatric illness. Further, that increasing extracellular serotonin—e.g., with selective serotonin reuptake inhibitors (SSRIs)—treats depression does not mean decreased serotonin causes depression.
I have a lot of trust in the science of medicine, but almost none in healthcare. It seems like the research is totally divorced from the medieval treatments I see doctors give all the time. "This is hardly news to neuropharmacologists" vs "laity and general practitioners believe ..." indeed.
1. https://www.nature.com/articles/s41380-023-02090-3
Yup, I would agree. The meta-research / methodological research and awareness here is really quite impressive, even though its conclusions are a bit grim and not well-known.
A good book on this is Mind Fixers: Psychiatry's Troubled Search for the Biology of Mental Illness. Describing the history of how many of these classes of drugs came about is pretty eye opening, I would say the book is pretty nuanced in its conclusions.
https://www.goodreads.com/en/book/show/40180010-mind-fixers
The title is a play on the Pulitzer prize winning article from the 80's.
https://web.archive.org/web/20041125092022/http://www.byline...
Have we reigned in the number of perscriptions?
Because the 1 in 10 stat I find seems a bit low, at least in my circle, and those are the ones who are open about it.
And the people I know have been on them approximately a decade. What baffles me is that a fair number of them triggered their own depressive episodes, and likely did need therapy and something at the time - but have all long since move past those "moments".
I am not sure, but recommendations to prescribe in mild cases have quietly been reigned in a bit by e.g. NICE https://www.nice.org.uk/guidance/ng222/chapter/Recommendatio....
"As effective as placebo" does not mean worthless. As you point out, placebo antidepressants are fairly effective.
It's a terrible bind. Patients want a pill to fix things, but if they know it's just a sugar pill, it doesn't work. It has to have active ingredients that might work. That's why there's little desire to change the status quo on antidepressants much. Anyone who reads the medical literature knows they're statistically underwhelming, but the experienced reality is that they help people a lot.
Talking therapies, CBT, exercise are all good alternatives but they take time and effort that a depressed person might not be able to manage. An antidepressant prescription they can get in 15 minutes.
> As you point out, placebo antidepressants are fairly effective.
This is a misunderstanding of concepts like regression to the mean, and also the active placebo elements involved.
> but the experienced reality is that they help people a lot
And the evidence is that the reality people think they are experiencing is wrong, i.e, they are improving and factually experiencing improvement, but misattributing the cause to the drug.
> "As effective as placebo" does not mean worthless
In one sense of worthless, perhaps, but since drugs have larger costs relative to placebo, well, we can argue they are worse than worseless in another.
Better instead to talk about cost-benefit tradeoffs, number-needed-to-treat vs number-needed-to-harm and etc though, and try to get better at prescribing more carefully to those they clearly benefit.
It’s unethical to prescribe a patient a placebo in a way that suggests that what they are receiving is scientifically proven.
In a clinical trial setting, you can prescribe a placebo, because the patient is fully aware and clearly consenting to the fact that they may receive a placebo. Lying to a patient, in a clinical setting, from a position of authority, is a completely different matter. The informed consent would be completely absent, the patient’s ability to make informed choices about their own healthcare would be undermined and withheld, and the provider would be deriving financial benefit from the patient and / or through insurance claims for what amounts to a scam.
The patient, who would be seeking a treatment from a trusted expert, would believe that they are receiving proven treatments in exchange for their time, patience, money, reduced quality of life due to side effects, and opportunity costs in terms of not going to a different provider or trying something else, but in reality their provider would be misleading them. Some patients would even die as a result of taking a particular placebo and depending on it—either because of side effects or due to the lack of effectiveness—when they tragically would have been better off trying a different approach or medication. How could a patient possibly give informed consent in such a scenario, for one thing? How could they meaningfully compare treatment options and make their own informed choices when the advice they receive includes lies?
Alas, some providers believe in placebo effects so much more strongly than their patients’ right to autonomy that when faced with complaints of side effects, they will just lie more and more to their patients in hopes that the side effects will go away, but that’s really just more gaslighting to people who are already in difficult situations.
What's your opinion of the claim that antidepressants have small impact on people with mild to moderate depression, but significantly more impact on people with severe depression [1]?
I ask as a nonexpert because this is a view I've read a few times from people I trust more than most, and I know two people who suffered from severe depression who credited SSRIs for getting them through.
[1] https://pubmed.ncbi.nlm.nih.gov/20051569/
Honestly, every time I look into if the "treatment by severity effect" is clearly established, I feel I come away only able to shrug. It is at least plausible, but hasn't been clearly established or refuted.
What does seem clear to me is that the whole cost-benefit considerations change in favor of anti-depressants when the depression is severe. I wouldn't say anti-depressants should be first-line treatments for ordinary depression, but for severe depression, I think they are a very reasonable first-line option.
Sure, they still might not help, but the costs / harms don't seem so bad compared to the potential costs / harms of leaving the severe major depression untreated, and the other options look all pretty terrible here too.
My anecdotal experience going on and off Paxil is that it does work for me, and no matter how badly I want to live Rx-free, I consistently devolve into a moody mess without them.
I can’t believe we’ve normalized anti depressants as a society.
I’m about to get downvoted into oblivion for this take though.
I’m not trying to discount mental health, I just think there are better solutions than drugs to fix your state of mind.
Also think that some people are dealt a tougher hand than most, and that for a small subset of humans, anti depressants are the most fitting cure.
Clothes too. If you're cold, why not just move to a tropical country where you can be naked, as nature intended?
Agreed. They have to be significantly helping at least some, but we can't say who these people are for certain yet, or how many there really are.
And yes, in some cases, no other options are possible, so even if the evidence is pretty dismal for their effectiveness, they are still broadly safe enough to definitely be worth a try. They probably just shouldn't be the first-line approach.
> I’m not trying to discount mental health, I just think there are better solutions than drugs to fix your state of mind.
Find one that's as effective on the general population.
I mean, sure, perhaps lifestyle changes are better. Can you get a higher percentage to change them and improve people's lives than we currently can with drugs?
As a top performer in school, I definitely think (and still point out), that you can get fantastically high results in SAT/GRE without paying any test prep service. I and many of my peers did it. There are better solutions than paying those services. But how many who don't pay do as well as those who do? I can tell them how to study as much as I can, but the reality is that statistically, people who attend will do better than if they don't.
From a medical standpoint, telling people to change how they live and think has a fairly low success rate. The best options usually don't work on the masses.
I don’t get why people are so negative about drugs. They’re just a medical treatment, with pluses and minuses. If they help and they’re not too costly then what’s the big deal? Half the population is addicted to caffeine and nobody cares. A huge number of people need medical intervention for other things and we don’t get this quasi moralistic opposition to them.
Agreed. The problem is largely that the pluses of antidepressants have been quite significantly overstated, and the minuses have been understated, meaning the cost-benefit equation is unfortunately quite different than what the general public assumes.
We don't want to get rid of them, we just need to recalibrate prescribing, and also to properly assess cessation at intervals more frequently than we have been.
Yeah, I’m open to the idea that their effectiveness may have been overestimated and they’re overprescribed as a result. But this “I can’t believe we’ve normalized antidepressants” “there are better solutions than drugs” stuff is just moralizing.
I suppose it can be moralizing, and probably is in the parent comment.
For me I still feel the surprise because I've followed the evidence carefully for well over a decade, and the methodological problems and lack of evidence for meaningful effectiveness have always been clear. I.e. it is clear standardized effect sizes are meaningless, and you need to determine important differences, as this is just basic science, but only a tiny handful of papers ever bothered.
So it feels very much like "how can we have normalized something so incredibly scientifically shaky", i.e. for me the moralizing is not "drugs are bad, how are we normalizing drugs" it is "how can an entire medical field and society so recklessly adopt something so obviously weakly supported". I.e. my dismay is more about the weak epistemic standards of society than it is about drugs.