- There is a real lack of transparency in communicating some of the long term impacts of SSRIs to new patients. When I was prescribed sertraline not one doctor mentioned the massive (and sometimes permanent!!) sexual side effects, the likelihood of weight gain or how brutal it would be to taper off.
Also, I ended up ignoring my doctor's (way too aggressive) tapering schedule and managing my own down-dosing with a pill crusher and a milligram scale. I went about 5x slower than the standard advice and avoided all of the worst side effects.
I don't think it would have changed my decision to start taking it but I would rather have known about all this up front so I could make a more informed choice.
- somewhat off topic but i’ve thought about tapering like this, but i’ve got wondered where can one get a calibrated milligram scale? or perhaps it doesn’t matter too much.
- You can also taper off by reducing dosage one day of the week at a time. Thats how I tapered off a 10mg Escitalopram prescription: every 4 weeks, I added another day of the week where I reduced my dosage by 5mg. Took about a year to fully taper off and had to pause for a month here and there to stabilize, but it was worth it.
However, it was equally important that I had a support structure & tools to replace what the SSRI was doing. For me that was mindfulness and therapy.
- if the substance has good water solubility, you can do this by dilution, measuring volume, without a scale.
sertraline for instance: https://pubchem.ncbi.nlm.nih.gov/compound/68617#section=Solu...
don't do this with medications with special coatings or other methods for controlling release (SR/XR/etc).
- Using distilled water would be a good idea as well.
- Relative precision is enough if you just want to get rid of pills
- you get a pill cutter. I was recommended to get one to ease in
- Amazon: https://www.amazon.com/s?k=calibrated+milligram+scale
---
They're common, cheap, and plenty of (recreational) drug dealers use them.
- They are also great for photo chemicals mixed from scratch.
- They're also fantastic for small measures for baking and cooking when it matters.
- Curious: What do you make where you need such accurate measurements?
I just eyeball everything when I cook. (For other things that I'm passionate about I'm much more careful.)
- Baking often rewards precision.
I'm also an eyeballer. I'm a decent cook but a truly lousy baker.
- Somewhere there’s probably a coffee nerd who wants to measure small fractions of a bean.
- Would you be able to taper by stretching out dosages, take a pill every 25 hours instead of 24?
- You can also do a volumetric taper if you don’t have an accurate milligram scale (and none of the ones on Amazon are accurate). Dissolve a larger, known amount of medicine in a known amount of water or propylene glycol, depending upon solubility of the medicine. Then dose the liquid by volume. For example, 1 gram of medicine in 1 liter of water = 1 mg per ml. You can easily dose even microgram amounts this way.
- AWS Gemini-20 below $100
Or a precision one for $$$
All the other sub-$100 ones are mostly junk, with a few decent ones. But just get the Gemini-20
- Like buying a five gallon boiling flask, one assumes this will get one put on a list in the US.
- You can just tell anyone who comes asking that you will not be harassed in your private domicile.
- Mine was a $30 gold scale from Amazon. Probably not accurate but provably consistent which is what I needed. I'd compare each dose and used a calibration weight to verify.
- Maybe another option is to dilute it with water so that you can use regular kitchen scales.
- The problem is that psychiatry is an absolute zoo. Ive heard that if you go to 10 doctors you'll get 10 different opinions based on the docs personal experience.
Even if there are trials for these medications, the field is not quantitative in practice. "Standard of care" is a myth.
- Definitely prefer psychologists and therapists over psychiatrists, but don't discount how much something like an SSRI can help
- But how does one know? According to some studies, spontaneous remission happens in about half the cases of depression in a given year.
It's happened to me plenty of times. That's why I refuse to medications. All I have to do is just wait it out.
I am not claiming no one gets any benefits, rather how can one be certain the benefits are actually not from something else? If the goal is to improve, then I suppose it does not truly matter. But I just like to understand things when I can.
- I regularly had a depression for years without even knowing it was a depression. Until a neurologist told me, after examination of brain imaging, it's best to take this pill for at least a week. Only after feeling its effect, I knew it was really depression causing the symptoms, even though I did not feel depressed! I felt exhausted and stressed and had several physical side effects like dizzyness and stomach ache.
- Part of diagnostic criteria is how long something lasts.
If you have a really good week you aren't going to get diagnosed with mania.
If you have a really good month where you quit your job, move to Italy, and try to start a new job carving marble statues (and you've never carved stone in your life), well those will all be factors in any diagnoses given.
On the other hand, if you feel sad because your dog died, no one should be writing you a script for anything.
But if your dog died and you can't even function enough to go to work for a month, yeah it is probably temporary, but maybe some help is warranted, be that therapy or meds.
- The one thing they will all agree on is that you need pills of one sort or another.
- Of course, because prescribing pills is the sole job of a psychiatrist. Go to a phycologist or therapist of you want to try to talk it out. If talking doesn't work, they'll send you to a psychiatrist for medication.
- Could you share the specific mg/week taper you did for Sertraline?
- I did 10% relative reduction in my dose per 2 weeks, until I got down to ~2-3mg and then went cold turkey from there. Very very conservative. The 10% relative part is important - if you dropped by a constant, say 5mg, proportionally you'd be doing bigger drops each time which is where people get into trouble, especially at low doses.
- You start with Marcus Aurelius and work your way up to Nietzsche.
- for anyone who's curious about the sexual side-effects, this subreddit has stories from the unlucky few
- The only medication for Premature Ejaculation that exists currently is a megadose of a special SSRI which has a short half life.
If you are a man, SSRIs are very likely to make you last longer in bed, and that is often a very bad thing.
If you are a woman, whatever the SSRI is treating may leave you better off than before, if you found the depression or anxiety to be an obstacle to your satisfaction.
Many people however don't have an effect that makes a meaningful difference.
That subreddit is awful though. It's full of the same energy as health woo communities.
>It's tragic that this time we won't be able to enjoy GTA 6, after we were able to enjoy Gta 5. Damn everyone who invented these destructive drugs.
Like, come on man.
- Are you referring to dapoxetine ? It's not approved in US and it's not really a "megadose” of a regular SSRI since it's a different molecule.
Also, this is not only medication for PE.. there are many other options like fluoxetine, citalopram, PDE5s, etc .
- Were you experiencing side effects that made you want to get off? For the vast majority of people there really are none.
- I experienced a lot of stuff I didn't really notice how bad they were until I was off of them. Anhedonia, apathy, lack of volition, and sexual side effects. I also have trouble remembering parts of my life when I was on SSRIs.
I don't regret trying or even taking them for extended periods. They make the bad thoughts go away and raised the floor for my mood. But they also put a pretty low ceiling on it, too. I was probably on them for too long but clearly medicine doesn't have a perfect framework for handling every corner of this space, so I don't really blame anyone. There's a goldilocks zone for drug, dosage, and treatment length and I don't think I was always in it.
I've talked to many people who have bad things to say about SSRIs. On the other hand, my girlfriend is on one right now and seems very satisfied.
- So, this is not supported by the data when people are asked.
Sexual effects alone hit about 50–70% people. Then you could face nausea, insomnia, profuse sweating when you’re still, emotional blunting, and weight gain.
I don’t want to discourage anyone, they can save lives. It is a net benefit for some people, but even then most people will experience side effects and wish they didn’t have to take them.
- > The most common side effects reported by patients in the study by Hu et al1 of 401 outpatients taking SSRIs were drowsiness (38%), dry mouth (34%), and sexual dysfunction (34%)
> which was conducted in 1999-2000, questioned patients about side effects via phone interviews within 75 to 105 days of starting antidepressant therapy. The side effects deemed most bothersome were sexual dysfunction (17%)
It's no where near those numbers.
https://pmc.ncbi.nlm.nih.gov/articles/PMC3181894/
You notice how the scientific numbers get inflated in anecdotes from 17-34% to 50-70%?
- “It's no where near those numbers”
“get inflated in anecdotes”
Just because one study has the number 34% in it, does not prove the numbers I gave were wrong and does not mean they are anecdotal.
This is something that’s been studied from many angles and there’s more than one number that’s defensible based on the context and dataset.
For example, even the study you cited says: “In a study of 344 patients by Montejo-Gonzalez et al, 58% of patients reported sexual dysfunction when physicians directly inquired”, and “14% with spontaneous reporting”.
In another example, a 1,000 patient study found 57.7–72.7% for common SSRIs. https://pubmed.ncbi.nlm.nih.gov/11229449/
The “scientific numbers” you allude to are not one value. It’s a body of research not one definitive number.
Taken a whole I don’t think anyone is being that mislead when it’s suggested more than half of people may experience these side effects.
- Thank you for providing sources.
- > phone interviews within 75 to 105 days of starting antidepressant therapy.
Different thing entirely from long-term effects.
- Do you have anything which shows long-term effects are 50-70%?
- Do you think the one 25 year old short-term study that you found by yourself is the only study that has been done, and that anything that deviates from it is a distortion?
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- You think the vast majority of people do not experience side effects from anti-depressants? Wild.
- FWIW findings about adverse events vary considerably:
> The proportion of patients reporting adverse events ranged from 16% to 98% (median 80%) under SSRI treatment and from 17% to 94% (median 70%) under placebo [1]
So the answer IMO depends on whether we can attribute adverse effects to treatment, which is difficult to disentangle from adverse effects of disease
I’m open to being shown more certainty if available from the literature but meta-analyses are high-strength evidence
[1] https://www.cambridge.org/core/journals/the-british-journal-...
- What's wild about that? What does the science say?
I've tried a variety and I can't say whether I've experienced side effects. That's just an anecdote but that's the thing with this discussion, that's all you will get. If people don't suffer side effects, they're not likley to get on HN and post about them, etc.
The bigger issue is the person dealing with these issues is taking them because they are not well-off. If you deal with reduced desire, for example, is that a side effect of the medication or is that a side effect of being depressed.
I think your "wild" is a little flippant or telling because it just points back to anecdotes.
- They don't post on HN but a cousin post references an entire subreddit dedicated to it.
They are also anecdotal, hundreds, thousands of people suffering side effects. Given dozen of millions people in the U.S alone are prescribed those things daily, that a drop in the ocean. But not everyone post on Reddit either
- Yes but again this is the exact example of anecdotes. Those not suffering aren't going to seek out subreddits to post about their non-problems. You can find a subreddit about everything, whether that's representative of anything or not.
- > Despite considerable improvements in side-effect profiles, antidepressants continue to be associated with a significant burden of side effects that affect, treatment adherence and quality of life. Hu et al1 studied 401 patients with depression who had recently been prescribed an SSRI, and found that, after 75 to 105 days of treatment, 86% of patients reported at least, one side effect, and 55% experienced one or more bothersome side effects.
- > In both research and clinical contexts, an important challenge is presented by the phenomenological overlap between side effects and residual symptoms of depression. Thus, fatigue, cognitive impairment, apathy, jitteriness and irritability, and sleep and appetite changes are core features of depression, but may also be related to antidepressant, treatment. In a small study of 43 depressed inpatients,6 which investigated the rate of somatic symptoms and complaints that were present before and after treatment, many symptoms often considered to be side effects of drugs were also present prior to treatment, including dry mouth, lightheadedness, sweating, tremors, and constipation. The distinction between residual symptoms and side effects is crucial, as they call for very different responses.
- Not OP, but my primary side effect being on Sertraline from 2002-2012 was lack of control over my anger or violent outbursts. I was primarily ok if things were good, but if something upset me, it would go from 0 to 10 in an instant. I did not even notice this as unusual until I got off the drug and it was a night and day difference how much more mellow I became. I have not been on any SSRI since then.
I was on a very low dose of Bupropion for about 5 years and did mostly well; it only made my existing brain fog slightly worse. I usually recommend that one over SSRIs due to my experiences.
EDIT: I forgot to mention the damn brain zaps on SSRIs. Even if I missed a dose by 18 hours, I would get the zaps.
- That's not true. https://pmc.ncbi.nlm.nih.gov/articles/PMC2719451/ places the figure experiencing side effects at 40%, with 25% reporting those effects as serious. It's also telling that only just under half of those experiencing side effects ever reported those side effects to their providers - likely contributing to doctors getting a skewed perception of the real adverse effects risk.
What's missing is also follow up - for some those effects don't resolve after stopping the drug.
- This is the same myth that women get told about hormonal birth control, it's not an "if" with side-effects of SSRIs, it's a "how much" and "when"
- It’s not a myth - the vast majority of women on birth control experience no side effects at all, and many actually get improvement in adjacent conditions like endometriosis and PCOS.
- I don't to my knowledge suffer side-effects.
Why are you certain about this?
- chemistry of complex systems
you don't experience side-effects now, but you will if you need to stop taking it
- Been on hormonal birth control for 20 years. I've stopped twice to get pregnant. No side effects. I don't know why you're so confident here.
- I already answered why, it's chemistry. Everyone has side effects, not everyone notices them. You can not introduce a medication, or any substance for that matter, into the human body that does not have any side effects — it's impossible.
- Normally when people say side effects they mean things that you can actually observe. Hence your earlier point about going off the meds and noticing a difference. If I don't notice any difference other than I don't think your point really stands.
- I agree that what you notice is none of my business!
- I have stopped taking it, I didn't have side effects.
- It's harrowing to discover how much of the healthcare system can act like the nervous system does not exist, and the tools available to them are the only tools available, whether it's a prescription, or a focused therapy.
The inability to make an informed choice when not knowing the options up front other than the recommendation is truly one of the worst parts of all of this kind of stuff. Medication can be a reasonable reality many times, but increasingly in hindsight it seems like there can be other things to check first, physiologically, etc.
The number of things that are prescribed through guessing at groupings of symptoms vs just testing or imaging where it's applicable is something I truly can never unsee once I learned about it.
Semi related, did you ever come across saffron in your journey and what did/didn't stand out to you about it?
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- You are absolutely right. In fact with the hit on men’s sexual ability sometimes or often times you could consider this a hit hot (very sinister framing) on the practical side, having in the best case no anxiety and being able to meet people and how are you supposed to date? Blue solution?
Men’s inability to perform is causing a huge hit on their psyche. So in any case consider wisely, I heard many accounts of very disappointed men.
It may help women, but that’s a different thing.
For men - only in rare cases to be considered if ever.
- You're going to hear about it when it happens because it really bothers people when it happens but you aren't going to hear how often it statistically happens.
I notice reduced desire but I'm depressed, too, it's hard to disentangle the effects, there is a ton of fud.
- I went cold turkey off of citalopram when I was a teenager and it was a pretty unpleasant two weeks of heart palpitations, but the immediate benefit of no longer experiencing emotional blunting made me avoid taking any more antidepressants for 10 years. I was prescribed it by a GP and never given any real support in my mental health or in coming off of it. It was a real black pill for me on the UK's treatment of mental health issues.
Last year I started taking buproprion (Wellbutrin) after seeing a private psychiatrist in Romania, and I found it beneficial, but ended up losing more than 10kg, and becoming malnourished to the point of my hair falling out. Again I stopped of my own accord, and buproprion has basically no cessation symptoms.
This spring I saw a psychiatrist through Romania's public health service who prescribed me vortioxetine (Brintellix/Trintellix) after I shared my history and it's been a game changer. I experience basically no side effects besides a slight reduction in libido, with no other effects on sexual function. It's really helped me to find my balance again. And I see a psychiatrist once a month paid for by my public health insurance with the medication fully comped. Vortioxetine has a half-life of 66 hours so the one time I did have to skip a day and a half, the withdrawal was not noticeable.
Just sharing this to say that there are good doctors and good meds out there, and that having low tolerance for one medication doesn't mean that you shouldn't talk to a doctor about it and try others.
- It can't be emphasized enough for me just how unpleasant side effects like heart palpitations, tachycardia and related conditions really are. For me at least, those kinds of conditions trigger something close to a panic attack which feels like a very deep seat primitive protective measure in our brains.
Laying in your bed trying to be restful and feeling your heart slamming away at 140 beats per minute with little you can do about it goes behind miserable into outright alarming, even if you are "used" to it.
- FWIW quitting any SSRI cold turkey is highly disrecommended vs gradual tapering over ~2–6 weeks but even that current guidance is probably too aggressive.
Something like one step down every 2–4 weeks or ideally hyperbolic tapering is better for neurobiology but that's also a PITA.
https://www.outro.com/blog/stopping-antidepressants-what-is-...
- I've heard similar stories. Different people react to the same med differently
- 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).
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- 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.
- This. If there is one thing I've learned it is certainly not that you can generalize from yourself to others, especially for medication and its side-effects and withdrawal effects. I get so sick from taking novalgin that its a medical emergency (Agranulocytosis). Apparently, this occurs in like 1 case in a million. Conversely, I've heard of horrible side-effects or withdrawals from other medications where I experienced absolutely none of them.
- I also went cold turkey from escitalopram about a decade ago, and my experience was not as tame as yours; my ideation kicked into 6th gear, with paranoia, nausea, and insanely intense and vivid dreams every night. That was while on a 10mg dose.
I have been on over-max-dose venlafaxine for nearly a year now. I think it has been an enormous improvement in my life on nearly every axis, but if I miss a dose by even a few hours I get zaps, confusion, and dizziness. What happens to me now if I become unable to access my meds for more than a couple of days really keeps me up some nights.
- Venlafaxine has also been a godsend for me. My doctor started me on ut first and past the two weeks of rebalancing (big ideation swings and so much calling to act on it...) and all kinds of pains (digestive mostly), it literally allowed me to smile again, which my wife realized hadn't happened in over a year.
I can relate to the feeling when missing a dose. No tolerance for being forgetful. Lots of anxiety brought by this tether... and the permanent anorgasmia (in my case) is sad but I was dying...
Sadly I built tolerance over 2 years and had to stop, taper off (horrible experience) and try others (most that were cited in this comment section). All had painful and very annoying side effects and tapering was a pain after trying and each time feeling so disappointed and tired. Most worked on reducing ideation but the costs (inability to concentrate, brain fog, sometimes inability to work) were too high.
Turns out tolerance to venlafaxine ebbs out after some time, so after a moment I was able to restart for a year until I didn't need antidepressants anymore.
I've learned reading forums of the gamut of experiences with antidepressants and just want to add a voice to 'they can work, great even, not perfect' and between dying and trying them (with clear open eyes about the tradeoffs) I'd advise trying.
- Venlafaxine has a small half-life so that might be why if you miss a dose by a few hours you'd get withdrawal symptoms. Drugs is leaving fast you body and so concentration is quickly decreasing. Apparently there's a extended-release, don't know if it's already what you have but maybe you could ask to try another SNRIs that has a longer half-life.
- Yep I’m on XR, I’ve tried taking half my dose twice daily instead, which did smooth out the effects a bit but also made me much more likely to miss a dose. Not really any other solution other than tapering afaict.
- Yes, or you could ask your doctor to go on another one with longer half-life.
At least that would give you more room to miss by a few hours a dose and not going haywire into withdrawal. Especially when anxiety is already a problem and withdrawal symptoms kicks back the anxiety stronger...
Hope you find something that suits you!
- 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.
- Your psychiatrist looked at you like you were crazy?
- These comments about brains zaps is the first time I've heard confirmation from what I've experienced.
I've had them every time I've started or stopped a *pine antidepressant.
Like, something rolls off the counter and my natural reaction would catch it.
Instead, my hand doesn't move, and a brain zap.
Physically painful.
- 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.
- A psychiatrist definitely does not always know these things. Mine told me there should be no Citalopram withdrawals and that I should taper by cutting my dose in half over a 2 week period.
They were absolutely wrong as I have serious withdrawal reactions to Citalopram. It took me a month of micro-dosing down to safely get off a drug I was on for 15 yrs. And even then I was having constant brain & body zaps, that feel like short circuiting, for a full month after I dosed down to nothing. 6 mos later & I still can't sleep more than 6 hrs.
How did I know this was going to happen? Going cold turkey when my script ran out. I even told my psych about it numerous times but they just brushed it off.
- You are assuming a lot about the competency of some specific doctor who knows where in the world...
- A GP nowadays is a triage person and nothing more. Sadly. My old school GP back in the day was a proper doctor. My current one is a really really nice guy who knows less about anything than I do. I literally tell him what to prescribe me and he doesn't know what it is. Whenever I have some issue he never diagnoses it but sends me off to radiology because those doctors will come up with a diagnosis for him. He then might treat if simple or more likely triage me to see a specialist.
I kind of find it cute to be able to be paid for this. I could do it easily and better but I would have to spend years studying medicine, which at 50 is not an option anymore
(this is just to my modern GP's job. I could definitely today NOT do my old proper full-on-doctor GP's job)
- Honestly, this is where chatbots and AI come into play and make an astonishing difference. I’m an AI realist/pessimist but its usefulness in general medicine is going to save millions of lives due to doctor ineptitude. They are after all just well read mechanics
- 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.
- 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”.
- > 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?
- Unfortunately many of the trials look like this : https://study329.org/ - the ghost written study concluded “Paroxetine is generally well tolerated and effective for major depression in adolescents.”
The reality of the actual trial data was very different - with catastrophic results for many.
- GP is talking about using SSRIs for treating arachnophobia, not depression.
- Exposure therapy does not work for everyone in all areas. Sometimes not at all.
Also, see the debate around discussing traumatic events in therapy immediately versus waiting a year.
Throwing people in the deep end doesn't always result in a swimmer :)
YMMV of course.
- I think you are the flip side of what you mentioned about the article. I don't see the article as saying withdrawal is catastrophic, in fact I see it being well balanced when stating numbers. But you just said many or most people don't experience that.
If I were to take your approach, and make generalized statements based on my own experiences, I would say many if not most actually do experience significant withdrawal symptoms for an extended period of time.
You need to take into account: dosage, age, health, life circumstances, and I would think even more before you can suggest even the slightest correlation or "average" experience.
I get what you're saying and I'm very glad it was easier for you than others, clearly. I think though, it's dangerous to others to make claims based on one person's experience.
- For sure. That’s all I wanted to provide: an alternative anecdote from the article which led with an anecdote of perhaps the worst case for withdrawals. If I’d read an article like this five years ago, I might not have gotten the help I needed.
- 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.
- Me too. I was prescribed escitalopram along with other SSRIs when I lost my mom. Even with tapering, I had brain zaps for a while. Before I could stop it all completely, I was ramped up again after I lost my wife. I'm not sure if I'd be actually functional or even be here if it weren't for these meds.
- What was the tapering like for an SSRI? Do you remember over what period of time and how it was decreased?
- It was monthly. I don't remember the order of the medications, but I remember the effects. The most prominent one were the brain zaps and some confusions, especially in the mornings. On the bright side, I had some creativity coming back to me and I started back on some of my creative outlets (mostly my wife and therapy helped me come back to reality). And my biggest relief was when my brain fog (sometimes I even forgot my colleagues' names) cleared up. But yeah, before I could stop it completely I was fast tracked back up on a different regimen of SSRI combinations after my wife's accident.
- 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.
- I can believe it. They are used for general anxiety disorder which I imagine can be kind of similar - an over-reaction to some stimuli.
- both my social phobia and my fear of dark almost vanished on venlafaxine. i take walks in the dark these days, what the fuck.
- 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.
- 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
- This is an absolute failure on the part of medical science. SSRIs went mainstream in 1988.
By 1992! We knew about withdrawal issues: https://www.wikidoc.org/index.php/SSRI_discontinuation_syndr...
Let's be generous and give it until the 2000s for the knowledge to spread and science to validate; and we're still left with 26 years of blundering around without IMO sufficient warning to patients about withdrawal risks.
I would wager some of the doctors who prescribe today were well past a glint in their father's eye when we started to know about this.
- Seemingly around the world, physicians are often nepo babies.
In the United States, our physicians are paid by taxes for grad school. The physicians decide the supply with an unelected private org ACGMe.
It really shows that despite the corruption, people will go to great lengths for health.
- I’ve been on a SSRI for 5 years and not once have I thought about getting off of it. It literally saved my life.
I remember a while life of depression and constant churn of recursive emotions destroying me.
I’m worried that too many people are downplaying the benefits that this drug for those of us that it has helped immensely. And it’s extra risky to be downplaying it while RFK jr is actively working to remove the drugs from the market.
- An unfortunate aspect of modern discourse and thinking is how black and white discussions can feel. Several sides of the topic can co-exist together and all be true, so (well, in my experience and reading):
- Some people really benefit from and even need SSRIs or other psychoactive drugs to function well in society.
- Too many people are prescribed them such that there may be more harm than good. They may have side effects or were prescribed them to deal with a situational problem that could have been better managed with therapy.
- Whether justified or no, a prescription is given with no off ramp provided. It's almost as if you're defective and the drug is fixing you, and the solution are pharmaceuticals, which again may be true for some subset of those prescribed. People clearly are trying to taper and are suffering.
More controversially, psychiatry is something of an art (if you're generous) or a racket. Because there's no way the "chemical imbalance in the brain" theory can be validated empirically. In the US you meet with one for 15m, get prescribed a cocktail of drugs, a few months later you report if it worked, and if not they'll up the dose or play around with the cocktail. I don't know how we call that stuff science.
- > In the US you meet with one for 15m, get prescribed a cocktail of drugs, a few months later you report if it worked, and if not they'll up the dose or play around with the cocktail. I don't know how we call that stuff science.
Is that not science? It's on a small scale but this is all they have to work on. We don't understand enough, it is all trial and error.
I note that not all psychs operate this way, mine would not give me a perscription until several visits in.
- Well, it's science if you consider the patient to be the subject of an experiment. But the point I was trying to make is - they don't directly measure serotonin or anything else in the brain. They can't see thoughts through a machine or measure 'chemical balance', whatever that is. They leave it to correlation - give drug, report result given by patient. It's like nutritional science, but even worse, because at least with nutritional science you can measure blood sugar or cholesterol. Psychology involves the outside world - relationships, financial security, social stresses, physical health, etc. Habits of mind. Traumas. So much more.
- I’m happy for your extreme good response to the drug. I’ve witnessed this type of response in my close circle once, and it is life saving medication in these situations.
I think it’s important to highlight that not every person has the same response to these medications. I think it’s absolutely something anyone struggling with depression should try, but there should be expectations about how long to stay on a medication before moving on.
- I think the issue is informed consent. If people find benefit in them by all means they should be able to take them. But currently these drugs are being given out for the most mundane issues, many of them temporary, after a 2 minute visit with a Primary Provider/GP, with little to no discussion on potentially permanent and serious effects, whether that be long term withdrawal or the equally life ruining PSSD. Neither of which seem to be particularly rare given the number of prescriptions.
- You don't always taper out to stop treatment. Changing medicine also needs tapering.
- > I’ve been on a SSRI for 5 years and not once have I thought about getting off of it.
I had this same outlook too. Was on one for about 6 years and then my first kid was born. I felt nothing emotionally when she came in to the world and I discussed this with my wife. Two years later, my second child was born and it was a radically different experience and I am glad I got off.
My GP warned me, "Don't cold turkey it, taper off, cut the dosage and ween off. Ask your wife to pay attention to your moods, if you go sour and can't recover, you may want to consider going back on."
Over those 6 years on it, I learned a lot about how to deal with the stress. I definitely think that's a missing key in the whole treatment process.
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- Chronic depression doesn't usually have a "cause" that you can fix without some form of treatment. It happens that these meds often do remove the extreme effects of depression and allow you to focus on other problems.
- > Chronic depression doesn't usually have a "cause"
Is that true or your guess?
- I have first hand experience. Also "depression" is different from "chronic depression". You can experience the former as the direct result of some cause.
- > I have first hand experience.
You can't have first-hand experience of "usually" where that applies to multiple people.
- Come on. Don’t roll into a conversation playing armchair expert criticizing others’ contributions when you’ve got nothing of substance to say.
You’re as capable of typing “causes of chronic depression” into a search bar as anyone else. The fact that you don’t do that indicates you don’t want to contribute. You just want to be argumentative.
- Riveting discussion. How about you reply with something of substance instead of just presumptuous and pedantic quips.
- I wonder if you feel the same about drug-based treatments for multiple sclerosis or ALS. Or hormone replacement therapy. Or palliative end of life care.
Sometimes treating symptoms is what we can do because we don’t have a cure.
- Obviously not.
- Then don’t ask about whether the drugs cure the disease or just “bury it further”.
Own your opinion and state clearly that you don’t believe depression is real. Don’t argue silly tangents that serve only to obfuscate your actual point.
- What might the difference between between ADHD and ALS though? One is a neurodegenerative disorder and the other is indiscernible from some ditsy airhead who can't be bothered to do things
- See how freeing that is? You can just be honest about your beliefs and others can choose to engage or not based on that instead of playing some silly game of pretending that treating symptoms is a bad thing.
It’s ironic that the current secretary of health believes that medicines like SSRIs are overprescribed while simultaneously believing that TRT is underprescribed. It’s interesting to see how people can accept their own “treat the symptoms” medicine as appropriate but deny others. Especially when the primary symptom of low T that most attest is lack of energy and motivation. Aka “can't be bothered to do things”.
- There's situational depression (my mom died, my girlfriend dumped me, etc.) and then there's depression. Winston Churchill called his The Black Dog. It is relentless and not related to any situation you are in. If you don't understand then be thankful.
The cause is not entirely clear. SSRIs do not help you "bury it." It's not an emotional problem or a lifestyle problem or anything like that. There's no "it" to bury. SSRIs seem to remove whatever cause is in your brain/nervous system. They literally are lifesaving drugs with almost no side effects for many people!
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- If it comforts you to believe that depression always has a discernable cause that can be fixed without medication then go ahead and keep believing that.
This particular comment about Churchill and your dismissal of the experience of many depressed people sounds pretty spiteful to me (to borrow your diagnosis). Maybe some self examination could help you
- He was raised by the nanny, parents were known to be distant. I'll rest my case
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- It's nasty because of the assumption that someone who is taking medication has "buried the cause further", in other words, done something to paper over the rent in their psyche that could have been fixed some other way.
In my case, I had depression for no apparent reason, and I went through dynamic psychotherapy, which is basically about finding that reason. That failed, I got worse, and basically was disabled after a few years. I finally found a medication, venlafaxine, that actually worked. My depression abated, I was no longer disabled. It has well-known withdrawal effects, so I tapered off of it very gradually. When I stopped, I was no longer suffering major depression. There was no removal of any particular cause.
- > In my case, I had depression for no apparent reason, and I went through dynamic psychotherapy, which is basically about finding that reason.
What was happening with you at that point, where were you at? Riding ecstatically high with your wife kids and large circle of friends, the constant socialising and good times?
- I can see that there is no point in continuing this conversation. I wish you the best and that you may never experience depression with your wonderously, fabulously ecstatic life.
- There are lots of people depressed for no reason. Look up Winston Churchill and his depression for a public example
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- Ok, Freud. You’ve successfully diagnosed the cause of Churchill’s chronic depression. Now what?
What is your treatment given that you’ve identified the cause as a past childhood experience. You got a time machine? Or do you treat the disease in the present?
- You dismissed ONE example. I guess you're right on the general case!
- Two different people gave that same Churchill example, it's obviously a common example that gets bandied around
- Oh it was fuckin you twice lol
- Yes, I didn't realize it was you in both threads either
- 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.
- > 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.
- 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.
- 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"
- > school crazy
Yep, that’s how I associate SSRIs.
- 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.
- for my snri i lessened the dose by 25% and that alone cost me a week of work, i was so fucked over. when i quit this i will for sure do the thing where you open the capsules and remove a little of the contents, gradually removing more each day.
i read online about people doing this and thought they were nutjobs. well, now i know.
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- If a fireman is trying to stop a house fire and suddenly they catch fire themselves, no one would argue that they need to focus on the house fire first.
Antidepressants are the same: they won't stop the bigger fire by themselves, but by preventing you from catching fire right now they give you the tools to deal with the larger problem more effectively that if you tried to do it while flailing around and screaming.
- man, you're all over this submission shitting on antidepressants and questioning people's experiences. it's irresponsible and really not cool.
- Not to mention benzodiazepines...
- "People legitimately need these drugs"
First. Do no harm.
- Going cold turkey is always the worse way to wean off a SSRI, but the half-life of the drug is also a good indicator of the intensity of the withdrawal. Also, some people might eliminate a drug faster than others, so the result is surely harder on some that others.
Doctors that tells you how to reduce the SSRI/SNRI are following what's available on the market, and generally the gap between doses is always huge and gives a big gap and so bigger withdrawal. Once I asked to a pharmacist if he could make smaller doses and he answered me to be like a good junky and open the capsules and cut them myself. I was a bit shocked at the moment, but at least it costs me less that him having to do it a that helped me greatly to reduce a SNRI without feeling too much symptoms.
So a good advice, is look at the half-life of the drug you are taking, and be a good junky and split the capsules or have liquid form to reduce by small amount.
Half-Life of Specific SSRIs
- Fluoxetine (Prozac): 4 to 6 days, with its active metabolite norfluoxetine lasting 7 to 16 days.
- Sertraline (Zoloft): Roughly 22 to 36 hours.
- Citalopram (Celexa): About 36 hours.
- Escitalopram (Lexapro): About 27 to 32 hours.
- Fluvoxamine (Luvox): 17 to 22 hours.
- Paroxetine (Paxil): About 21 to 24 hours.
Half-Lives of Common SNRIs
- Venlafaxine (Effexor): About 5 hours for immediate-release (extended-release has an effective transit/clearance profile, though parent half-life remains short); its active metabolite (desvenlafaxine) has a half-life of about 11 hours.
- Desvenlafaxine (Pristiq): About 11 hours.
- Duloxetine (Cymbalta): About 12 hours (range of 8 to 17 hours).
- Levomilnacipran (Fetzima): About 12 hours.
- SSRI's saved my life with no side effects that I can discern, yet I still have the urge to try and get off of them from time and so do friends and family of mine that also benefit from them. Maybe that urge needs more study because it is not taking us in a good direction. I'm not saying that because of the difficulty of weaning off, but because of the benefits of staying on. For those of us that need them, trying to wean off of them is like trying to wean off of I don't know, vitamin C or something else essential. Don't do it! Be glad you found something that helps! Keep taking it!
- I've been on 40mg citalopram for about 20 years now. I've tried a few times to come off either tapering or cold turkey and in all cases it's been horrendous. My biggest worry is that I'll never be able to come off them as I'm on such a high dosage, even if it was tapered off over a very long period of time.
- Hey, don't lose hope. I got prescribed and took 30 mg of Citalopram for about 10 years to treat general anxiety. At some point, I wanted to stop taking it because of the emotional numbness (and also because of a tendency toward mildly aggressive episodes).
I gradually reduced the dosage from 30 to 20 mg (over the time of 3 to 4 months), then down to 10 mg (for another 2–3 months), and then I finally reduced it to 5 mg (half a 10-mg tablet) over a period of 4–6 weeks. I told my doctor beforehand, they only told me that I should fade it out slowly. But please excuse me for not knowing the exact time frames of the tapering process any more. I took my time at the beginning of the tapering and moved more quickly toward the end.
During and afterwards I didn’t notice any severe side effects, aside from the fact that the recurring emotions really overwhelmed me at times. Not only that, but I would cry at the slightest hint of emotional and romantic scenes in movies and series, which lasted for about three months. Nowadays, I feel quite normal. I miss the slight comfort Citalopram gave me, but I have my feelings back, I feel more myself again. If a bit more anxiety is the price for that, then so be it.
- I said it elsewhere, but it took me a month of micro dosing down to get off my 40mg/day citalopram habit, which I had been on for 15 years. And even on my own super slowed down schedule I still experienced massive side effects. Good luck to you if you ever decide to wean yourself off of it & always remember to keep backup citalopram in case you can't get your script refilled right away.
- Thanks, I appreciate it.
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- > Likewise, a 2025 study found that people with dementia who were taking antidepressants experienced more rapid cognitive decline. “Sometimes we think a lot about medications when we start them, but we don’t think enough about stopping them at some point,” says Sara Garcia Ptacek, a neurologist at the Karolinska Institute in Sweden, who worked on the study.
My aunt had Alzheimer's and had to be put on anti-anxiety medication just so that her caretaker could manage her. (This was at the point where she no longer recognized her children, but recognized her siblings.)
Even if it accelerated her eventual end, it certainly improved the situation. She would have been impossible to take care of otherwise.
That being said, before Alzheimer's, she was a very anxious person and often difficult. If she was medicated earlier in life, would it have accelerated the onset of Alzheimer's?
- All cases are possible with S{S|N}RIs (I am a doctor but I know a little regexp). Patients that took them for two months and never needed again and others that cannot stop them after 20y. The start, the stop and every restart of the drug needs an indication so it should be approached with the same care as any medical decision.
It's not right to call it withdrawal. These drugs are not addictive like benzos or alcohol are. If any symptom reappears it's just that the mental disease most usually changed form after so long time. As for the sexual dysfunction, a common known side effect is that they kill (delay or eliminate) the orgasm. Libido and male erection are affected by so many psycho-social, somatic and genetic factors that it's usually difficult to spot the exact relation with these drugs.
- > It's not right to call it withdrawal. These drugs are not addictive like benzos or alcohol are.
What does “not addictive” matter? Clearly, SSRIs are something that induce a dependency, because the withdrawal symptoms are horrific. A drug doesn't need to give you a high to create a dependency problem.
> If any symptom reappears it's just that the mental disease most usually changed form after so long time.
How do you know that? This is a problem with some other kinds of psychiatric medications too (certain antipsychotics for example), the reckless assumption that anything that happens after cessation of the drug was just an underlying symptom that the drug had suppressed. That could be the case, but you mustn't just take it for granted.
I think most worrying is the cases where a drug has only a placebo effect until the point of withdrawal. If your underlying bias is towards assuming the drug is effective, then the disaster following withdrawal might make you think the drug was holding it back this whole time. But in fact, the drug may have caused the entire harm.
- The sexual side effects can be much much worse, and far more permanent than delayed orgasm or low libido - https://www.pssdnetwork.org
It's also not difficult to spot - the complete removal of libido, sometimes permanently for life, with these drugs has been seen in animal models, and also is not present in other classes of ADs. A lifetime of chemical castration effectively.
Clinicians really have been misinformed about these drugs, the awareness campaigns of the 90s still cast a long shadow, with many not really truly understanding the actual potentially permanent and serious effects of these drugs, or assuming that they're rarer than they are (they aren't rare) - because that's what the pharmaceutical company campaigns have told them.
- Right! No thread on antidepressants is complete without a downplaying of PSSD
- I was on Cymbalta for a while for non mental health related issues (nerve pain caused by MS).
I absolutely had withdrawal when I needed to go off of it, and I can say with certainty that the mental effects of going off of it were not just the reappearance of the underlying mental health issues since there weren't any. My emotional regulation was in the toilet, I was extremely irritated, I'd cry constantly, I was horny as hell, etc.
- There’s a lot of focus on negatives in comments. I will say ssris probably saved my life and I have had zero side effects to date. It’s easy to say “just suck it up and power through it”. That advice can kill people
- This topic always draws out the contrarians. It's like vaccine discussion.
- Perhaps because various SSRI users have contrary outcomes?
- Sure. I always find the more extremist responses (you can find some towards the bottom) confusing because the only side effect I've ever been aware of is not wanting to die.
I just think there's a lot of fud around this and I have friends who have never taken them that were very ready to jump in on the discussion about how they destroy lives.
- I'm observing ~3 categories of SSRI negativity in this comment section:
1. Those who have directly experienced negative outcomes from SSRIs or observed negative outcomes in people they care about
2. Those who feel that the medical establishment should more loudly caution about the side effects of SSRIs
3. Those making something tantamount to claims that depression is a natural phenomenon which has been collectively constructed as a mental illness
For (1) and (2) I have only compassion and modest disagreement. For (3), I have nothing but disdain.
- 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.
- Yeah, this is exactly why I couldn’t stay on it. I already deal with GAD and OCD, and whatever benefits it had for the depression were directly counteracted by the return of acute anxiety.
It was truly hellish. Feeling like I had this energy that I needed to use, while also feeling so anxious that I didn’t want to leave the apartment.
I know it works really well for some people but I was definitely not one of them.
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- Thank you, that answer makes a lot of sense.
- Just want to underscore that this is the right answer.
- Doctor gave it to me and I reacted paradoxically to it. Worse depression and even more peculiar I picked up smoking again. I never felt such an urge to smoke in my life. Over the years I've been looking for an explanation for that reaction but wasnt able to find anything
- Or Auvelity, which is a newer one that mixes Bupropion and DXM.
- My doctor tried me on Bupropion for ADHD and I think it caused my BorderlinePD to get much worse, so definitely YMMV.
- It has a long and scary list of side effects, good if it works for you
- They all do and my reading has always been that bupronion has less scary side effects than e.g. escalitopram.
- There's a medicine named escalate-o-pram?
- Probably a misspelling of escitalopram, aka Lexapro.
- https://en.wikipedia.org/wiki/Killing_of_the_Clancy_children...
While her husband was gone, Lindsay strangled their three children one by one with exercise bands in the basement. She then attempted suicide by cutting her wrists and neck and jumping from a second-story window.[6][27] Lindsay sustained spinal cord injuries from the fall and was hospitalized; she remains paralyzed from the waist down as of 2026.[31][32] A forensic toxicologist later testified that Lindsay's blood showed evidence of Remeron, Lamictal, Trazodone, and Seroquel.[33] - I am by no means advocating against taking anti-depressants, I am just sharing my own experience. I have to say this because I have seen people with severe depression make night and day transformations off of these medications and know they can work.
For me, it wasn't an SSRI, but a norepinephrine-dopamine reuptake inhibitor - often prescribed for treatment-resistant depression. In my early 20's, I had tried everything, nothing seemed to work, then these treated the physical symptoms pretty well - I got my energy and motivation back, sleep normalized.
After several years though they stopped working. We upped the dose until there was nowhere left to go. At the dose I was taking, it was very important to take it at the precise right time or you could spiral into some very bad symptoms. Drink at all, or just a little too much, could spiral you into an episode. I finally decided that it was worth being depressed than what I was dealing with physically and emotionally on the drug, so I stopped it.
It was a rough month or two but I entered a new treatment program, the doctor found I was severely D3 deficient. We worked on my sleep habits, nutrition, diet - finally discovering what I had was seasonal affective disorder. So we have a plan for those months, and honestly, it's been 2 years off of them and I have never felt better.
Depression is a complicated condition, there's no one treatment in my mind, it's a lot of contributing factors. I won't take them again, especially since there's a moderate chance these drugs actually worsen depression and highly increase risk of suicide. Doctors will just prescribe them without much warning, and that is what I hate, not the drugs themselves.
- Lookup "occupancy chart antidepressant", study the chart. There is an exponential drop-off at lower doses. Hence to taper off without feeling it, one needs to cut smaller and smaller doses, (or liquify) which may be impractical.
- Interesting; I wasn't aware that 20mg was considered the minimum effective dose for fluoxetine. I tried tapering from 20mg to 15mg (alternating 10/20) after ~4 years and was absolutely fine; I then tried the next step down to 10mg and crashed hard. Probably going to stay on it for life now, which is fine; I never really experienced any negative side effects.
- Zoloft for me (Sertraline) years ago. Was on for a few years and came off cold-turkey when it didn't seem to help any more.
My life outside my head was crazy enough. My mind then matched it. I don't regret taking it, but it is a real trap of taking sanity from your own future and paying it back later. Advice I received was if my body could handle it, I should stay on it forever. I didn't like that idea, though. Among the negative side effects, the chemical sexual drive suppression caused its own problems. YMMV of course.
- >The baffling science of SSRIs: how do they really work?
- SSRIs not Benzodiazepines. Withdrawals from the later can be life-threatening if you abruptly stop after prolonged use.
- While you are entirely correct that immediate withdrawal of benzos is life-threatening, the same is true for short-acting SSRIs/SNRIs.
For eg, when admitted to a psych ward, there are a handful of things that the hospital will continue giving to a patient and gradually taper. Benzos, SSRIs/SNRIs, anti-psychotics, anti-convulsants & alcohol.
I mention this just to urge folks not to go cold-turkey on SSRIs/SNRIs as it can be life-threatening.
- "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 don’t think “most doctors” is accurate any more, but a doctor prescribing a month of klonopin for insomnia needs some urgent continuing professional development.
- 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 also been told the 2 week reduction (reduce by half every two weeks) schedule and agree it is also not nearly long enough. I really wish you could get incremental decreasing doses over the course of months to properly ween. If I ever have to do it again I will be taking a much more concerted longer period, really being specific on the tailing dosages. The body and brain needs way more time than we think
- This is a serious issue, but for a humorous sci fi take on this issue, go read The Lust Lizard of Melancholy Cove by Christopher Moore.
It deals with a small town psychiatrist who takes a whole town off of anti-depressants, and an ancient monster is summoned from the depths attracted by all the heightened emotions and terrorizes the town.
- I’ve known two people who experienced psychosis after quitting their meds. One was retired and rode it out, but the other quit his job and ended up being committed, totally upending his life.
- 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.
- Atomoxetine can cause some wild mood-related side effects, just as an FYI for anyone considering it. For me, it made me perpetually pissed off, and made me feel like I had a cold. I’m jealous of people it works well for though - seems like a great drug when it works!
- I stopped looking into drugs when I stopped having problems.
- I've tried 20-some-odd antidepressants titrating off and on and usually back off again.
Mirtazapene (ATeCA) is the only one that could manage my depression. Unfortunately, it leads to severe weight gain that my health plan's formulary refuses to cover GLP-1 for because obesity is considered "a choice". It's the only one where the depression mostly goes away and the side-effects aren't life-threatening/-debilitating for me. If I forget a single dose at night or anytime I go to sleep without taking it first, I end up with almost exactly the feeling of an alcohol hangover. It's also a pretty powerful antihistamine. I also usually can't get to sleep if I don't take it. :/
Vortioxetine gave me horrific myoclonus and vestibular symptoms.
Atomoxetine is mostly for ADHD and gave me tachycardia, profuse sweating, uncomfortable nervousness, and anxiety. It didn't do shit for my ADHD or depression.
YMMV.
- 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.
- Withdrawing from citalopram after dropping out of college was one of the worst summers of my life. Brain zaps are real.
- 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.
- > bipolar
I think this is more relevant than people give it credit for. While bipolar depression and unipolar (major) depression might generally be functionally indistinguishable from the outside, they seem to have genuinely different origins within the body and brain.
And the drugs seem to be far more powerful for people with bipolar.
That's both good and bad. Good, because between mood stabilizers and very careful use of antidepressants, many people with bipolar can genuinely achieve complete treatment, or close enough to pass as complete. Which is wonderful! Bad because antidepressants and (hypo)mania are a dangerous combination, and the antidepressants can have more kick than one would normally expect. They'll often cause a patient's first manic episode, which can be very bad on its own but might get things on the right treatment course. (Of course, they often still do nothing much at all.
I think the tapering may be related as well. I was eventually diagnosed with bipolar II and I've never really had to taper off anything that didn't have a black-box warning about tapers (either intrinsically or due to blood-pressure effects, which are worth taking seriously). I've stopped some things cold which one really shouldn't stop cold. I didn't really notice much other than the bad side effects causing the stop going away.
> I do have "extra money" and am able to pay extremely qualified and expensive doctors
I don't really have "extra money" but I still do this anyway. My psychiatrist is $500 an hour, out of pocket, no insurance accepted period. He actually listens. It's worth it.
- None of my doctors spoke of the withdrawal side effects. But they'd happily prescribe stuff.
I was on SSRI (Sertraline) for around a year, and it absolutely demolished my libido, to a point where I became repulsed by it and actively avoided anything sexual with my wife. Luckily, I didn't gain any weight but the sexual side effects were brutal. I eventually visited a couple other doctors, same story, keep sertraline, increase the dose and here are some multivitamins, good luck bro.
Eventually had enough of the bull** and stopped it all cold turkey, both Sertraline and Lamotrigine, no tapering off or anything. The headaches that followed were brutal but for me it was way better than the risk of ruining my marriage.
A year later, I went back for another try, got prescribed Bupropion and Lamotrigine (again) but neither made any difference, they basically had the same effect as the water I drank with them. So again, stopped them cold turkey and vowed to never get any drugs for my depression and anxiety, and came out with the conclusion that therapy is broken. They'd happily prescribe meds than actually get to the bottom of the issue, it's a symptomatic treatment.
- 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.
- Oof, this tracks with my experience on the NHS… it seems like extreme busyness comes off as a lack of due care.
One time I met a psychiatrist after moving to a new area. In our very first meeting he takes me off a medicine I’ve been on for nearly 7 years, cold turkey. Then? _Zero_ follow-up, no check-ins, and I can’t get an appointment on my own for months. The decision may have been wise, leaving out specifics here, but the lack of follow-up really was negligent.
- 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.
- Myself I tapered Paroxetine without any pill cutters or special techniques and had no physical problems... But I did have something like a manic episode that lasted for about six months, had a psychogenic fever, lost more than 30 pounds in a few months (I was working out like a "maniac" and eating a mostly liquid diet at times to take stress off my TMJ) and was very high functioning in most respects despite being under the influence of a system of delusions.
- The relevant book is The Maudsley Deprescribing Guidelines Antidepressants, Benzodiazepines, Gabapentinoids and Z-drugs by Mark Horowitz and David Taylor (2024).
This book is for medical professionals, but if you find your doctor doesn't have the relevant training then worth to educate yourself. The TL;DR is that you need to go really slowly in the final steps.
Horowitz also has many talks and podcast appearances on youtube. Example old video https://www.youtube.com/watch?v=LRr09mvMEAU but he has many more recent ones.
I don't have any direct experience with this, but I've been watching my best friend struggle with widthdraw symtoms for many year, and I also know from doctor friends that they are not trained on de-prescribing protocols.
- By the way - turning off scripts allows the original to load without paywall. (Probably not using Chrome.)
- I think about 10 years ago maybe even more than that maybe 15 years ago I had a conversation under a different name on hacker news and I was telling them about my antidepressant withdrawal.
I was downvoted and ridiculed. Told it was just my mental illness and it was all in my head. I even attempted to show the mechanism but people thought that was not enough.
Now I see this. It makes me angry. No one listens to the mentally ill and our experiences.
By the way, this is also true for and drugs that act on receptors. Like most antipsychotics. It’s is even true for GLP1 drugs.
This is a form of addiction that is not see only because the “craving” is absent. It is an addiction which fits not tell you what you are addicted to.
Psychiatry is the worst practice right now. There has been zero progress and even less compassion.
- 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.
- > 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.
- > 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.
He probably did inform me, I was probably not paying attention at that time. Family does not know the details either, I'm dealing with this myself.
Anyway: depression is the least of my issues now, the clock is ticking.
Right now I'm sorting out my affairs without letting the kids know.
- 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.
- 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.
- > 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 just one part of why NNT as usually reported 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.
If you reformulate NNT competently to count number of people needed to be treated to ensure one has (on expectation) a minimally important difference in the depression scales, then the NNT gets even larger than is typically reported.
- +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.
- 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"
- 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.
- >>Right now I have bigger problems than just depression.
Just depression?! You might want to grab a little empathy before writing off something that has been a major problem in a large chunk of the populations lives. In fact, "just depression" has caused me to try to take my life multiple times. I can hardly see a "bigger problem" out there..
- reading some of the parents other comments, i dont think they were trying to downplay depression in general, and i dont think they meant any offense.
they were, perhaps, slightly careless in their choice of words. that's all.
- There are absolutely people with bigger problems than depression. For example, I have MS, and my mental health is absolutely one of my less concerning problems. There are so many options for mental health + the treatments are much easier to access than a lot of my symptom management meds + DMT. People undergoing chemo. People with ALS. People with bipolar (who can't take a lot of first line depression treatments) or other more complex mental health issues like schizophrenia.
None of this is to downplay depression, but there are absolutely people for whom 'just depression' would be accurate. Migraines suck, but someone with cluster headaches might call them 'just migraines' and they wouldn't be wrong.
- You didn't word it like that though. And I'd argue that for people with MDD, and without those comorbidities you listed, depression is a huge problem.
- I'm not the GP; I'm a separate person who was providing potential context.
Something can be a huge problem and still be small potatoes to people having catastrophic problems, and often those of us in very, very dire circumstances are tone policed to within an inch of our lives and have to constantly consider normal people above ourselves (and make no mistake, people with MDD are closer to normal than somebody with ALS or severe cancer). We're never allowed to express anger, never allowed to talk about having it harder, have to stop and attend to the feelings of others while ours are ignored, etc.
Also, no offense, but depression can end up making people very self-centered. It's your illness that makes you think that what you're going through is more important and worse than what anyone else is going through, and it's not. (And it's not for me either: there are definitely people who have it worse than me and could say they wish their problem was 'just' MS. I just wouldn't get offended by that.)
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- >In a generation these drugs are likely going to be seen as a big mistake and a medical scandal.
Of course the next generation will deal with a bunch of other drugs where the side effects are underplayed. The playbook of the mainstream medical industry is a common one.
- Since when do we allow people to push conspiracy nonsense on this website?
- This comment section is absolutely full of people ready and willing to insist that people with depression simply need to cheer up and get over it. And all I can say is: I hope someone shows them a similar level of compassion when they are at their lowest.
- Most of the problems I would say are related to the modern isolated Nuclear family.
See that programmer sat next to you that is not a nice person? Well some kid had no choice but to have him as a parent.
Throw in a society that doesn’t value teachers and pays them below many other jobs and the kid spends all his day and evenings with no one to guide and nurture him or her.
- Certainly we are all an alchemical output of our nurturing environments and our intrinsic characteristics, and I don't dispute that we could likely dramatically lower the incidence of severe mental illness by improving our culture's capacity for care and solidarity. It's tough out there, for children and adults.
- Truly, the cause of all this suffering is not enough antinatalism. You've cracked the code.
- Actually what they're saying is that most people did not have a lot of nurturing adults in their lives growing up, from which they've learned that the adult thing to do is to isolate themselves and avoid nurturing other people. Which they're presenting as a bad thing. The reason they bring up the "nuclear family" is an appeal to prehistory, in which we probably would have been raised by a much larger social group than mom and dad, to include other relatives and friends, and that this would give us more opportunities to be included and nurtured by a wide variety of people.
- You don't need to go back to prehistory, you can just go back a few hundred years before the urbanization brought forth by the industrial revolution. We had millennia of written record by then.
- There is no modern isolated Nuclear family. There's mostly broken homes now, and that is the root cause of most of the problems.
- Are you one of those religious Bible loons who believes couples need to stay together even if it’s a disaster relationship.
As you are wrong if you are. Children suffer more in bad parent relationships
- Sadness is a symptom. Mind/Body is saying something is wrong and it needs to be changed. Medication just dulls the pain. It is not a solution. The real solution is changing the way of life so that it becomes more fulfilling.
Happiness is not a easy thing to achieve. You need to fix the body, eat right, exercise, control/watch your thoughts, let go of things beyond control, enjoy what is in front of you instead of chasing some imaginary future.
- It's an awful thing to suffer and full sympathy to anyone who does. What unfortunately has happened as well is that the drug companies have successfully convinced the public, providers and sections of the media that any criticism of their products is criticism of people who suffer.
There are very serious concerns about the safety and effectiveness of these drugs, but the companies consistently attempt to misdirect that, seeking to portray the criticisms as "stigmatizing" sufferers or "fear mongering", neither of which is true.
- I am as critical of Big Pharma as anyone else, but you can't seriously imply that our society places a certain amount of social stigma on people who take medication for mental illness. Some US insurance companies make it more difficult to get medication for mental illness because they often argue against the need for the medication.
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- "Eschew flamebait. Avoid generic tangents."
- Diagnosed with ADHD as an adult, and on stimulants (went through 3 kinds before we found one that seemed to help).
What "high"? Our brain chemistry literally works differently than neurotypical people and the stimulants don't get us high. In fact they often have a calming effect. I had to fight not to fall asleep at my desk two days this week (Not entirely the medication's fault, lotta family stress wrecking my sleep).
Does tolerance eventually cause the dosage to increase or the medication to cycle? Yes. But as others have mentioned taking the weekend off (or hell, just forgetting periodically in my case) mitigates that to a large extent. And, since there is such a hard time acquiring the medication even with a prescription skipping weekends or vacations has the benefit of seeing people through the inevitable shortage their pharmacy will have.
- > What "high"? Our brain chemistry literally works differently than neurotypical people and the stimulants don't get us high. In fact they often have a calming effect.
Is this actually true? I see this repeated a lot. The one time I increased dosage of Adderall too quickly, I felt very calm and almost "normal" again, but I attributed this to a mild euphoria because euphoria is technically the effect one gets when high on these drugs. When I see people repeat what you said, I begin to question if that was just the drug working as intended. Sadly I ended up having to get off the drug shortly after this because A) I got too spooked about how nice it was and didn't want to chase this feeling and B) I noticed the "crash" phase resulted in deep suicidal ideation.
- My statement was perhaps too broad. It is possible for ADHD people to get high off their medications, yes. But that is a signal the dosage is too large. Normal dosage and usage won't get a person "high" in the traditional sense, much in the same way injecting insulin into a healthy person is bad but a diabetic person requires it for standard function, however too high of a dose would still be bad for a diabetic person too.
Suicidal ideation as a side effect is bad. I'm sorry you had that experience.
- > In fact they often have a calming effect.
That's clucky addiction mate same reason opioids can make addicts chatty and full of life again if they've been struggling to score all day
- Its not addiction at all. I literally forget it once or twice a week on average, even on work days. I don't think you know what you're talking about.
- Right but amphetamines are supposed to have the opposite effect. You’ve seen people on meth, do they look calm to you?
- people whose life is amazing don't go through the process of getting stimulants (or even SSRIs) prescribed to them. psychiatrists know about this. the plan is usually to cycle the meds. is this great and works every time? no. is this better than the alternative? yes.
ADHD is not great. and in many cases it's so bad people die from "not paying attention", and Ritalin (methylphenidate) is visibly helping people avoid those early deaths.
- One should not question the seriousness of ADHD or the benefits of an appropriate treatment plan.
One should question the rate of which it is diagnosed, and who is getting diagnosed.
- > One should question the rate of which it is diagnosed, and who is getting diagnosed.
The medical consensus after multiple enquiries in the UK has come to:
1. The rate of diagnosis is far too low (the evidence of this being we're catching people as adults who should've been caught as children).
2. Our diagnostic criteria aren't inclusive enough (we have historically missed inattentive presenting ADHD, we have historically missed ADHD presenting in women)
These results are politically unpalatable so the enquiry is I think currently being run for the third time, but signs point to ADHD overdiagnosis being a hoax/fake news/whatever you call it.
- I say this as someone with ADHD:
The issue is that ADHD is not real in the organic sense. Well, at least the evidence is scant. It's more of a description than a disorder. It's not something one "has."
I like to compare ADHD to racial categorization of people. Race is not real in a biological sense, but it's definitely real in a social sense.
I am probably butchering what I am trying to say so, just read this if you want to understand someone(s) that can communicate eloquently.
- > These results are politically unpalatable so the enquiry is I think currently being run for the third time, but signs point to ADHD overdiagnosis being a hoax/fake news/whatever you call it.
And here's one for you: hundreds of thousands of scroungers and workshy young adults are saying they have ADHD to get pip and other perks... Because this is even less of a charade than back pain used to be, you can legit go on holiday with ADHD, they even give people mobility passes in the UK for ADHD, screwing over people in actual wheelchairs who really do suffer in society
- One should ask if the benefits outweigh the costs regardless of arbitrary thresholds for diagnosis.
ADHD medications are generally safe, and many objections to their use appear to stem more from normative objections to medicating attention and behaviour than from evidence-based concerns about patient welfare.
- > ADHD medications are generally safe
Just like methodone is considered safe, doesn't mean you'll become a clucky mess after doing it for two decades.
- My anecdata as a college aged kid on ADHD meds with friends who want a stimulant prescription:
Psychs will put you on an SSRI first, and then atomoxetine (non-stim ADHD med) before prescribing the good stuff.
The kids who want to party and/or study harder don’t take the stuff that doesn’t get you high. The kids that are struggling with basic stuff bear with it, and usually follow up to me with surprise that the non-stimulant is actually helping them.
Of course, we usually do graduate to the good stuff. So I understand the sentiment, and often question my own reliance on the drugs.
- One characteristic of ADHD is that many people don't build up tolerance, or only minor tolerance, to therapeutic doses of some stimulants including amphetamines.
It's really not the same as what's being discussed here.
- That is not a characteristic of ADHD. Th most damaging thing to ADHD is the myth that the medications affect people with ADHD differently. It is the most pseudoscientific piece of information that is commonly repeated.
As for tolerance, it absolutely happens. Most people do not stay on the medications for a long enough time to really feel the tolerance to begin with. Sure, in a clinical trial of four to six weeks, it might not be noticed. I've been on them for well over a decade, and it's a night and day difference.
- I was at the same dose of concerta for a decade. I just recently increased to the next dosage.
At this rate I'll top out of dosage sometime around when I retire.
It really isn't on my list of concerns.
- I think this is a very different problem. I'm prescribed those "happy pills" as you call them. I forget to take them regularly, in fact I think you may have just reminded me to take mine as long as I remember by the end of this comment.
There isn't a high, in fact if I don't modulate how I eat and hydrate, I don't feel it. But if I get the timing just right, with the correct breakfast and everything, I can just barely manage to do the boring tasks that normally my brain will do nearly anything to distract me from.
Eventually tolerance does build, I manage that by taking weekends off and every 6 months or so, I'll take 1-2 weeks off cold turkey.
I need this shit to remotely participate in the bullshit gauntlet we call an economy. Without it, I'm essentially disenfranchised. I can get a job by channeling some hyper-focus long enough to show I'm not incompetent, but once the daily grind sets in, the rent payments don't stop.
These medicines are a by-product of the society we produced. We refuse to refine the society so we medicate the incompatibility.
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- > You think you must have something wrong with you because you think nobody finds life and work boring?
> Struggling in life isn't an illness
Do you think it's possible that some people struggle 100x more? Should they not get help?
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- I'm sure everyone's different but for me, weekdays on and weekends off seems to handle avoiding the tolerance. I don't need to be nearly as focused when I'm off work.
- I don't get any "high" from ADHD meds, at least not in the way any sane person would interpret the word "high".
They help me focus at work, but they aren't enjoyable.
- You’re upset that they banned the illegal drugs but not the legal ones? They probably just need more education to reach your level of logical thinking.
- "Happy pills?" Are you kidding me? Are you anti-vax as well?
- I'm so sick of this moralistic attitude toward psychiatric drugs. "Happy pills"? Come on. There are ways to work around tolerance. Even if there aren't, what's so terrible about a temporary improvement?
I'd wager most of us use some sort of vision correction. This does nothing to fix the underlying problem or even halt the progression, and most of the treatments leave us with a lifelong dependency on them. And yet nobody goes around derisively referring to "happy lenses" and talking about how stupid optometrists are.
There are legitimate doubts about the effectiveness of some psychiatric drugs. I don't believe ADHD drugs are among them. Regardless, that should be framed as a need for better education and dissemination of the information, better studies to determine effectiveness and better treatment regimens, and new drugs that do a better job. It should not be framed as "happy pills" with this derisive attitude just because the condition I take medication for is a brain condition rather than something like a heart condition.
- > Even if there aren't, what's so terrible about a temporary improvement?
Is it temp though? ADHD is a list of symptoms with no verdict on the cause. What exactly is the plan beyond the amphetamines? A lot of people I see simultaneously want diagnosing but not curing. It's like the double think required to say not having a symptom can actually be having one. As in, "Despite what I can achieve, I still struggle, and that counts as not being able to do it at all". Why do people never mask a language delay for instance? If masking is something all AuDHD people do, why is it always faculties largely intact but they find stuff hard (harder than whatever you feel, despite not having such a great theory of mind they seem to be aware of how other minds work just fine)
- You sure seem to spend a lot of mental energy on judging people.
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- What if the drugs just make us... better? As in happier, less stressed, and more suited to what modern life requires from us.
Happiness isn't necessary to pass on your genes. Most animals, especially prey animals, spend much of their lives scared, because death is inevitable otherwise. We've now created a safe and pleasant environment our ancestors could only dream of, yet many of us are still unhappy. There's no real evidence we were broadly happier in the distant past either, we're just a different kind of unhappy now.
Seems to me we've developed a tool that makes people feel better and function better, perhaps by blunting some of the vestigial leftover emotions we needed when every tree might have had a sabre-tooth tiger hiding behind it.
- "more suited to what modern life requires from us." This part scares me because I would prefer that we rearrange our economic and social world so that people can have more free time, more vacation, more relaxation, and way more social time too.
I have known many people in my personal life in the united states who have an extremely stressful and depressing life due to external stressors (job, debt) and in response are on powerful psichiatric meds with the sometimes-severe withdrawal problems mentioned in this thread.
- It shouldn't be an excuse for not making people's lives better long term, but you also have to treat people where they are in life.
In some ways, certain problems seem to emerge from modern lives being too comfortable for the environment our brains are adapted for, but it's not as if unhappiness is a new thing, we just have better tools to treat it now. My life is about as good as any life can reasonably be expected to be economically, and I have as much social interaction as I want... but I'm still anxious (without sertraline).
It really seems like humans have been fairly unhappy throughout history, are fairly unhappy now in the best societies, and are fairly unhappy now in the worst societies too. We're a pretty unhappy species prone to quite a lot of mental health problems. Only difference being that in the past, eventually hunger would override your unhappiness and you'd have to get up and do something about it, which would take your mind off worrying about dying from that worsening foot infection and mourning over the twelve kids you've had die in their childhood.
I would also suggest that being overly negative around psychiatric meds itself can be harmful. I know many people who lived deeply unhappy lives and avoided taking them for years over fears of side effects and things they'd read about, only for them to eventually give in and wonder why they hadn't done it years ago. They do have side effects, but man, as a N=1, all I can say is sertraline improved every single aspect of my life. It's indescribable how much I owe to that compound.
- What if the drugs just make us... better?
What if, indeed. You are in a thread that discusses the side effects and addiction.
>Seems to me
Are you a good candidate for a control? Let me ask you seriously… could you stop taking them and function?
“Seems to me” that you are at best a little biased here.
- I could function. I would be a lot more anxious. I'd probably function better in certain scenarios, just ones that I'm unlikely to encounter.
About 80% of people are prescribed psychiatric medications at some point in their life. Add in how many people use non-prescribed ones (smoking, alcohol, illicit drugs) for psychological support and you're going to have a hard time finding a control.
- > far too high for a social good
Not sure what you're basing this on -- hopefully not just your impression after reading things online.
- lol, I know plenty of people offline that are addicted to this shit too. It’s just that this forum and Redditors cheerlead about their addictions willingly. Most people are shyer about it.
- Sorry, I didn’t realize you also had anecdotal evidence. lol
- Most of us have no idea how many non-commenting readers w/o first-hand experience are just reading, and so no ability to draw any conclusions about the number of ones who comment with first-hand experience. 100 people out of a 1000, and 100 people out of a million, are very different things.
- I am also shocked that every time an article about guitar playing is posted the sheer number of posters who play guitar themselves. I mean what are the chances?
- I mean… are you saying this is effectively an SSRI forum?
Actually, you know what? Tracks.
- An HN post like this will gather like what, at most two dozens of anecdotes from a highly self selected user pool of maybe a million top? Is this how you base your "sheer number" on? Is this how you judge what is good or bad for your definition of social good?
I got some other news for you, buddy. https://news.ycombinator.com/item?id=49444514
- lol, don’t worry about asking someone if they’re addicted to some bug pharma product… they’ll be right along to defend it!
- Wait til you hear about microplastics!
- 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/
- > 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.
- In the practices in which I've worked, proper screening and expertise in treatment delivery boost outcome rates significantly. We see well over 60% success rates with the first round.
> This is the only factually true statement in your entire comment.
You read something you disagree with so you decided to call me a liar rather than discuss. I'm not wasting any more on time on you.
- 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.
- 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.
- > 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.
- No, I have proof, I work in mental health, I'm part of our research committee's board, I see the actual data from our patients, other studies, the discussions about the data, etc. You simply completely ignored my core statement. I spelled out why different studies report different outcomes, and they're genuinely big problems.
You don't have to like it or agree with it but don't try to dismiss me, you linked 4 studies you don't even understand because you misrepresented the data they report. One of them actually PROVES my point. Another is a metastudy which is only useful for indicating future research avenues, not drawing clinical decisions. And lastly one proves my point about multi-drug failures requiring a change in treatment.
Antidepressants save lives and I will fight tooth and nail to preserve their access by patients.
- > You simply completely ignored my core statement.
Most of it was junk, or included stuff about TMS which has zero relevance to antidepressants. Here's the junk:
> 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.
Sorry, but, no, going from passively suicidal to normal function (including not getting out bed) would move HAM-D and almost other other depression rating scales massively, so we would see this in studies, but we don't. This doesn't pass the sniff test.
Could antidepressants help with other symptoms that are milder than suicidality, but which are not measured? Plausibly, but why would I trust you, a faithful zealot (literally: you will "fight tooth and nail", and "antidepressants are amazing")? Where are the papers? You are too biased to take at word.
> We're engaged in a long term 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.
Great, when it is published, I look forward to reading it. Doctors have felt this way since the dawn of time though, and since you are a zealot, I don't care until I see the paper.
That being said, yes, there is broad evidence that combination treatments (e.g. antidepressants + psychotherapy) are generally better than either alone, and it is quite reasonable when there is proper, regular communication amongst those teams that it is a bit better still. There are studies looking at this, but again, you find average effect sizes that really fail to meet anything like a minimally important difference.
And again in these cases it remains unclear how much of the patients that do experience clinically meaningful change are changing because of the antidepressants (or how much of the meaningful difference can be attributed to the antidepressants). It's the same basic problem, the science here is really, really poor.
> a metastudy [which] is only useful for indicating future research avenues, not drawing clinical decisions
Nonsense, you'd better be thinking about and looking at these kinds of things when making clinical decisions.
> You linked 4 studies you don't even understand because you misrepresented the data they report. One of them actually PROVES my point
You've shown me nothing to indicate you have a better understanding, none of them prove anything you are saying. Best you can say is some interpretations of some studies looking at the distribution of the treatment effect might be consistent with more individuals receiving antidepressants having large positive effects, but, as I said, this is remains only weakly supported in general, i.e. it isn't a clear finding and just remains a "maybe".
The MID issue is huge, and that you work in this area on a research committee board and can't deal with this, and appeal to authority without seeming to understand the basic measurement issues at hand here, is deeply concerning. As a true believer, your beliefs about the efficacy of esketamine are also widely overstated, and, we can be sure, ignore the MID issue as usual.
Nice try though.
EDIT: Okay, since burnte is too lazy to do the work, I did some looking for proper MID-based responder analyses. There are a some, and one is with eskatimine [1], and finds:
> By Day 28, 86.5% of patients reached or exceeded the PHQ-9 [MID] in the esketamine/AD group compared to 70% in the placebo/AD group. The most appropriate [MID] for the MADRS was -10 points. By Day 28, 78.2% of patients reached or exceeded the MADRS [MID] in the esketamine/AD group compared to 65.0% in the placebo/AD group.
So this is real research! And maybe esketamine really is something new. But then, why is competent research nearly impossible to find and results always presented in a way that aren't clinically interpretable and/or prevent seeing the distributions in a way that could easily answer these questions? Hmmm, maybe because the placebo vs. treatment distributions look so similar, like this: https://www.nature.com/articles/s41398-022-01882-5/figures/1
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- 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.
- "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.
- 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.
- Thanks for the paper, it is actually quite crazy to think about when SSRI are basically the standard to treat depression.
I recently read a book about "The brain energy theory of mental illnesses"[1] which encapsulates depression and found it pretty compelling.
It seems to be a relatively new and active area of research[2], so there is hope!
[1]: https://books.google.fr/books/about/Brain_Energy.html?id=GIx... [2]: https://pubmed.ncbi.nlm.nih.gov/38183680/
- 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.
- Here are a few additional reports:
>1. Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis. Conclusions: SSRIs might have statistically significant effects on depressive symptoms, but *all trials were at high risk of bias and the clinical significance seems questionable*. SSRIs significantly increase the risk of both serious and non-serious adverse events. The potential small beneficial effects seem to be outweighed by harmful effects.
>2. The trouble with antidepressants: why the evidence overplays benefits and underplays risks. Widespread prescribing has not reduced mental disability or suicide, raising questions about the assessment of evidence on effectiveness and safety of antidepressants
>3. In search of a dose–response relationship in SSRIs—a systematic review, meta-analysis, and network meta-analysis. Conclusions: There is no conclusive level I or level II evidence of a clinically meaningful dose–response relationship of SSRIs as a group or of single substances. High SSRI doses are not recommended as routine treatment.
>4 The serotonin theory of depression: a systematic umbrella review of the evidence "We did not identify *any* trials using ‘active placebo’ or ‘no intervention’ as control interventions. "
[1] https://pubmed.ncbi.nlm.nih.gov/28178949/
[2] https://www.bmj.com/content/370/bmj.m3200
- 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.
- Note that it's not uncommon for even more widely prescribed medication to have no firmly established mechanism of action. Acetaminophen/paracetamol is probably the best example.
Ultimately medication is prescribed based on evidence from clinical trials, whether or not the mechanism of action is fully understood. SSRIs work to help with depression in clinical trials when compared to placebo, so they get prescribed.
- 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....
- 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.
- 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.
- Wait, I finally found a paper that properly presents the results in a way that lets you decide for yourself! See figure 2 here: https://pmc.ncbi.nlm.nih.gov/articles/PMC9344377/#f2, you want to focus on the second plot with the dotted and dashed lines.
Basically, both placebo and drugs can have huge responses, but basically, for severe depression, yes, it looks like the drug is more likely to have a large positive effect than the placebo is likely to have a large positive effect.
There are still a lot of limitations, main one being that study criteria generating the data for this would exclude most cases of really high severity actually seen in practice. Also "blinding" is mostly BS in these kinds of studies, and antidepressants have massive, noticeable effects, so the proper comparison is really an active placebo, and we really can't be sure the whole apparent antidepressant effect is basically just "woah, I can really feel this doing shit", basically, at some level, and this is still bad because the placebo vs. drug difference is still super tiny and below what we would consider typical minimal clinically important differences.
So still hard to say. But, yeah, there is a good chance the drugs are more effective in severe cases, and, technically, you should definitely treat in a severe case.
- 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.
- 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.
- I tend to feel the same way. The medication is obviously useful in some cases and for some conditions, but there's also a pushback against the notion that it isn't the best solution for other cases and conditions. There are cases where other solutions might be healthier, especially in the long term, but the availability of a potential pharmaceutical fix interferes.
And look at the new batch of weight-loss drugs. It's a similar circumstance. It's a wonder drug in many ways, helps so many people that wouldn't have been helped otherwise. Yet, also being used in some cases as a shortcut to avoid a behavioral change that would be advantageous for a person to do.
It is important to remember that there are people for whom these drugs are literal lifesavers. And at the same time, there are those for whom the drugs enable avoidance of fixing a root cause.
- 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 can't believe we've normalized taking insulin as a society. There are better ways than drugs to fix your Type 2 diabetes.
- 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.
- The downsides to these drugs are pretty well understood and not generally that bad, right? Can we really say it's "reckless" to attempt to treat people with something that's fairly safe and see if it helps them?
This is what really rubs me the wrong way and makes me call it moralizing. There's this implicit foundation of "drugs bad" that's basically straight out of D.A.R.E. You're supposed to avoid drugs, but we might make an exception if they treat a serious problem and there are no alternatives.
Once in a while I'll take Tylenol or ibuprofen for a headache. Do they actually help? Hell if I know. Is it "reckless" to do this when I don't know if it actually does anything? Absolutely not. Antidepressants aren't as safe as those are, but at least some of them seem like they're safe enough to say, let's give this a try and see how it goes.
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- There's hundreds of years of "depression isn't real and even if it was real the only treatment is to take a walk in the woods!!" and like a decade of "man, ssris are great, they really helped me".
Public responses have probably not finished overcorrecting.
- Fair.
But imo the issue with that might be that “just man up and go take a walk” may still be better advice than “hey kid with your underdeveloped brain… take this maybe psychoactive drug that absolutely changes your brain chemistry in ways we absolutely do not understand causing almost certain addiction with effectively zero supervision unless you self-report murderous and psychotic tendencies! Don’t mind that I’m making kickbacks on every subscription!!”
In terms of possible damage to self and others. And to long term society.
- 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.
262 points by eutropheon 1 day ago | 331 comments