Doctors are finally learning to manage antidepressant withdrawal
newscientist.com
newscientist.com
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.
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
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.
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).
---
They're common, cheap, and plenty of (recreational) drug dealers use them.
I just eyeball everything when I cook. (For other things that I'm passionate about I'm much more careful.)
I'm also an eyeballer. I'm a decent cook but a truly lousy baker.
Any juice can take the roll of lime or lemon (in cocktails or baking) by adding a bit of citric or malic acid. Orange juice is 1% citric acid, so add 3g citric and 2g malic per 100g juice and now you can make an orange daiquiri or "key" orange pie.
Emulsifiers get goopy if you use a lot, but can make a smooth syrup in small amounts. You can make a nice syrup from any nut milk with a small amount of xanthan and gum arabic.
There's a wide array of ingredients including xanthan and gum arabic used in tiny amounts in gluten free baking
Even $500 analytical balances like [0] can struggle with 1mg resolution, but I’d trust them a lot more. Generally you need to throw away the least significant digit of precision with digital scales.
0: https://ussolid.com/products/u-s-solid-0-1-mg-analytical-bal...
Also, note that while your $500 scale may be necessary for absolute accuracy, splitting 10mg is not the same as finding exactly 10mg.
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.
I notice reduced desire but I'm depressed, too, it's hard to disentangle the effects, there is a ton of fud.
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.
Also, this is not only medication for PE.. there are many other options like fluoxetine, citalopram, PDE5s, etc .
Even if there are trials for these medications, the field is not quantitative in practice. "Standard of care" is a myth.
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.
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.
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 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
I never found a sub reddit talking about the side effects of mineral water, how eating apples regularily lowered their libidos, on that sleeping on a mattress made them senile.
At some point common sense primes over what funded science wants people to believe.
The side effects exist since some doctors do warn about them, one may also find them in the counter indications mentioning those things. It isn't unfounded.
What's taboo today is to criticize SSRIs over prescriptions. Odd, given that over 25% of the U.S population are taking them, or some other form of legal psycho active substance, just to be able to "function".
> 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-...
Why are you certain about this?
you don't experience side-effects now, but you will if you need to stop taking it
In my personal circle I only new of a single woman who had no issues. The majority had all flowers off issues. During and afterwards. No most of the time it got downplayed or simply ignored but doctors and society a like. I'm personally glad that birth control pills are not longer sold as a wonder pill because many woman suffered needlessly and the worst part is that many did not knew that is was the pill in the first place.
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.
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.
> 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%?
Different thing entirely from long-term effects.
“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.
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.
What's missing is also follow up - for some those effects don't resolve after stopping the drug.
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?
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.
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”.
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?
The reality of the actual trial data was very different - with catastrophic results for many.
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 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.
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.
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)
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.
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).
This isn’t a one size fits all area of medicine.
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 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.
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!
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.
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.
I've been on celexa for a decade now and have always wondered what it would be like if I ever had to come off.
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.
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.
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 think it is more about tapering at a tolerable rate than any particular extended duration.
It will be interesting to see how the guidelines change once they're updated.
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.
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.
At some point, we have to trust that even if one or two of those fail, the information is readily available and issued four times before you start.
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.
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.
- 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.
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.
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.
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.
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.
Yep, that’s how I associate SSRIs.
I liken SSRIs to carpet bombing - also their mechanism to increase seratonin in the brain is by making something else not use it (reuptake inhibition). We’re guessing that other thing isn’t a big deal. But who knows. Serotonin is produced in the gut and it controls melatonin, which controls our sleep. It’s all connected in a bizarre way.
It's like inserting objects into the body's event loop and hoping it produces the desired effects as it circulates, only to find that everything reacts to the event, not just the parts we want.
i read online about people doing this and thought they were nutjobs. well, now i know.
First. Do no harm.
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.
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.
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.
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).
It is a second-line treatment for a reason. Great when it works. Harmful when it does not.
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.
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.
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?
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 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.
I have seen and treated a large number of people with SSRIs, and the majority are incredibly thankful. I spoke to a patient yesterday who told me his Sertraline saved his life following a suicide attempt a few months ago. I saw a patient last year who fantasized constantly about murdering his colleagues at work. Fluoxetine cured him completely and he was incredibly grateful to not be tortured by those thoughts anymore. Some have had sexual side effects, but in my experience switching SSRIs often cures these. They aren't perfect drugs, but on balance they help a lot of people.
I do not think engaging with the above sort of network is a good idea, I suspect a large amount of these people suffer from psycho-social causes of libido/orgasm loss and being part of an echo chamber telling you that change is permanent will only reinforce that idea if indeed it is a psychosocial change.
I practice in the UK so things may be different here. I've never heard of a patient with persisting sexual symptoms following an SSRI switch. Certainly hear about a lot more psychosomatic conditions in the US than we seem to see here. I think a lot of this is downstream from the US fee-paying healthcare model where the implication is that doctors want to make money.
As a side note, and I find myself saying this a lot on HN, but most of you are not doctors. There are a huge amount of unknown unknowns in medical practice that the layperson is unaware of. I wouldn't even think about commenting on any technical subject with the amount of confidence most commenters here give with single-digit sample sizes, or using self-reinforcing internet forums as evidence. Frankly what we say in the consultation room and what patients walk away with is often different. All doctors know SSRI's have side effects and in my experience all counsel on these. There's probably something for us to improve there with communication, but after you explain side effects and give a leaflet explaining those again, and the patient still claims you didn't tell them about a side effect, I feel like there's not much more we can do.
Also, NewScientist is a poorly written pop-sci publication. It has constant inaccuracies and misinterpretations of the evidence. I cancelled my sub years ago when they were bought by the Daily Mail.
There is some utter pseudoscience in this thread and some completely misunderstandings of how medical practice works. The body is infinitely complex on a biochemical level and we have a very limited understanding of the interplay between all systems. Just because the serotonin theory has been disproven by one systematic review does not mean SSRIs are a bad treatment or do not work, it just means we do not fully understand their mechanism of action. These are not the same thing.
I suspect some SWE's or similar in this thread are used to having the complete understanding of a system and the levers involved, this is simply not the case for the human body.
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.
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.
Isn't that the definition of addictive?
I imagine many diabetics crave insulin when they cease its usage.
Quitting coffee might give someone headaches, bit more tiredness, difficulty concentrating, etc.. But that is just the body trying to achieve homeostasis.
Many diabetics would have horrible withdrawal effects from ceasing their insulin usage -- a substance they cannot live without. They take it everyday and their life depends on it. But many live perfectly normal, functional lives. They do not break into cars to steal radios to pawn off for more insulin.
However, jeopardizing your family’s future by taking out a second mortgage on your home just so you can keep gambling -- while you’re already drowning in debt -- and telling yourself, "If my wife finds out, she’ll divorce me and take the kids. But this is the time I win big. This time will be different."
That, right there, might be the purest form of addiction there is. All without any physical dependence at all. Gambling addiction also has the highest suicide rate amongst all addictions.
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.
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.
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.
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.
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.
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.
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.
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.
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]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.
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.
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 get that life can be unpleasant, but it just feels like it's so many people.
I really have a hard time believing it needs to be so many.
It's normal to feel bad.
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.
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.
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.
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.
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.
That said, yes; walking is the best medicine for me.
I've got two friends who didn't benefit from it, so it isn't a miracle cure for everyone, sadly.
> 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.
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.
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.
But many people don't need anything more than acute treatment, so what about them?
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.
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.
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.
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.
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..
they were, perhaps, slightly careless in their choice of words. that's all.
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.
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.)
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.
As you are wrong if you are. Children suffer more in bad parent relationships
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.
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.
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/
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...
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".
> Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity. Most studies found no evidence of reduced serotonin activity in people with depression compared to people without, and methods to reduce serotonin availability using tryptophan depletion do not consistently lower mood in volunteers. High quality, well-powered genetic studies effectively exclude an association between genotypes related to the serotonin system and depression, including a proposed interaction with stress.
> The chemical imbalance theory of depression is still put forward by professionals, and the serotonin theory, in particular, has formed the basis of a considerable research effort over the last few decades. The general public widely believes that depression has been convincingly demonstrated to be the result of serotonin or other chemical abnormalities, and this belief shapes how people understand their moods, leading to a pessimistic outlook on the outcome of depression and negative expectancies about the possibility of self-regulation of mood. The idea that depression is the result of a chemical imbalance also influences decisions about whether to take or continue anti-depressant medication and may discourage people from dis-continuing treatment, potentially leading to lifelong dependence on these drugs.
https://www.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.
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).
>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
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.
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.
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/
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.
Depression is highly heterogenous, and I am glad the medication helped you.
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.
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.
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.
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.
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.
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
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.
> 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.