Antidepressants aren't just used for depression, they're also used to treat a spectrum of anxiety disorders like OCD and panic disorder, although the doses used to treat anxiety disorders are much higher than those used for depression. I don't think the BDNF-related hypothesis explains the efficacy of antidepressants in treating anxiety disorders, but I could be wrong.
Under the maladaptive neuroplasticity theory which motivates the BDNF connection, I think anxiety could be taken into account naturally: just as depression is a maladaptive persistent overlearned estimate of the world as threatening, unrewarding, and pointless, which persists despite regular experiences which should falsify those beliefs and lead to learning (but doesn't), anxiety is persistent overestimation of risks which persist despite regular experiences of dangerous risks not happening which should lead to learning (but doesn't). So if boosts to neuroplasticity can help a depressive learn that life doesn't suck, it makes sense if boosts could also help an anxious person learn that life isn't so dangerous.
> just as depression is a maladaptive persistent overlearned estimate of the world as threatening, unrewarding, and pointless
That we can look at the lives of millions of people in America in 2021 and call their abject misery 'maladaptive' or 'overlearned' is ghastly. I know I'm supposed to offer more in an HN comment, and I'm not trying to call you names. But if I told that to someone in psychotherapy I'd deserve more than just losing my license.
I don't doubt that looking inside people's biology for clues about what's going on when they suffer these kinds of anguish is interesting or potentially helpful, but I can say two things quite confidently on the matter:
1) After 60 years of dominance, the biological-psychiatric project's track record is dismal and has failed to move any population-level needle on the levels of suffering it tries to study and ameliorate
2) Focusing on biology at the expense of questions about "context" or "environment" or "maybe this depressive is reacting exactly appropriately to their horrible existence" is a staggering waste of brainpower and money and time, and it leaves me at a loss for words. Outside of the social strata represented on HN (and probably within it to some degree) the world is "threatening, unrewarding, and pointless" for vast numbers of human beings, and I'd challenge anyone to sit in front of such a person and tell them to their face that it isn't. If there exist "regular experiences which should falsify those beliefs and lead to learning (but doesn't)", I got news for you: those experiences aren't prompting "learning" because they're not enough. This is like telling hungry people to feel more full after feeding them a saltine cracker.
You can't "cure" depression by pumping people full of prescribed psychotropics - the major mental health effort of the past half century - any more than you can do so by pumping them full of vodka. Address poverty, address violence, address a litany of social ills - and I mean really address them - and you'll see what happens to depression.
That I never understood. US is an extremely rich country. Of course there are poor people, but there are lots of not poor people. In my country we don't have money if one does not work. He'll die from starvation. Well, probably some friends will help him not to die, but you got the idea. If you don't have a house, you don't really have any recourse, you have to live in basements under buildings and you'll eventually die as usual temperatures at winter are around -20 Celsius degrees. You can be beaten to death by some crazy person (well, at least you can't be shot, as guns are prohibited). People drive like crazy, so you can be killed by a car accident. If something unjust happens, you can't really rely on police, it might be corrupt and it happens in everyday life. If you need something from government, you might need to bribe the officials and I'm talking about ordinary person needs, not some enterprise stuff. I don't think that there are many grown-up people who did not bribe officials in their life.
Life is miserable here. And people don't run to hang themselves. They are trying to find happy moments and relish in those moments.
It's absolutely normal for a man to live in misery. Our humanity lived in misery for thousands of years and billions of people are living in misery right now. Our brain should be adapted to it by now.
Agreed, but depression in modern wealthy countries could potentially be less due to objectively comparable misery and pain on average and more due to a combined physiological, neurological, and psychological stagnation effect. It's very common to feel a profound dearth of meaning, purpose, higher goals, terminal goals, interpersonal connection, physical ambulation, sunlight, fresh air, or any idea of anything they should be doing but mindlessly scrolling some stream of text and projected imagery like a drug addict taking their 9th hit of the day while not actually feeling anything from it.
I know it's a tired trope to throw around at this point, but it just shows there are countless variables that factor into one's mood and disposition and sense of motivation even before you dig down to the neurological and biological levels. Leave a healthy, well-fed, "rich" rat or chimpanzee alone in a low-stimuli, not very large room for long enough and they'll often become depressed. Embed someone born in a wealthy country into an indigenous group and they often report feeling more alive and not depressed. Do the reverse and you often get the reverse.
And of course many people feel all these things not due to any sort of stagnation they have any personal control over but due to neurological systems which may be difficult to alter. Or both.
I think the original reply post may have partly misinterpreted what the commenter was trying to say. The hypothesis being discussed is something like that even if you reintroduce the rat back to its previous happy environment, their potential predictive processing dysfunction may cause them to not be able to do anything but treat all stimuli the same: not worth caring about or trying to derive enjoyment from.
> Life is miserable here. And people don't run to hang themselves. They are trying to find happy moments and relish in those moments.
What country is this? Your domain seems to indicate Kazakhstan, but they have one of the highest suicide rates in the world, so I suppose that's not it?
Depression is maladaptive. My environment was shitty and that’s part of how I developed depression, but depression didn’t make surviving that easier. It made it far, far worse. There were also good things in my life; but I couldn’t experience pleasure from those good things because of the depression. Even after I got out of that environment I couldn’t enjoy life.
Meds were a godsend. They allowed me to escape from depression long enough to deal with depression. Could I have done so even while still in a shitty environment? Probably, because the key ingredients for me were: meds, learning to identify good things, and not burying my feelings.
That’s not to say we shouldn’t be solving all these problems, but in the meantime let’s not tear down things that work for people because they don’t directly address a more intractable root cause.
There's a quotation from Abraham Maslow that I really like, which I think is similar to your point.
> I am deliberately rejecting our present easy distinction between sickness and health, at least as far as surface symptoms are concerned. Does sickness mean having symptoms? I maintain now that sickness might consist of not having symptoms when you should. Does health mean being symptom-free? I deny it. Which of the Nazis at Auschwitz or Dachau were healthy? Those with a stricken conscience or those with a nice, clear, happy conscience? Was it possible for a profoundly human person not to feel conflict, suffering, depression, rage, etc.? In a word if you tell me you have a personality problem, I am not certain until I know you better whether to say "Good" or "I'm sorry". It depends on the reasons. And these, it seems, may be bad reasons, or they may be good reasons.
I’ve used ADs as a “band-aid”: something for three months or so at a time when necessary, to stop me a) killing myself [though thankfully it’s been a long long time since I had those intrusive thoughts] and b) giving me just enough “normality” to go and make whatever changes I can that pushed me in the direction of an episode or made an extant one worse, and lastly c) give me enough motivation that I can work properly with my psychologist/psychotherapist.
I’ve had very good “reasons” for my crippling depression, but usually I can’t see the forest for the trees to work out what it is while deep inside the episode.
Luckily for me, citalopram works with basically no side effects when taken for a couple of months. I’m glad that’s the case, but I’ve seen so many of my friends get no relief from ADs at all, along with so many (sometimes life altering!) side effects, that it makes me sad at times.
Lastly, buprenorphine is remarkable for me in terms of its anti depressive effect. Once monthly Buvidal injection not only solves my past issues with drug abuse, but neatly solves my depression. Fascinating stuff.
> just as depression is a maladaptive persistent overlearned estimate of the world as threatening, unrewarding, and pointless, which persists despite regular experiences which should falsify those beliefs and lead to learning (but doesn't), anxiety is persistent overestimation of risks which
people with depression have been shown to have a more accurate perception of reality. it's the rose-colored glasses view which is adaptive.
Is it actually maladaptive or society wide is it normal and adaptive? If everyone was so easily influenced or moved into different states - perhaps then the traits differentiating those who are more conservative or more liberal in their behaviours wouldn't be possible. There are lessons to be learned from suffering, your own and others - and people becoming so imbalanced that they are stuck in suffering is easily arguable as a canary for society and signal for how we treat others.
I thought life sucked and was on anti anxiety medications for year then realized I was simply allergic to half the food I was eating.
Your ancestors and my ancestors stuck around long enough to reproduce and raise their kids without offing themselves from depression, has something changed to make the environment less conducive to being a living human?
Obvious fallacy here: we are all descendants of those humans who survived - at least until having children. Those who offed themselves early are selected out of the genepool.
Note the above is not to suggest that there’s not a number of factors of a modern environment that we’re not properly/perfectly adapted for. But the handwavy “people weren’t depressed and anxious in the old days” is an illusion.
You'd be surprised what people can put up with cheerfully. A relative of mine turned out, around high school or so, to be allergic to wheat (which is in half the stuff you eat). It gave him regular diarrhea. He had grown up with it and simply assumed it was normal. How would he know otherwise? (A version of the 'typical mind fallacy' https://www.lesswrong.com/posts/baTWMegR42PAsH9qJ/generalizi... one might say.)
It's not as if people go around saying, 'good morning! I had my usual poop today, a good #3 on the Bristol stool scale, placing me within 1SD of the human norm! And yourself?' 'Likewise, likewise; good checking in with you and discussing our morning defecation, as is very normal for us human beings, ha ha.'
Start an elimination diet. Chicken and green vegetables are a good starting point.
I did chicken and sweet potatoes for a month. Had a ton of issues go away.
I dont believe that people have anxiety disorders for no reason at all...
e.g. an autistic teenager who got beaten up for being socially clueless or abrasive. Anxiety might be the thing that saved them from being seriously harmed.
A perfect show of how little is know about the effect of those drugs:
>they're also used to treat a spectrum of anxiety disorders like OCD and panic disorder
A massive amount of people treated for depression have panic disorder because of these drugs, so they can treat or induce the same thing in different people.
Without going into too much detail on my own situation, in addition to other meds I'm also on Modafinil. This is mainly to combat fatigue side effects, but modafinil is also a very good (for me at least) anti-depressant. I'm depressed less often on it, and when depressed it keeps me much more functional. There's a decent body of research in its use for this purpose as a second-line anti-depressant, such as: https://pubmed.ncbi.nlm.nih.gov/16035049/
Not all doctors are familiar with its use in this way. When I had to switch doctors after mine retired, I had to educate them in its use so that they would continue prescribing it.
It is also not an automatic approval by insurance companies. However, if denied by your insurance, you can get it at a fairly reasonable price using GoodRX.
If you're still struggling after what you're already one, and have gone through a few other options (and maybe even if you haven't) then I would highly recommend talking to your doctor about this.
Something to keep in mind though is that this will, mostly in the first week, impact your sleeping patterns. Taking it first thing in the morning would be the best time, and perhaps ask your doctor about using an over-the-counter sleep aid such as diphenhydramine during initial usage.
Out of curiosity, do you feel antidepressive qualities from other dopaminergic substances? (Part of modafinil's mechanism of action is thought to be dopaminergic.) Also, do you feel like you might have ADHD?
Just asking this out of curiosity, because I'm also someone who consistently experiences antidepressive effects from modafinil. Though for me it's typically more of a feeling that lasts for about 1 - 4 hours after use rather than a steady, stable mood lifting effect.
I took modafinil for about 6 months while having under treated depression. It only seemed to improve wakefulness like super caffeine minus jitters and anxiety.
Like mainly sleep “aids”, DPH just puts you into a fatigued state that is unlike naturalistic sleep. If insomnia / rumination / etc would otherwise keep one up and the diphenhydramine allows one to fall asleep and get a night of suboptimal sleep as opposed to no sleep, it’s of course worth it, but otherwise stay well away.
Interestingly almost everything that induces sleep harms the actual sleep quality. However I remember reading that GHB appears to improve sleep architecture, although I’ve never tried it personally
In general, DPH seems like a terrible anticholinergic and obsolete antihistamine with limited uses. My ex-stepfather abused it nightly as a "sleep aid," his personality altered, became very depressed, and I think entered a pre-dementia/Alzheimer's state sooner than he would've otherwise.
Probably not a good idea to experiment personally with GHB because it's Class I in the US and associated with date-rape, but it's worth considering in studies and research.
It does seem to be the case that disordered sleep is the keystone of depression; I can also confirm missing one dose of mirtazapine at night feels exactly like an alcohol-induced hangover in the morning. I suspect depression accumulates during sleep.
Interestingly, mirtazapine is a powerful H1 antihistamine that induces sleep at lower doses that are swamped by noradrenergic effects at higher doses. I would guess patients on mirtazapine have fewer incidents of seasonal allergies.
1. Modafinil is the opposite of a sleep aid, so the first paragraph doesn't really apply.
2. Using GHB/Alcohol/Marijuana to help you feel more rested really depends on if the person has a medical condition or not. All of these drugs will suppress REM sleep (so will your typical SSRI), which for the average person may not be a good thing. However, those with narcolepsy have a much higher rate of REM sleep, preventing their body from going into deep sleep and thus (says the hypothesis) they don't get the awakeness/alerting benefits from sleep.
Interestingly, those with depression and PTSD also have increased rates of REM sleep, so there is an interesting question of causality there.
The first paragraph was about diphenhydramine (DPH) as a sleep aid. And I agree with the point. Any time I’ve tried to use it to help me sleep it sets me off on a downward spiral of bad sleep habits.
"Reductions in the amount of REM sleep and increases in REM sleep onset latency are seen after taking antidepressants, both in healthy volunteers and in depressed patients. Antidepressants that increase serotonin function by blocking reuptake or by inhibiting metabolism have the greatest effect on REM sleep. The decrease in amount of REM sleep appears to be greatest early in treatment, and gradually diminishes during long-term treatment, except after monoamine oxidase inhibitors when REM sleep is often absent for many months."[1]
I agree that the two data points are paradoxical, and I'm not sure what to make of it. Personally I have a much larger than average amount of REM sleep (confirmed by professionals when I was tested for narcolepsy/daytime sleepiness), but I do not have vivid dreams and seldom recall dreaming at all, despite talking and moving in my sleep. Nevertheless it's quite interesting.
One hypothesis could be that less time in REM sleep leads to more intense bursts of REM, thus more vivid dreams? Or perhaps I am lacking knowledge and there is more to dreams than REM sleep.
Trazodone actually improves sleep quality when you take it for insomnia. Oddly I looked it up and apparently there is no evidence it objectively improves start time for sleep, but it sure feels like it does.
Melatonin isn't too bad for actual sleep I think, but almost all supplements give you way too much - something like 1/3mg is enough. It does give me really bad dry eyes in the morning for some reason.
Trazodone knocks me out. It also makes me lethargic the following day and less productive. I would only take half the lowest available dose (cut the lowest dose in half with a pill cutter) and it still gave me greatest sleep than anything else I'd ever tried. I still take it for flights and business travel (weird hotels) but otherwise it's too much for me.
For a number of years, Mirtazapine helped me sleep, although it reduced dreaming to nil. Interestingly, the antihistamine sedation effect of it decreases at increased doses.
If you decide to switch up your medications, the strongest combination I ever found was Latuda and Remeron. Remeron also has a fairly light side effect profile for an anti-depressant, though weight gain can be a problem for a lot of people who take it.
