I overestimated the efficacy of my anti-depressant and now believe that it was mainly placebo.
What evidence was it that led you to this conclusion?
DISCLAIMER: I’m curious about this because I had the opposite experience; right now I’m just curious but this is a reminder to myself not to get argumentative about the fact that people have different subjective experiences and chemical reactions to things.
My average happiness and productivity declined over the last two months from around 8 to 5 on a scale of 10 (I measure those things every day through introspection and write it down). Previously the average was almost never below 6-7 in any given week. I also didn’t change my diet, exercise regimen, etc. and there were no difficult experiences I had to handle. Heck, I even doubled the dose of my anti-depressant—with no effect.
I still think that this anti-depressant has some effect only that it isn’t nearly as great as I imagined and that a changing worldview or belief-system can have a far higher impact.
In fact that makes it look like the medication was having a negative effect. That’s a little unsettling, although I guess antidepressants are highly variable in how they work with different people?
That seems like a really huge change though, especially considering you say you didn’t change your diet/exercise/stress level/etc. Rather than saying “mainly placebo” I would have said “had a significant negative effect on my mood” with that data!
Sorry, I probably haven’t expressed myself clearly. I still believe (~60%) bupropion has some, small positive effects for me and that my mood would be even worse if I didn’t take it. Here’s a more detailed story:
I’ve taken this anti-depressant for quite some time, for around 8-9 months. At first I noticed a definite increase in mood and productivity (or so it seemed). I also tried to eliminate confounding effects and so stopped to take it for a week or so—and my happiness declined significantly! However, I was still concerned about placebo-effects so I made some “blind” tests (i.e. took capsules either containing bupropion or not, but without my knowledge which containing which). The next day I guessed if I had taken a mere placebo or not, and I was right about 85% of the time (n was only 7, but still...) ’cause my mood was worse when I only took a placebo.
I also took two pills on some days and it felt like I had much more energy and was way happier. So Bupropion seemed like a true panacea to me.
Unfortunately, my mood started to decline around two months ago therefore I went to my psychiatrist and he doubled my dose. This was around a month ago but didn’t really help.
Are you sure you’re not just building up a resistance/dependence? I tried anti-depressants but they eventually stopped really doing anything, I believe somewhere between 6 months to a year after starting them. I think resistance is pretty common.
Also, most anti-depressants take a while to kick in, so I suspect any day-to-day dosage changes are going to be more about withdrawal symptoms than anything else.
My first tought was poop-out, but that doesn’t happen with bupropion, only with SSRIs, right? You shouldn’t stop and start again the same antidepressant (and, to a lesser extent, antidepressants in the same family, or that target the same neurotransmitter), this will build resistance.
With SSRIs, poop-out tends to be resistance at any dose, not tolerance. I’ve had poop-out from placebo (WTF?) and larger doses don’t work there either.
A week is a bit short for a test, but bupropion is unusually fast so that’s a decent test. Why are you trying to correct for the placebo effect at all? Improvement from placebo is real and desirable, and there’s probably a feedback loop between placebo- and drug-related improvement that helps even further.
How many antidepressants have you tried? You might just be on the wrong one. How large is your dose? If you’re at 300mg/day trying going up to 450 is possible, though I’m not very optimistic. Does your depression have a seasonal pattern at all, and if so could the weather be responsible for the mood drop? You seem oddly trusting in self-experiment and advice from strangers; why are you seeking recommendations besides your psychiatrist’s? Cost?
Yeah, poop-out could be the culprit. However, this would also suggest that the positive effects were mainly placebo because, as you mention in your second comment, the most reasonable account of poop-out is that the placebo effect wears off.
I was correcting for placebo cause I wanted to try lots of different antidepressants and other drugs and see which “really” work. But I guess you’re right; the placebo effect is pretty amazing and one shouldn’t risk eliminating it by over-zealous self-experimentation.
I haven’t tried any other antidepressants since I fear the side-effects of SSRIs/SNRIs and MAOIs seem like too much of a hassle (although selegiline sounds pretty good). But I’m rationalizing. I definitely should try some new stuff.
In the past I was fairly happy during the summer or at least happier than in the winter so the weather has probably nothing to do with my current low. I also didn’t change the brand of my antidepressant.
You seem oddly trusting in self-experiment and advice from strangers; why are you seeking recommendations besides your psychiatrist’s? Cost?
Nah, it has nothing to do with money. My psychiatrist costs me basically nothing.
So, why do I prefer self-experimentation and seek out advice from strangers?
Well, I don’t think very highly of my psychiatrist or doctors in general to begin with (not especially eager for a long discussion about the reasons).
Furthermore, I learned a huge deal about my body through self-experimentation that I almost certainly couldn’t have learned otherwise.
Do you know more than I do about models of poop-out? That thing is annoying and I want to know about it.
You can get some interactions from trying too many antidepressants. For example, having been on SSRIs may make you build a tolerance to other SSRIs. This appears to be a big reason why psychiatrists like to stop early, along with side effects and convenience. Still there is some value in exploration.
For comparing antidepressants you probably want open-label tests, and comparing meds directly against each other rather than with placebo.
SSRIs are pretty damn tame; which side effects are you afraid of? Sexual side effects can be a major pain but they’ll go away when you go off the meds. Vanilla-ice-cream side effects (nausea, headache, somnolence, insomnia, diarrhea, constipation, dry mouth, sweating, weight gain) are common to the majority of meds, and they all go away except the weight gain. So you should at least try them unless you have some very unusual reason. If you’re worried about weight gain, try fluoxetine (which is the usual first resort, and combines well with bupropion) or sertraline.
MAOIs are freaky shit. I hear they’re very effective, but they have so many side effects and contraindications that they’re often not worth it.
TCAs have a reputation for being effective. Apparently the reason they fell out of style is that they don’t tolerate small lapses (unlike e.g. fluoxetine with its absurdly long half-life) and that a couple’s week worth is a fatal dose, which is very bad for suicidal patients.
“Throw lots of things at depression” is an area of expertise of psychiatrists, so consider trusting them more.
[…]argue that side effects enhance the placebo effects of antidepressants by confirming to patients that they are taking the active medication and thereby increasing their expectation of improvement.
There’s some evidence that poop-out can affect any antidepressant, perhaps any med. The dominant theory is “When a med doesn’t work, it can work at first due to placebo effect, but then be conditioned out of working”.
Have you been taking the exact same form of bupropion? Different brands of the same med can work differently for some people. Also, if you’re taking sustained/extended-release pills, this will have affected your experiments.
I assume you’re telling all of this to your psychiatrist and following their advice. In addition, speaking with a psychologist about your concerns. Ask yourself if you might have bipolar disorder or seasonal depression rather than just depression. Anti-depressants don’t work great in a lot of those cases, and in the case of bipolar disorder, it makes your mood swings worse. Also try multiple drugs, they don’t all target the same mechanisms.
As for non-professional/medication steps, you should probably follow some of lukeprogs advice on happiness (find it from the sequences page). He covers the literature on what has empirically been shown to make people happier. It’s not intuitive.
it isn’t nearly as great as I imagined and that a changing worldview or belief-system can have a far higher impact.
This illustrates how your intuition about what makes you happy is wrong. It’s not having a certain model of reality or willing your mind to do something from the inside, it’s about finicky lizard-brain mood machinery and daily doses of beating it into happiness by feeding it tiny doses of positive external experiences.
Meta-Note: This is great! We should make this into a monthly or bi-monthly recurring thread like “Rationality Quotes” or “What are you working on?”.
Back to the topic: I overestimated the efficacy of my anti-depressant and now believe that it was mainly placebo.
What evidence was it that led you to this conclusion?
DISCLAIMER: I’m curious about this because I had the opposite experience; right now I’m just curious but this is a reminder to myself not to get argumentative about the fact that people have different subjective experiences and chemical reactions to things.
My average happiness and productivity declined over the last two months from around 8 to 5 on a scale of 10 (I measure those things every day through introspection and write it down). Previously the average was almost never below 6-7 in any given week. I also didn’t change my diet, exercise regimen, etc. and there were no difficult experiences I had to handle. Heck, I even doubled the dose of my anti-depressant—with no effect.
I still think that this anti-depressant has some effect only that it isn’t nearly as great as I imagined and that a changing worldview or belief-system can have a far higher impact.
That’s a pretty intense effect!
In fact that makes it look like the medication was having a negative effect. That’s a little unsettling, although I guess antidepressants are highly variable in how they work with different people?
That seems like a really huge change though, especially considering you say you didn’t change your diet/exercise/stress level/etc. Rather than saying “mainly placebo” I would have said “had a significant negative effect on my mood” with that data!
Sorry, I probably haven’t expressed myself clearly. I still believe (~60%) bupropion has some, small positive effects for me and that my mood would be even worse if I didn’t take it. Here’s a more detailed story:
I’ve taken this anti-depressant for quite some time, for around 8-9 months. At first I noticed a definite increase in mood and productivity (or so it seemed). I also tried to eliminate confounding effects and so stopped to take it for a week or so—and my happiness declined significantly! However, I was still concerned about placebo-effects so I made some “blind” tests (i.e. took capsules either containing bupropion or not, but without my knowledge which containing which). The next day I guessed if I had taken a mere placebo or not, and I was right about 85% of the time (n was only 7, but still...) ’cause my mood was worse when I only took a placebo. I also took two pills on some days and it felt like I had much more energy and was way happier. So Bupropion seemed like a true panacea to me.
Unfortunately, my mood started to decline around two months ago therefore I went to my psychiatrist and he doubled my dose. This was around a month ago but didn’t really help.
I hope this clears things up! ;)
Are you sure you’re not just building up a resistance/dependence? I tried anti-depressants but they eventually stopped really doing anything, I believe somewhere between 6 months to a year after starting them. I think resistance is pretty common.
Also, most anti-depressants take a while to kick in, so I suspect any day-to-day dosage changes are going to be more about withdrawal symptoms than anything else.
Yeah, increasing tolerance is probably one of the main factors. But I thought I could counter that with the doubling of the dosage.
Yup, I guess it’s likely that the negative day-to-day effects were mostly withdrawal symptoms.
What do you recommend? Just not taking antidepressants for a while?
My first tought was poop-out, but that doesn’t happen with bupropion, only with SSRIs, right? You shouldn’t stop and start again the same antidepressant (and, to a lesser extent, antidepressants in the same family, or that target the same neurotransmitter), this will build resistance.
With SSRIs, poop-out tends to be resistance at any dose, not tolerance. I’ve had poop-out from placebo (WTF?) and larger doses don’t work there either.
A week is a bit short for a test, but bupropion is unusually fast so that’s a decent test. Why are you trying to correct for the placebo effect at all? Improvement from placebo is real and desirable, and there’s probably a feedback loop between placebo- and drug-related improvement that helps even further.
How many antidepressants have you tried? You might just be on the wrong one. How large is your dose? If you’re at 300mg/day trying going up to 450 is possible, though I’m not very optimistic. Does your depression have a seasonal pattern at all, and if so could the weather be responsible for the mood drop? You seem oddly trusting in self-experiment and advice from strangers; why are you seeking recommendations besides your psychiatrist’s? Cost?
Disclaimer: I’m a nutjob who reads Crazy Meds and Neuroskeptic, not a psychiatrist.
Yeah, poop-out could be the culprit. However, this would also suggest that the positive effects were mainly placebo because, as you mention in your second comment, the most reasonable account of poop-out is that the placebo effect wears off.
I was correcting for placebo cause I wanted to try lots of different antidepressants and other drugs and see which “really” work. But I guess you’re right; the placebo effect is pretty amazing and one shouldn’t risk eliminating it by over-zealous self-experimentation.
I haven’t tried any other antidepressants since I fear the side-effects of SSRIs/SNRIs and MAOIs seem like too much of a hassle (although selegiline sounds pretty good). But I’m rationalizing. I definitely should try some new stuff.
In the past I was fairly happy during the summer or at least happier than in the winter so the weather has probably nothing to do with my current low. I also didn’t change the brand of my antidepressant.
Nah, it has nothing to do with money. My psychiatrist costs me basically nothing.
So, why do I prefer self-experimentation and seek out advice from strangers? Well, I don’t think very highly of my psychiatrist or doctors in general to begin with (not especially eager for a long discussion about the reasons).
Furthermore, I learned a huge deal about my body through self-experimentation that I almost certainly couldn’t have learned otherwise.
Do you know more than I do about models of poop-out? That thing is annoying and I want to know about it.
You can get some interactions from trying too many antidepressants. For example, having been on SSRIs may make you build a tolerance to other SSRIs. This appears to be a big reason why psychiatrists like to stop early, along with side effects and convenience. Still there is some value in exploration.
For comparing antidepressants you probably want open-label tests, and comparing meds directly against each other rather than with placebo.
SSRIs are pretty damn tame; which side effects are you afraid of? Sexual side effects can be a major pain but they’ll go away when you go off the meds. Vanilla-ice-cream side effects (nausea, headache, somnolence, insomnia, diarrhea, constipation, dry mouth, sweating, weight gain) are common to the majority of meds, and they all go away except the weight gain. So you should at least try them unless you have some very unusual reason. If you’re worried about weight gain, try fluoxetine (which is the usual first resort, and combines well with bupropion) or sertraline.
MAOIs are freaky shit. I hear they’re very effective, but they have so many side effects and contraindications that they’re often not worth it.
TCAs have a reputation for being effective. Apparently the reason they fell out of style is that they don’t tolerate small lapses (unlike e.g. fluoxetine with its absurdly long half-life) and that a couple’s week worth is a fatal dose, which is very bad for suicidal patients.
“Throw lots of things at depression” is an area of expertise of psychiatrists, so consider trusting them more.
There has been talk about side effects actually enhance the placebo effect.
From Efficacy and Effectiveness of Antidepressants: Current Status of Research:
More ideas:
There’s some evidence that poop-out can affect any antidepressant, perhaps any med. The dominant theory is “When a med doesn’t work, it can work at first due to placebo effect, but then be conditioned out of working”.
Have you been taking the exact same form of bupropion? Different brands of the same med can work differently for some people. Also, if you’re taking sustained/extended-release pills, this will have affected your experiments.
I was on an SSRI so I’m not sure any of my experience is actually relevant to bupropion.
If your depression has an obvious cause, fix that instead. I was depressed because of grad school, and I got better when I graduated.
Yes, it does, thank you!
I assume you’re telling all of this to your psychiatrist and following their advice. In addition, speaking with a psychologist about your concerns. Ask yourself if you might have bipolar disorder or seasonal depression rather than just depression. Anti-depressants don’t work great in a lot of those cases, and in the case of bipolar disorder, it makes your mood swings worse. Also try multiple drugs, they don’t all target the same mechanisms.
As for non-professional/medication steps, you should probably follow some of lukeprogs advice on happiness (find it from the sequences page). He covers the literature on what has empirically been shown to make people happier. It’s not intuitive.
This illustrates how your intuition about what makes you happy is wrong. It’s not having a certain model of reality or willing your mind to do something from the inside, it’s about finicky lizard-brain mood machinery and daily doses of beating it into happiness by feeding it tiny doses of positive external experiences.