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MixedNuts comments on Have you changed your mind lately? On what? - Less Wrong Discussion
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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.
And finally, "mere strangers" - like e.g. gwern or wedrifid - offered advice that improved my life immensely (I definitely have to reciprocate here...) often consisting of methods that are controversial or even downright illegal, thus unlikely to be recommended by the average doctor.
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.