If the last option is true, then the endpoints of this study, and most other studies on antidepressants in general, are entirely missing the forest for the trees.
This seems like the most likely scenario to me. I appreciate the need and desire to have a conclusive, defensible, formally rigorous answer to this question, but also, in some sense the answer very obviously has to end up being “Yes, but both ‘depression’ and ‘antidepressant’ are probably somewhat confused or overloaded categories that none of our available endpoints or diagnostic metrics demultiplex well enough to satisfy anyone or match patients’ lived experiences.”
I’m one patient who has been on bupropion for depression for ~6 years, and I truly cannot imagine a study that would convince me that it “didn’t work” for me, in the ways that actually matter. The effects on my mind kick in sharply, scale smoothly with dose, decay right in sync with half-life in the body, and are clearly noticeable not just internally for my mood but externally in my speech patterns, reaction speeds, ability to notice things in my surroundings, short term memory, and facial expressions.
I’m on both for the past year (vs just sertraline for prev decade). Love the extra energy and reduction in anxiety I’ve experienced from the buproprion.
On at least 5 different occasions I’ve tried weaning myself gradually off of sertraline. Every time I fall back into depression within a month or two. My friends and family then beg me to go back on it ASAP.
“cannot imagine a study that would convince me that it “didn’t work” for me, in the ways that actually matter. The effects on my mind kick in sharply, scale smoothly with dose, decay right in sync with half-life in the body, and are clearly noticeable not just internally for my mood but externally in my speech patterns, reaction speeds, ability to notice things in my surroundings, short term memory, and facial expressions.”
The drug actually working would mean that your life is better after 6 years of taking the drug compared to the counterfactual where you took a placebo.
The observations you describe are explained by you simply having a chemical dependency on a drug that you have been on for 6 years.
I suppose, but 1) there has been no build-up/tolerance, the effects from a given dose have been stable, 2) there are no cravings for it or anything like that, 3) I’ve never had anything like withdrawal symptoms when I’ve missed a dose, other than a reversion to how I was for the years before I started taking it at all. What would a chemical dependency actually mean in this context?
My depression symptoms centered on dulled emotions and senses, and slowed thinking. This came on gradually over about 10 years, followed by about 2 years of therapy with little to no improvement before starting meds. When I said that for me the effects kicked in sharply, I meant that on day three after starting the drug, all of a sudden while I was in the shower my vision got sharper, colors got brighter, I could feel water and heat on my skin more intensely, and I regained my sense of smell after having been nearly anosmic for years. I immediately tested that by smelling a jar of peanut butter and started to cry, after not crying over anything for close to 10 years. Food tasted better, and my family immediately noticed I was cooking better because I judged seasonings more accurately. I started unconsciously humming and singing to myself. My gait got bouncier like it had been once upon a time before my depression all started. There was about a week of random euphoria after which things stayed stable. Over the first few months, if I missed my dose by even a few hours, or if I was otherwise physically or emotionally drained, I would suddenly become like a zombie again. My face went slack, my eyes glazed over, my voice lost any kind of affect, my reactions slowed down dramatically. By suddenly, I mean it would happen mid-conversation, between sentences. These events decreased to 1-2x/month on an increased dose, and went away entirely a few years later upon increasing my dose again. I have also, thankfully, had no noticeable side effects. Obviously a lot of other things have happened in 6 years, many quite relevant, that I don’t feel like getting into here, but those are mostly related to me regaining the ability to build capacity to actually live my life.
Yes, it is theoretically possible a placebo could have done that. I don’t think it is plausible, or that any study (maybe I should say, any study that did not include me? Even then I’m not sure what a study on me-now could entail that would be convincing).
I do realize my experiences on these meds are atypical, my depression presented somewhat unusually, and SNRIs are not SSRIs. I got extremely lucky. But that was kind of my point in my original comment.
This seems like the most likely scenario to me. I appreciate the need and desire to have a conclusive, defensible, formally rigorous answer to this question, but also, in some sense the answer very obviously has to end up being “Yes, but both ‘depression’ and ‘antidepressant’ are probably somewhat confused or overloaded categories that none of our available endpoints or diagnostic metrics demultiplex well enough to satisfy anyone or match patients’ lived experiences.”
I’m one patient who has been on bupropion for depression for ~6 years, and I truly cannot imagine a study that would convince me that it “didn’t work” for me, in the ways that actually matter. The effects on my mind kick in sharply, scale smoothly with dose, decay right in sync with half-life in the body, and are clearly noticeable not just internally for my mood but externally in my speech patterns, reaction speeds, ability to notice things in my surroundings, short term memory, and facial expressions.
Do you have any opinion on bupropion vs SSRIs/SNRIs?
I’m on both for the past year (vs just sertraline for prev decade). Love the extra energy and reduction in anxiety I’ve experienced from the buproprion.
On at least 5 different occasions I’ve tried weaning myself gradually off of sertraline. Every time I fall back into depression within a month or two. My friends and family then beg me to go back on it ASAP.
I don’t have nearly enough information to have an opinion on that.
“cannot imagine a study that would convince me that it “didn’t work” for me, in the ways that actually matter. The effects on my mind kick in sharply, scale smoothly with dose, decay right in sync with half-life in the body, and are clearly noticeable not just internally for my mood but externally in my speech patterns, reaction speeds, ability to notice things in my surroundings, short term memory, and facial expressions.”
The drug actually working would mean that your life is better after 6 years of taking the drug compared to the counterfactual where you took a placebo.
The observations you describe are explained by you simply having a chemical dependency on a drug that you have been on for 6 years.
I suppose, but 1) there has been no build-up/tolerance, the effects from a given dose have been stable, 2) there are no cravings for it or anything like that, 3) I’ve never had anything like withdrawal symptoms when I’ve missed a dose, other than a reversion to how I was for the years before I started taking it at all. What would a chemical dependency actually mean in this context?
My depression symptoms centered on dulled emotions and senses, and slowed thinking. This came on gradually over about 10 years, followed by about 2 years of therapy with little to no improvement before starting meds. When I said that for me the effects kicked in sharply, I meant that on day three after starting the drug, all of a sudden while I was in the shower my vision got sharper, colors got brighter, I could feel water and heat on my skin more intensely, and I regained my sense of smell after having been nearly anosmic for years. I immediately tested that by smelling a jar of peanut butter and started to cry, after not crying over anything for close to 10 years. Food tasted better, and my family immediately noticed I was cooking better because I judged seasonings more accurately. I started unconsciously humming and singing to myself. My gait got bouncier like it had been once upon a time before my depression all started. There was about a week of random euphoria after which things stayed stable. Over the first few months, if I missed my dose by even a few hours, or if I was otherwise physically or emotionally drained, I would suddenly become like a zombie again. My face went slack, my eyes glazed over, my voice lost any kind of affect, my reactions slowed down dramatically. By suddenly, I mean it would happen mid-conversation, between sentences. These events decreased to 1-2x/month on an increased dose, and went away entirely a few years later upon increasing my dose again. I have also, thankfully, had no noticeable side effects. Obviously a lot of other things have happened in 6 years, many quite relevant, that I don’t feel like getting into here, but those are mostly related to me regaining the ability to build capacity to actually live my life.
Yes, it is theoretically possible a placebo could have done that. I don’t think it is plausible, or that any study (maybe I should say, any study that did not include me? Even then I’m not sure what a study on me-now could entail that would be convincing).
I do realize my experiences on these meds are atypical, my depression presented somewhat unusually, and SNRIs are not SSRIs. I got extremely lucky. But that was kind of my point in my original comment.