What do you think of patients cycling through antidepressants until they find one that works for them? I've heard of people doing that, but after reading about how ambiguous it is whether an antidepressant is working, I don't see how it's possible. That is, even if there is one random antidepressant per patient that actually works, I don't see that you could find it by trial and error.
Well... maybe you could if the effect size for that patient's own antidepressant is much larger than the typical effect size we see in the trials, which I guess is what you'd expect if every patient has their own antidepressant and the trials are averaging responders and non-responders.
Like you said though, there are so many things that get in the way of knowing whether or not they've found the "right one" when their symptoms improve, or if something else is going on. I think spontaneous remission is the biggest factor here. A good trial of an antidepressant for most people is going to take, at *minimum*, 2-3 months to allow for observation of efficacy and dose adjustments. Do that for 3 antidepressants and enough time has passed that you would expect about 40% of individuals trying this strategy to have experienced spontaneous remission already.!
One point that came to me, it seems the medication choice for psychosis feels more consequential, a 0.1 difference in SMD feels greater in the average psychotic patient than the average depressed one.
My perception of my institution's threshold is that it's a fairly high bar. Usually not eating/drinking or severe psychomotor retardation to the point that they're nonfunctional.
My threshold is much lower. To me, ECT seems like a very safe and very effective method of alleviating depression that we consider it far too late in the course of treatment. I've often been a bit perplexed why we're so willing to let depressed patients suffer for longer than we need to. That said, I'm also the sort of weirdo who thinks that we should be reaching for the MAOIs relatively quickly (like maybe after 1-2 failed SSRI/SNRIs +/- a failed TCA) though.
Edit after realizing I didn't actually answer the question: I would consider ECT in any patient with severe depressive symptoms regardless of medication trials, and in moderate cases with multiple failed treatments and/or a long duration of current episode.
I basically agree. I have a higher bar recommending it for depression in younger people given potential cognitive side effects, unless it's very severe, especially bipolar depression, or multiple failed meds and life is truly miserable. I also prefer unilateral when possible to minimize the side effects.
I agree MAOIs are underused, but there's also an availability problem. I was going to prescribe a guy phenelzine recently but there just wasn't any in stock anywhere...
I'd be surprised if in 10-15 years SSRIs are still being prescribed at the rates they are today. But that's just a gut feeling, could very well be wrong.
Placebo response is much higher for the medications we treat with ssri's than the ones we treat with anti-dopaminergics (although soon we will have to add antimuscarinic (KarXT)). This will make it harder to have higher efficacy because of math!
Thanks Tom, love reading your stuff too! I have a draft about lithium, though the draft is empty. I look at it occasionally and then remember that I have less complicated things to write about :D
What do you think of patients cycling through antidepressants until they find one that works for them? I've heard of people doing that, but after reading about how ambiguous it is whether an antidepressant is working, I don't see how it's possible. That is, even if there is one random antidepressant per patient that actually works, I don't see that you could find it by trial and error.
Well... maybe you could if the effect size for that patient's own antidepressant is much larger than the typical effect size we see in the trials, which I guess is what you'd expect if every patient has their own antidepressant and the trials are averaging responders and non-responders.
I think this is what many patients end up doing.
Like you said though, there are so many things that get in the way of knowing whether or not they've found the "right one" when their symptoms improve, or if something else is going on. I think spontaneous remission is the biggest factor here. A good trial of an antidepressant for most people is going to take, at *minimum*, 2-3 months to allow for observation of efficacy and dose adjustments. Do that for 3 antidepressants and enough time has passed that you would expect about 40% of individuals trying this strategy to have experienced spontaneous remission already.!
Third time's the charm
One point that came to me, it seems the medication choice for psychosis feels more consequential, a 0.1 difference in SMD feels greater in the average psychotic patient than the average depressed one.
What's your (or your institution's) threshold for recommending ECT for depression?
My perception of my institution's threshold is that it's a fairly high bar. Usually not eating/drinking or severe psychomotor retardation to the point that they're nonfunctional.
My threshold is much lower. To me, ECT seems like a very safe and very effective method of alleviating depression that we consider it far too late in the course of treatment. I've often been a bit perplexed why we're so willing to let depressed patients suffer for longer than we need to. That said, I'm also the sort of weirdo who thinks that we should be reaching for the MAOIs relatively quickly (like maybe after 1-2 failed SSRI/SNRIs +/- a failed TCA) though.
Edit after realizing I didn't actually answer the question: I would consider ECT in any patient with severe depressive symptoms regardless of medication trials, and in moderate cases with multiple failed treatments and/or a long duration of current episode.
I basically agree. I have a higher bar recommending it for depression in younger people given potential cognitive side effects, unless it's very severe, especially bipolar depression, or multiple failed meds and life is truly miserable. I also prefer unilateral when possible to minimize the side effects.
I agree MAOIs are underused, but there's also an availability problem. I was going to prescribe a guy phenelzine recently but there just wasn't any in stock anywhere...
I'd be surprised if in 10-15 years SSRIs are still being prescribed at the rates they are today. But that's just a gut feeling, could very well be wrong.
This is fantastic Dr. Wendell.
Another pertinent point of consideration, hot off press:
https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2818945?utm_campaign=articlePDF&utm_medium=articlePDFlink&utm_source=articlePDF&utm_content=jamapsychiatry.2024.0994
Placebo response is much higher for the medications we treat with ssri's than the ones we treat with anti-dopaminergics (although soon we will have to add antimuscarinic (KarXT)). This will make it harder to have higher efficacy because of math!
I am a staunch opponent of math for this reason and many others.
Great write up as always - looking forward to the edition on bipolar / lithium 😉
Thanks Tom, love reading your stuff too! I have a draft about lithium, though the draft is empty. I look at it occasionally and then remember that I have less complicated things to write about :D