OK, no evidence the authors took into account the mixed-effect model used to test for differences between groups over time in their power calculations, but can't you/someone run the more complex and appropriate power calculations to check how far from reasonable the sample size actually is considering the statistical model used?
How do we know that ECT's benefits aren't from anesthesia?
ECT seemed to get a lot better when they started anesthetizing people for the procedure, which is exactly what you'd expect if anesthesia was the active thing here.
Good point, ECT does beat ‘sham’ ECT (both given under general anaesthesia), though there is also a big placebo response - https://pubmed.ncbi.nlm.nih.gov/18580816/
Fantastic article Thomas, we have also been debating this one in our circles and your piece sums up a lot of our thoughts but you have made them explicit. Thank you!
The study amply proves the power of expectancy. If people thought they got ketamine (but actually received placebo) they improved 42%. But, if they thought they got placebo, (but actually got ketamine), they improved 25%. There was no difference between placebo and ketamine efficacy in the people who got placebo. (Graph B). So, people's beliefs had a profound effect on their improvement, and the power of belief over-rode the impact of the chemical that was put in their bodies.
Yes. "I feel better, therefore I got the special chemical." However, it still shows how belief over-rode the impact of the chemical. Interestingly, the people who guessed neither, and received placebo, did better than those who guessed neither and received ketamine. Does this mean placebo is a better 'anti-depressant' than ketamine, when the person has no belief about what they received? Is ketamine actually a pro-depressant, when belief is factored out of the equation? This needs extensive replication, of course.
Even if the effect size of ketamine is large, it’s still worth working out how it exerts an antidepressant action, don’t you think? I assume that was the authors’ motivation and seems like they used robust methodology, apart from the underpowered sample size.
I’m not familiar with GABAergic drugs blocking the antidepressant effect - please do share studies if available!
OK, no evidence the authors took into account the mixed-effect model used to test for differences between groups over time in their power calculations, but can't you/someone run the more complex and appropriate power calculations to check how far from reasonable the sample size actually is considering the statistical model used?
Good point!
I’m sure someone could, but think it involves specifying more parameters and running simulations - not something I can do easily/quickly.
One issue worth noting:
ECT is ALSO done under anesthesia.
How do we know that ECT's benefits aren't from anesthesia?
ECT seemed to get a lot better when they started anesthetizing people for the procedure, which is exactly what you'd expect if anesthesia was the active thing here.
Good point, ECT does beat ‘sham’ ECT (both given under general anaesthesia), though there is also a big placebo response - https://pubmed.ncbi.nlm.nih.gov/18580816/
Nice discussion!
Fantastic article Thomas, we have also been debating this one in our circles and your piece sums up a lot of our thoughts but you have made them explicit. Thank you!
The study amply proves the power of expectancy. If people thought they got ketamine (but actually received placebo) they improved 42%. But, if they thought they got placebo, (but actually got ketamine), they improved 25%. There was no difference between placebo and ketamine efficacy in the people who got placebo. (Graph B). So, people's beliefs had a profound effect on their improvement, and the power of belief over-rode the impact of the chemical that was put in their bodies.
It could also be the reverse, right? Participant felt better, therefore guessed they were in the active treatment arm.
Yes. "I feel better, therefore I got the special chemical." However, it still shows how belief over-rode the impact of the chemical. Interestingly, the people who guessed neither, and received placebo, did better than those who guessed neither and received ketamine. Does this mean placebo is a better 'anti-depressant' than ketamine, when the person has no belief about what they received? Is ketamine actually a pro-depressant, when belief is factored out of the equation? This needs extensive replication, of course.
Thanks for reading and commenting!
Even if the effect size of ketamine is large, it’s still worth working out how it exerts an antidepressant action, don’t you think? I assume that was the authors’ motivation and seems like they used robust methodology, apart from the underpowered sample size.
I’m not familiar with GABAergic drugs blocking the antidepressant effect - please do share studies if available!