4 ms·

Unfortunately, without access to the full article, I can't say for sure what the authors argue, but another possible explanation for the long delay between trea

by KingMob 12y ago

Unfortunately, without access to the full article, I can't say for sure what the authors argue, but another possible explanation for the long delay between treatment onset and the reduction of depression is that SSRIs act as an active placebo. If so, SSRIs are "active" because they do change something in the brain (unlike a corn starch placebo), but a placebo because the thing changing (serotonin levels) is unrelated to depression. However, since we know something is changing, we believe we'll get better... and thus, we do. (Think of an active placebo like menthol in dandruff shampoo. Menthol makes the scalp tingle and convinces us it's working, but does nothing for the scalp itself.) Regardless, there's a lot of gaps and unexplained weirdness in how antidepressants work, so there's still a lot of work to be done.

benbreen 12y ago
The active placebo idea strikes me as a plausible one here, and came up in a 2011 article by a former editor of the New England Journal of Medicine which I found pretty thought-provoking: http://www.nybooks.com/articles/archives/2011/jun/23/epidemic-mental-illness-why/ http://www.nybooks.com/articles/archives/2011/jun/23/epidemi... Here's what I thought was the key takeaway from the piece: "Altogether, there were forty-two trials of the six drugs. Most of them were negative. Overall, placebos were 82 percent as effective as the drugs, as measured by the Hamilton Depression Scale (HAM-D), a widely used score of symptoms of depression. The average difference between drug and placebo was only 1.8 points on the HAM-D, a difference that, while statistically significant, was clinically meaningless. The results were much the same for all six drugs: they were all equally unimpressive. Yet because the positive studies were extensively publicized, while the negative ones were hidden, the public and the medical profession came to believe that these drugs were highly effective antidepressants. Kirsch was also struck by another unexpected finding. In his earlier study and in work by others, he observed that even treatments that were not considered to be antidepressants—such as synthetic thyroid hormone, opiates, sedatives, stimulants, and some herbal remedies—were as effective as antidepressants in alleviating the symptoms of depression. Kirsch writes, “When administered as antidepressants, drugs that increase, decrease or have no effect on serotonin all relieve depression to about the same degree.” What all these “effective” drugs had in common was that they produced side effects, which participating patients had been told they might experience."
- heurist 12y ago
  Could it also be that a slight adjustment in any area indirectly triggers adjustments in areas that are related to depression? It seems like even a small difference in the balance of all the complicated systems in the brain could potentially have a large effect on overall well-being. Placebo might kick it into the right behavior but the small change might be what allows the placebo to work...? Maybe that's all a placebo is in the first place, I'm not well read on that.
  - geoelectric 12y ago
    Total speculation, but maybe it works similarly to immune response accelerators like interferon--things that unbalance brain chemistry in general generate a compensating response that sometimes ends up correcting the original problem.
  - Alex3917 12y ago
    > Could it also be that a slight adjustment in any area indirectly triggers adjustments in areas that are related to depression? Yes, that's what's happening. Basically any sensory stimulation alleviates depression, including (but not limited to) raising or lowering the levels of pretty much any neurotransmitter.

by KingMob 12y ago

benbreen 12y ago

The active placebo idea strikes me as a plausible one here, and came up in a 2011 article by a former editor of the New England Journal of Medicine which I found pretty thought-provoking: http://www.nybooks.com/articles/archives/2011/jun/23/epidemic-mental-illness-why/ http://www.nybooks.com/articles/archives/2011/jun/23/epidemi... Here's what I thought was the key takeaway from the piece: "Altogether, there were forty-two trials of the six drugs. Most of them were negative. Overall, placebos were 82 percent as effective as the drugs, as measured by the Hamilton Depression Scale (HAM-D), a widely used score of symptoms of depression. The average difference between drug and placebo was only 1.8 points on the HAM-D, a difference that, while statistically significant, was clinically meaningless. The results were much the same for all six drugs: they were all equally unimpressive. Yet because the positive studies were extensively publicized, while the negative ones were hidden, the public and the medical profession came to believe that these drugs were highly effective antidepressants. Kirsch was also struck by another unexpected finding. In his earlier study and in work by others, he observed that even treatments that were not considered to be antidepressants—such as synthetic thyroid hormone, opiates, sedatives, stimulants, and some herbal remedies—were as effective as antidepressants in alleviating the symptoms of depression. Kirsch writes, “When administered as antidepressants, drugs that increase, decrease or have no effect on serotonin all relieve depression to about the same degree.” What all these “effective” drugs had in common was that they produced side effects, which participating patients had been told they might experience."

heurist 12y ago
Could it also be that a slight adjustment in any area indirectly triggers adjustments in areas that are related to depression? It seems like even a small difference in the balance of all the complicated systems in the brain could potentially have a large effect on overall well-being. Placebo might kick it into the right behavior but the small change might be what allows the placebo to work...? Maybe that's all a placebo is in the first place, I'm not well read on that.
- geoelectric 12y ago
  Total speculation, but maybe it works similarly to immune response accelerators like interferon--things that unbalance brain chemistry in general generate a compensating response that sometimes ends up correcting the original problem.
- Alex3917 12y ago
  > Could it also be that a slight adjustment in any area indirectly triggers adjustments in areas that are related to depression? Yes, that's what's happening. Basically any sensory stimulation alleviates depression, including (but not limited to) raising or lowering the levels of pretty much any neurotransmitter.