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Re: All ADs Better than Placebo for Major Depression Tabitha

Posted by linkadge on February 24, 2018, at 11:54:44

In reply to Re: All ADs Better than Placebo for Major Depression, posted by Tabitha on February 24, 2018, at 10:05:11

Hi Tabitha,

I am not saying that there are research flaws for this study. I am saying that there are data / sample size flaws / limitations.

If you notice, agomelatine is on the list of one of the most effective antidepressants. Do you think this is accurate?

Firstly, there is publication bias. Newer medications are likely more susceptible to publication / sponsorship bias. In the early process of drug development and marketing, funding can often be connected to industry. Older (off patent) drugs are no longer money makers and hence tend to be studied more in an unbiased fashion.

Depression treatment is a much larger industry than it was 20-30 years ago. As such, there is much more money resting on the approval of new drugs - and more money in the establishment of the notion of superiority of new drugs (in order to gain market share).

A second limitation is the number of studies. Obviously, the fewer studies that exist, the more susceptable the meta-results are to the outcome of those particular studies. Hence, the data for those medications is less reliable than that of more studied medications. The combination of these two is likely why newer medications appeared to come out ahead of older ones.

Another complication is length of administration and clinical scales used during the study. Not all double blind studies use the same rating scales, or data measures. This makes it hard to compare two studies using different methodology.

For example, mirtazapine is known to have a very strong effect on certain depression symptoms (i.e. anxiety, sleep, appetite) early in treatment. In a shorter term clinical trial, mirtazapine would look superior to many SSRIS (simply owing to the dramatic reduction in anxiety, and sleep measures) yet may not be as effective longer term (or address core depression as well as other medications). A similar argument can be made for agomelatine, which has a prominent effect on sleep measures.

Clinical experience suggests that 'poop-out' is more prevalent with some medications vs. others. Clinical trials are likely not long enough to factor this in (in the overall efficacy of a drug).

An excerpt from the Wikipedia article on agomelatine:

"However, the body of research on agomelatine has been substantially affected by publication bias, prompting analyses which take into account both published and unpublished studies.[4][17][18] These have confirmed that agomelatine is (statistically) approximately as effective as more commonly used antidepressants (eg SSRIs), but some qualified this as "marginally clinically relevant",[18] being only slightly above placebo."

Similarly, many clinical trials are used to assess whether the drug can lift depression in the short term. I don't know to what extent this meta analysis included longer term follow up studies, to see if the benefits of a particular drug still existed (and outweighed comparator drug effects) in the long term.

Another flaw is the lack of inclusion of unpublished data. I don't think companies are required to publish failed drug trials. Even though some voluntarily do, this is more of a recent shift. Hence there is a lot of data which simply never sees the light of day to get incorperated into such meta analysis.

Another issue with studies of this regard is the mathematical models used. For example, not every drug has been compared to every drug. Hence there are large data gaps that cannot be easily filled in with mathematical analysis.

For example, until the CATIE antipsychotic study, it was assumed (and purported supported by the data) that the atpyicals were more effective, better tollerated with fewer side effects than typicals. CATIE refuted this and actually suggested that an older drug (perphenazine) was just as effective and well tollerated than newer atypicals. CATIE (afaik) was not industry sponsored.

Is escitalopram really better than lofepramine? Who knows?

Linkadge



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