a story: the epilogue…

Posted on Thursday 31 December 2015

I thought I needed two endings. The first would emphasize the importance of Data Transparency to allow us to thoroughly vet these industry-funded productions like the examples of these Atypical Antipsychotic Augmentation of Treatment Resistant Depression trials. Then the second ending would say that these industry-funded approval-oriented RCTs are way over-valued and no basis for drug usage – that’s the job of practitioners, academics, and patients in the wide world of clinical medicine. But on re-reading it, those two seemingly dichotomous points of view just kind of ran together in the writing. Which one is the more important one? Both. I couldn’t keep them apart even when  I was trying…
    December 31, 2015 | 4:08 PM

    So what of the “seasoned” clinicians who swear, based on their own clinical experience, by the value of augmentation with this class of medications? Often with patients who they view as experiencing depressions as part of a bipolar spectrum? And, who often place less value RCTs because of criticisms similar to those you express? And might have no more respect for many KOLs than you. What can best help patients and less seasoned clinicians navigate all this?

    December 31, 2015 | 6:12 PM

    1boringyoungman, I cannot respond for Mickey, but here is what I would say:

    1) It is absurd to believe these drugs help with depression. These drugs are the most depressing drugs in existence. They suck the life out of you, which is why non-compliance is so high. No one feels better on these drugs – at least as a result of the drug.

    2) “seasoned” clinicians are often wrong about treatments, particularly where placebo effects are high, as is the case here. If given in a low dose, antipsychotic drugs will act similarly to SSRIs – that is they will generate enough side effects to be noticeable and potentially harness an enhanced placebo effect. The reason you can get an effect when “augmenting” in “treatment-resistant” depression is because time heals a lot of depressions. In studies that constantly switch drugs to find “the right one”, you can get positive effects over and over again by switching drugs and there is no rhyme or reason to which drugs are more effective. The same is true here: the antipsychotic at a low enough dose simply acts as an enhanced placebo in the same way that another SSRI would. At a higher dose it would be too detrimental to function, but a lower dose can suffice – at least until escalating dosages take their toll.

    3) Note also that, as Mickey emphasized, the effect sizes are very small. If your study is large enough you can generate a significant effect with small effect size for any substance that has noticeable side effects. This has been amply demonstrated at this point. There are probably a dozen or more completely different types of chemicals – many of them totally unrelated to each other – that have produced positive results for treatment of depression.

    January 1, 2016 | 1:53 PM

    “Then the second ending would say that these industry-funded approval-oriented RCTs are way over-valued and no basis for drug usage – that’s the job of practitioners, academics, and patients in the wide world of clinical medicine.”

    I came to this conclusion a long time ago.

    There is a plausible mechanism that would result in both buspirone and aripiprazole (and now vilazodone) working for augmentation (vilazodone would augment itself). It is the reason that I recommend buspirone augmentation rather than AAP augmentation except in true bipolar depression – those people who have actually had naturally occurring manic or hypomanic episodes.

    When a psychiatrist sees thousands of patients, his/her experience starts to greatly exceed the Ns in small and large studies. Depending on how he or she conducts that practice – they may know a lot more about various treatment practices than is or will be available in clinical trials. It is after all why we “practice” medicine.

    It has been my experience that augmentation practices with buspirone is generally benign, but there is still a clear incidence of serotonin syndrome that leads me to the verge of recommending it only if the patient is a reliable enough to call me with problems and they monitor their own blood pressure, pulse, and body temperature. It also makes me cringe when I see these practices adopted by physicians who don’t know how to prescribe or monitor these drugs.

    James O'Brien, M.D.
    January 1, 2016 | 2:53 PM

    Here’s something a “seasoned” doctor should know: first try a sedating antidepressant at night before using antipsychotics on nonpsychotic people. Something as simple as (very) low dose Elavil or Desyrel does the job with all the complications.

    And if it turns out to be a time limited mood problem, you can later drop the meds in sequence. TD is not time limited.

    Since Elavil is off patent, however, there is no monied interest promoting it’s use.

Sorry, the comment form is closed at this time.