“Treatment-Resistant” Depression2021-11-27

How weary, stale, flat, and unprofitable seem to me all the uses of this world!

W. Shakespeare, Hamlet

“Treatment-Resistant” depression (TRD), in our clinical and research experience of two decades, is in the vast majority of cases an undiagnosed/underdiagnosed bipolar disorder. These individuals do poorly long term on antidepressants, which can make them be in mixed states, agitated, and suicidal.

TRD can be safely and effectively treated if viewed as a bipolar spectrum disorder. In our experience most patients do very well long-term on a mood stabilizer. In particular, low dose lithium.

This is not a new concept, one of my mentors from my time at UCSD, the late great Hagop Akiskal and his followers first proposed this decades ago based on clinical experience. Nowadays, we are rediscovering this truth with cutting edge digital and molecular biomarkers. We like to say in-house that there is no treatment-resistant depression, just science-resistant psychiatry.

Bipolar patients are very susceptible to hope, hence strong placebo effects for any new treatment, but that is not sustained long term and then they plunge again into the abyss of despair. So the key is to document with biomarkers and demonstrate a sustained effect for any new compound being developed.

Festina lente. Or as the Navy Seals like to say, “Slow is smooth, and smooth is fast”.

Live. Happier. Longer.