Overview (part 1 in a series)
Panacea was a goddess known for having a cure-all, which is why her name now means “a solution to every problem.” This series comprises a critique of an RCT, recently published in JAMA, in which the authors concluded that the treatment was something of a panacea.
Lexapro the panacea
You might not have noticed, what with the mid-term election campaigning and the brouhaha about the great South American refugee invasion, but last year in mid-summer the Journal of the American Medical Association (JAMA) published findings from a “randomized clinical trial” of escitalopram versus placebo in patients with depression and “acute coronary syndromes” (ACS).1 The trial authors concluded that short-term treatment of depression (up to 24 weeks) resulted in a pronounced long-term benefit (up to 10 years) for what they called the “MACE” outcome: basically, a composite of death, heart attacks, and something called “percutaneous coronary intervention” (PCI). (In case you’re wondering, PCI is a little like getting your coronary arteries polished pipe-cleaner style.)
If you’ve ever heard of escitalopram, you might call it “Lexapro,” and you probably know that it’s an antidepressant. If so, then you might also be wondering why these researchers conducted a study that looked at differences in heart disease outcomes for an antidepressant, and you wouldn’t be alone. I was too. My first thought was that maybe this was a “safety” type of clinical trial, in which the researchers looked at potential adverse effects of the drugs — but I was wrong. Instead, the researchers were making the case that the benefits of briefly treating mild depression (for less than 6 months) could result in a 31% lower risk for major cardiovascular problems over the next decade.
While it’s plausible to believe that treating depression is good for overall health, the short-term nature of the treatment combined with the long-term persistence of highly pronounced benefits makes this finding highly suspicious, and suggests a thorough examination is warranted. After discussing the article in my Journal Club class (co-taught with a colleague to 3rd-year PharmD students), the take-home message is that this study offers little-to-no evidence to support their conclusions. That’s because investigators either deliberately or carelessly misrepresented and misinterpreted their results.
If you’d like to know more about how to interpret a poorly-done study, I’m going to share follow-up posts that explain several aspects. The topics are listed below. Each will become a link as soon as each post is available.
- Confounding bias
- A key analysis was cross-sectional
- Post-hoc analyses
- Discordant findings during treatment and follow-up phases
- Hawthorne effect and/or detection bias
- Selection bias
- Data anomalies
- Ethical questions
- Kim J-M, Steward R, Lee Y-S, et al. Effect of escitalopram vs placebo treatment for depression on long-term cardiac outcomes in patients with acute coronary syndrome: A randomized clinical trial. JAMA. 2018;230(4):350-7.