Guilt by Association in Medical Research?

I saw some interesting items in AMA MorningRounds lately. And I found another item that fit the theme they shared–association is not the same as cause and effect. One of them was about new research that seems to draw an association between antidepressant use and infection with Clostridium difficile, This organism causes severe diarrhea, can lead to delirium and death, and is associated with various risk factors including being older than 65, treatment with antibiotics, being hospitalized, and others you can find at the Centers for Disease Control, Clostridium difficile Infection in Outpatients, Maryland and Connecticut, USA, 2002–2007 – Vol. 17 No. 10 – October 2011 – Emerging Infectious Disease journal – CDC.

One thing you don’t get from the news story is a very important caveat from the authors of the study itself, “We cannot completely discern whether it is the pathophysiology of depression itself or the treatment for depression that is the major driver of these findings”. Association is not the same thing as cause and effect.

So patients shouldn’t stop the antidepressant their doctors prescribe without talking it over first. If you get diarrhea, first let your physician figure out whether it’s Clostridium difficile, then get proper treatment for it, which might include a fecal “transplant”, which is not so much a transplant per se as it is an implantation, Fecal Transplantation for the Treatment of Clostridium difficile Infection.

And let’s all wash our hands with soap and water–thoroughly, please.

Next up is a study finding an association between antidepressants and perioperative mortality risk,

JAMA Network | JAMA Internal Medicine | Perioperative Use of Selective Serotonin Reuptake Inhibitors and Risks for Adverse Outcomes of SurgeryPerioperative SSRI Use and Adverse Outcome Risk

Guilt by association again, and the authors’ own words tell a more well-rounded story, “However, risks for mortality were attenuated in patients with a depression diagnosis and patients receiving antidepressants. Rather than being a risk factor itself, use of SSRIs in patients with depression may simply be a marker for other factors, such as more severe mood disorders, poorer functional status, neuropathy, or chronic pain, many of which are associated with a higher risk for readmission or mortality.”

You don’t get that nuanced message if you read only the news story, Antidepressants linked to increased risks after surgery – Times Of India.

The next item is about whether delirium itself is associated with poor outcomes in elderly demented patients or is a function of the severity of medical illness and other factors, an either/or reasoning that Dr. Sharon Inouye (the developer of the delirium screening tool, Confusion Assessment Method or CAM and the nonpharmacologic approach to preventing delirium in the hospitalized elderly, Welcome to the Hospital Elder Life Program (HELP)) and others took issue with, pointing out that a both/and approach might be wiser:

JAMA Network | JAMA Internal Medicine | The Meaning of Delirium

JAMA Network | JAMA Internal Medicine | The Meaning of Delirium—Reply

The message is clear; we should tolerate ambiguity, think more creatively, and allow for complexity as one of many determinants of research outcomes.