The ‘chicken and egg’ question
Experts welcomed the findings, saying they supported their observations and validated the idea of looking outside the gut for complicating factors in patients with GERD, but some questioned the clinical relevance of the Mendelian randomization.
Approached for comment, Amir E. Masoud, MD, medical codirector, Hartford HealthCare Neurogastroenterology and Motility Center, Fairfield, Conn., said the study’s most important contribution is increased recognition of the connection between GERD and anxiety or depression.
“There is a psychological component” to GERD, he said, and it is an “important area for investigation and possible intervention for patients who don’t respond to traditional therapies.”
Dr. Masoud singled out the study design. The researchers “tried to tee this up with something we’ve always thought about,” he told this news organization, referring to the “chicken and egg” question about the relationship between GERD and anxiety or depressive symptoms.
As such, it provides evidence for a common observation in the clinic, he said. “A lot of times, when a therapy that should work does not work for something like GERD, for example, we tend to think of psychological factors that could be playing a role.”
No longer a taboo topic
Rena Yadlapati, MD, medical director, Center for Esophageal Diseases, UC San Diego Health, told this news organization that the study is “validating, in terms of the conversations with patients and some of the nontraditional methods we are trying to explore in their management.”
She noted the bidirectional relationship revealed by the Mendelian randomization, but cautioned that the approach relied on a small number of studies and hasn’t been utilized in gastroenterology as much as in other fields.
“We need to understand that this is hypothesis generating, and there are probably some important limitations,” she added, even if the results “certainly make sense.”
From a clinical perspective, the idea of anxiety or depression being linked to GERD has been a “taboo topic” for a long time, Dr. Yadlapati said.
“But if we can effectively communicate that relationship between the brain and gut and this whole cyclical process [to patients], there’s power to gain patient insight and engagement.”
Another key aspect is to consider a psychological referral for patients, as well as engaging them with “simple things like relaxation strategies and diaphragmatic breathing and referring them to people who can do cognitive behavioral therapy.”
Dr. Yadlapati emphasized that “it doesn’t necessarily have to be a psychologist. There are a lot of other ways to provide that access to patients.”
Practical clinical implications
Philip O. Katz, MD, director of motility laboratories, division of gastroenterology, Weill Cornell Medicine, New York, said that the study, like many of its kind, reinforces that there are multiple cofactors associated with managing patients with reflux disease.
As for the bidirectional relationship identified through the Mendelian randomization, he was skeptical about its clinical value and pointed out that the odds ratios are “relatively small.”
“It is commonplace for people to look for genetic predispositions to a lot of disease,” Katz told Medscape Medical News, but, “in clinical practice, I don’t believe that it’s particularly meaningful, to be honest.”
However, there is no doubt that GERD symptoms are augmented by times of what is generically called “stress,” he added.
“Regardless of those findings, it doesn’t change the way I view the importance of this article, which is when someone’s not responding to medication to look for reasons other than the original diagnosis,” Dr. Katz said.
“There is so much overlap between true GERD and symptoms that sound like GERD” that clinicians need “to be aware that both anxiety and depression are cofactors,” he said.
Dr. Talley is supported by funding from the National Health and Medical Research Council (NHMRC) to the Centre of Research Excellence in Digestive Health, and he holds an NHMRC Investigator grant. He declared relationships with Norgine, Bristol Myers Squibb, Allakos, Bayer, Planet Innovation, twoXAR, Viscera Labs, Dr Falk Pharma, Sanofi, Glutagen, ISOVive, BluMaiden, Rose Pharma, Intrinsic Medicine, Comvita Manuka Honey, GlaxoSmithKline Australia, and AstraZeneca; and holds numerous patents. Dr. Masoud declared no relevant relationships. Dr. Yadlapati declared relationships with Medtronic, Phathom Pharmaceuticals, Ironwood Pharmaceuticals, and RJS Mediagnostix. Dr. Katz declared relationships with Phathom Pharma, Sebella, and Syneos.
A version of this article first appeared on Medscape.com.