Panic Disorder and Gastroesophageal Reflux

It is my opinion, based on endoscopy and 24 hour gastric and esophageal pH studies that the gastrointestinal problems, so very common in panic disorder are a result of abnormal bile flow. Cholecystokinin (CCK) has long been known as a central nervous system neurotransmitter involved in anxiety. CCK is even better known as the primary regulator of bile flow, usually stimulated by food entering the GI tract. Abnormal bile flow backwards (refluxing) into the stomach is caustic and quickly causes bile gastritis. Bile is alkaline, and the stomach demands an acidic environment. When bile refluxes into the stomach, the stomach secretes acid in an attempt to neutralize the bile. Unfortunately bile is sticky and does not mix easily with stomach acid and often copious amounts of acid are produced causing bloating and increasing pressure on the gastroesophageal junction. This increased pressure causes gastroesophageal reflux. This reflux can manifest as heartburn, sinusitis or aspiration asthma or laryngitis. If the bile flows down the intestines, it is irritating and rapidly pushed through the intestines ?so rapidly that fecal incontinence can result.

The abnormality of bile flow in panic has been published and presented at a peer reviewed American College of Gastroenterology meeting as well as a peer reviewed article in the International Journal of Psychosomatics. The clinical effects of this abnormality have not been formally published and are not well known by most clinicians.

Psychiatrists do not tend to associate irritable bowel syndrome (IBS) and gastroesophageal reflux (GERD) with panic and usually defer treatment to internists who typically consider the problem to be primary hypersecretion of acid. Prescription of a H2 receptor blocker is most common (Tagamet, Zantac, Axid, Pepsid) and this does help somewhat, however the primary stimulus for reflux, the bile in the stomach, is a stronger stimulus for acid secretion than the H2 receptor blockade can handle. Another approach is to use a proton pump inhibitor (Prilosec or Prevacid) which pretty much shuts down the mechanism by which acid is secreted. Unfortunately the caustic bile continues to cause gastritis.

My approach involves 1) use of alprazolam as a CCK antagonist (we have documented the potent CCK antagonism of alprazolam) to inhibit bile secretion. We have found that dosages as low as 0.5 mg before sleep can work, or 0.5 mg 45 minutes before meals and at bedtime 2) use of Carafate ?a substance that binds with the bile salts rendering them less alkaline and much less caustic as well as to adhere to damaged mucosa forming a "bandage" and promoting healing of the damaged tissue and 3) use of a proton pump inhibitor to reduce acid secretion which can also occur on the basis of bile gastritis.

Most doctors feel that Carafate is not of much use in GERD or IBS and this is probably true unless these problems are a part of the panic disorder syndrome. Carafate is an extremely benign medication that coats the stomach and esophagus but is virtually unabsorbed into the system. It can interfere with absorption of some other medications, but not the psychotropics or proton pump inhibitors. I use Carafate 30 to 45 minutes before meals (1 gram) and two grams before sleep, the time when the most bile is secreted. Results with Carafate in addition to the other agents mentioned, or use of Carafate alone suggest that it is of major importance in the treatment of panic disorder related GERD (sinusitis, heartburn, aspiration) or IBS with prominent bile related diarrhea and fecal incontinence.