Some of the most frequently prescribed medications in the U.S. are anxiety drugs. Also included on the list of common prescriptions: proton pump inhibitors, such as Nexium and Prilosec.

Proton pump inhibitors (PPIs) have been associated with several severe, even life-threatening side effects when used frequently over an extended period of time. What is not generally known is that mixing PPIs with anti-anxiety prescriptions such as Xanax or Valium can also have serious health consequences.

Drug interactions have become a growing issue with an aging population and patients who may take several different types of medications concurrently. A review article published in the European Journal of Gastroenterology and Hepatology in May 2001, focused on drugs that specifically interact with PPIs — including anti-anxiety medications.

Anti-anxiety meds are members of a class of drugs known as benzodiazepines (colloquially, “benzos”). They are considered by the medical profession to be mild sedatives or tranquilizers. The first benzodiazepine drug was Librium (chlordiazepoxide), introduced by Hoffmann-LaRoche in 1960. The company followed that one in 1963 with Valium, which was was a more powerful, longer-lasting version of Librium. By the late 1970s, Valium had become the most popular prescription drug in the U.S.

One of the selling points of benzodiazepines is their safety over their predecessors, barbituates (i.e., phenobarbital). When used by themselves in low dosage for brief periods, there is little danger. Deaths from overdose are rare unless taken in large amounts in combination with alcohol or opiates. Benzodiazepines can be habit-forming, however, and are abused for recreational purposes.

Benzodiazepine drugs work by augmenting the effect of a brain chemical known as gamma-aminobutyric acid (GABA), which inhibits neuron connections (synapses) in the brain, producing a calming effect (for this reason, some benzodiazepines are also used to control seizures). The most commonly-prescribed benzodiazepine drugs are metabolized (activated) by a group of enzymes (biochemical catalysts) known as cytochrome P450 (CYP450). These enzymes are produced in the liver and are involved in the mechanism of many medications and herbal supplements.

This is where benzodiazepines’ interactions with PPIs begin. Like Valium, Xanax, and other benzodiazepine drugs, PPIs such as Prilosec and Nexium are metabolized by CYP450 enzymes. This leads to an interaction in which the effects of benzodiazepines are amplified – in some cases, to a dangerous degree. Some patients who have experienced this interaction describe it as “feeling stoned.” Taking benzodiazepines and PPIs together can lead to mental impairment,  dizziness, and loss of coordination. Unfortunately, many physicians seem to be unaware of this interaction, even though the dangers have been known for over two decades


Other commonly-prescribed medications that interact with PPIs include anticoagulants (including warfarin, Plavix, and NOACs such as Xarelto and Eliquis), anti-seizure medications such as Dilantin (phenytoin), diuretics, Lanoxin (digoxin, used to treat arrhythmia), and even iron supplements. 

Because of their many side effects, PPI’s should be used sparingly and only for short periods of time. They can also cause many risky interactions. If your doctor recommends treatment with a PPI, be sure that s/he is aware of any other medications you may be taking.

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K.J. McElrath is a former history and social studies teacher who has long maintained a keen interest in legal and social issues. In addition to writing for The Ring of Fire, he is the author of two published novels: Tamanous Cooley, a darkly comic environmental twist on Dante's Inferno, and The Missionary's Wife, a story of the conflict between human nature and fundamentalist religious dogma. When not engaged in journalistic or literary pursuits, K.J. works as an entertainer and film composer.