Up to 90% of horses treated for gastric ulcers with omeprazole can experience a recurrence of ulcers when they stop taking this drug.
Horses can develop rebound acid hypersecretion (RAHS) after the discontinuation of omeprazole. Higher levels of stomach acid often lead to new ulcers being formed, particularly if the underlying causes of ulceration have not been addressed.
This is frustrating for both horse owners and veterinarians, leading to reduced performance and well-being in the horse. Why do so many horses experience ulcer rebound and what can be done to prevent these gastric lesions from coming back?
Some performance horses are maintained on omeprazole year-round to reduce the risk of recurrence.
But long-term omeprazole use is not advised because this drug can interfere with the digestibility and absorption of certain nutrients in the diet. Keeping a horse on omeprazole is also an expensive proposition.
Instead, you can prevent ulcer relapse in your horse by supporting their gut health, identifying risk factors, and adopting research-backed feeding and management practices.
Omeprazole for Ulcer Treatment
GastroGard, a slow-release form of omeprzole, is the only FDA-approved treatment to resolve and prevent gastric ulcers in horses. Due to the high prevalence of Equine Gastric Ulcer Syndrome (EGUS) in performance and pleasure horses, the use of this drug is widespread.
Omeprazole is a proton pump inhibitor that works by decreasing the production of stomach acid. By raising the gastric pH (lowering stomach acidity), omeprazole creates a more favourable environment to allow existing ulcers to heal.
Although omeprazole treatment is effective at resolving existing ulcers in the squamous region of the stomach, it is not a long-lasting effect. Omeprazole needs to be given continuously to inhibit the secretion of gastric juices.
Evidence of Ulcer Rebound in Horses
These studies demonstrate that 4 mg/kg of omeprazole given daily is effective in reducing ulcer number and severity. However, when treatment is stopped, ulcers are likely to form again.
In one study, 90% of horses had a recurrence of ulcers after being taken off of the 4 mg/kg daily dose of omeprazole. 
To avoid this, some veterinarians recommend gradually reducing the dose to 1 or 2 mg/kg after 28 days. However, even with this strategy, 16-20% of horses develop new lesions or worsening lesions during the period of reduced omeprazole dosing. 
Furthermore, performance horses that are most at risk of ulcer rebound may not be able to use omeprazole continuously.
Competitions require that horses undergo a 72-hour withdrawal period from this drug prior to competition. This could be enough time for ulceration to occur. 
Careful attention needs to be paid to horses discontinuing omeprazole use. There are strategies you can use to reduce the risk of ulcer rebound, which we will discuss later on in this article.
Why Do Ulcers Come Back in Horses?
This question is still an active area of research. However, the following mechanisms have been hypothesized to contribute to the high rates of ulcer recurrence in horses.
Rebound Acid Hypersecretion
After cessation of omeprazole treatment, rebound gastric hyperacidity and ulcer recurrence are common.
Gastric acid production occurs in parietal cells of the stomach, which secrete acid in response to several signals including histamine and the hormone gastrin.
Gastrin is secreted in response to a meal and triggers histamine secretion from enterochromaffin-like (ECL) cells in the stomach. Together histamine and gastrin stimulate parietal cells to produce stomach acid.
When acid is secreted and gastric pH decreases, a negative feedback loop turns off gastrin secretion. 
Omeprazole works by inhibiting the final step of acid production in parietal cells. This increases gastric pH which allows gastrin production to rise. Gastrin also triggers the proliferation of ECL cells that produce histamine.
Once treatment with omeprazole is discontinued and acid secretion is no longer blocked, the parietal cells respond to higher levels of gastrin and histamine by secreting more acid. The result is a hyper-acidic environment, which can lead to new lesions in the stomach lining. 
Although these mechanisms have mostly been shown in humans and animal models, horses treated with 4 mg/kg of omeprazole per day had a two-fold increase in gastrin levels after 14 days.  This suggests similar mechanisms could be occurring in horses.
Decreased Efficacy Over Time
Another possible explanation for ulcer recurrence during and after omeprazole treatment is a loss of efficacy over time.
One study showed that the ability of omeprazole to completely heal ulcers decreased over time when 4 mg/kg of daily omeprazole was continued for 90 days.
The percentage of horses with squamous ulcers that showed complete healing at 30 days was 29%. This dropped to just 11% of horses showing complete healing at 90 days. 
Potential reasons for decreased efficacy over time include reduced owner compliance and upregulation of omeprazole breakdown. In horses given 4 mg/kg daily, the bioavailability (measured as total circulating amount) decreased by 50% after 29 days. 
Omeprazole is catabolized via hepatic cytochrome 450 in other animals and this process is upregulated with ongoing treatment. 
The cytochrome 450 pathway is used to catabolize many xenobiotics. This is not only a concern for omeprazole bioavailability but also the efficacy of other drugs or therapeutics that are given concomitantly.
If environmental or dietary factors that caused the ulcers in the first place have not been addressed, ulcers are likely to come back once omeprazole treatment is stopped.
Common causes of ulcers include:
- Intermittent feeding
- High intensity exercise, particularly on an empty stomach
- Feeding large quantities of grain
- Limited access to water
- Trailering and changes in environment
- Changes in social grouping
- High levels of stress
The best way to reduce your horse’s ulcer risk is to ensure they have continuous access to forage and water, limit their stress, never exercise on an empty stomach, and avoid intense competition schedules.
For some high-level performance horses, it may not be possible to decrease their training schedules. This can lead to many horses being maintained on long-term omeprazole treatment at a lower dose to prevent gastric ulcers in performance horses.
However, ongoing research suggests that omeprazole may not be suitable for long-term use. It can have unintended effects on digestion and metabolism and may increase fracture risk.
Other Concerns with Omeprazole Use
Ulcer rebound is a major concern when a horse is put on omeprazole, but keeping your horse on this drug may not be the best strategy. Not only is omeprazole expensive, it has been observed to cause negative effects in other animals and horses including:
- Reduced digestibility of protein
- Decreased absorption of minerals, incluing calcium and magnesium
- Increased fracture risk
- Increased risk of colic when given along with bute
Effects on Digestion and Metabolism
Omeprazole maintains a less acidic gastric environment for up to 16 – 18 hours after administration.  While this may be beneficial for ulcers, reducing acidity in the stomach can negatively affect the digestion of feed.
Gastric acids are required to activate enzymes that initiate the processes of protein and carbohydrate digestion. In a less acidic environment, activation of these enzymes is impaired, which can affect the digestion of protein and carbohydrates in the foregut.
If too much protein and carbohydrate reaches the hindgut, it can lead to hindgut acidosis.
Research shows that omeprazole treatment for 11 days alters biomarkers of lipid, protein and mineral digestion in horses. This includes increased plasma cholesterol, decreased magnesium and decreased phosphorus levels. 
In another study, calcium digestibility was negatively affected by omeprazole treatment.