Effect of amitriptyline in functional heartburn

Treatment of gastroesophageal reflux disease (GERD) fails in a small proportion
of patients. As GERD is one of the most prevalent chronic disorders in the
western world, this small proportion of therapy-resistant patients encompasses
a substantial part of the patient population.
Many of the patients presenting with typical reflux symptoms who do not respond
to the current standard of care (i.e. proton pump inhibition), do not have
gastro-esophageal reflux disease. Functional heartburn is an important
differential diagnosis in this respect, and can be confirmed or excluded by
performing a 24h pH/impedance recording: patients with functional heartburn do
not have pathological acid reflux and the symptom-reflux association analysis
is typically negative.
The management of functional heartburn is often challenging as evidence-based
pharmacological options are not available. The use of visceral pain modulators
such as tricyclic antidepressants is generally accepted, even though the
clinical trials to support their use are likewise lacking.
Antidepressants are generally used in the treatment of pain-predominant
functional gastro-intestinal disorders such as functional dyspepsia and
irritable bowel syndrome. Their use is defended by the assumption that
antidepressants have central analgesic actions, and there is increasing
evidence of central nervous system dysfunction in functional gut disorders. In
addition, antidepressants could reduce the severity of psychological symptoms
such as anxiety and depression. These are thought to exacerbate the symptoms in
FGD, although this assumption is controversial and the antidepressant dose used
for visceral analgesia is considered to be too low to have significant effects
on the psychological state.

To assess the effect of amitriptyline on gastro-esophageal symptom severity and
on esophageal sensitivity to acid perfusion and balloon distension in patients
with documented functional heartburn.

Double blind placebo controlled, randomized cross-over design

treatment with placebo or amitriptyline 25-50 mg daily for 6 weeks in a
crossover design, with an 8 week washout period in between

discomfort associated with the esophageal sensitivity test
side effects from the use of amitriptyline. The most common side effects are
dry mouth, constipation, blurred vision, palpitations, weight gain, drowsiness,
dizziness, tremors, headache, nausea, sweating, and low blood pressure.