A recent theme on this blog has been the difficulty of studying inexpensive therapies. The issue is that there are not strong incentives for pharmaceutical companies to invest in treatment trials when the potential for profits is meager. Fortunately, there are other funding mechanisms. A recent study (NJ Talley et al. Gastroenterol 2015; 149:340-9), sponsored by the NIH, still was challenging. One of the reasons is that when medicines are already approved by the FDA that can be used off-label and this can undermine recruitment.
Due to difficulty with enrollment, the researchers of this current study expanded to a total of 8 sites (initially 5) and settled for 292 patients rather than their goal of 400. After a baseline washout of 2- to 4-week with assessment, patients with Rome II criteria for functional dyspepsia (FD) were assigned in a randomized, double-blind trial to either placebo, amitriptyline 50 mg, or escitalopram 10 mg for 10 weeks.
- History of depression and not using antidepressants.
- Symptom resolution with antisecretory therapy (eg. proton pump inhibitors)
- History of esophagitis, ulcers, or organic gastrointestinal disease
- Major physical illness
- Drug/alcohol abuse
- Nonsteroidal anti-inflammatory drugs
- Required: previous normal EGD within 5 years
- 18-75 years
- “ulcer-like dyspepsia” pain centered in the upper abdomen is the predominant symptom
- “dysmotility-like dyspepsia” non pain symptom predominates: fullness, bloating, early satiety, and nausea
- Adequate relief was noted in 40% of placebo-treated, 53% of amitriptyline-treated, and 38% of escitalopram-treated patients
- Ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief compared with placebo for odds ratio of 3.1
- Delayed gastric emptying was associated with being less likely to report adequate relief with an odds ratio of 0.4
- Safety: while adverse effects were common, “there was no overall difference between the 3 arms (except in neurologic symptoms, with highest rates in the escitalopram arm) suggesting that…TCAs will be generally well tolerated at low doses.”
The associated editorial (pages 270-2) notes that the overall benefits of amitriptyline were modest. They also reviewed the NORIG study (JAMA 2013; 310: 2640-9) which examined nortriptyline and placebo for idiopathic gastroparesis (n=130). Similar to this study from Talley et al, the NORIG study found a lack of response to tricyclic antidepressants in this cohort with delayed gastric emptying and dysmotility; “the lack of efficacy in patients with dyspepsia with delayed gastric emptying suggests the possible utility of scintigrahic testing to select patients” for amitriptyline therapy.
Bottomline: This well-designed study supports the use of amitriptyline, but not escitalopram for the use of FD, mainly in those with pain-predominant symptoms.
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