Nortriptyline misses mark in functional dyspepsia trial

The tricyclic antidepressant nortriptyline is only as good as placebo in terms of reducing symptoms of functional dyspepsia in preselected patients, according to the results of a multicentre randomized controlled trial.

A total of 69 patients with functional dyspepsia participated in the trial. These patients were preselected based on cytochrome P450 2D6 (CYP2D6), the primary enzyme responsible for nortriptyline metabolism.

The patients were randomly assigned to receive treatment with nortriptyline in an escalating low-dose regimen (10 mg at weeks 1–2, 25 mg at weeks 3–4, and 50 mg at weeks 5–12; n=33) or placebo (n=36) for 12 weeks. The primary outcome was clinical response, defined as a decrease of at least 30 percent in functional dyspepsia symptoms for 50 percent of the last 10 weeks of the treatment period.

The percentage of patients who achieved clinical response did not significantly differ between the nortriptyline and placebo groups (45 percent vs 58 percent; odds ratio [OR], 0.574, 95 percent confidence interval [CI], 0.211–1.560; p=0.276).

Adverse events were similar between the nortriptyline and placebo groups.

In the nortriptyline group, plasma concentration of the drug was substantially higher in responders than nonresponders (13 vs 9 μg/L; p=0.003). Notably, patients who believed they were administered nortriptyline were more likely to achieve clinical response than those who believed they received a placebo (77 percent vs 36 percent; OR, 11.439, 95 percent CI, 2.138–61.201; p=0.004).