The antidepressant mirtazapine improved weight loss, early satiation, nausea, and other signs and symptoms in patients with functional dyspepsia, said the authors of a placebo-controlled pilot study published in the March issue of Clinical Gastroenterology and Hepatology.

The findings suggest that mirtazapine “has the potential to become the treatment of choice for functional dyspepsia in patients with weight loss, and evaluation in larger multicenter studies is warranted,” said Dr. Jan Tack and his associates at the University of Leuven, Belgium.

Functional dyspepsia, one of the most prevalent gastrointestinal disorders, is characterized by early satiation, postprandial fullness, and epigastric pain and burning in the absence of underlying systemic or metabolic disease. Up to 40% of affected patients lose weight, an “alarm symptom” that until now has lacked effective treatment, the researchers said.

Mirtazapine, an antagonist of the H1, alpha2, 5-hydroxytryptamine (5-HT)2c, and 5-HT3 receptors, often causes weight gain when used to treat depression. Therefore, the investigators designed a double-blind single-center pilot trial of 34 patients with functional dyspepsia who had lost more than 10% of their original body weight. After a 2-week run-in period, half the patients were randomized to 15 mg of mirtazapine every evening and the other half to placebo (Clin Gastroenterol Hepatol. 2016 Jan 9. doi: 10.1016/j.cgh.2015.09.043 ).

The average weight of placebo patients remained almost unchanged throughout the trial, while patients on mirtazapine gained an average of 2.5 + 0.6 kg by week 4 (P = .003 for between-group comparison) and 3.9 + 0.7 kg, or 6.4% of their original body weight, by week 8 (P less than .0001). Mean scores on a validated dyspepsia symptom severity (DSS) questionnaire improved significantly between baseline and weeks 4 (P = .003) and 8 (P = .017) for mirtazapine but not placebo. Directly comparing the two groups in terms of the DSS revealed a large effect size that trended toward significance (P = .06) at week 4 but not at week 8 (P = .55). However, mirtazapine significantly outperformed placebo in measures of early satiety, quality of life, gastrointestinal-specific anxiety, and nutrient tolerance, “mostly with large effect sizes,” the investigators said.

Mirtazapine did not affect epigastric pain or gastric emptying, and had little effect on postprandial fullness. Moreover, 2 of 17 patients in the mirtazapine group dropped out of the study because of unacceptable levels of drowsiness, which is a common side effect of the medication.

Many patients with functional dyspepsia respond inadequately to first-line treatment with acid-suppressive or prokinetic drugs, the investigators noted. While tegaserod, buspirone, and acotiamide can improve gastric accommodation, it is unknown if they promote weight gain. The results for mirtazapine are promising, but the pilot trial included only tertiary care patients, and the small sample size precluded separate analyses of patients with postprandial distress syndrome as opposed to epigastric pain syndrome, the researchers said.

The study was funded by Leuven University, the FWO, and the KU Leuven Special Research Fund. Mirtazapine and placebo were supplied by MSD Belgium. The investigators had no disclosures.