Mirtazapine for Functional Dyspepsia

In a randomized, placebo-controlled pilot study (J Tack et al. Clin Gastroenterol Hepatol 2016; 385-92) with 34 patients (29 women, median age 35.9 years), the authors showed improved dyspepsia symptom scores at weeks 4 and 8 compared with baseline.

Background: Mirtazapine is an antidepressant which is associated with weight gain and improvement in nausea.

Methods: The treatment group received 15 mg each day.

Results:

  • Compared with the control group, these was improvement in early satiety, quality of life, GI-specific anxiety, nutrient tolerance, and weight loss.
  • Two patients in the treatment group dropped out due drowsiness.  Interestingly, the trend of improvement was greater at week 4 then for week 8.
  • The authors note that epigastric pain and burning did not improve.

Limitations: small number of patients, and tertiary care patient population

My take: more studies are needed for this vexing problem

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

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Does buspirone help functional dyspepsia?

A recent randomized, double-blind, placebo-controlled crossover functional dyspepsia (FD) trial showed that 4 weeks of treatment with buspirone (10 mg TID) improved overall symptom severity, including early satiety and bloating (Clin Gastroenterol Hepatol 2012; 10: 1239-45).

This study enrolled 17 patients (13 women) with a mean age of 38.5 years.  There were two 2-week treatment periods and a 2-week washout in between.  Patients filled out a dyspepsia symptom score before treatment and at the conclusion.  In addition, patients underwent gastric emptying by using breath tests and barostat measurement.

Overall symptom score was improved with buspirone compared to placebo: 7.5 ± 1.3 vs. 11.5 ± 1.2.  Symptoms of postprandial fullness, early satiety, and abdominal bloating all improved significantly.

Buspirone treatment increased gastric accommodation compared with placebo: 229 ± 28 vs. 141 ± 32 mL respectively.  Overall, gastric emptying was not affected by buspirone treatment; however, delayed emptying of liquids was evident (half-life = 64 vs. 119 minutes respectively).

The effect of buspirone on FD appears to be primarily related to improvement in gastric accommodation.  Impaired accommodation has been identified in about 40% of FD patients.  Buspirone which is a 5-HT1A receptor agonist acts on cholinergic nerve endings and leads to relaxation of the proximal stomach.

Buspirone also is used for the treatment of anxiety.  In the present study, baseline anxiety scores were not correlated to symptom improvement but these scores were not followed at the end of treatment.

In this small study, buspirone was well tolerated and had similar adverse events as placebo.  In previous studies, it has been associated with light-headedness, dizziness, and nausea.

Given the small scale of the study, it would be premature to consider buspirone a proven treatment for FD; however, this study provides the framework for larger studies to determine more conclusively the role of buspirone for FD.

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A cure for satiety

A safe cure for excessive appetite is a holy grail in pharmacology.  Although gluttony is a much more pervasive problem that poor appetite, an effective cure for satiety is also needed.  In the clinical setting, poor appetite remains a common problem with and without underlying problems.  Treatments to this point, such as cyproheptadine or megestrol, may be useful in some patients.  Better treatments are needed.  One drug of interest is ghrelin (Cancer 2012; DOI: 10.1002/cncr.27430).

The introduction summarizes ghrelin’s biologic activity: “Ghrelin is an endogenous ligand for the growth hormone (GH) secretagogue receptor and is secreted predominantly by gastric endocrine cells.  It induces dose-dependent, GH-releasing activity; stimulates appetite and food intake; and triggers a positive energy balance through a central mechanism involving hypothalamic neuropeptides.”

Plasma ghrelin levels decrease after gastric resection, helping to maintain weight loss. Therefore, the stomach may act as endocrine organ to maintain appropriate weight. Exogenous administration may increase appetite.

This cited article reports a prospective randomized placebo-controlled phase 2 study in which ghrelin was administered to 21 patients with esophageal cancer, receiving cisplatin-based chemotherapy; the dosage was 3 μcg/kg twice daily for 1 week.  A placebo group  (n=20) received saline.  The ghrelin group consumed 18.2 kcal/kg/day compared with 12.7 kcal/kg/day.  A measure of appetite, an appetite visual analog score, was also higher in the ghrelin-treated patients, 6.2 vs 4.1.  Patients in the ghrelin group had fewer adverse effects of chemotherapy related to anorexia and nausea than patients in the control group.  One patient receiving ghrelin stopped therapy because of excessive diaphoresis.

Although this medication is being studied in adult chemotherapy patients, down the road ghrelin and potential analogs may have a role in pediatric patients with a variety of disorders which inhibit their appetite.

Additional references:

  • -Adachi S, Takiguchi S, Okada K, et al. Effects of ghrelin administration after total gastrectomy: a prospective, randomized, placebo- controlled phase II study. Gastroenterology. 2010;138:1312-1320.
  • -NEJM 2002; 346: 1623-30, 1662. Plasma ghrelin levels decrease after gastric resection.   Therefore, stomach may act as endocrine organ to maintain appropriate weight. However, ghrelin levels are reduced in obesity; so it is not clear that further reduction of these levels is clinically important.
  • -Gastroenterology 2003; 125: 1492. Review of ghrelin.
  • -Yamamoto K, Takiguchi S, Miyata H, et al. Randomized phase II study of clinical effects of ghrelin after esophagectomy with gastric tube reconstruction. Surgery. 2010;141:31-38.
  • -Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature. 2001;409:194-198.
  • -Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone- releasing acylated peptide from stomach. Nature. 1999; 402:656- 660.
  • http://www.surgjournal.com/article/S0039-6060(09)00784-3/abstract
  • http://pennmedicine.adam.com/content.aspx?productId=16&pid=16&gid=50495 Review of cited article.