Functional Dyspepsia, 2016

Nicholas J. Talley; Marjorie M. Walker; Gerald Holtmann


Curr Opin Gastroenterol. 2016;32(6):467-473. 

In This Article


Drugs that relax the gastric fundus may improve functional dyspepsia symptoms, particularly PDS. Amano et al.[31] report that the serotonin type 4 agonist, mosapride, in 14 healthy volunteers, relaxed the fundus as measured by a barostat balloon but did not alter visceral sensation. However, this was a single administration study and functional dyspepsia patients were not evaluated. Another prokinetic drug, acotiamide, is available in Japan for the treatment of functional dyspepsia; this drug increases acetylcholine availability in gut nerve synapses. Yamawaki et al.[32] compared acotiamide and the proton pump inhibitor (PPI) rabeprazole alone and in combination for 4 weeks in 81 patients with functional dyspepsia. Acotiamide in combination with the PPI appeared to be most efficacious in PDS, but this was not a randomized study and the results need to be considered cautiously. Of interest, acotiamide appeared to increase ghrelin levels, and ghrelin increases appetite and reduces nausea, which may in part explain the benefit of this compound.

Degranulation of duodenal mast cells may release histamine, and uncontrolled observations suggest antihistamine therapy may benefit functional dyspepsia. The antihistamine and antiserotonin drug cyproheptadine has been reported, in children, to relieve functional dyspepsia symptoms, but randomized controlled trials are lacking.[33]

Centrally acting drugs are often prescribed in clinical practice for patients with poorly controlled functional dyspepsia symptoms, but this has been empirically driven because of a lack of clinical trial evidence to guide clinicians. An excellent meta-analysis[34] has summarized the available trial data through 2015. Low-dose tricyclic antidepressant therapy is superior to placebo in functional dyspepsia, with the largest trial suggesting those with pain and those with normal gastric emptying are the most likely to respond. On the other hand, there is no evidence that selective serotonin reuptake inhibitors (SSRIs) or selective norepinephrine uptake inhibitors (SNRIs) are superior to placebo, and their use at this time for functional dyspepsia is not appropriate.[1] A combination of an antipsychotic (flupenthixol) with a tricyclic was reported to be efficacious in a single trial; sulpiride and levosulpiride, both atypical antipsychotics, were also reported to be efficacious in functional dyspepsia. None of these antipsychotics are available in the USA.

Another approach is to prescribe the tetracyclic antidepressant mirtazapine, which is a histamine receptor H1 blocker as well as a serotonin receptor 5-HT2C and 5-HT-3 blocker and [alpha]2 adrenergic receptor blocker. Mirtazapine stimulates appetite and can help nausea too. Tack et al.[35] in an excellent proof-of-concept trial enrolled 29 women with early satiety and weight loss (if gastric disaccommodation is severe, leading to excessive early satiety, weight loss may occur in functional dyspepsia). No established therapy is available for this functional dyspepsia subgroup with weight loss. Patients were randomized to 15 mg of mirtazapine or placebo for 8 weeks. Overall, the trial primary endpoint of overall dyspepsia severity was not reached. However, there were positive signals, with anxiety, early satiety, and weight loss significantly improving on active therapy. A larger trial is now needed to assess mirtazapine, which was well tolerated in the dose prescribed.