Functional dyspepsia is a heterogeneous disorder. It involves many pathogenic factors and different pathophysiological disturbances, including delayed gastric emptying, impaired accommodation, and hypersensitivity to gastric distention. Treatment of the underlying pathophysiological abnormality seems logical, but the main pharmacotherapeutic options include acid suppression, prokinetic drugs, and antidepressants [6
], all of which have limited effects. Herbal formulations are widely used to treat FD in China and many other areas in the world. However, the available evidence of the efficacy of these formulas is inadequate.
This multi-center, randomized, double-blind, placebo-controlled study indicates that modified LiuJunZi decoction is effective in the management of symptoms associated with FD and gastric emptying. The effects appeared to last for up to 4 weeks after completion of treatment, and were particularly beneficial for postprandial fullness and bloating and early satiety. Patients receiving modified LiuJunZi decoction treatment demonstrated significantly better outcomes (both clinically and statistically) on all the outcome measures compared with patients receiving placebo. Moreover, no adverse events were reported during the study.
The evaluation of treatment effects in FD is difficult and there is currently no gold standard. In our study, we used two different parameters as the main target variables. The TDS scale included almost all symptoms associated with FD, and the SDS scale included information on the four principal symptoms of FD, measured in terms of the frequency, intensity and level of discomfort. The main target variables were recorded by both investigators and patients. We also assessed gastric emptying with radiopaque barium markers as a more objective outcome. Another difficulty in clinical trials with patients with FD is the remarkable placebo response. It has been shown that one third of patients with FD will respond to placebo in short-term trials [28
], and the proportion may be even higher in long-term studies. In our study, we made a great effort to make the treatments in the two groups indistinguishable for the patients. A placebo of similar appearance, smell and taste to the active concoction was used. To ensure that the patients were not able to discriminate between placebo and active treatment, 20 healthy volunteers participated in a randomized taste and visual assessment of the placebo and active medication. Eight volunteers correctly identified the active compound as active, whereas twelve volunteers considered the placebo preparation to be the active compound. Thus, it is reasonable to assume that the medication was given in an appropriately blinded manner. Despite the well-known high response rate to placebo in FD, we found significantly greater improvements in dyspepsia symptoms and gastric emptying in patients receiving the CHM compared with placebo-treated patients.
In TCM, injury by food or drink, emotional injury, and congenital defects are main pathogenic factors of FD. All these pathogenic factors cause abnormal function of the upper abdomen, spleen and stomach. Spleen-deficiency and qi-stagnation exist throughout the course of the disease. The herbal formula provided to patients in this study was a modified LiuJunZi decoction. All the herbs matched well, and could replenish the deficiencies, and harmonize and regulate the qi. Because the function of the spleen and stomach recovered, all the dyspepsia symptoms were abated and the gastric emptying improved. This is accordance with previous studies [15
] which showed physiological effects of LiuJunZi decoction and some other herbal medicines in the modified LiuJunZi decoction. In Japan, LiuJunZi decoction is used for functional dyspepsia and has been found to improve the symptoms in patients, regulation of gastrointestinal function and hormone secretion [29
]. However, herbal preparations are complex and contain a number of active ingredients that may work together. The multiple effects of different active ingredients may be of benefit for the variety of different symptoms that occur in functional gastrointestinal disorders. However, more studies are needed to explore the mechanisms of action and properties of the identified components. FD is a common, chronic and recurrent functional gastrointestinal disorder. This study used a short treatment period and follow-up and a relatively small number of patients, so there is ample room to enhance the evaluation of efficacy and safety by further studies.