Postprandial Distress Syndrome – Symptoms, Treatment

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Postprandial Distress Syndrome (PDS)/Functional dyspepsia (FD), defined by the Rome consensus as to the presence of functional symptoms originating from the gastroduodenal, is one of the most common functional gastrointestinal disorders. FD is subdivided into postprandial distress syndrome (PDS), with meal-related symptoms such as postprandial fullness and early satiation, and epigastric pain syndrome (EPS), with meal-unrelated symptoms such as epigastric pain or burning. We used a literature search for a narrative review of the current state of knowledge regarding PDS. The pathophysiology of PDS is heterogeneous, and disorders of gastric sensorimotor function, as well as low-grade duodenal inflammation, have been implicated. Although prokinetic agents may provide the most pathophysiology-oriented treatment option, there is a paucity of suitable agents, and proton pump inhibitors are the traditional first-line therapy. Other options include agents that enhance gastric accommodation, such as acotiamide and 5-HT1A agonists, neuromodulators such as mirtazapine, and traditional medicine approaches. Expert commentary: PDS is highly prevalent, with probably heterogeneous underlying pathophysiology. Motility modifying agents and neuromodulators are the cornerstone of PDS therapy, but there is a need for high-quality studies of new therapeutic approaches.

Functional dyspepsia is one of the most common functional gastrointestinal disorders and affects more than 20% of the population.  There are three different subtypes:

  • Epigastric pain syndrome (EPS),
  • Postprandial distress syndrome (PDS), and
  • Overlapping PDS and EPS.

Pathophysiology

Although the exact mechanism is not well understood, the pathophysiology of functional dyspepsia is complex. Several different mechanisms are thought to contribute to each subtype. Traditionally, functional dyspepsia has been attributed to disturbances in gastric physiologic factors divided into macroscopic and microscopic mechanisms. Macroscopic mechanisms include gastroesophageal reflux (GERD), delayed gastric emptying, and visceral hypersensitivity alterations in the nervous system. Microscopic mechanisms include impaired barrier function, altered sensitivity to duodenal acid or lipids, and gastroduodenal inflammation. Additional mechanisms include environmental insults like food inducing gastroduodenal physiologic changes, infections causing inflammation, and allergen exposure can lead to eosinophil recruitment in genetically predisposed patients. Psychological factors like anxiety and depression can cause a negative stimulus to the brain-gut axis, suggesting that there is central processing of visceral stimuli from sensations in the gastrointestinal tract.

Causes of Postprandial Distress Syndrome

The etiology of functional dyspepsia/Postprandial Distress Syndrome is likely multifactorial; however, the exact cause is not clearly understood.  Several risk factors have been seen to be associated with the condition.

  • Enteric infections: H. pylori, Escherichia coli O157, Campylobacter jejuni, and Salmonella.
  • Recent antibiotic use
  • Use of non-steroidal anti-inflammatory drugs
  • Being overweight
  • Smoking
  • Psychosocial dysfunction
Medications
Diseases

 Symptoms Of Postprandial Distress Syndrome

Diagnosis of Postprandial Distress Syndrome

Postprandial Distress Syndrome is diagnosed based on the Rome IV criteria.  It is defined by the presence of one or more of the following symptoms: epigastric pain or burning, early satiety, and postprandial fullness in the absence of structural disease using imaging or endoscopy. First, patients should be tested and treated for Helicobacter pylori (H. pylori) if they are less than 60 years of age. Then, further treatment consists of symptom management with proton pump inhibitors (PPI), H2 receptor antagonists (H2RA), prokinetic agents, and even antidepressants. Alarms symptoms such as weight loss, dysphagia, or vomiting, or if greater than age 60, warrant an endoscopic evaluation.

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History and Physical
  • Typical symptoms can be divided into the subtypes PDS and EPS, and there exists an overlap between the two syndromes. These symptoms can be acute or chronic. PDS patients report loss of appetite, early satiation, nausea, retching, vomiting, and bloating.
  • In EPS, patients have stomach cramping and other upper abdominal pain. Some symptoms are non-gastrointestinal. Patients often report associated diaphoresis, headache, sleep disorders, and irritable bladder.
  • Functional dyspepsia symptoms usually do not progress and lack red flag signs of unintentional weight loss, dysphagia, night sweats, and persistent vomiting. Patients usually have an unremarkable physical exam, and this can assist in excluding other diagnoses.
Evaluation

The American College of Gastroenterology (ACG) recommends the routine use of upper endoscopy in patients older than 60 years to rule out malignancy, especially in the setting of red flag signs. If patients do not respond to treatment, it is reasonable to pursue more specialized testing specific to the symptoms.

In addition to a physical exam and questions about your symptoms, a doctor may perform the following tests. To exclude organic causes, evaluation can start with laboratory tests, including blood count, complete metabolic panel, thyroid function, and inflammatory markers.

Treatment of Postprandial Distress Syndrome

Treatment can be challenging, where the main aim is symptom control. Initial management begins with an explanation of the diagnosis and discussing the patient’s expectations for treatment. If it is suspected, H. pylori eradication is recommended as the first treatment for all patients with functional dyspepsia, as this improves symptoms and decreases the risk of peptic ulcers and gastric cancer. After this, treatment is a two-step process.

Then, if symptoms persist, subsequent treatment with tricyclic antidepressants, or prokinetic agents like metoclopramide and acotiamide are pursued. Adjunctive or alternative non-pharmacologic therapies include psychotherapy, herbal supplementation, lifestyle modification, dietary interventions, acupuncture, and electrical stimulation.

Treatment algorithm for dyspepsia, modified from ()

  • Proton pump inhibitors
  • Helicobacter pylori eradication treatment
  • Phytotherapy
  • Antidepressants
  • Psychotherapy.

Acid-suppressing medications

Numerous multinational randomized controlled trials of proton pump inhibitors (PPI) have demonstrated a significant favorable effect against functional dyspepsia compared with placebo [. One meta-analysis showed a 10 to 20% higher treatment effect for PPI than for placebo with a number needed to treat of patients [. In subgroup analysis, the PPI effects are limited to epigastric pain syndrome or dyspeptic symptoms with accompanying [, , .

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Further general measures

  • Conflict resolution in the psychosocial domain
  • Encouraging the patient to take responsibility
  • Relaxation exercises
  • Treatment alliance for long-term care
  • Psychotherapeutic options

Despite the positive study data, the PPIs have not been approved for the treatment of functional dyspepsia in Germany. In the context of the recent public discussion of the potential side effects of PPIs, it can be stated that when used according to the indications these drugs are very safe, particularly since they are not employed for long-term management of functional dyspepsia [.

Eradication of Helicobacter pylori in functional dyspepsia

The effect of H. pylori eradication treatment in functional dyspepsia has been the subject of a large number of placebo-controlled trials. Meta-analyses of all of these studies show a significant difference with an NNT of 15 [, . After H. pylori eradication in H. pylori-positive functional dyspepsia, around 10% of patients stay symptom-free in the long term, while in the remaining patients the symptoms persist or return despite extirpation. It remains a topic of controversy in the literature on whether H. pylori-associated dyspepsia is a subgroup of functional dyspepsia or represents an independent entity [, .

However, this discussion is irrelevant in clinical practice. In view of the absence of causal treatments for functional dyspepsia, H. pylori eradication is an important treatment option because of its curative potential. For this reason, it is recommended in German and international guidelines [.

Treatment options

  • Proton pump inhibitors
  • Helicobacter pylori eradication treatment
  • Phytotherapy
  • Antidepressants
  • Psychotherapy

In the current guideline of the German Society for Gastroenterology, Digestive and Metabolic Diseases (Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten, DGVS) [ H. pylori eradication is a “can” indication. The potential side effects of antibiotic treatment must always be taken into consideration in the course of decision making.

Postprandial distress syndrome: first-line

A prokinetic is usually offered as a first-line treatment, but options vary by country and remain restrictive. Very limited data support the use of domperidone, a dopamine antagonist, and the same applies to metoclopramide [rx,rx]. Cisapride, a serotonin type 4 (5HT4) agonist and serotonin type 3 (5HT3) antagonist, has been withdrawn in most countries because of QT prolongation, but it was superior to placebo in cases with FD [rx]. Tegaserod, a 5HT4 agonist, was marginally better than a placebo [rx], while mosapride is probably not efficacious [rx], and itopride is of uncertain benefit over placebo [rx].
Acotiamide is approved for FD in Japan. The drug relaxes the gastric fundus and accelerates gastric emptying in humans [rx]. A modest but significant benefit over placebo was observed in FD, with 52% of those on acotiamide for over 4 weeks responding, compared with 35% on the placebo, based on a global assessment of the overall treatment effect [rx]. Complete loss of meal-related symptoms occurred in 15% of those on acotiamide versus 9% on a placebo, which was significant statistically but arguable in terms of clinical efficacy [rx]. Other drugs also relax the gastric fundus and may have a value in treating FD, including the anti-anxiety drug and serotonin type 1a agonist buspirone and tandospirone, and the anti-migraine drug and serotonin type 1 agonist, sumatriptan [rx,rx], but data remain limited.

Centrally acting therapy

If first-line therapy fails, a centrally acting drug may be considered. In the Functional Dyspepsia Treatment Trial conducted in North America, a low dose tricyclic antidepressant (amitryptiline 50 mg) was compared with a selective serotonin reuptake inhibitor (SSRI) in antidepressant dosing (escitalopram 10 mg) and a placebo over 3 months with a 6-month follow-up post-therapy [rx]. The SSRI performed no better than the placebo, which was consistent with other clinical data on a selective serotonin-norepinephrine reuptake inhibitor (SNRI), venlafaxine [rx]. On the other hand, the tricyclic antidepressant appeared to provide a modest benefit for FD, especially in those with pain [rx]. Patients with ulcer-like FD, likely equivalent to EPS, who were given amitriptyline were over 3-fold more likely to report adequate relief than were those who received the placebo, although the patient diaries showed that meal-related symptoms also benefited compared with the placebo. Interestingly, tricyclics can theoretically slow gastric emptying, and those with delayed gastric emptying were less likely to report adequate relief on amitriptyline compared with FD patients with normal emptying. Notably, antidepressant therapy did not change psychological distress measures and did not alter gastric emptying rates.
Another promising approach is the use of the tricyclic antidepressant mirtazapine. Although mirtazapine does not alter gastric function [rx], results from a preliminary randomized controlled trial of FD suggest benefits over a placebo [rx]. Levosulpiride is an atypical antipsychotic drug that is a benzamide derivate and dopamine [rx] antagonist; in cases with FD, it may be as efficacious as cisapride, but more data are needed, including large placebo-controlled trials [rx].
Psychological therapies are of uncertain benefit in FD, although positive trial data have been reported [rx]. However, combining medical therapies with psychological therapy may provide better outcomes, although large-scale trials are needed to confirm these observations [rx,rx].

Phytotherapy and complementary treatment options

Eradication of Helicobacter pylori

In view of the absence of causal treatments for functional dyspepsia, H. pylori eradication is an important treatment option because of its curative potential. For this reason, it is recommended in German and international guidelines.

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Phytotherapeutics have long been used in medicine. Numerous placebo-controlled trials have shown a significant positive effect of phytotherapy compared with placebo in the treatment of functional dyspepsia [, . Combined preparations are often used to treat functional dyspepsia. Mostly these are fixed combinations of peppermint and caraway oil or mixtures of bitter candytuft, wormwood, gentian, and angelica root, usually in combination with spasmolytic and sedative extracts such as chamomile, peppermint, caraway, and lemon balm. Phytotherapeutics exert a spasmolytic tonus-stimulating and/or sedative effect on the gastrointestinal tract and this may relieve the symptoms of functional dyspepsia [[. In a meta-analysis of three placebo-controlled trials, treatment with STW 5 for 4 weeks was significantly superior to placebo [. A subsequent larger multicenter placebo-controlled trial over a period of 8 weeks confirmed the treatment effect [. In the wake of numerous positive placebo-controlled studies, phytotherapy is now recommended in German and international guidelines for use against functional gastrointestinal disorders, in particular functional dyspepsia and IBS [, . Treatment of functional dyspepsia with digestive enzymes has also been studied, whereby the clinical action of the fixed combinations of gastric mucosal extract and amino acid hydrochlorides that are used is exerted not via substitution but by supporting the proteolytic release of amino acids.

Antidepressants and psychotherapy

Phytotherapy

Phytotherapeutic preparations are mostly fixed combinations of peppermint and caraway oil or mixtures of bitter candytuft, wormwood, gentian, and angelica root, usually in combination with spasmolytic and sedative extracts such as chamomile, peppermint, caraway, and lemon balm.

Antidepressants are used after the failure of the above-mentioned treatments. Efficacy has been confirmed for tricyclic antidepressants but not for serotonin reuptake inhibitors [. The largest study to date investigated the effect of amitryptiline (25 mg for 2 weeks, then 50 mg for 10 weeks), escitalopram (10 mg for 12 weeks). While escitalopram showed no effect, amitryptiline reduced the burden of the predominant symptom, abdominal pain, significantly compared with placebo [. Other studies have also shown that antidepressants are particularly effective against dyspepsia symptoms when the predominant complaints are abdominal and/or mental comorbidity. There are also data supporting the use of psychotherapy, which should be considered particularly in the case of treatment resistance [,

Prokinetics

Because motility disorders are a possible underlying cause of functional dyspepsia, prokinetics can be considered for treatment.[, . Cisapride and domperidone were the substances mostly studied. Cisapride was withdrawn from the market some time ago owing to cardiotoxicity, while the adverse effects of domperidone and metoclopramide mean that their use is restricted, particularly in long-term treatment. Thus, there are currently no prokinetics that can be used in daily clinical practice. The selective 5-HT4 agonist prucalopride is effective against functional dyspepsia when the indication for treatment is refractory obstipation, but no controlled trials have been performed so prucalopride has not been licensed. Acetamide (a muscarinic autoreceptor inhibitor and cholinesterase inhibitor), itopride, and levosulpiride (both selective dopamine-D2 antagonists) are further prokinetically active pharmaceuticals that have proven effective in controlled studies but have not yet been approved for use in Germany [.

References

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