Gut-brain axis is defined as the relationship of gastrointestinal with brain function and mental status. Mental stress is associated with personality-dependent gastric acid secretion changes. Moreover, gastric inflammation leads to anxiety and depression-like behaviors via the neuroendocrine pathways especially in female1.
One of the most common functional gastrointestinal disorders (FGIDs) in the world is FD. Most patients with FD develop anxiety and depression. In addition, patients with depression had a tendency to develop FD as well.2 The FD is a common presenting symptom for H. pylori infection. It had been estimated that over half of the world’s population is infected with H. pylori, which may give it a significant role in the brain-gut axis and links it with psychiatric disorders like depression3.
Moreover, it had been observed that the efficacy in ulcer treatment and H. pylori eradication is increased when antidepressants such as tricyclic antidepressant (TCA) or selective serotonin reuptake inhibitors (SSRIs) are added to the standard regimens against H. pylori. It had been suggested that receptors for serotonin were up-regulated when patients had H. pylori gastritis4.
This study aims to assess the relationship between psychiatric disorder and H. pylori gastritis and if antidepressant drugs play any role in treating patients with chronic H. pylori gastritis.
MATERIALS AND METHODS
Study area: The study was conducted at a private hospital in the Kingdom of Bahrain. Data were collected retrospectively (from January 2016 to December 2019) from gastroenterology and hepatology center database.
Subjects: All patients who visited the gastroenterology and hepatology center for dyspeptic symptoms during the study period (n = 96). Dyspepsia was defined according to Rome III as the presence of at least one symptom of the followings: early satiation, postprandial fullness, epigastric pain or epigastric burning symptoms fulfilled for the last 3 months with onset at least 6 months before diagnosis5.
Stool Ag detection for H. pylori was done by commercially available Testmate Rapid Pylori Antigen (TRP) immunochromatography kit, according to the manufacturer's instructions (Testmate rapid pylori antigen [TRP]; Wakamoto Pharmaceutical Co., Ltd., Tokyo, Japan). The TRP is a sensitive, cheap and easy method for the initial diagnosis of H. pylori infection. It is an immunochromatography based approach against H. pylori catalase. MAb 21G2 and anti-mouse IgG polyclonal antibody were immobilized onto nitrocellulose membranes. One drop of the stool sample suspension was placed on the specimen application region of the test strip. After 10 min, if native catalase H. pylori antigens were present in the samples, both the control and test lines were red6.
Patients had been examined endoscopically and two antral biopsies were taken during endoscopy within 2 cm of the pylorus with a standard 2.8 mm cup proved to perform rapid urease test H. pylori7.
Hamilton Anxiety Rating Scale (HAM-A) was used to evaluate and measure the severity of anxiety symptoms. The scale consists of 14 items; each item was defined by a series of symptoms. psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety) were measured by using the scale.
Each item was scored on a scale of 0 (not present) to 4 (severe). The severity of anxiety was measured according to the total score range; mild severity = <17, mild to moderate=18-24, moderate to severe = 25-308.
Hamilton Depression Rating Scale (HDRS) was the assessment scale for depression. The scale consists of 17 items related to symptoms of depression experienced over the past week and emphasis on melancholic and physical symptoms of depression.
A total score of 0-7 was considered as a normal range or clinical remission, while a score of 20 or more was considered moderate severity or more9.
All patients with H. pylori were given quadruple therapy (rabeprazole 20 mg+ amoxicillin 1.0 g+ clarithromycin 0.5 g+ colloidal bismuth subcitrate solution 10 mL, bid) for 2 weeks. Patients positive for H. pylori and had psychiatric disorders, in addition to quadruple therapy, were given TCA at night (tryptizol 20 mg) and one of SSRI drugs (escitalopram 10 mg once daily, sertraline 25 mg once daily, or paroxetine) in the morning time. All patients’ records were checked for H. pylori eradication and improvement of severity of FD symptoms for six months. Follow up records were collected from the central database.
Follow up of persistent H. pylori infection after eradication therapy was monitored using Urea Breath Test (UBT) as it is the gold standard and by stool Ag detection ( it needs at least 4 weeks after treatment due to delayed fecal elimination of H. pylori antigens or coccoid forms after successful eradication)10. After treatment courses were completed, results were monitored starting at 4-5 weeks after treatment, then after 2 months and continued for 6 months post-treatment. Failure was defined as the persistence of FD symptoms that were not sufficiently controlled and positive H. pylori by urea breath test.
Statistical analysis: Data were collected and tabulated by using health electronic system and then analyzed using statistical software SPSS version 24 (IBM Corp., Chicago, Illinois, USA). Descriptive statistics of demographic variables were calculated including frequencies, percentages, means and ranges.
Out of 96 dyspeptic patients, H. pylori was positive in 53 patients by both stool Ag detection and rapid urease test (55.2%), with the most common complaints at initial presentation was epigastric burning. The majority of H. pylori patients were females 35 (66%), out of them 18 (51.4%) were <50 years old (Table 1).
By using the HADS questionnaire, psychiatric disorders were diagnosed in 60 patients of FD (62.5%). Females:Males ratio was 3:1.
Psychiatric status was evaluated in H. pylori patients and it was found that 25 of 53 H. pylori patients (52.8%) had psychiatric disorders. The most common psychiatric disorder was anxiety in 19 patients (67.9%) and 9 patients (32.1%) were diagnosed with depression (Fig. 1).
Both groups of H. pylori patients (with and without psychiatric disorders) had completed their treatment regimen. Twenty-six out of twenty-eight patients (92.9%) who received antidepressant treatment plus the standard quadruple regimen, had successful treatment outcomes with two consecutive negative UBT (<50 dpm) at 4 and 5 weeks following completion of treatment. Two of these UBT-negative patients (7.6%) had positive stool Ag at 1 month following treatment and became negative after 2 months (Fig. 2).
Out of the remaining 25 H. pylori patients (without psychiatric disorders) who received only the standard quadruple regimen, only 14 (56%) had successful treatment outcomes with two consecutive negative UBT (<50 dpm) at 4 and 5 weeks following completion of treatment. Five of these UBT-negative patients (35.7%) had positive stool Ag at 1 month following treatment and became negative after 3 months. Eradication rates increased to 88 % (22 out of 25) after 2 months (Fig. 2).
The therapeutic efficacy of H. pylori eradication was significantly increased (p<0.05) in the patients group who received antidepressant treatment plus the standard quadruple regimen.
Distribution of H. pylori patients according to psychiatric disorders
||25% shows psychiatric disorders patients
Successful treatment outcomes at 4 and 5 weeks
Demographic characteristic of H. pylori patients
The FD symptoms had declined dramatically after H. pylori eradication therapy and antidepressant treatment.
The prevalence of H. pylori infections varies in different populations and according to different socioeconomic groups11. In the developed countries the prevalence ranged between 10-30%12. High prevalence rates of H. pylori-associated gastritis among Bahraini dyspeptic adults had been reported by Huerta-Franco et al.13, where it reached 75% and by Kabeer et al.14 who found it to be 57% among Bahraini children presenting with recurrent abdominal pain. A similarly high prevalence was reported in this study among FD patients (55.2%). Epidemiological reports concluded male predominance of H. pylori infection. However, in the present study, the majority of H. pylori patients were females (66%) and more than half of them were <50 years old. This was in agreement with Kamath et al.15, who found that H. pylori infection was significantly associated with the female gender.
The interconnection between psychiatric disorders and H. pylori gastritis and its association with failure of H. pylori eradication had been in consideration. Patients with functional dyspepsia commonly have H. pylori infection, anxiety and depression16. Piriyapong et al.17 concluded that females below 50 years of age with seropositive H. pylori gastritis had a higher risk of psychological distress and depression. Shimoyama et al.18 reported that 40.7% of functional dyspepsia and H. pylori-positive patients had at least one psychiatric illness; the most common was depression. Takeoka et al.19 found the prevalence of H. pylori and depression in patients with functional dyspepsia was 29.2%. This study was parallel with previous studies, where H. pylori patients were evaluated for their psychiatric status using the HAM-A and HDRS questionnaire and it was found that 52.8% of them had either depression or anxiety.
Effect of combined medical treatment of H. pylori and psychiatric disorders had been studied and evidence of the synergistic effect of antidepressant drugs adjuvant therapy alongside standard antibiotics regimen (triplet or quadruplet drug therapy) to eradicate H. pylori is still not sufficiently strong. Moreover, the antibiotics regimen of H. pylori infection may develop neuropsychiatric symptoms that typically resolve after the discontinuation of the antibiotics20. Wang et al.21 concluded that anxiolytic drugs and antidepressants have peculiar effects on functional dyspepsia of H. pylori. Wang et al.21 found that using antipsychotic and TCA antidepressant (flupentixol and melitracen) combined with quadruple therapy in anxiety and depression patients led to a significant reduction in the recurrence rate of peptic ulcer and improvement of H. pylori eradication. A similar finding of improvement of H. pylori eradication in patients who received SSRIs agents and TCA in addition to quadruple therapy for 2 weeks. Zainaldeen et al.22 showed similar results of the significant improvement in symptoms of FD in the group that received medical therapy along with cognitive behavioral therapy. On the other hand, Takeoka et al.19 explained the poor improvement in the severity of dyspepsia in their psychiatric patients by lack of antidepressant drug treatment and depending only on counseling therapy which may be inadequate or insufficient duration and lack of compliance. Despite the acceptable reliability of HAM-A, it could not discriminate between anxiolytic and antidepressant effects and somatic anxiety versus somatic side effects. Moreover, HDRS could not assess atypical symptoms of depression (hypersomnia and hyperphagia) that are not assessed.
High prevalence of H. pylori infections in functional dyspepsia patients in the Kingdom of Bahrain. There is a clear association between psychiatric disorder and H. pylori infection. Added antidepressant drugs to standard antibiotic regimens may have a role in the improvement of FD symptom and H. pylori eradication. However, further studies should evaluate this finding due to the limited number of studied patients in this study.
This study discovered the correlation between psychiatric disorders and H. pylori infection that can be beneficial for psychiatrists to study psychosomatic disturbances in their patients. This study will help the researchers to uncover the critical areas of the brain-gut axis that many researchers were not able to explore. Thus a new theory on effective treatment of H. pylori using antidepressant drugs may be arrived at.