Edited by: Qinghua He, Southwest University, China
Reviewed by: Xueling Zhu, National University of Defense Technology, China; Zhang Bing, Hunan University of Chinese Medicine, China
†These authors have contributed equally to this work.
Specialty section: This article was submitted to Psychopathology, a section of the journal Frontiers in Psychiatry
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To assess the correlation between the incidence of non-erosive reflux disease (NERD) and mental and psychological factors, deepen the understanding of the pathogenesis of NERD and explore effective treatments.
NERD patients with mood disorders who met the inclusion criteria were randomly divided into a drug treatment group, a psychotherapy group, and a psychotherapy combined with drug treatment group. Before and after treatment, the patients were retrospectively analyzed using the gastroesophageal reflux disease Questionnaire, Hamilton Depression Scale, Hamilton Anxiety Scale, and SF-36 Quality of Life Scale.
All three treatments were found to relieve patients’ symptoms and improve their quality of life to some extent. The psychotherapy combined with drug treatment group showed the best overall curative effect. The Hamilton Depression and Anxiety Scale scores were significantly lower in the psychotherapy-alone group and psychotherapy combined with drug treatment group than in the drug treatment alone group at 4, 8, and 12 weeks (
Medication, psychotherapy, and psychotherapy combined with medication can relieve clinical symptoms and improve quality of life to varying degrees in patients with NERD.
Gastroesophageal reflux disease (GERD) is a disease in which the gastroduodenal contents reflux into the esophagus, causing such symptoms and complications as acid reflux, heartburn, and post-sternal pain (
Studies have shown that the incidence of NERD has been increasing annually (
Cognitive-behavioral therapy (CBT) is a psychotherapeutic method that focuses on establishing correct personal cognition through cognitive education and behavioral skills to correct patients’ errors or distortions and to alleviate and eliminate psychological disorders and somatic symptoms. It is quicker and more efficient than other types of psychotherapy (
However, there are few studies of the therapeutic effects of CBT on NERD, and the mechanism underlying psychotherapy for NERD is not yet clear. In the present work, we explore the correlation between the incidence of NERD and mental and psychological factors and the efficacy of CBT combined with conventional drug treatment of NERD and so deepen the understanding of the pathogenesis of NERD and explore effective treatment.
A total of 115 patients with NERD who were diagnosed with mood disorder in the Departments of Gastroenterology at Xiangya Hospital and Yiyang Central Hospital from September 2016 to June 2017 were selected. The study was approved by the ethics committees of both hospitals, and all the patients signed the informed consent forms.
Meet the NERD diagnostic criteria: (1) patients with typical heartburn, reflux, and other symptoms lasting for more than 1 month and occurring an average of more than three times per week; (2) patients meeting the previous conditions who also have reflectance disease questionnaire (RDQ) scores over 12 points despite gastroscopy indicating no esophageal mucosal damage (
Patient’s HAMA >7 points and <21 points, HAMD >7 points and <24 points, or both.
(1) Dysfunction or failure of vital organs; (2) diabetes or neurological disease; (3) contraindications for drugs used in the study; (3) any previous treatment for reflux esophagitis, anxiety, or depression; (5) disinclination to cooperate with the questionnaire or poor medication compliance. Patients were excluded if they met one or more of these conditions.
The RDQ is currently the most widely recognized and widely applied GERD diagnostic scale in the world, and its validity and reliability in GERD diagnosis have been confirmed (
Hamilton Anxiety Rating Scale (HAMA): HAMD and HAMA were used to assess the severity of depression and anxiety, respectively. HAMD contains 17 items yielding a maximum score of 52, with higher scores indicating greater depressive symptom severity. HAMA consists of 14 items.
Hamilton scales are assessed before initiation of treatment and 4, 8, and 12 weeks after initiation of treatment [HAMA score: >7 points and <14 points indicates possible anxiety; >14 points and <21 points indicates definite anxiety; >21 points, certainly have significant anxiety. HAMD score: >7 points and <17 points indicates mild depression; >17 points and <24 points indicates moderate depression; >24 points, indicates severe depression (
SF-36, which has been documented to have acceptable reliability and validity, is used widely to evaluate people’s health-related quality of life. SF-36 is a universal scale that evaluates eight aspects of health-related quality of life: physical functioning, role-physical, bodily pain, general health (GH), vitality (VT), social functioning (SF), RE, and mental health (MH) (
(1) RDQ symptoms and results of HAMD and HAMA before and after intervention; (2) results of SF-36 before and after intervention.
Patients with NERD who met the criteria were randomly divided into three groups: a drug treatment group, a psychotherapy group, and psychotherapy combined with drug treatment group. There were 12 male and 23 female participants in the drug treatment group (
The patients in the drug treatment group took omeprazole (Trade name: Losec, Sweden AstraZeneca Pharmaceutical Co., Ltd., SFDA approval number: J20080097) 40 mg orally twice a day; domperidone (Xi’an-Janssen Pharmaceutical Co., Ltd. Company, SFDA approval number: H10910084) 10 mg orally every time three times a day for a total of 12 weeks according to doctor’s orders. Patients in the psychotherapy group received CBT alone. Patients in the psychotherapy combined with drug treatment group received the same psychotherapy as in the psychotherapy group and also took conventional drugs.
In the psychological treatment group and psychotherapy combined with drug treatment group, psychological counselors gave a preliminary diagnosis of psychological problems on the patients and proposed psychological assessment reports. After the establishment of the relationship between the two involved parties, both jointly came to an agreement to formulate a psychotherapy program and perform psychotherapy with CBT twice a week. The details are as follows.
(1) Clarify the bad cognition regarding the patients’ own symptoms and the distorted perception of themselves and identify automatic thinking; (2) perform the appropriate checks to cultivate an objective basis to help patients rationally analyze their condition, and provide as detailed and patient an explanation as possible of the test results and the prevalence of illness, especially the patients’ suspected symptoms; (3) explain the possible etiology, pathogenesis, treatment, and clinical efficacy of NERD, and psychological factors in the pathogenesis of NERD and cognitive therapy in the relief of NERD symptoms; (4) use authenticity testing and other techniques to help patients alter wrong or distorted cognition and promote cognitive changes.
(1) Introduce emotion and emotional causes and analyze the cycle by which negative emotions and symptoms reinforce each other. Guide patients to use ABC theory to change cognition and improve mood. (2) Master and practice self-discipline training. (3) Guide behavior to help patients develop good eating habits.
During the implementation, the first interview was completed by a professional psychological counselor, and then the patients regularly (twice a week) underwent psychological treatment in the form of small groups to form a treatment alliance, and each patient can benefit from feedback from others and enhance the confidence of treatment. Patients are also required to keep daily records of reflux symptoms, diet, changes in lifestyle, and other matters in the form of homework, which helps identify the interrelationships and determine what the causes of the symptoms are, to allow for appropriate adjustments. In this process, doctors and researchers can also identify patients’ cognitive errors in a timely manner and promptly correct them to ensure that treatment will go smoothly.
Regular follow-up (at 4, 8, and 12 weeks), for scale measurement and RDQ symptom score, and symptoms were recorded and evaluated by the assessors.
The patients’ RDQ scores were used to declare their treatment effective or ineffective after 12 weeks of treatment. Improvement rate
= [(pretreatment score − post treatment score)/pretreatment score] × 100%, improvement rate ≥50% is effective, <50% is ineffective (
We used SPSS 20.0 for data analysis and statistics. HAMD and HAMA of each group before and after treatment were compared and the symptom scores of each group were compared using ANOVA for repeated measurement. The quality of life before treatment and 12 weeks after treatment were compared using paired-samples
There was no significant difference between HAMD scores before treatment in each group (
Comparison of HAMD scores before and after treatment in each group.
Drug treatment group | Psychotherapy group | Psychotherapy combined with drug treatment group | η2 | ||
---|---|---|---|---|---|
Pretreatment | 14.26 ± 3.721 | 14.03 ± 2.948 | 14.63 ± 4.068 | 0.281 | 0.003 |
After 4 weeks | 14.29 ± 3.304 | 13.85 ± 2.607 | 10.13 ± 2.747 | 24.438 |
0.180 |
After 8 weeks | 14.11 ± 3.954 | 10.55 ± 3.419 | 8.98 ± 2.281 | 24.052 |
0.178 |
After 12 weeks | 14.03 ± 3.981 | 8.28 ± 3.302 | 6.63 ± 2.579 | 51.787 |
0.318 |
Comparison of HAMD scores before and after treatment in each group.
Comparison of HAMA scores before and after treatment in each group.
Drug treatment group | Psychotherapy group | Psychotherapy combined with drug treatment group | η2 | ||
---|---|---|---|---|---|
Pretreatment | 15.29 ± 3.383 | 14.98 ± 3.893 | 15.23 ± 4.098 | 0.072 | 0.001 |
After 4 weeks | 15.17 ± 4.376 | 14.75 ± 4.634 | 11.13 ± 3.688 | 10.660 |
0.088 |
After 8 weeks | 14.86 ± 3.942 | 11.25 ± 3.418 | 7.18 ± 2.459 | 50.872 |
0.314 |
After 12 weeks | 15.11 ± 4.013 | 7.85 ± 3.294 | 4.75 ± 2.048 | 102.89 |
0.481 |
Comparison of HAM scores before and after treatment in each group.
Symptom scores before treatment showed no significant differences between groups (
Comparison of symptom scores before and after treatment of patients in each group.
Drug treatment group | Psychotherapy group | Psychotherapy combined with drug treatment group | η2 | ||
---|---|---|---|---|---|
Pretreatment | 22.26 ± 9.516 | 22.78 ± 9.744 | 22.08 ± 7.934 | 0.064 | 0.001 |
After 4 weeks | 17.51 ± 6.840 | 21.00 ± 6.013 | 15.35 ± 5.066 | 9.083 |
0.076 |
After 8 weeks | 14.97 ± 5.732 | 16.73 ± 6.425 | 10.50 ± 3.602 | 14.203 |
0.113 |
After 12 weeks | 8.86 ± 3.836 | 10.60 ± 3.855 | 6.45 ± 2.521 | 14.641 |
0.117 |
Comparison of symptom scores before and after treatment of patients in each group.
SF-36 scores in NERD patients improved in all categories in the drug treatment group, psychotherapy group, and psychotherapy combined with drug treatment group (Table
Comparison of SF-36 scores before and after treatment (M ± SD).
Drug treatment group | Psychotherapy group | Psychotherapy combined with drug treatment group | ||||
---|---|---|---|---|---|---|
Pretreatment | After 12 weeks | Pretreatment | After 12 weeks | Pretreatment | After 12 weeks | |
Physical functioning | 84.03 ± 7.46 | 87.74 ± 6.31a | 84.28 ± 7.29 | 85.63 ± 7.76b | 83.10 ± 9.06 | 91.90 ± 6.24a,b,c |
Role-physical | 50.49 ± 7.13 | 55.63 ± 8.89a | 50.00 ± 18.15 | 52.93 ± 15.91 | 50.83 ± 22.56 | 63.00 ± 20.01a,c |
Bodily pain | 61.94 ± 8.44 | 67.00 ± 6.88a | 61.90 ± 20.44 | 64.00 ± 21.59 | 64.68 ± 22.41 | 77.00 ± 15.97a,b,c |
General health | 70.74 ± 8.12 | 75.89 ± 8.72a | 71.60 ± 17.58 | 79.90 ± 15.76a | 71.35 ± 19.05 | 84.10 ± 16.38a,b |
Vitality | 56.14 ± 19.14 | 62.2 ± 19.22a | 55.93 ± 20.36 | 63.10 ± 21.99a | 55.95 ± 21.72 | 74.28 ± 18.11a,b,c |
SF | 70.60 ± 20.13 | 78.6 ± 18.69a | 70.50 ± 19.18 | 80.83 ± 14.99a | 72.85 ± 17.68 | 87.83 ± 13.48a,b |
RE | 51.97 ± 26.07 | 57.4 ± 23.95a | 51.58 ± 20.21 | 64.03 ± 21.72a | 50.58 ± 22.44 | 73.08 ± 21.18a,b |
Mental health | 60.40 ± 15.37 | 66.7 ± 20.21a | 60.63 ± 18.68 | 73.30 ± 12.28a | 61.08 ± 18.34 | 76.93 ± 14.05a,b |
The χ2 test showed a significant difference (χ2 = 15.53,
Effects of 12 weeks of treatment in each group.
Cases | Validity (%) | Invalidity (%) | |
---|---|---|---|
Drug treatment group | 35 | 26 (74.29) | 9 (25.71) |
Psychotherapy group | 40 | 23 (57.5) | 17 (42.5) |
Psychotherapy combined with drug treatment group | 40 | 38 (95) | 2 (5) |
The results of this study show that the three methods of treatment can all improve patients’ symptoms and quality of life to different degrees. Patients given psychotherapy combined with drug therapy and those given psychological treatment alone showed significantly more pronounced decreases in Hamilton depression, anxiety scale, and RDQ scores after 4, 8, and 12 weeks of treatment than patients who received drug treatment alone. Psychotherapy and drugs in combination showed the best overall curative effect.
The results of this study showed that there was no significant difference in the HAMD and HAMA scores between before initiation of at treatment regimen involving medication alone and after 4, 8, and 12 weeks of such treatment (
There were no significant differences in HAMD, HAMA scores and RDQ symptom scores between before and at the end of 4 week treatment in the psychotherapy group (
The cognitive factor is the bridge between the physical and psychological symptoms of NERD patients. Cognitive therapy contributes to the treatment of mental and physical diseases such as NERD by blocking the feedback cycle by which psychological factors and symptoms reinforce and exacerbate each other. Many studies have found that CBT is effective in patients with functional chest pain (
The main NERD medications tend to work through acid suppression and improving gastrointestinal motility. They are less effective in treating the mood disorders associated with NERD (
This may be because CBT promptly improves somatic symptoms, which can relieve the psychological stress and fear associated with the disease, thus alleviating negative emotions such as anxiety and depression (
In summary, the etiology of NERD is not yet completely clear. The current studies maintain that it is related to acid reflux, esophageal hypersensitivity, esophageal mechanical stimulation, motility disorders, psychological and social factors, and other factors. They also maintain that the patient’s psychological and spiritual factors also play the role in the pathogenesis of NERD and that they can be why the symptoms persist. Therefore, conventional acid suppression and motility drug treatment combined with psychotherapy for NERD is worth promoting.
This work has some specific limitations: Small sample size and hospital-based samples representing more severe cases limit the generalizability of our findings. In the process of psychological treatment, patients’ individual differences can have a pronounced impact. Some patients experienced rapid results from CBT, and others had much subtler results. CBT may be more suitable for patients with NERD than other forms of psychological therapy, and this must be taken into account when designing a personalized treatment plans. Second, the relationship between NERD and patients’ MH needs to be verified in further studies.
All patients provided their informed written consent. The study was approved by the Ethics Committee on Human Experimentation of Xiangya Hospital and Yiyang Central Hospital and was conducted in accordance with the principles contained in the Declaration of Helsinki for studies in humans.
KW, AL, and XL conceived and designed the experiments. YZ, PL, JL, JY, and ZL conducted the experiments and collected data. XL, JY, and FD analyzed the results. XL and FD wrote the main manuscript text. All authors reviewed the manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.