Pharmacological and Non-pharmacological Treatments of Irritable Bowel Syndrome and Their Impact on the Quality of Life: A Literature Review

Irritable bowel syndrome (IBS) is a non-organic gastrointestinal disorder that adversely affects the quality of life (QoL). The etiology of the disease is not fully understood, and appropriate treatment is still a matter of debate. Therefore, we feel that a review that describes the different treatment methods of treatment is needed to provide the correct clues. A comprehensive literature search was performed on PubMed, including randomized clinical trials and review articles. We carefully reviewed the different treatment options mentioned in the published research papers and compared their results to address the treatment options for IBS. The current literature review reveals that pharmacological treatments such as antidepressants, vitamin D, probiotics, and antispasmodic drugs and non-pharmacological treatments including cognitive-behavioral therapy (CBT), acupuncture, anise, and diet modification can help control the symptoms of IBS and improve the QoL of patients.


Introduction And Background
Irritable bowel syndrome (IBS) is a non-organic gastrointestinal disorder that has a negative impact on the quality of life (QoL). Currently, the diagnosis of IBS is based on new Rome IV criteria as a recurring abdominal pain related to two or more of the following conditions: defecation-related, associated with an increase in the stool frequency, and associated with a disparity in stool quality [1]. Symptom onset should occur at least six months before the diagnosis, and symptoms should be presented in the last three months, on average, and at least one day in a week.
The prevalence of IBS is approximately 9-23% worldwide, with a devastating impact on the QoL. Hence, we wanted to find out if IBS could be associated with psychological problems. The currently available treatment options, both pharmacological and non-pharmacological, can help in controlling symptoms. However, a knowledge gap still exists. We aim to find the best possible treatment options for IBS, which would help to treat this condition and improve the QoL for patients.

Mechanism of IBS
IBS symptoms have unclear etiology, and there is no specific treatment available to treat IBS patients. Recent studies show that symptoms of IBS most likely occur due to the gut-brain axis imbalance as evidenced by increased abdominal pain during periods of stress. Stress can cause a change in intestinal motility and permeability along with microbiota imbalance as some cases developed IBS due to alteration of the gut microbiota as a result of an infection [1,[2][3][4][5][6][7][8][9][10]. In contrast, some believe it to be mostly caused by psychological disorders. According to Spiller et al., at least 50% of the IBS patients can be described as depressed, anxious, or hypochondriacs and over 60% of IBS patients receiving tertiary care had presented with a psychiatric disorder, most commonly depression, anxiety, or both [11].

Psychological disorders and their relation to IBS
Stress can modify and exacerbate central pain circuity and, therefore, it may be related to the development of visceral pain, which is related to IBS. A study has shown that IBS could be related to mental disorders as about 50-90% of IBS patients meet the criteria of psychiatric disorder, mainly anxiety, panic disorder, and major depressive disorder [12]. Another study has shown that catastrophizing, which is defined as expecting a negative outcome, is more common in IBS patients [13]. Hence, IBS can be associated with pain-catastrophizing thinking with a propensity to magnify the seriousness of the illness.

Treatment options
We are currently aware of the multi-systemic reasons behind the occurrence of IBS symptoms and the role of psychological disorders in its development or exacerbation. However, it needs to be further established as to how psychological treatment plans can be used as an effective way to resolve IBS symptoms. This psychosomatic visceral pain link can help us to illustrate several treatments that can help reduce symptoms in patients with IBS and improve their QoL.
The objective of this review is to focus on the treatment options for IBS and the effect of using different interventions to control IBS symptoms. It compares various studies discussing cognitive behavioral therapy (CBT), antidepressants, probiotics, anise, acupuncture, vitamin D, and diet modification as management options for IBS. The literature review aims to provide an insight into current treatment options for controlling IBS symptoms and improving the QoL.

Materials and methods: data collection
The data were collected from PubMed using Medical Subject Headings (MeSH) keywords "Irritable bowel syndrome, physiology, pathology, epidemiology, psychology, and therapy." The following inclusion criteria were applied in the order given; clinical trial and review studies, articles involving only human subjects, articles published in English only, and those involving subjects aged 19-44 years. The collection of the articles for the study was done in an ethical manner.

Results
Using MeSH keywords on PubMed, a total of 5,780 papers were collected, of which 651 were used for filtering. The details of the articles obtained by applying MeSH keywords and inclusion criteria in PubMed are given below ( Table 1)  Each of the 651 studies identified was evaluated individually based on the abstract. Among them, 163 articles were nonduplicated, and 67 were found to be non-relevant while screening the abstracts. Another 12 articles were excluded after the full-text screening since the patient age was out of the age range for our study. And one more article was removed during data extraction as it was a systemic review that included different age groups.
Finally, 83 relevant articles were chosen for this review article. The current literature review analyzes a total of 16 full-text articles that study different treatment options for controlling IBS symptoms.

Discussion
Although IBS is not a life-threatening condition, it puts a heavy burden on healthcare resources. Treating a patient for one year costs around $355-3,344, and the condition has a very drastic effect on the QoL of patients [14]. The condition has an unknown mechanism, and it has been found to alter intestinal motility and cause stress and microbiota imbalance, which explains the treatment options available now [1,[2][3][4][5][6][7][8][9][10]. In this review, we included 83 papers on PubMed, which addressed the various treatment options available for IBS. We also engage in a comparison of these studies.
It has been found that many IBS patients respond to treatment to some extent. However, others do not due to various factors or the disparity in severity. In light of this, we review both pharmacological and non-pharmacological treatments that aimed to provide the best control of IBS symptoms and their effects on QoL. Our review aims to provide a complete overview of these treatment options to determine their efficacy in treating IBS in light of these previous studies.

Effect of Cognitive Behavioral Therapy on IBS
One study has discussed cognitive behavioral therapy (CBT) as a treatment option for controlling IBS symptoms compared with other possibilities as an educational exercise [15]. Another one has discussed its mechanism by drawing a connection between emotion, behavior, and cognition as a treatment option for IBS [16]. Overall, all these studies generally endorse using CBT for IBS (

Effect of Anti-psychological Pharmacological Treatment on IBS
Antidepressants and antipsychotic medications can be a treatment option for IBS. Many of the studies illustrate that some of these drugs, such as duloxetine, have shown a positive effect on patients with generalized anxiety disorder (GAD) along with IBS [21]. Tianeptine and amitriptyline have a positive impact on irritable bowel syndrome with diarrhea (IBS-D) [22]. Imipramine can also be used to treat IBS [23]. One study showed that citalopram could be useful while another study questioned this conclusion; both studies discussed the effect of citalopram on IBS symptoms away from its impact as an antidepressant ( Table 3).

Effect of Probiotics on IBS
One study has shown that probiotics could improve IBS symptoms, while another one has indicated that it might aggravate the IBS symptoms, specifically bloating [28,29]. We reviewed six studies relating to probiotics, and three of them showed that the probiotic effect is no stronger than that of placebo; one study showed that the probiotic effect on improving QoL is related to its impact on depression symptoms and not on IBS symptoms [30]. On the other hand, the other three showed that probiotics do have a positive effect on controlling IBS symptoms ( Table 4). The study compared the effects of probiotic Symbioflor-2 (E-Coli product) with that of placebo on abdominal pain score and showed that probiotic has a more significant effect than placebo

Effect of Other Treatment Options on IBS
There are plenty of other treatment options that might improve IBS symptoms. These options include a low fermentable oligo-, di-, mono-saccharides, and polyols (FODMAP) diet, anise, vitamin D, acupuncture, and antispasmodic drugs [35][36][37][38][39]. The following table provides the details of the studies that examined the effects of each of these options on controlling IBS symptoms (

Limitation of the study
Our literature review has some limitations. The study is limited in its analysis in terms of patient age (all patients involved were <45 years old) and does not include observational and non-randomized clinical trials. More studies are needed to explore the primary treatment of IBS to minimize its effects on QoL and reduce the burden on medical resources.

Conclusions
This literature review discussed the pharmacological and non-pharmacological treatment strategies for IBS based on previous studies. Based on our findings, we can conclude that the use of methods including CBT, anti-psychological medications, probiotics, and other approaches such as acupuncture, anise, and diet modifications can help control the symptoms of IBS and improve the QOL of patients.

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work.
Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.