CME Author: Zeena Nackerdien
Study Authors: Marie Skov Kristensen, Thora Majlund Kjærulff, et al.
Target Audience and Goal Statement: Gastroenterologists, psychiatrists, and primary care physicians
The goal was to examine the influence of antidepressants on the disease course of patients with inflammatory bowel disease (IBD) — i.e., ulcerative colitis (UC) and Crohn’s disease (CD).
- Can the effects of antidepressants modify the course of IBD?
- Is there a patient subpopulation in which antidepressants will exert the most pronounced effects?
Synopsis and Perspective:
While psychiatric comorbidities can alter the course of any disease, it is not completely understood how mood disorders are associated with IBD; however, a previous large cohort study has shown that symptoms of depression and, to a lesser extent, anxiety can trigger disease relapse among patients with IBD. Although subsequent studies underscored that treatment with antidepressants may have a beneficial impact on IBD activity, the interpretation of these results has been subject to methodological limitations such as small populations and short observation periods.
The results of a new review of a nationwide Danish registry showed that use of antidepressants significantly lowered relapse rates, particularly in CD. Marie Skov Kristensen, MSc, RN, of the University of Southern Denmark in Copenhagen, and colleagues, assessed the data for 42,890 patients registered with an incident diagnosis of CD (30.5%) or UC (69.5%) in the Danish National Patient Register during the period of 2000 to 2017.
Information on antidepressant use and proxy measures of disease activity (healthcare and drug utilization) was extracted from national population registers, and Poisson regression was performed to estimate disease activity rates by antidepressant use adjusted for confounders. The analyses were performed stratified by IBD subtype and type of antidepressants.
The percentage of females with UC was 52.5% (median age of 42) and for CD, 54.9% (median age of 34). About 5% of patients in both groups had anxiety or depression, and about 80% in both groups had started antidepressant therapy before developing IBD, with about 20% having their first antidepressant prescription after developing IBD.
Nearly 28% of the cohort filled at least one prescription for an antidepressant. Following a 180-day lag period from the date of IBD onset, a total of 94,277 antidepressant prescriptions were redeemed in the study period.
Solo or combination regimens of antidepressants used included selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic and tetracyclic antidepressants (mirtazapine). Antidepressant users in both IBD groups had a significantly lower risk of starting step-up medication (corticosteroids and anti-tumor necrosis factor [TNF] agents) and IBD-related hospitalization, when taking into account all measures of disease activity.
Lower rates of disease activity were found among patients with CD (incidence rate ratio [IRR], 0.51; 95% CI, 0.43–0.62) and UC (IRR, 0.67; 95% CI, 0.59–0.75) with no use of antidepressants before IBD onset. After the researchers adjusted for confounders, there was a lower IRR of disease activity in antidepressant users vs non-users for patients with CD (IRR, 0.75; 95% confidence interval [CI], 0.68–0.82) and UC (IRR, 0.90; 95% CI, 0.84–0.95).
Kristensen and co-authors noted that a strength of the study was its inclusion of a large unselected IBD population with a long follow-up period, allowing for capturing the long-term influence of antidepressants. Study limitations, the team said, were a lack of information on medication adherence, the fact that an observational study design limits an inference of causality, and the possibility that the findings may not be generalizable to patients with mild IBD (by definition proxy measures for IBD such as step-up medication and hospitalization are related to patients with moderate or severe disease).
Asked for his perspective, Miguel Regueiro, MD, of the Cleveland Clinic, who was not involved in the research, said: “In my own practice, patients in whom we address depression also seem to improve their physical IBD symptoms – there is a clear mind-to-gut link in IBD, and as healthcare providers treating IBD, we need to take this into account.”
Many IBD patients have psychological conditions that are exacerbated by the stress of having IBD, and anxiety and depression in turn adversely affect their disease, he told MedPage Today. “The main question that has not been answered is causality — meaning, do psychological conditions trigger or cause IBD, or does IBD trigger or cause psychological disease?”
Source Reference: Inflammatory Bowel Diseases, Dec. 14, 2018, DOI: 10.1093/ibd/izy367
Study Highlights: Explanation of Findings
In the study, antidepressant treatment was found to be beneficial on the disease course of patients with UC and CD, especially in patients who did not use these medications prior to the onset of their gastroenterological conditions. The favorable effects were more pronounced in patients with CD compared with those with UC. The trend in favor of antidepressants persisted over the course of IBD, regardless of whether the antidepressant was used as monotherapy or mixed with the drugs.
The findings are in keeping with previous evidence from the literature, Kristensen and co-authors noted. For instance, Benjamin Macer and colleagues conducted a systematic review to evaluate the efficacy of antidepressants on IBD activity, and secondarily, on anxiety and depression, and concluded that although larger, randomized trials were still needed, the evidence did suggest that antidepressants may have a beneficial effect on the course of IBD. In addition, a study by Alexandra Frolkis et al. concluded that “depression increases the risk of IBD, which may be mitigated by the use of antidepressants in the treatment of depression.”
On the other hand, there are also other studies with conflicting data. Kristensen and colleagues wrote that they interpret the varying interpretations of previous studies to the use of small samples (<100 patients), short observation periods (≤2 years), and the use of inconsistent outcome measures, making it very difficult to make comparisons with the current study. Unlike prior underpowered studies, the current study also had sufficient statistical power to examine an association between antidepressant use and IBD activity, Kristensen and co-authors added.
They hypothesized that patients treated with antidepressants before IBD onset may not benefit further from the potential anti-inflammatory effect of the drug when treated for coexisting psychiatric conditions after IBD onset. In addition, the team wrote, “patients treated with antidepressants before IBD onset may be more vulnerable during the disease course due to mental challenges unrelated to IBD, leading to an increased risk of disease relapse.”
In addition, the mechanism of action is not clear — i.e., whether the beneficial influence of antidepressants on IBD course derives from mood improvements or anti-inflammatory properties of the medications. While the natural course of IBD is unknown, it is thought to be influenced by imbalanced production of pro-inflammatory cytokines — for example, TNF-α and elevated recruitment of leukocytes to the site of inflammation. Antidepressants could potentially lower pro-inflammatory cytokine levels, or the altered IBD course might be due to a potential role of the medications in brain-gut interactions.
In addition, the researchers said, despite the high levels of anxiety and depression among patients with IBD, they may not be receiving appropriate psychiatric treatment: Antidepressants have the potential to be an adjuvant to conventional therapy for IBD, similar to the treatment for irritable bowel syndrome, the team wrote, emphasizing, however, the need for randomized clinical trials.
“This study highlights the importance of screening for behavioral health in our IBD patients,” Regueiro said. “Those who have depression and anxiety should be treated. This is a very important part of the overall management of CD and UC and has been understated until recent studies, such as this Danish study.”
Diana Swift wrote the original story for MedPage Today.
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner