Journal Article Annotations
2022, 4th Quarter

GI Psychiatry

Annotations by Ashwini Nadkarni, MD
January, 2023

Depression is associated with increased disease activity in patients with ulcerative colitis: A propensity score-matched analysis using a nationwide database in Japan.
Use of Benzodiazepines and Z-Drugs in Inflammatory Bowel Disease.

PUBLICATION #1 — GI Psychiatry

Depression is associated with increased disease activity in patients with ulcerative colitis: A propensity score-matched analysis using a nationwide database in Japan.

Hideaki Oyama, Rintaro Moroi, Kunio Tarasawa, Yusuke Shimoyama, Takeo Naito, Atsushi Sakuma, Hisashi Shiga, Yoichi Kakuta, Kiyohide Fushimi, Kenji Fujimori, Yoshitaka Kinouchi, Atsushi Masamune

Abstract: JGH Open. 2022 Nov 15;6(12):876-885. doi: 10.1002/jgh3.12836. eCollection 2022 Dec.

Background and aim:
The incidence and prevalence of psychiatric disorders are elevated in patients with inflammatory bowel disease (IBD). Whether psychiatric disorders could affect the clinical course of IBD is uncertain and controversial. We aimed to evaluate the impact of psychiatric disorders, particularly depression, on the clinical course of IBD using a nationwide database in Japan.

Methods:
We collected data on admissions with IBD using the Diagnosis Procedure Combination database system introduced in Japan. We divided eligible admissions into IBD with and without depression groups using propensity score matching and compared the rates of surgery, use of molecular targeted drugs and biologics, systemic steroid administrations, and in-hospital death. We also conducted a logistic regression analysis to identify clinical factors affecting surgery, the use of molecular targeted drugs and biologics, and systemic steroid administrations.

Results:
The rates of surgery, use of two or more molecular targeted drugs, systemic steroid administrations, and in-hospital deaths in the ulcerative colitis (UC) with depression group were higher than in the UC without depression group. Multivariate analysis of UC showed that depression increased the odds of systemic steroid administrations, use of two or more molecular targeted drugs, and surgery. However, analysis of Crohn’s disease showed that only steroid administrations were associated with depression.

Conclusion:
Our study demonstrated an association between a worse clinical course of UC and depression. Although this result indicates that depression might be associated with increased disease activity in patients with UC, the causal relationship is still unclear. Further prospective studies are warranted.

Annotation

The finding:
This was a cross-sectional study which used a nationwide database from Japan to evaluate the impact of psychiatric disorders, particularly depression, on the clinical course of IBD. The authors compared the disease activity of IBD patients with and without concomitant depression. In multivariate analyses of patients with UC, depression was found to increase the odds of systemic steroid administrations, use of two or more molecular targeted drugs, and surgery; after analysis of patients with CD, depression was found to increase the odds of only systemic steroid administrations.

Strength and weaknesses:
This study demonstrated an association between concomitant depression and a worse clinical course of UC. Thus far, a very limited number of studies have clarified the association between clinical recurrence of UC and psychological disorders, including depression. This study indicated that depression could be a cause of worsening disease activity rather than depression being a result of a poor clinical course. However, the database utilized in this study did not contain details of patients’ conditions, such as the period when IBD disease activity worsened, endoscopic and pathological findings, laboratory data, computed tomography findings, and information on intestinal and extra-intestinal manifestations—the authors only indirectly evaluated disease severity by investigating the therapeutic agents used and the surgery rate. Additionally, the database included only admissions and not out‐of‐hospital patients. Hospitals were typically acute‐care and relatively large‐volume hospitals which may affect generalizability. Although the incidence of depression is known to be 6–7% in Japan, the results contain a much smaller number of cases with depression. Finally, results could not demonstrate a causal relationship between these two entities. Further prospective studies are needed to clarify the nature of this clinical relationship.

Relevance:
The results of this study reinforce that the disease activity of patients with UC who have depressive symptoms could be improved by prompt intervention performed by a C-L psychiatrist, which might ultimately contribute to an improved prognosis. Further investigation is warranted to clarify this issue.

PUBLICATION #2 — GI Psychiatry

Use of Benzodiazepines and Z-Drugs in Inflammatory Bowel Disease.

Charles N Bernstein, John D Fisk, Randy Walld, James M Bolton, Jitender Sareen, Scott B Patten Alexander Singer, Lisa M Lix, Carol A Hitchon, Renée El-Gabalawy, Lesley A Graff, Alan Katz, Kelcie Witges, James J Marriott, Ruth Ann Marrie; CIHR Team in Defining the Burden and Managing the Effects of Psychiatric Comorbidity in Chronic Immunoinflammatory Disease

Abstract: Am J Gastroenterol. 2022 Dec 1;117(12):2046-2054. doi: 10.14309/ajg.0000000000001955. Epub 2022 Aug 22.

Introduction:
We estimated the incidence and prevalence of benzodiazepine and Z-drug (separately and jointly as BZD) use in the inflammatory bowel disease (IBD) population compared with matched controls without IBD and examined the association of mood/anxiety disorders (M/ADs) with the use of BZD from 1997 to 2017.

Methods:
Using administrative data from Manitoba, Canada, we identified 5,741 persons with incident IBD who were matched in a 1:5 ratio to controls on sex, birth year, and region. Validated case definitions were used to identify M/AD. Dispensations of BZD were identified. Multivariable generalized linear models were used to assess the association between IBD, M/AD, and BZD use.

Results:
In 2016, the incident age/sex-standardized benzodiazepine use rates per 1,000 were 28.06 (95% confidence interval [CI] 26.41-29.81) in the IBD cohort and 16.83 (95% CI 16.28-17.39) in controls (adjusted rate ratio = 1.69 [95% CI 1.56-1.79]). Benzodiazepine incidence rates were higher for women with IBD than men, but the RR between cases and controls were similar for men and women. The incident age/sex-standardized Z-drug use rate per 1,000 was 21.07 (95% CI 19.69-22.41) in the IBD cohort. This was 1.87-fold higher than in controls (95% CI 1.73-2.01). In 2017, approximately 20% of persons with IBD used benzodiazepines and 20% used Z-drugs. There was a sub-additive effect of both benzodiazepine and Z-drug uses between IBD and M/AD after adjusting for covariates.

Discussion:
The use of BZD is more common in people with IBD than in population controls. Strategies to reduce the use of BZDs in persons with IBD and to offer alternative management strategies for M/ADs, sleep disorders, and other symptomatic concerns are needed

Annotation

The Finding
In this retrospective cohort study, the authors examined whether the incidence and prevalence of benzodiazepine and Z-drug use in the IBD population of Manitoba differed from that of an age-, sex-, and geographically-matched population without IBD. They examined the pattern of their use over a 20-year period that preceded the recent change in prescribing practice standards. They also investigated the association of mood/anxiety disorders with the use of these agents in IBD and non-IBD cohorts. The authors found a high burden of BZD use in the Manitoba IBD population over a 20-year period. In 2017, approximately 20% of Manitobans with IBD were using BZD, with approximately half using benzodiazepines and half using Z-drugs. Persons with IBD and M/AD (mood/anxiety d/o) were more likely to be continuous users (29.6%) than those without M/AD (17.6%). Notably, even among IBD cohort members who did not have comorbid M/AD, there was a higher incidence and prevalence of BZD use than that among members of the control cohort without M/AD. This could reflect psychiatric comorbidity, which was not captured in the administrative data, or sleep disturbances, which the authors did not examine.

Strength and weaknesses:
Despite the high burden of BZD use in the general population, the authors note that no other population-based studies estimate BZD use in the IBD population. Particular strengths include the use of a population-based sample and validated administrative definitions for IBD and psychiatric diagnoses and the comprehensive access to all prescription drugs dispensed for the population. Limitations include missing a significant proportion of those cohort members with clinical anxiety or depression who do not present to a physician or medical facility with these diagnoses or simply remain undiagnosed

Relevance:
Benzodiazepines are associated with adverse consequence including falls. In addition, co-prescribing of BZD in IBD patients increases the likelihood of fatal opioid overdose. When consulting with gastroenterology practices, C-L psychiatrists should recognize that patients with IBD are likely to be prescribed BZD and how such prescribing is more likely to be associated with mood or anxiety disorders.