Sertraline and microscopic colitis

HSA would like to update healthcare professionals on the potential risk of microscopic colitis associated with the use of sertraline.

Sertraline is a selective serotonin reuptake inhibitor that has been registered in Singapore since 1992 for the treatment of depression, obsessive compulsive disorder, panic disorder, post-traumatic stress disorder, social phobia and pre-menstrual dysphoric disorder. Diarrhoea is a common adverse drug reaction (ADR) associated with the use of sertraline.

About microscopic colitis

Microscopic colitis is a rare inflammatory disorder of the colon. It presents with chronic, non-bloody diarrhoea, abdominal pain, weight loss and fatigue. It can be divided into two subtypes, namely lymphocytic colitis or collagenous colitis, which are clinically indistinguishable but have different histopathologic features. Both subtypes are typically characterised by a marked and diffuse excess of lymphocytes interspersed among the surface colonocytes and within the lamina propria. In collagenous colitis, a subepithelial collagen band can be seen in the colon on biopsy in addition to increased intraepithelial lymphocytes.

The exact mechanism of microscopic colitis  is poorly understood; an inflammatory mechanism triggered by environmental factors such as an infection, toxin or drugs has been suggested.

Published literature

1. Case-control study1

In 2013, a Spanish prospective case-control study which investigated the epidemiological risks factors in microscopic colitis found sertraline to be associated with an increased risk for lymphocytic colitis. The study included 120 patients with collagenous colitis, 70 with lymphocytic colitis and 128 controls from teaching and community hospitals across Spain from March 2007 to May 2010. Drug exposure before the onset of diarrhoea (for cases) or at study recruitment (for controls) was recorded for medicines taken ≥ 3 days per week for ≥ 2 weeks. Of the patients recruited, seven lymphocytic colitis cases and none of the controls took sertraline, contributing to a statistically significant association between sertraline intake and lymphocytic colitis [odds ratio 17.5 (2.0-149.2)]. These findings were similar to those from an earlier case-control study and were in line with the documented association of sertraline with high likelihood of triggering microscopic colitis.

2. Case reports2-4

Three case reports of microscopic colitis related to the use of sertraline described patients who presented with prolonged non-bloody diarrhoea lasting from over 20 days to three months, resulting in substantial weight loss of up to 20 kg in one report from the literature. In all three cases, microscopic colitis associated with sertraline was diagnosed based on temporal association with sertraline initiation and biopsies from the colon and/or rectum that revealed an increase in intraepithelial lymphocytes, which is characteristic of the condition. All the patients recovered upon discontinuation of sertraline.

International situation

In January 2020, the European Medicines Agency (EMA) identified the signal of microscopic colitis from the European spontaneous adverse event reporting database. Following a review of the available evidence in the database and in literature, the EMA requested for the product labels of sertraline-containing products to be updated to state ‘microscopic colitis’ as an undesirable adverse effect with unknown frequency.⁵ Similar regulatory actions were also taken by the Australian Therapeutic Goods Administration (TGA).⁶

Local situation

To date, HSA has received five ADR reports of diarrhoea associated with the use of sertraline, none of which involved microscopic colitis.

Based on post-marketing experience, the association of microscopic colitis with sertraline use has been reported overseas and in published literature. HSA is working with the product registrants of sertraline-containing products to update the local package insert to include microscopic colitis as an adverse event that has been observed in the post-market setting.

HSA’s advisory

While microscopic colitis related to the use of sertraline can result in severe prolonged diarrhoea and substantial weight loss, published case reports revealed that the condition resolved progressively following swift cessation of sertraline . Healthcare professionals are advised to consider the possibility of this adverse event in patients on sertraline who present with prolonged or severe diarrhoea.

References

1. Inflamm Bowel Dis 2013;19:411-7

2. Psychosomatics 2015, 56(3):316-7

3. Gastroenterology 2016; 150:326-7

4. Actas Esp Psiquiatr 2018; 46(5):200-4

5. https://www.ema.europa.eu/documents/prac-recommendation/prac-recommendations-signals-adopted-11-14-may-2020-prac-meeting_en.pdf ↗ (opens in new tab)

6. https://www.tga.gov.au/publication-issue/sertraline-and-microscopic-colitis ↗ (opens in new tab)