None listed
Conditions
Brief summary
Background: Studies have shown that antidepressants may reduce inflammation in animal models of colitis. The present trial aims to examine whether fluoxetine added to standard therapy for Crohn’s disease (CD) maintains remission, improves quality of life and/or mental health in humans with CD as compared to placebo. Methods / Design: A parallel randomised double-blind placebo controlled trial was conducted. Participants with clinically established CD, in remission or with only mild symptoms, were randomly assigned to receive either fluoxetine 20mg daily or placebo, and followed for 12 months. Participants provided blood and stool samples and answered questionnaires measuring mental health and quality of life. Linear mixed-effects models were used to compare groups on the outcome variables. Results: Of the 26 randomised participants, 14 were randomised to receive placebo and 12 to receive fluoxetine for 12 months. Overall, 14 (53.8%) participants were male. The mean age was 37.4 (13.2) years. Fluoxetine had no effect on IBD activity measured using the CDAI (F(3, 27.5) =.064, p=.978) or the calprotectin (F(3, 32.5)= 1.08, p=.371) during the 12-month period of observation. Similarly, there was no impact of fluoxetine on physical (p=.645), psychological (p=.884), social (p=.649), or environmental quality of life (QoL) (p=.992), on anxiety (p=.979) or depressive symptoms (p=.956) as compared to placebo. Conclusion: 20mg of fluoxetine daily does not appear to improve the course of CD, QoL or mental health over 12 months of observation as compared to placebo. The trial documents the difficulty of conducting antidepressant trials with human subjects suffering from CD .
Interventions
Fluoxetine was selected based on previous research showing its anti-inflammatory properties in humans, and in relation to IBD based on findings of studies examining animal models of colitis. Previous human studies have recommended a dose of 20mg daily (which is considered a low therapeutic dose when used in the treatment of depression) and the length of study to be at least 3 to 8 weeks in order to show fluoxetine’s efficacy. However, the present study was concerned with the longitudinal efficac
Fluoxetine was selected based on previous research showing its anti-inflammatory properties in humans, and in relation to IBD based on findings of studies examining animal models of colitis. Previous human studies have recommended a dose of 20mg daily (which is considered a low therapeutic dose when used in the treatment of depression) and the length of study to be at least 3 to 8 weeks in order to show fluoxetine’s efficacy. However, the present study was concerned with the longitudinal efficacy of fluoxetine as an agent modifying the course of IBD and psychological parameters, and thus treatment was provided for 12 months with the dose of 20mg daily administered orally. A Generic Health brand of fluoxetine was purchased from the RAH pharmacy and the placebo was an inactive tablet produced by Pharmaceutical Packaging Professionals as recommended by the same pharmacy. Treatment with fluoxetine is currently not part of standard practice in gastroenterology, however, in our case-note audit we demonstrated that a life-time use of antidepressants in our IBD patients is approx. 30% and thus many patients would have been exposed to antidepressants, including fluoxetine. In the audit, we did not identify any major adverse-events related to the use of antidepressants in IBD and the interview we conducted with IBD patients currently taking antidepressants demonstrated their acceptance by this population.
Sponsors
University of South Australia
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion criteria Patients had to meet ALL of the following criteria: 1). Established diagnosis of CD; 2). Remission or only mild symptoms of CD (CDAI <150); 3). Have flared CD in the last 12 months (as documented by their treating doctor and demonstrated by either raised inflammatory markers, augmented therapy, high CDAI or calprotectin); 4). Be on stable dose of all their current CD therapies for 12 weeks; 5). Be 18 years old or older; 6). Have a sufficient knowledge of English to understand and answer questionnaires. 7). Have the ability to consent to the study.
Exclusion criteria
Exclusion criteria Patients were excluded if they met ANY of the following: 1). Have serious uncontrolled mental illness (e.g. schizophrenia) or are alcohol/substance dependant; 2). Currently taking antidepressants; 3). Currently receiving psychotherapy; 4). Currently taking steroids >15mg or equivalent; 5). Are allergic to fluoxetine or any component of placebo; 6). Are pregnant or breastfeeding; 7). Have cognitive impairment.
Outcome results
None listed