Use of the antidepressant mirtazapine (Remeron) was associated with reduced rates of mortality, cirrhosis, and liver transplantation in primary biliary cholangitis (PBC) patients, a registry study indicated.

“This protective association of mirtazapine was independent of the role of depression, prescription of other antidepressants, or the use of ursodeoxycholic acid, wrote a group led by Mark Swain, MD, MSc, from the University of Calgary in Alberta, Canada, and colleagues in PLOS ONE. “We suggest that these findings support the examination of mirtazapine as a potential novel therapy for PBC patients.”

This atypical antidepressant has multiple effects, improving anxiety, addiction, insomnia, nausea, and anorexia, and is therefore also widely prescribed for patients not suffering from depression but suffering other consequences of chronic diseases, including autoimmune conditions such as PBC.

“Initially, the most striking thing about the findings was that, traditionally, when someone has a chronic disease, their outcomes are worse, so we went in expecting worse outcomes in patients with depression,” Swain told MedPage Today. “So we realized there was something independent of depression at work and found the benefit of having depression was explained by the drug mirtazapine whether the patients were depressed or not.”

Swain and associates based their findings on what they said is the first study of the effects of depression and antidepressants on outcomes in PBC. Using the large general-practice database of the U.K. Health Improvement Network, they identified 1,177 adult patients (92% female) diagnosed with PBC during 1974-2007. Of these, 86 (7.3%) had a diagnosis of major depressive disorder at least 90 days before PBC diagnosis, while 79 (6.7%) had a depression diagnosis within 90 days of PBC diagnosis.

PBC patients with prior or current depression were younger than those without depression (median ages 59 and 58 versus 63 years, P=0.009), and were more commonly female (93% and 96% versus 87%, P=0.02). Prevalence of coexisting liver disease was similar among the three groups (P=0.19). About 70% were on ursodeoxycholic acid (UDCA), the mainstay of PBC treatment.

Of PBC patients without a diagnosis of depression, 24.6% were using antidepressants after their PBC diagnosis, while 11.1% had used antidepressants before PBC diagnosis. As for mirtazapine, 27 (2.7%) of the 1012 participants with no depression were using mirtazapine, 3 (3.5%) of the 86 with previous depression were taking it, and 5 (6.3%) of the 79 with current depression were on this drug.

The cumulative incidence of mortality at 3, 5, and 10 years was 6.5%, 13.4%, and 25.4%, respectively. The cumulative incidence of decompensated cirrhosis at 3, 5, and 10 years was 4.1%, 6.6%, respectively; for liver transplantation it was 13.0% and 0.1%, 2.0%, 4.0%, respectively.

During a median follow-up of 92 months, overall decompensated cirrhosis, liver transplant, and mortality rates were similar across the three study groups. Overall mortality was 27.1% for the non-depression cohort, 19.8% for previously diagnosed with depression, and 26.6% for currently depression (P=0.34).

Strikingly, after studying all classes of antidepressants, the investigators found the use of mirtazapine after PBC diagnosis was significantly protective. The adjusted hazard ratio was 0.23 (95% CI 0.07±0.72) against poor hepatic outcomes and remained statistically significant in patients using the current mainstay of medical treatment, ursodeoxycholic acid (UDCA): HR 0.21 (95% CI 0.05±0.83).

Keith D. Lindor MD, of Arizona State University in Phoenix, who was not involved in the study, told MedPage Today, “This retrospective study shows an interesting correlation between the use of the antidepressant in patients with PBC, despite depression itself not being linked to poorer clinical outcomes. This finding needs to be followed in a prospective randomized trial to see if this observation can be confirmed.”

Indeed, the Calgary group said it’s planning to launch a clinical trial to further investigate the effects of mirtazapine in PBC patients.

Addressing study limitations, the authors cited the potential for misclassification errors because of its reliance on a database based on general practitioners’ electronic medical records. Furthermore, the study was not able to evaluate the biochemical response to UDCA as this information was not provided in the database. In addition, an epidemiological association cannot prove causality or explain the biological mechanism of mirtazapine’s beneficial effect in PBC.