The Role of Mirtazapine in the Pathogenesis and Therapy of Chronic Liver Disease

Abstract:

Depression is a common comorbidity in patients with chronic liver disease (CLD) and is associated with poorer clinical outcomes. Due to concerns about hepatic metabolism and limited tolerability, the use of traditional antidepressants is often restricted. Mirtazapine is a noradrenergic and specific serotonergic antidepressant. Driven by its unique rigid tetracyclic scaffold and enantiomeric properties, Mirtazapine exhibits multi-target binding that may affect multiple shared pathways in CLD and depression. Preclinical studies have shown that in models of metabolic Dysfunction-Associated Steatotic Liver Disease, cirrhosis, and hepatocellular carcinoma, Mirtazapine can attenuate liver tissue injury, suppress hepatic stellate cell activation, and modulate inflammatory responses and oxidative stress levels. Additionally, the drug may provide indirect clinical benefits by alleviating patients’ depressive symptoms, improving sleep quality, and promoting appetite recovery. However, mirtazapine is consistently associated with a range of metabolic adverse effects, including weight gain, insulin resistance, and hepatic steatosis. These effects may exacerbate the metabolic burden in patients with CLD, thereby limiting its clinical utility. Therefore, when prescribing this agent to patients with comorbid depression, clinicians must carefully balance its anti-inflammatory and anti-fibrotic benefits against metabolic risks to achieve rational individualized medication.