Mirtazapine in Cancer-Associated Anorexia and Cachexia: A Double-Blind Placebo-Controlled Randomized Trial.

Context: Few pharmacological interventions are available for cancer-associated anorexia and cachexia. Mirtazapine has been suggested for use in cancer-associated anorexia and cachexia.

Objectives: This study was conducted to assess the efficacy and tolerability of mirtazapine in cancer-associated anorexia and cachexia.

Methods: A double-blind placebo-controlled randomized trial. The study included 120 incurable solid tumour patients with anorexia (appetite loss ≥4 on 0 - 10 scale, 10 = maximum appetite loss), cachexia (>5% body weight loss over 6 months or >2% plus body mass index <20) and depression score ≤3 on 0-6 scale (6 = extreme feelings of depression). Patients were 1:1 randomized to receive mirtazapine 15mg daily at night for 8 weeks or placebo. The primary endpoint was change in appetite from baseline to day 28. Other outcomes included changes in quality-of-life, fatigue, depressive symptoms, body weight, lean body mass, handgrip strength, inflammatory markers, adverse events and survival.

Results: 48 (80%) patients in the mirtazapine arm and 52 (87%) in the placebo were assessable for the 1ry endpoint. Appetite score increased significantly with mirtazapine as well as with placebo (P < 0.0001 each). The increase in appetite score did not differ significantly between the two arms in the per-protocol and intention-to-treat analysis (P = 0.472 and 0.462, respectively). Mirtazapine was associated with significantly less increase in depressive symptoms and higher prevalence of somnolence. The change in other outcomes did not differ significantly between mirtazapine and placebo.

Conclusion: Mirtazapine 15mg at night for 28 days is no better than placebo in improving the appetite of incurable solid tumor patients with cancer-associated anorexia and cachexia.