Mirtazapine in cancer-associated anorexia cachexia: A randomised, double-blind, placebo-controlled trial

Abstract

Abstract Background The available options to manage cancer-associated anorexia-cachexia syndrome (CACS) are limited. At standard doses, the tetracyclic antidepressant mirtazapine causes appetite stimulation and weight gain. Based on limited evidence, it is used in cancer-associated anorexia. This trial was conducted to assess the efficacy and safety of mirtazapine in patients with CACS. Methods A double-blind randomized placebo-controlled trial. Included patients were adults with advanced solid tumors, weight loss ≥5%, appetite loss score ≥ 4 on 0 to 10 scale (10 = maximum appetite loss), and depression ≤3 on 0 to 6 scale (6 = extreme feelings of depression). Patients were randomized to receive mirtazapine 15\xa0mg /day or placebo. The primary end-point was the change in appetite on a 0 to 10 appetite scale (where 10 is the best appetite possible) at week 4. Other assessed outcomes included changes in body weight, lean body mass, handgrip strength, depression (measured by the Hospital Anxiety and Depression Scale [HADS]), and quality of life (measured by Functional Assessment of Anorexia/Cachexia Therapy [FAACT] questionnaire). Results From 120 allocated patients, 100 completed 4 weeks treatment (48 in the mirtazapine arm and 52 in the placebo). After 4 weeks of treatment there was no significant difference between the two arms in the change from baseline in appetite or other outcome measures (Table 1). The change in the HADS depression score differed significantly in favour of mirtazapine. Sleepiness was significantly more prevalent in the mirtazapine arm (p\xa0=\xa00.01) and only one patient discontinued treatment due to excess sleepiness. Table: LBA86 . Change in outcome measures from baseline to day 28 Mirtazapine Placebo p Median (Interquartile range) Appetite score 2 (0-2) 2 (0-2) 0.401 Body weight (kg) -0.8 (-1.5 – 0.9) -0.6 (-1.4 – 0.2) 0.94 Lean body mass (kg) -0.16 (-1.1 – 1.1) -0.37 (-1 – 0.4) 0.411 Handgrip strength (kg) -0.76 (-1.5 – 0.8) 0 (-1 – 0.8) 0.376 FAACT Anorexia-cachexia scale 4 (1 – 5.8) 4 (0 – 6) 0.997 HADS Depression score 1 (0.3 – 2) 2 (1 – 2) 0.022 Conclusions Compared to placebo, mirtazapine 15mg at night did not improve appetite, body weight, hand-grip strength or quality of life in advanced cancer patients with anorexia cachexia. Clinical trial identification NCT03254173. Legal entity responsible for the study The authors. Funding Cairo University. Disclosure All authors have declared no conflicts of interest.