Use of mirtazapine for appetite stimulation and weight gain in cancer-associated cachexia and anorexia: A systematic review

ObjectiveLimited guidance is available for the treatment of anorexia/cachexia in cancer patients. Appetite stimulation and weight gain are documented side effects of mirtazapine, so there is growing interest in its potential use this patient population. The objective of this review is to evaluate the safety and efficacy of mirtazapine for appetite stimulation and weight gain in cancer-associated cachexia/anorexia (CACS).Data sourcesA literature search was performed in December 2025 using PubMed, Embase and CENTRAL to screen for randomized controlled trials meeting the designated inclusion and exclusion criteria.Data summaryFive randomized controlled trials were reviewed. Two studies compared mirtazapine to placebo, two compared mirtazapine to megestrol acetate, and one compared mirtazapine to olanzapine. Overall risk of bias was low for two studies, with some concerns identified in three studies. While mirtazapine demonstrated significant improvement in appetite from baseline in most studies, it was only when compared to olanzapine that mirtazapine significantly improved appetite compared to a control. Conversely, one study demonstrated superiority of megestrol, and the remaining three studies did not identify a difference in appetite outcomes between mirtazapine and the control group. Secondary outcomes analyzed included weight and energy intake, though no significant differences were noted between mirtazapine and the control group in any study. Rates of adverse effects were similar between mirtazapine and all comparator arms.ConclusionsThe included studies did not demonstrate consistent improvement in appetite outcomes with use of mirtazapine, although use was associated with low risk of harm. More trials involving larger patient populations and longer study durations may be warranted to establish its role in CACS.