Mirtazapine improves caloric intake compared to placebo in patients with advanced non-small cell lung cancer

1. While perceived appetite did not differ between study groups, patients receiving mirtazapine had significantly increased caloric consumption compared with the placebo group.

2. Mirtazapine is well-tolerated, with nightmares being one of the primary significant adverse events, but the difference was insignificant at both the 4- and 8-week follow-up points.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Anorexia is an extremely common outcome of patients with lung cancer, and results in decreased caloric intake and weight loss leading to cachexia, reduced function, and lower survival rates. There are only a few medications or approaches that can ameliorate this and there is no official recommendation on pharmacologic intervention. One medication, mirtazapine, is proposed to both increase appetite and body weight through its action as a 5HT₂/5HT₃ receptor antagonist. This study explored the outcomes of mirtazapine in patients with advanced non-small cell lung cancer (NSCLC) and anorexia on subjective appetite, caloric intake, as well as safety, as measured by adverse events (AEs). Subjective appetite was no different between the placebo and experimental groups throughout the trial, however, the group receiving mirtazapine did have increased energy intake compared to the placebo group at both the 4- and 8-week period. In the first 4-week period, carbohydrate calories comprised the difference, while at the 8 weeks, fat calories were the primary macronutrient that differed between groups. The number of AEs in each group was similar, with no difference in gastrointestinal or nonhematologic AEs reported. In the mirtazapine group, there were more reported nightmares as compared to the placebo group at 2 weeks, but this difference was not significant at both the 4- and 8-week period. Limitations to this study include a small sample size included in this study with a sizeable dropout incidence, which contributes to decreased power overall. Also, since the patients received variable cancer treatments which may interact differently with the study drug, the results should be interpreted with caution. Overall, the results from this study suggest that mirtazapine holds promise as a well-tolerated medication to alleviate anorexia associated with advanced NSCLC.

Click to read the study in JAMA

Relevant Reading: Management of cancer cachexia: ASCO Guideline

In-Depth [randomized controlled trial]: This randomized, double-blind controlled trial was completed in a tertiary cancer centre located in Mexico. A total of 86 patients were included in this study and were assigned in a random 1:1 fashion into groups: mirtazapine (n = 43) or placebo (n = 43). Those in the mirtazapine group received 15mg daily for the first 15 days of the study, followed by a dose escalation to 30 mg daily until the end of the 8-week trial. Similar dosing increases were completed in the placebo arm. At 4 weeks into the trial, the group receiving mirtazapine had increased caloric intake at 26.1% of their required, compared to the placebo group at 8.8% of required calories, with the mirtazapine group consuming a greater amount of carbohydrates overall (43.4g; 95% confidence interval (CI), 13.1-73.8g) versus the placebo group (5.5g; 95% CI, -20.2-31.3g). While the increased energy intake at the 8-week mark was not significantly different between groups, only the mirtazapine group met 100% of their nutritional requirements. There was a significantly higher increase in fat calorie intake in the mirtazapine group (14.5g) compared to the placebo group (0.7g). Nightmares were significantly more frequent in the mirtazapine group at 2 weeks into the trial, with a p-value of 0.009 reported.

Image: PD

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