Riechelmann, R.P., Burman, D., Tannock, I.F., Rodin, G., & Zimmermann, C. (2010). Phase II trial of mirtazapine for cancer-related cachexia and anorexia. American Journal of Hospice and Palliative Care, 27, 106–110.

To determine the proportion of patients who gained at least 1 kg at the end of week 4. Secondary endpoints were the proportion of patients whose appetite or health-related quality of life (HRQOL) improved at week 4.

Patients received the starting dose of 15 mg of mirtazapine orally at bedtime for three days. Thereafter they received 30 mg daily provided they tolerated the medication. Patients were weighed on a mechanical scale and were assessed for appetite change and side effects prior to starting the mirtazapine and at weeks 2, 4, and 8. HQOL was measured at baseline and at weeks 4 and 8. Demographics (age, gender, concurrent medications, disease site, and Eastern Cooperative Oncology Group performance status) were also assessed. Toxicity was assessed at every visit.

• The study reported on 17 patients with metastatic cancer experiencing weight loss.
• Mean patient age was 66 years, with a range of 49–86 years.
• The sample was 53% female and 47% male.
• Cancer types were gastrointestinal, breast, lung, gynecologic, and hematologic.
• Patients experienced weight loss of more than 5% during the previous two months or a score of more than 5 out of 10 on the Edmonton Symptom Assessment Scale.

• Single site
• Outpatient setting
• Princess Margaret Hospital, Toronto, Canada

• Patients were undergoing multiple phases of care.
• The study has clinical applicability for end-of-life and palliative care.

The study was an eight-week, open-label, noncomparative phase II trial.

• Mechanical scale    
• Edmonton Symptom Assessment Scale (ESAS)–appetite
• Functional Assessment of Anorexia/Cachexia Therapy (FAACT)–HQOL

At week 4, 4 of 17 patients (24%) had weight gain of 1 kg or more (range: 1–3.6 kg). One patient maintained weight, and  two patients lost weight. Of the patients who gained weight, all improved by 2 or more points on the ESAS for appetite (range = 2–6 points). One of the responding patients demonstrated improved HQOL by 16 points, and three maintained HQOL. Mirtazapine was well tolerated, but two patients withdrew from the study due to side effects.

Nearly a quarter of patients in this study gained at least 1 kg after four weeks of therapy. Another quarter maintained their weight. While the results of the study indicate that mirtazapine appears to be a potentially useful agent in the management of cancer-related cachexia and anorexia, this study was small, with only four patients in each group.

• The study had a small sample size, with less than 30 participants.
• The study occurred at a single institution.
• The study had a high attrition rate.
• Placebo effect could have contributed to results.
• The study lacked randomization and a control arm.
• The study was also not blinded, and there could have been some placebo effect on the ESAS or FAACT.
• Alternatively, patients recruited to this study had advanced cancer and may have been experiencing a decline in health that pharmacology cannot reverse. Therefore, while encouraging, the study results should be interpreted with caution.

The pathophysiology of cachexia is complex. There is currently no standard treatment for managing cancer-related cachexia. Mirtazapine may be a potential agent useful in the management of cachexia; however, additional research is necessary.