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1 Associate Professor and Director, Memory Loss Clinic, Division of
Geriatrics, Department of Internal Medicine, Sealy Center on Aging, University
of Texas Medical Branch, 301 University Boulevard, Route 0460, Galveston,
Texas 77555, fax 409/772-8931,
muraji{at}utmb.edu
2 Assistant Professor, Department of Internal Medicine, Sealy Center on
Aging, University of Texas Medical Branch
3 Professor, Division of Geriatrics, Department of Internal Medicine, Sealy
Center on Aging, University of Texas Medical Branch
4 The Bill and Louise Bauer Distinguished Chair in Cancer Research,
Professor and Director, Division of Hematology/Oncology, Director, Oncology
Clinical Trials Office, UTMB Comprehensive Cancer Center, University of Texas
Medical Branch
Published Online, July 10, 2007. www.theannals.com, DOI 10.1345/aph.1K131
Because of its inhibition of the serotonin (5-HT) receptors of the 5-HT2 and 5-HT3 subtypes and its enhanced activity at the 5-HT1 postsynaptic receptor, mirtazapine is a potential "one-stop" treatment for depression and comorbid symptoms in older patients with cancer.3-5 Consistent with our clinical experience in cancer care, recent studies have provided evidence supporting the efficacy of mirtazapine in the treatment of depression and comorbid symptoms in patients with cancer and other medical disorders.5-8
Cancer cachexia is often exacerbated by depression. Cachexia is an independent predictor of functional loss and mortality. Several studies have documented the association between mirtazapine use, appetite improvement, and subsequent weight gain.6,8-9 A 6 week, open-label, crossover trial of mirtazapine in 20 older (mean 60 y) patients with advanced cancer showed a significant improvement in appetite of these patients, leading to an average weight gain of 0.9 kg.8 These patients also experienced improvement in their sleep, mood, and overall quality of life. Controlled clinical trials are needed to clarify the role of mirtazapine as a potential treatment for cancer-related anorexia and cachexia.
Cancer-associated nausea and vomiting, a significant source of poor quality of life and morbidity, can be due to highly emetic chemotherapy (eg, cisplatin), radiation therapy, opiate analgesics, or the direct effects of the underlying malignancy. Highly emetic chemotherapy increases synthesis and release of 5-HT from the alimentary tract. The 5-HT stimulates vagal 5-HT3 receptors, leading to activation of the brain stem emetic center.10 The most commonly used antiemetics (eg, ondansetron) are central 5-HT3 receptor antagonists. Similar to ondansetron, mirtazapine is an antagonist at central 5-HT3 postsynaptic receptors.4 Several open-label studies have reported on the antiemetic properties of mirtazapine.8-11 A study of 20 older patients with advanced cancer reported improvement of nausea after 6 weeks of mirtazapine 15-30 mg daily.8 Another open-label study of 19 women undergoing chemotherapy and radiotherapy for breast, uterocervical, or ovarian cancer showed resolution of nausea and anorexia in response to mirtazapine therapy.9
An advantage of mirtazapine is its low cost when compared with the most widely used cancer antiemetics (eg, ondansetron).3,7 Mirtazapine adverse effects include constipation, drowsiness at low doses, and, rarely, reversible neutropenia. Unlike the selective serotonin-reuptake inhibitors, mirtazapine is associated with fewer gastrointestinal adverse effects (eg, nausea, vomiting, diarrhea). This makes mirtazapine an antidepressant of choice for depressed patients with cancer who are at risk of chemotherapy-related nausea.4,6
Published studies suggest that mirtazapine is a potential "one-stop" antidepressant with beneficial effects on cancer-associated anorexia, nausea, vomiting, and cachexia. Randomized, controlled clinical trials are needed to determine the best antidepressant for depression and comorbid symptoms in older patients with cancer.
References
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