Rethinking Mirtazapine: Evidence and Best Practices for Managing Unintentional Weight Loss in Older Adults

Introduction 

Mirtazapine is often prescribed to older adults experiencing unintentional weight loss, especially in complex cases involving cancer, AIDS, congestive heart failure, or advanced chronic obstructive pulmonary disease (COPD) due to its appetite-stimulating properties. However, recent evidence and clinical guidelines suggest that this practice warrants reevaluation, particularly among pharmacists managing geriatric care (Arrieta et al., 2024). 

Rationale for Use 

Mirtazapine, a tetracyclic antidepressant, exerts its effects by antagonizing α2-adrenergic autoreceptors and heteroreceptors, as well as serotonin 5-HT2 and 5-HT3 receptors (Apotex Corp, 2023). While weight gain is a known side effect, its therapeutic use for appetite stimulation remains controversial. Some studies have shown increased caloric intake and improved macronutrient consumption in cancer patients, but findings across broader geriatric populations are inconsistent (Arrieta et al., 2024; Avena-Woods & Hilas, 2012). 

Clinical Guidelines and Recommendations 

The American Academy of Family Physicians advises against using mirtazapine or other prescription appetite stimulants solely for weight gain in older adults (American Academy of Family Physicians [AAFP], n.d.). Evidence does not support improvements in quality of life or survival, and the appetite-stimulating effect is most justifiable only when depression is also present. Pharmacists should be cautious about initiating mirtazapine for appetite alone, especially in the absence of depression.

Alternative, Evidence Based Approaches 

Nonpharmacologic strategies remain the preferred first-line approach. These include dietary modifications tailored to patient preferences, enhancing the mealtime environment, and assisted feeding when necessary. Addressing underlying causes with a multidisciplinary approach, including dietitians, speech therapists, and social workers, is emphasized over reliance on medication. Nutritional supplements may aid caloric intake but should not substitute primary meals, and flavor enhancers can help increase food consumption, though results vary (Alibhai et al., 2005). Pharmacologic options should be reserved for specific cases where depression coexists with weight loss and only after careful evaluation of risks and benefits.

Implications for Clinical Practice 

Pharmacists play a critical role in identifying potentially inappropriate medication use and guiding deprescribing efforts. Routine reassessment of mirtazapine’s indication is necessary. Its use should be reserved for patients with both depression and weight loss who may benefit from its dual therapeutic effects. Educating patients and providers about the risks and lack of evidence for appetite stimulants in older adults without depression is essential. Clinicians should avoid reflexive prescribing of appetite stimulants and instead prioritize multidisciplinary, evidence-based interventions, including gradual deprescribing when appropriate.

References

• Alibhai, S. M., Greenwood, C., & Payette, H. (2005). An approach to the management of unintentional weight loss in elderly people. Canadian Medical Association Journal, 172(6), 773–780. https://doi.org/10.1503/cmaj.1031527

  
  

• American Academy of Family Physicians. (n.d.). Avoid using prescription appetite stimulants or high-calorie supplements for treatment of anorexia or cachexia in older adults. Choosing Wisely. https://www.aafp.org/pubs/afp/collections/choosing-wisely/183.html

  
  

• Apotex Corp. (2023, June). Mirtazapine [Package insert]. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=82a644f9-d9f6-4398-83db-8a1446c183e0

  
  

• Arrieta, O., Cárdenas-Fernández, D., Rodriguez-Mayoral, O., et al. (2024). Mirtazapine as appetite stimulant in patients with non–small cell lung cancer and anorexia: A randomized clinical trial. JAMA Oncology, 10(3), 305–314. https://doi.org/10.1001/jamaoncol.2023.5232

  
  

• Avena-Woods, C., & Hilas, O. (2012). Antidepressant use in underweight older adults. Consultant Pharmacist, 27(12), 868–870. https://doi.org/10.4140/TCP.n.2012.868