Treatment of Depression with Loss of Appetite
For a patient with depression and loss of appetite, initiate treatment with mirtazapine 15 mg at bedtime, as it simultaneously addresses both the depressive symptoms and appetite loss through its unique pharmacologic profile. 1
Rationale for Mirtazapine as First-Line Treatment
Mirtazapine is uniquely positioned to address both components of this clinical presentation:
Appetite stimulation is a documented effect: In U.S. controlled clinical studies, appetite increase was reported in 17% of patients treated with mirtazapine compared to 2% for placebo, with weight gain of ≥7% body weight occurring in 7.5% of mirtazapine-treated patients versus 0% for placebo. 1
Antidepressant efficacy is established: Mirtazapine is FDA-approved for treatment of Major Depressive Disorder in adults and functions as an effective antidepressant medication. 1
Dosing strategy: Start at 15 mg at bedtime and titrate based on response. The sedating effects can be beneficial for patients with comorbid insomnia, which commonly accompanies depression. 1
Alternative Pharmacologic Options
If mirtazapine is contraindicated or not tolerated, consider these alternatives based on clinical context:
For Palliative Care or Cancer-Related Depression with Cachexia
Megestrol acetate (400-800 mg/day) or olanzapine (5 mg/day) are recommended when life expectancy is measured in months to years and increased appetite is an important quality of life goal. 2
Megestrol acetate improves appetite in 1 of 4 patients and increases weight in 1 of 12 patients, though clinicians must weigh this against a 1 in 6 risk of thromboembolic phenomena. 2
Olanzapine 5 mg/day has demonstrated efficacy for both appetite stimulation and depression in cancer-related anorexia/cachexia. 2
Dexamethasone 2-8 mg/day can be considered as an appetite stimulant, particularly in palliative care settings. 2
For Standard Depression Treatment
Selective serotonin reuptake inhibitors (SSRIs) remain appropriate for depression treatment, though they typically do not address appetite loss and may occasionally worsen it:
Fluoxetine 60 mg daily is FDA-approved for bulimia nervosa and can treat comorbid depression, though paradoxically it may cause weight loss despite increased appetite in some patients. 2, 3
SSRIs are recommended for comorbid depression in various clinical contexts. 4
Critical Safety Considerations
Contraindications and Drug Interactions
Do not use mirtazapine if the patient:
- Is taking or has taken a monoamine oxidase inhibitor (MAOI) within the last 14 days 1
- Is being treated with linezolid or intravenous methylene blue 1
- Has a known allergy to mirtazapine 1
Monitoring Requirements
Screen for and monitor:
Suicidal ideation: All patients, especially those under 24 years of age, require close monitoring for emergence or worsening of suicidal thoughts, particularly in the first few months of treatment or with dose changes. 1
Agranulocytosis risk: Advise patients to report fever, chills, sore throat, or flu-like symptoms immediately, as mirtazapine carries a risk of severe neutropenia. 1
QTc prolongation: Exercise caution in patients with cardiovascular disease, family history of QT prolongation, or those taking other QTc-prolonging medications. 1
Serotonin syndrome: Particularly when combining with other serotonergic drugs including triptans, tramadol, fentanyl, or St. John's Wort. 1
Common Adverse Effects to Anticipate
Somnolence occurs in 54% of mirtazapine-treated patients and may impair performance of activities requiring alertness. Advise patients to avoid alcohol and benzodiazepines. 1
Weight gain is expected and therapeutic in this context, but monitor for excessive gain. 1
Addressing Underlying Mechanisms
Evaluate Reversible Causes
Before or concurrent with pharmacologic treatment, assess for:
Nutritional deficiencies: Depression is associated with increased risk of vitamin D, folate, and zinc deficiency. 2
Medication effects: Review all current medications for gastrointestinal side effects that may contribute to appetite loss. 2
Food insecurity: More common in individuals with depression and requires social work intervention. 2
Comorbid conditions: Rule out oropharyngeal candidiasis, gastroparesis, or other physical causes of reduced intake. 2
Neurovegetative Symptom Pattern
The appetite loss in depression follows a specific pattern characterized by decreased desire to eat, reduced hunger, increased early satiety, and diminished pleasure from eating at meal initiation. 5 Understanding this pattern helps distinguish primary depressive appetite loss from other causes.
Adjunctive Non-Pharmacologic Interventions
While pharmacotherapy is the primary intervention, integrate:
Nutritional counseling: Smaller, more frequent meals may reduce early satiety and improve total intake. 2
Psychotherapy: Cognitive behavioral therapy addresses both depression and maladaptive eating patterns. 2
Treatment of comorbid anxiety: Diet-related anxiety and food fears may require specialized intervention from an eating disorder dietitian. 2
Discontinuation Precautions
Never abruptly discontinue mirtazapine. Discuss any tapering regimen with the patient, as abrupt discontinuation can cause withdrawal symptoms. 1 This is particularly important given the dual benefit on mood and appetite that patients may be experiencing.