Prioritize nutritional rehabilitation and weight restoration as the primary intervention for both the eating disorder and depressive symptoms before initiating antidepressant pharmacotherapy

Depressive symptoms in anorexia nervosa are frequently driven by the physiological effects of malnutrition including alterations in tryptophan metabolism and serotonin synthesis. Antidepressants have limited evidence for efficacy in underweight patients with anorexia nervosa and may be poorly tolerated due to altered pharmacokinetics in malnourished states. The treatment plan should include close monitoring of depressive symptoms with planned reassessment for pharmacotherapy once nutritional status has meaningfully improved. This approach reflects current evidence and guidelines for comorbid anorexia nervosa and depression.

Initiate fluoxetine at a standard dose immediately

Because it is the only SSRI with FDA approval for an eating disorder and has demonstrated efficacy for both anorexia nervosa and major depressive disorder. Treating the depression pharmacologically will improve the patient's motivation and engagement with nutritional rehabilitation, creating a positive therapeutic cycle. Fluoxetine's appetite-stimulating effects at higher doses may also directly address the restrictive eating pattern. Delaying antidepressant treatment in a patient with passive suicidal ideation is clinically inappropriate regardless of the nutritional context. Fluoxetine has FDA approval for bulimia nervosa, not anorexia nervosa. No medication has FDA approval for the treatment of anorexia nervosa.

Start mirtazapine at 15 mg at bedtime as it provides the dual benefit of antidepressant efficacy and appetite stimulation with weight gain

Making it the ideal agent for this specific comorbid presentation. Mirtazapine's antihistaminic properties promote both appetite and sleep, addressing the catabolic state while simultaneously treating depressive symptoms. Its noradrenergic and serotonergic mechanisms function independently of tryptophan availability, circumventing the reduced serotonin synthesis that limits SSRI efficacy in malnourished patients. This agent represents the strongest pharmacological match for the unique pathophysiology of comorbid anorexia nervosa and depression.

Initiate bupropion at a low dose with gradual titration as it has the most favorable side-effect profile among antidepressants for eating disorder patients due to its lack of sexual dysfunction and weight-neutral properties

Bupropion's dopaminergic and noradrenergic mechanism provides antidepressant efficacy through pathways unaffected by the tryptophan depletion seen in malnourished states. Weight neutrality is preferred over weight-promoting agents because pharmacologically-induced weight gain may increase body image distress and undermine the patient's developing internal motivation for recovery. Starting at a low dose with careful monitoring mitigates the already small seizure risk in this population. Bupropion is strictly contraindicated in patients with current or prior history of anorexia nervosa or bulimia nervosa due to significantly elevated seizure risk.