What is the recommended starting dose of fluoxetine (Prozac) for a patient with a history of anorexia nervosa and a previous adverse reaction to bupropion (Wellbutrin), who is being treated for depression?

Fluoxetine Starting Dose for Depression in a Patient with Anorexia Nervosa History and Prior Bupropion Adverse Reaction

Start fluoxetine at 20 mg once daily in the morning, as this is the FDA-approved initial dose for major depressive disorder and is particularly appropriate given this patient's history of anorexia nervosa, which is an absolute contraindication to bupropion. 1

Critical Safety Considerations in This Patient

Bupropion is absolutely contraindicated in patients with current or prior diagnosis of anorexia nervosa due to substantially increased seizure risk. 2 This patient's previous adverse reaction to bupropion may have been related to this underlying contraindication, making fluoxetine a safer alternative. 3

• Fluoxetine has been studied specifically in anorexia nervosa patients and appears to be well-tolerated even in the presence of medical comorbidity. 4
• Unlike bupropion, fluoxetine does not lower seizure threshold and is not contraindicated in eating disorders. 2

FDA-Approved Dosing Protocol

The recommended starting dose is 20 mg/day administered in the morning. 1

• After several weeks, if insufficient clinical improvement is observed, a dose increase may be considered. 1
• The dose range for depression is 20 to 60 mg/day, though doses up to 80 mg/day have been well tolerated in OCD studies. 1
• The maximum fluoxetine dose should not exceed 80 mg/day. 1

Special Considerations for Bulimia Nervosa

If this patient has bulimia nervosa rather than restricting-type anorexia nervosa, fluoxetine 60 mg/day is the FDA-approved dose and the only pharmacological treatment with proven efficacy. 5, 1

• The American Psychiatric Association recommends that adults with bulimia nervosa be treated with eating disorder-focused cognitive-behavioral therapy and that fluoxetine 60 mg daily also be prescribed, either initially or if there is minimal or no response to psychotherapy alone by 6 weeks of treatment. 5
• In controlled trials for bulimia nervosa, only the 60 mg dose was statistically significantly superior to placebo in reducing binge-eating and vomiting frequency. 1, 6
• For some patients, it may be advisable to titrate up to the 60 mg target dose over several days rather than starting at this dose. 1

Dosing Adjustments for Special Populations

A lower or less frequent dosage should be used in patients with hepatic impairment, elderly patients, or those with concurrent disease or on multiple concomitant medications. 1

• Dosage adjustments for renal impairment are not routinely necessary. 1

Timeline for Therapeutic Effect

The full therapeutic effect may be delayed until 5 weeks of treatment or longer. 1

• Patients should be monitored within 1-2 weeks of initiation for worsening depression, suicidal ideation, or behavioral changes. 7
• Allow 6-8 weeks at an adequate dose before determining treatment response and considering modification. 7

Pharmacogenetic Considerations

CYP2D6 poor metabolizers may experience significantly higher fluoxetine concentrations, potentially requiring dose adjustments. 5

• Single-dose fluoxetine at 20 mg had an area under the curve that was 3.9-fold higher in poor metabolizers versus extensive metabolizers. 5
• Long-term fluoxetine at 20 mg/day can convert an average of 43% of extensive metabolizers to poor metabolizer phenotype through auto-inhibition. 5
• The FDA has issued safety labeling changes stating that fluoxetine should be used with caution in CYP2D6 poor metabolizers due to QT prolongation risk. 5

Clinical Advantages in This Patient Population

Fluoxetine may help patients with anorexia nervosa maintain healthy body weight as outpatients by improving eating behavior and reducing obsessionality, depression, and anxiety. 8

• In an open trial, 29 of 31 anorexia nervosa patients maintained weight at or above 85% average body weight after 11 months on fluoxetine. 8
• Restrictor-type anorexics responded significantly better than bulimic/purging-type anorexics. 8
• Depressive symptoms diminished in anorexia nervosa patients treated with fluoxetine, and this was associated with weight gain. 4

Common Pitfalls to Avoid

Do not use bupropion in any patient with current or prior eating disorder diagnosis, as this substantially increases seizure risk. 2, 3

• Clinicians must screen for anorexia nervosa and bulimia nervosa histories prior to prescribing bupropion. 3
• The stimulant and anorexic effects of bupropion contribute to its abuse potential, particularly among eating disorder patients. 3

Do not discontinue fluoxetine abruptly, as symptoms associated with discontinuation have been reported. 1

• The physician may consider tapering fluoxetine gradually, particularly in pregnant women during the third trimester. 1