What is the recommended titration schedule for fluoxetine (selective serotonin reuptake inhibitor)?

Fluoxetine Titration Schedule

The recommended titration schedule for fluoxetine begins with 10 mg every other morning, gradually increasing to a maximum of 20 mg every morning for most conditions. 1

Initial Dosing and Titration

• For adults with depression, OCD, or anxiety disorders, start with 10 mg every other morning (or 10 mg daily for some patients) 2, 1
• After 1-2 weeks, if tolerated, increase to 10 mg daily 1, 3
• After another 1-2 weeks, if needed and tolerated, increase to 20 mg daily (standard therapeutic dose) 1
• Fluoxetine has a very long half-life (1-3 days for fluoxetine, 4-16 days for its active metabolite norfluoxetine), which means side effects may not manifest for a few weeks 2, 4

Condition-Specific Titration

Major Depression

• Start with 10 mg every other morning or 10 mg daily 1
• Gradually increase to 20 mg daily over 1-2 weeks 1
• Maximum recommended dose is typically 20 mg daily, though doses up to 80 mg daily have been used in clinical practice 1, 4

Obsessive-Compulsive Disorder (OCD)

• Adults: Start with 10 mg daily, increase to 20 mg daily after 2 weeks 1
• Further increases may be considered if insufficient clinical improvement is observed 1
• Effective dose range is 20-60 mg daily 1, 5
• Maximum dose should not exceed 80 mg daily 1

Panic Disorder

• Start with 10 mg daily 1
• After 1 week, increase to 20 mg daily 1
• Some patients with panic disorder may benefit from starting at an even lower dose (5 mg daily) and gradually increasing 3
• Doses above 60 mg daily have not been systematically evaluated 1

Special Populations

• Elderly patients: Use lower starting doses (e.g., 10 mg every other day) and slower titration 1
• Hepatic impairment: Lower or less frequent dosing should be used 1
• Patients with panic disorder: May benefit from starting at lower doses (5 mg) due to higher sensitivity to side effects 3

Alternative Dosing Strategies

• Once-weekly dosing: For maintenance treatment after stabilization on daily dosing, some patients may be maintained on once-weekly dosing (10-60 mg once weekly) due to the long half-life of fluoxetine and its active metabolite 6
• Dose increases for relapse: For patients who relapse while on 20 mg daily, increasing to 40 mg daily may restore response in approximately 57% of patients 7

Common Pitfalls and Considerations

• Fluoxetine is activating and may cause insomnia if taken later in the day; morning dosing is preferred 2
• Side effects are typically dose-related and include nausea, anxiety, insomnia, anorexia, diarrhea, nervousness, and headache 4
• Due to its very long half-life, side effects may not appear immediately but can develop over several weeks of treatment 2
• Patients with panic disorder may be particularly sensitive to side effects and may benefit from starting at lower doses (5 mg) 3
• Abrupt discontinuation should be avoided; however, due to the long half-life, fluoxetine typically has a self-tapering effect 1

By following this titration schedule and adjusting based on individual response and tolerability, most patients can achieve optimal therapeutic benefit with minimal side effects.