What are the next steps for an adult patient with depression, taking Prozac (fluoxetine) 10mg, who reports no improvement in symptoms after an adequate trial period?

Management of Inadequate Response to Prozac 10mg

Increase the dose to 20mg daily and reassess after 4-6 weeks, as 10mg is a subtherapeutic dose for most adults with depression. 1

Immediate Action: Dose Optimization

• The FDA-approved starting dose for depression is 20mg daily, with 10mg reserved only for initial titration in panic disorder or patients requiring cautious dosing. 1
• The current 10mg dose is below the therapeutic range for major depressive disorder, making treatment failure expected rather than surprising. 1
• Increase to 20mg daily immediately, as this is the standard therapeutic dose where efficacy has been demonstrated in controlled trials. 1
• Allow a full 6-8 weeks at 20mg before declaring treatment failure, as this is the minimum duration needed to assess antidepressant response. 2

If No Response After 8 Weeks at 20mg

Switch to a different antidepressant class or augment with bupropion, as continuing ineffective SSRI monotherapy beyond 8 weeks delays recovery. 3, 4

Switching Strategy (Preferred for True Non-Response)

• Switch to venlafaxine (SNRI) 37.5-75mg daily, titrating to 150-225mg, as SNRIs demonstrate statistically significantly better response and remission rates than SSRIs in treatment-resistant depression. 3, 4
• Alternative: switch to sertraline 50mg daily, titrating to 150-200mg, which has similar efficacy to fluoxetine but may work through individual pharmacogenetic differences. 5
• Approximately 21-25% of patients achieve remission when switching to another antidepressant after initial SSRI failure. 3

Augmentation Strategy (Preferred for Partial Response)

• Add bupropion SR 150mg daily, titrating to 300-400mg, as augmentation achieves remission rates of approximately 50% compared to 30% with SSRI monotherapy alone. 4, 6
• Bupropion augmentation has significantly lower discontinuation rates due to adverse events (12.5%) compared to buspirone augmentation (20.6%, p<0.001). 4
• Alternative augmentation: add aripiprazole 2-5mg daily, titrating to 10-15mg, which is FDA-approved as adjunctive therapy for treatment-resistant depression. 6, 7

Critical Monitoring Requirements

• Assess for suicidal ideation during the first 1-2 months after any dose change or medication switch, as suicide risk is greatest during this period. 3
• Use standardized depression rating scales (PHQ-9 or HAM-D) every 2-4 weeks to objectively track response. 3
• Monitor for behavioral activation syndrome (increased agitation, anxiety, restlessness) within 24-48 hours of dose increases. 3

Common Pitfalls to Avoid

• Do not continue 10mg indefinitely—this dose is inadequate for treating major depression in most adults. 1
• Do not switch medications before allowing adequate trial duration (6-8 weeks at therapeutic dose of 20mg minimum). 2
• Do not add multiple medications simultaneously, as this prevents identification of which intervention is effective. 3
• Do not exceed fluoxetine 60mg daily without clear indication, as higher doses increase side effects without additional benefit for depression. 1

Duration of Continuation Therapy

• Continue treatment for 4-9 months after achieving satisfactory response in patients with a first episode of major depressive disorder. 3
• For patients with recurrent depression (2+ episodes), consider years to lifelong maintenance therapy. 3

Adjunctive Psychotherapy Consideration

• Add cognitive-behavioral therapy (CBT) to medication, as combination therapy demonstrates superior efficacy compared to medication alone for depression. 2
• CBT can be initiated immediately while optimizing medication dose, providing synergistic benefit. 2