Switching from Fluoxetine 90mg Extended Release to Sertraline
Direct Switching Protocol
Due to fluoxetine's exceptionally long half-life (4-6 days for the parent compound and 4-16 days for its active metabolite norfluoxetine), you can discontinue fluoxetine 90mg extended release abruptly and start sertraline 50mg daily the next day without a taper or washout period. 1, 2
Why Fluoxetine is Unique
- Fluoxetine does not require gradual tapering before switching because its long elimination half-life provides a built-in "self-taper" that minimizes withdrawal symptoms 2
- The discontinuation syndrome occurs less frequently and less severely with fluoxetine compared to shorter-acting SSRIs like sertraline, paroxetine, or venlafaxine 3, 2
- A direct switch from fluoxetine to sertraline has been studied and demonstrated safety without loss of depression control or substantial adverse effects 4
Sertraline Initiation and Titration
- Start sertraline at 50mg daily immediately after discontinuing fluoxetine 90mg 1, 4
- Increase sertraline by 25-50mg increments every 1-2 weeks as tolerated, targeting a therapeutic range of 50-200mg daily (maximum 200mg daily) 1
- The conversion ratio studied was 50-75mg sertraline for every 20mg fluoxetine, suggesting your patient on fluoxetine 90mg would require approximately 225-337mg sertraline equivalent, but start conservatively at 50mg and titrate to clinical response 4
Critical Monitoring Schedule
- Contact the patient within the first week (in-person or telephone) after initiating sertraline to assess for adverse events including behavioral activation, anxiety, agitation, or suicidal ideation 1
- Monitor weekly for adverse events and efficacy during weeks 2-4 1
- Continue monitoring every 1-2 weeks during dose titration until therapeutic dose is achieved 1
- Watch for serotonin syndrome symptoms within the first 24-48 hours after starting sertraline, including mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 3, 1
Expected Adverse Effects
- Common sertraline side effects emerging in the first few weeks include nausea, diarrhea, headache, insomnia, dizziness, dry mouth, and fatigue 3
- Sertraline may require twice-daily dosing at low doses in some patients, though most tolerate once-daily dosing 3
- Discontinuation due to adverse events is generally low with sertraline (6% in comparative studies) 5
Key Safety Warnings
- All SSRIs carry an FDA black-box warning for suicidal thinking and behavior through age 24 years, with pooled absolute rates of 1% for antidepressants versus 0.2% for placebo (number needed to harm = 143) 3
- Sertraline is associated with discontinuation syndrome if stopped abruptly in the future, characterized by dizziness, fatigue, myalgias, headaches, nausea, insomnia, paresthesias, and anxiety 3
- Monitor for behavioral activation/agitation, which may emerge early in treatment and typically resolves with dose reduction 3
Common Pitfalls to Avoid
- Do not taper fluoxetine before switching - this unnecessarily prolongs the transition and provides no benefit given fluoxetine's pharmacokinetics 2
- Do not implement a washout period - fluoxetine's long half-life means therapeutic levels persist for weeks after discontinuation, making a washout period both unnecessary and potentially harmful due to untreated depression 6, 2
- Do not start sertraline at high doses (≥100mg) during the switch, as this increases risk of adverse effects including anxiety and agitation 1
- Avoid combining sertraline with other serotonergic agents (tramadol, dextromethorphan, St. John's wort, certain opioids) due to serotonin syndrome risk 3