How to switch from fluoxetine (Prozac) to paroxetine (Paxil)?

Switching from Fluoxetine to Paroxetine: Protocol and Considerations

When switching from fluoxetine to paroxetine, a direct switch without a washout period is safe and well-tolerated due to fluoxetine's long half-life. 1

Pharmacokinetic Considerations

• Fluoxetine has an extended half-life (2-3 days for parent compound, 7-9 days for active metabolite norfluoxetine), which provides a natural tapering effect when discontinued 2, 3
• Paroxetine exhibits nonlinear pharmacokinetics due to CYP2D6 enzyme saturation, which can lead to disproportionate increases in plasma concentrations with dose increases 4
• Paroxetine itself inhibits CYP2D6, potentially complicating the transition if started at high doses 4

Switching Protocol

• Start paroxetine at 20 mg/day the morning after the last dose of fluoxetine 1
• No washout period is required between fluoxetine and paroxetine due to fluoxetine's long half-life providing a natural taper 1
• Begin with the recommended starting dose of paroxetine (20 mg/day) as established in clinical trials 5
• Monitor closely for the first 24-48 hours after initiating paroxetine for any adverse effects 4

Monitoring During Transition

• Be vigilant for signs of serotonin syndrome (confusion, agitation, tremors, hyperreflexia, autonomic instability) during the first 1-2 weeks of transition 6, 4
• Watch for emergence of discontinuation symptoms which may be masked by fluoxetine's long half-life but could emerge as fluoxetine levels decrease 2
• Monitor for drug interactions, particularly with medications metabolized by CYP2D6, as paroxetine is a potent inhibitor of this enzyme 4

Special Considerations

• For elderly patients, debilitated patients, or those with severe renal or hepatic impairment, start paroxetine at 10 mg/day 5
• CYP2D6 poor metabolizers may have plasma concentrations up to 7-fold higher than extensive metabolizers, requiring more cautious dosing 4
• Be aware that paroxetine has more anticholinergic effects than fluoxetine and may not be ideal for older adults 4

Potential Adverse Effects

• Paroxetine has been associated with a more pronounced discontinuation syndrome than fluoxetine if missed doses occur 6, 2
• Higher doses of paroxetine are associated with increased dropout rates due to adverse effects 4
• Paroxetine may have a higher risk of QT prolongation in susceptible individuals compared to some other SSRIs 4

Long-term Management

• Maintain the patient on the lowest effective dosage of paroxetine 5
• Periodically reassess the need for continued treatment 5
• If dose adjustments are needed, make changes in 10 mg/day increments at intervals of at least 1 week 5

If Discontinuation Is Eventually Needed

• Unlike fluoxetine, paroxetine requires a gradual taper when discontinuing due to its shorter half-life 6, 2
• A gradual reduction in dose rather than abrupt cessation is recommended to minimize discontinuation symptoms 5
• If intolerable symptoms occur during discontinuation, resuming the previously prescribed dose may be considered before attempting a more gradual taper 5

By following this protocol, patients can safely transition from fluoxetine to paroxetine while minimizing the risk of adverse effects or discontinuation symptoms.