Paroxetine Dosing Considerations

Pharmacokinetic Considerations

The American College of Physicians, as reported by the Mayo Clinic Proceedings, notes that paroxetine is metabolized by CYP2D6, which is subject to genetic polymorphism, and in poor metabolizers, the median area under the curve of a 30-mg dose was 7-fold higher compared to extensive metabolizers 1
The Mayo Clinic Proceedings reports that higher SSRI dosing, including paroxetine, in patients with OCD and major depressive disorder was associated with higher dropout rates due to adverse effects, with a strength of evidence supported by clinical trials 1
The Mayo Clinic Proceedings also states that the PM phenotype was associated with higher plasma concentrations compared to the EM phenotype, highlighting the importance of considering CYP2D6 genotype in dosing 1

The Mayo Clinic Proceedings suggests that dose increases should occur at intervals of at least 1 week to allow for steady-state concentrations, which are reached after 7-14 days, and that higher dosing requirement for OCD makes the potential risk of toxic blood levels particularly clinically relevant 1
Consider CYP2D6 genotype testing in patients experiencing adverse effects at standard doses, as poor metabolizers may require lower maximum doses, as recommended by the Mayo Clinic Proceedings 1