What is the maximum recommended dose of paroxetine (selective serotonin reuptake inhibitor) per day?

Maximum Dose of Paroxetine

The maximum recommended dose of paroxetine is 60 mg per day for obsessive-compulsive disorder (OCD) and panic disorder, while the maximum dose is 50 mg per day for major depressive disorder, and 40 mg per day for elderly or debilitated patients and those with severe renal or hepatic impairment. 1

Standard Maximum Dosing by Indication

Major Depressive Disorder

• The maximum dose should not exceed 50 mg per day 1
• Patients are typically started at 20 mg/day, with dose increases in 10-mg increments at intervals of at least 1 week 1
• Clinical trials demonstrated effectiveness in the range of 20-50 mg/day 1

Obsessive-Compulsive Disorder (OCD)

• The maximum dose should not exceed 60 mg per day 1
• The recommended target dose is 40 mg daily, starting at 20 mg/day with increases in 10-mg increments 1
• Patients were dosed in a range of 20-60 mg/day in clinical trials 1

Panic Disorder

• The maximum dose should not exceed 60 mg per day 1
• The target dose is 40 mg/day, starting at 10 mg/day with increases in 10-mg increments at weekly intervals 1
• Clinical trials demonstrated effectiveness in the 10-60 mg/day range 1

Social Anxiety Disorder

• While safety has been evaluated at doses up to 60 mg per day, available information does not suggest additional benefit for doses above 20 mg/day 1
• The recommended and initial dosage is 20 mg/day 1

Generalized Anxiety Disorder (GAD)

• The recommended effective dosage is 20 mg/day 1
• There is insufficient evidence to suggest greater benefit for doses higher than 20 mg/day, though clinical trials evaluated doses of 20-50 mg/day 1

Post-Traumatic Stress Disorder (PTSD)

• The recommended starting and established effective dosage is 20 mg/day 1
• Clinical trials evaluated doses of 20-50 mg/day, but fixed-dose studies did not show sufficient evidence for greater benefit at 40 mg/day compared to 20 mg/day 1

Special Population Dosing Restrictions

Elderly, Debilitated, or Impaired Patients

• Maximum dose should not exceed 40 mg per day in elderly patients, debilitated patients, and those with severe renal or hepatic impairment 1
• The recommended initial dose is 10 mg/day for these populations 1
• Plasma concentrations and area under the curve are greater, and elimination half-life is prolonged in elderly patients and those with hepatic or severe renal impairment 2

Important Pharmacokinetic Considerations

CYP2D6 Metabolism and Dose-Related Toxicity

• Paroxetine is metabolized by CYP2D6, which is subject to genetic polymorphism 3, 2
• In poor metabolizers (PMs), the median area under the curve of a 30-mg dose was 7-fold higher compared to extensive metabolizers (EMs), though this declined to 1.7-fold with long-term use 3
• Higher SSRI dosing (including paroxetine) in patients with OCD and major depressive disorder was associated with higher dropout rates due to adverse effects 3
• The PM phenotype was associated with higher plasma concentrations compared to the EM phenotype 3

Saturable Metabolism

• Metabolism of paroxetine by CYP2D6 is saturable 2
• With repeated administration, bioavailability increases and pharmacokinetics may become nonlinear in some patients, especially when dosage is increased 2

Clinical Caveats

• Dose increases should occur at intervals of at least 1 week to allow for steady-state concentrations, which are reached after 7-14 days 1, 2
• The higher dosing requirement for OCD makes the potential risk of toxic blood levels particularly clinically relevant 3
• Higher doses during the first few weeks of treatment can lead to lower tolerability, less treatment adherence, and poorer outcomes 3
• Consider CYP2D6 genotype testing in patients experiencing adverse effects at standard doses, as poor metabolizers may require lower maximum doses 3