What are the recommended starting doses and titration schedules for paroxetine in adults with major depressive disorder, obsessive‑compulsive disorder, panic disorder or generalized anxiety, and how should the dose be adjusted for elderly patients or those with hepatic impairment?

Paroxetine Dosing Guidelines

Starting Doses for Major Depressive Disorder

For adults with major depressive disorder, start paroxetine at 20 mg once daily in the morning, which is both the recommended starting dose and the established effective dose. 1

• The FDA label specifies that dose changes should occur in 10 mg/day increments at intervals of at least 1 week. 1
• In clinical trials, paroxetine 10–50 mg/day was significantly more effective than placebo and at least as effective as tricyclic antidepressants. 2, 3
• Maximum dose should not exceed 50 mg/day for depression. 1

Starting Doses for Anxiety Disorders

For obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, and PTSD, the recommended starting dose is 20 mg once daily, which is also the established effective dose. 1

• For OCD specifically, clinical trials demonstrated efficacy at 20–60 mg/day, with 40 mg and 60 mg doses showing superior efficacy (6–7 point YBOCS reduction) compared to 20 mg (4 point reduction). 1
• For panic disorder, paroxetine 10–60 mg/day was significantly more effective than placebo in reducing panic attack frequency. 4
• For generalized anxiety disorder, there is insufficient evidence to suggest greater benefit at doses higher than 20 mg/day. 1
• Dose increases should occur in 10 mg/day increments at intervals of at least 1 week. 1

Dosing for Social Anxiety Disorder

Start paroxetine at 20 mg once daily for social anxiety disorder; clinical trials used a dose range of 20–50 mg/day. 1

• Paroxetine is the only SSRI currently approved for social anxiety disorder, making it a unique first-line option. 2, 3
• Maintenance therapy should continue on the lowest effective dose, with periodic reassessment. 1

Elderly Patients and Special Populations

For elderly patients, debilitated patients, or those with severe renal or hepatic impairment, start at 10 mg/day—half the standard adult dose. 1

• Increases may be made if indicated, but dosage should not exceed 40 mg/day in these populations. 1
• Elderly patients have 70–80% higher plasma concentrations than younger adults due to reduced clearance. 1
• Patients with creatinine clearance below 30 mL/min have approximately 4-fold higher plasma concentrations; those with creatinine clearance 30–60 mL/min or hepatic impairment have approximately 2-fold increases. 1
• Paroxetine is generally well tolerated in elderly patients aged 65–75 years, though few studies exist for those over 75. 5

Titration Schedule and Monitoring

Allow at least 1 week between dose increases of 10 mg increments to account for paroxetine's pharmacokinetics. 1

• Steady-state plasma concentrations are reached after 7–14 days (approximately 4–14 days in various studies). 6, 1
• The elimination half-life is approximately 21 hours, consistent with once-daily dosing. 1, 6
• Paroxetine exhibits nonlinear pharmacokinetics due to saturable metabolism via CYP2D6; plasma concentrations after 40 mg daily are only 2–3 times greater than after 20 mg daily, not doubled as expected. 1

Maintenance Therapy Duration

For patients who respond to paroxetine, continue treatment for at least 4–12 months after symptom remission for a first episode. 7

• For major depressive disorder, relapse rates over 1 year were significantly lower with paroxetine (15%) compared to placebo (39%). 1
• For anxiety disorders (OCD, panic disorder, social anxiety disorder, GAD), maintenance therapy for 24 weeks to 1 year has demonstrated sustained benefit or relapse prevention. 2, 3
• Dosage adjustments should maintain patients on the lowest effective dose, with periodic reassessment. 1

Discontinuation Protocol

Taper paroxetine gradually rather than stopping abruptly to minimize discontinuation symptoms. 1

• If intolerable symptoms occur after dose reduction, resume the previously prescribed dose and then decrease more gradually. 1
• A gradual taper over 10–14 days is recommended to avoid discontinuation syndrome (dizziness, paresthesias, anxiety, irritability). 7
• Monitor patients for discontinuation symptoms regardless of the indication. 1

Critical Safety Considerations

Paroxetine should be avoided in elderly patients when possible due to its high anticholinergic burden and increased risk of adverse effects compared to other SSRIs. 7

• Paroxetine has the highest rates of sexual dysfunction among SSRIs and strong anticholinergic effects. 8
• It is a potent CYP2D6 inhibitor, creating significant drug interaction risks. 8, 1
• The American Geriatrics Society recommends avoiding paroxetine in older adults due to anticholinergic properties. 7
• Preferred SSRIs for elderly patients are sertraline and escitalopram due to better safety profiles. 7

Drug Interactions and Contraindications

Allow at least 14 days between discontinuation of an MAOI and initiation of paroxetine, and vice versa. 1

• Do not start paroxetine in patients receiving linezolid or methylene blue due to serotonin syndrome risk. 1
• If urgent treatment with linezolid or methylene blue is required, stop paroxetine promptly and monitor for 2 weeks or 24 hours after the last dose of linezolid/methylene blue. 1
• Paroxetine inhibits CYP2D6 and can increase levels of drugs metabolized by this enzyme, including desipramine, risperidone, and atomoxetine. 1

Common Pitfalls to Avoid

• Do not use paroxetine as a first-line agent in elderly patients—choose sertraline or escitalopram instead due to lower anticholinergic burden and fewer drug interactions. 7
• Do not increase doses more frequently than weekly intervals—paroxetine's saturable metabolism means plasma levels rise disproportionately with dose increases. 1
• Do not exceed 40 mg/day in elderly or renally/hepatically impaired patients—these populations have markedly elevated drug levels. 1
• Do not stop paroxetine abruptly—the discontinuation syndrome is well-documented and can be severe. 1