What is the recommended use and dosage of Paroxetine (Selective Serotonin Reuptake Inhibitor) for treating major depressive disorder?

Paroxetine for Major Depressive Disorder

For major depressive disorder, start paroxetine at 20 mg once daily in the morning, with or without food, and increase by 10 mg increments at weekly intervals up to a maximum of 50 mg/day if needed for adequate response. 1

Initial Dosing Strategy

• Begin with 20 mg/day as a single morning dose, which is the FDA-approved starting dose for major depressive disorder 1
• Administer with or without food, though morning dosing is preferred to minimize sleep disturbance 1
• The therapeutic range in clinical trials was 20-50 mg/day 1

Dose Titration

• Increase in 10 mg/day increments only if patients fail to respond to the initial 20 mg dose 1
• Wait at least 1 week between dose adjustments to allow adequate time for therapeutic effect 1
• Maximum dose should not exceed 50 mg/day for major depressive disorder 1
• Assess therapeutic response and adverse effects within 1-2 weeks of treatment initiation, and modify treatment if adequate response is not achieved within 6-8 weeks 2

Duration of Treatment

• Continue treatment for 4-9 months for first-episode major depressive disorder 2
• For patients with 2 or more previous episodes, longer duration therapy is beneficial 2
• Maintenance therapy efficacy has been demonstrated for up to 1 year with average doses around 30 mg/day 1
• The full antidepressant effect may be delayed, so patience is required before declaring treatment failure 1

Special Populations and Considerations

Elderly Patients

• Lower doses (10-40 mg/day) are appropriate for patients aged ≥60 years 3, 4
• Both controlled-release and immediate-release formulations are effective and well-tolerated in elderly patients, including those with chronic depression 5

Pharmacogenetic Considerations

• Consider CYP2D6 genetic testing in patients with poor response or unusual side effects, as paroxetine is primarily metabolized through this pathway 2
• CYP2D6 poor metabolizers may have significantly higher blood levels and require lower doses 2
• This genetic variation can substantially affect drug levels and tolerability 2

Comparative Context

• Select paroxetine based on adverse effect profile, cost, and patient preferences rather than efficacy alone, as all second-generation antidepressants have similar comparative efficacy 2
• Cognitive behavioral therapy is equally effective and should be strongly considered as an initial treatment option 2
• Paroxetine is generally better tolerated than tricyclic antidepressants 3, 4

Common Pitfalls and Caveats

• Paroxetine causes more sedation, constipation, sexual dysfunction, discontinuation syndrome, and weight gain compared to other SSRIs 6
• The most common adverse events include nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor, and decreased appetite 3, 4
• Paroxetine is categorized as Pregnancy Class D and is not indicated for pediatric use 6
• Do not abruptly discontinue due to risk of discontinuation syndrome; taper gradually 6