Paxil (Paroxetine) Dosing
The recommended starting dose of Paxil is 20 mg once daily for major depressive disorder, with a therapeutic range of 20-50 mg/day, while obsessive-compulsive disorder and panic disorder require different dosing strategies. 1
Major Depressive Disorder
- Start at 20 mg once daily, typically taken in the morning with or without food 1
- The starting dose of 20 mg/day is also the minimum effective dose 2
- For most patients, 20 mg/day will be the optimal dose 2
- If inadequate response after 1-3 weeks, increase in 10 mg increments at weekly intervals to a maximum of 50 mg/day 1, 2
- Maintenance dosing averages approximately 30 mg/day for sustained efficacy up to 1 year 1
Obsessive-Compulsive Disorder (OCD)
- Target dose is 40 mg daily 1
- Start at 20 mg/day and increase in 10 mg increments at weekly intervals 1
- Dosing range in clinical trials was 20-60 mg/day, with maximum dose of 60 mg/day 1
- Higher dosing (60 mg) has demonstrated superior efficacy compared to lower doses for OCD 3
- Long-term maintenance demonstrated lower relapse rates compared to placebo over 6 months 1
Panic Disorder
- Target dose is 40 mg daily 1
- Start at 10 mg/day (lower than depression dosing) 1
- Increase in 10 mg increments at weekly intervals 1
- Clinical trial dosing range was 10-60 mg/day, with maximum of 60 mg/day 1
- The lower starting dose helps minimize initial anxiety exacerbation that can occur with SSRIs in panic disorder 4
Other Anxiety Disorders
- Social anxiety disorder: 20 mg/day (both starting and recommended dose) 1
- Generalized anxiety disorder and PTSD: 20-60 mg/day range 5, 6
Special Populations
Elderly Patients
- Start at approximately 50% of the standard adult dose (around 10 mg/day) 3
- Therapeutic range in elderly: 20-40 mg/day 2
- Paroxetine has increased plasma concentrations and prolonged half-life in elderly patients 4
- Avoid use in older adults when possible due to increased anticholinergic effects compared to other SSRIs 3
Renal Impairment
- Reduce dose in renal impairment 3
- Severe renal impairment results in increased plasma concentrations and prolonged half-life 4
Hepatic Impairment
- No dose reduction required for hepatic disease 3
- However, hepatic impairment does increase plasma concentrations and prolong half-life 4
Important Clinical Considerations
Pharmacokinetic Properties
- Paroxetine undergoes saturable first-pass metabolism via CYP2D6, resulting in nonlinear pharmacokinetics at higher doses 3, 4
- Bioavailability is approximately 30-60% due to extensive first-pass metabolism 7
- Steady-state achieved in 7-14 days with a half-life of approximately 24 hours 4
- 95% protein bound in plasma 4
Critical Warnings
- Black box warning for treatment-emergent suicidality, particularly in adolescents and young adults 3
- Strong CYP2D6 inhibitor - avoid concomitant use with tricyclic antidepressants due to risk of elevated TCA levels 3, 7
- Avoid use with MAOIs due to serotonin syndrome risk 8
Discontinuation
- Gradual taper required to avoid discontinuation syndrome (dizziness, fatigue, headaches, nausea, insomnia, sensory disturbances, anxiety) 8
- Unlike fluoxetine with its long half-life, paroxetine's shorter half-life (24 hours) necessitates more careful discontinuation 8
Comparative Context
- Paroxetine has more anticholinergic effects than other SSRIs, making it less preferred in older adults 3
- It is not a preferred first-line SSRI for depression; citalopram, escitalopram, and sertraline are preferred due to more favorable adverse effect profiles 3
- However, paroxetine is the only SSRI approved for all five anxiety disorders plus major depression, making it valuable for comorbid presentations 5, 6