Paroxetine Extended Release (ER): Recommended Use and Dosage
Paroxetine ER is FDA-approved for major depressive disorder, obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder, generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD), with standard dosing starting at 20 mg/day as a single morning dose, which is both the initial and often optimal dose for most patients. 1
FDA-Approved Indications
Paroxetine (including ER formulations) is approved for:
- Major depressive disorder 2, 1
- Obsessive-compulsive disorder 2, 1
- Panic disorder 2, 1
- Social anxiety disorder (social phobia) 2, 1
- Generalized anxiety disorder 2, 1
- Post-traumatic stress disorder 2, 1
Dosing Recommendations by Indication
Major Depressive Disorder
- Starting dose: 20 mg once daily in the morning (with or without food) 1
- Therapeutic range: 20-50 mg/day 1
- For non-responders at 20 mg, increase in 10 mg increments at intervals of at least 1 week 1
- Maximum dose: 50 mg/day 1
- The 20 mg starting dose is also the minimal effective dose and will be optimal for most patients 3
Obsessive-Compulsive Disorder
- Starting dose: 20 mg/day 1
- Target dose: 40 mg/day 1
- Increase in 10 mg increments at intervals of at least 1 week 1
- Therapeutic range: 20-60 mg/day 1
- Maximum dose: 60 mg/day 1
- Higher dosing (60 mg) has demonstrated superior efficacy for OCD compared to lower doses 2
Panic Disorder
- Starting dose: 10 mg/day (lower than other indications) 1
- Target dose: 40 mg/day 1
- Increase in 10 mg increments at intervals of at least 1 week 1
- Therapeutic range: 10-60 mg/day 1
- Maximum dose: 60 mg/day 1
Social Anxiety Disorder
- Recommended and initial dose: 20 mg/day 1
- Therapeutic range: 20-60 mg/day 1
- Available evidence does not suggest additional benefit for doses above 20 mg/day 1
Generalized Anxiety Disorder
- Starting and established effective dose: 20 mg/day 1
- Therapeutic range: 20-50 mg/day 1
- Insufficient evidence suggests greater benefit to doses higher than 20 mg/day 1
- Increase in 10 mg increments at intervals of at least 1 week if needed 1
Post-Traumatic Stress Disorder
- Starting and established effective dose: 20 mg/day 1
- Therapeutic range: 20-50 mg/day 1
- In fixed-dose studies, 40 mg/day did not show greater benefit compared to 20 mg/day 1
- If dose changes indicated, increase in 10 mg increments at intervals of at least 1 week 1
Duration of Treatment
- First episode of major depression: Continue for 4-12 months after remission 4
- Recurrent depression: Prolonged treatment may be beneficial 2, 4
- Long-term efficacy has been demonstrated for up to 1 year with average doses around 30 mg 1
- For chronic conditions (OCD, panic disorder, social anxiety disorder, GAD, PTSD), continuation is reasonable for responding patients 1
- Periodically reassess patients to determine need for continued treatment 1
Critical Pharmacokinetic Considerations
Nonlinear Pharmacokinetics
- Paroxetine exhibits nonlinear pharmacokinetics due to CYP2D6 enzyme saturation, leading to disproportionate plasma concentration increases with dose escalation 4
- Paroxetine itself inhibits CYP2D6, with long-term use of 20 mg/day converting approximately 43% of extensive metabolizers to functional poor metabolizers 4
Genetic Variation
- CYP2D6 poor metabolizers may have plasma concentrations up to 7-fold higher than extensive metabolizers with standard dosing 2, 4
- Consider CYP2D6 genetic testing before significant dose increases in patients with poor initial tolerance or unusual response 4
- Poor metabolizers may require lower doses or more cautious titration 2, 4
Special Population Considerations
Elderly Patients
- Paroxetine should generally be avoided in older adults due to anticholinergic effects 2, 4
- If used, therapeutic range is 20-40 mg/day 3
- Preferred alternatives for elderly include citalopram, escitalopram, sertraline, mirtazapine, venlafaxine, or bupropion 2
Children and Adolescents
- Paroxetine has a black box warning for treatment-emergent suicidality in adolescents and young adults 2
- Paroxetine has been associated with increased risk of suicidal thinking or behavior compared to other SSRIs 2
- Parental oversight of medication regimens is paramount 2
Important Safety Considerations
Discontinuation Syndrome
- Paroxetine has the highest risk of discontinuation syndrome among SSRIs due to its shorter half-life 2, 4
- Characterized by dizziness, fatigue, myalgias, nausea, sensory disturbances, anxiety, and irritability 2
- Gradual dose reduction over 10-14 days is recommended when discontinuing 2
Drug Interactions
- Monitor for interactions with CYP2D6-metabolized medications (risperidone, atomoxetine, tricyclic antidepressants) 2, 4
- Avoid combination with MAOIs due to serotonin syndrome risk 2
- Exercise caution when combining with other serotonergic drugs 2
- Monitor for serotonin syndrome symptoms within 24-48 hours after dose increases 2, 4
Cardiac Considerations
- Potential for QT prolongation in susceptible individuals 4
- Consider ECG monitoring for patients with cardiac risk factors 4
Common Adverse Effects
- Most common: nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor, decreased appetite 5, 6
- Approximately 63% of patients experience at least one adverse effect 2
- Higher doses associated with increased dropout rates due to adverse effects 4
Practical Dosing Algorithm
- Start at indication-specific dose (10 mg for panic disorder, 20 mg for all others) 1
- Assess response at 1-3 weeks 1, 3
- If inadequate response and good tolerance: Increase by 10 mg increments at minimum 1-week intervals 1
- Monitor closely for 24-48 hours after each dose increase for adverse effects or serotonin syndrome 4
- If poor tolerance at standard doses: Consider CYP2D6 genetic testing or switch to alternative antidepressant 4
- Maintain on lowest effective dose once response achieved 1