What is the initial dosage of paroxetine (Selective Serotonin Reuptake Inhibitor - SSRI) for a patient with post-traumatic stress disorder (PTSD) who has previously been on sertraline (SSRI)?

Initial Paroxetine Dosage for PTSD

Start paroxetine at 20 mg once daily in the morning for PTSD treatment, which is both the recommended starting dose and the established effective dose according to FDA labeling. 1

FDA-Approved Dosing Protocol

• The FDA label specifies 20 mg/day as both the recommended starting dosage and the established effective dosage for PTSD. 1
• Administer as a single daily dose with or without food, usually in the morning. 1
• In clinical trials, paroxetine was effective at doses ranging from 20 to 50 mg/day for PTSD. 1
• If dose changes are indicated, increase in 10 mg/day increments at intervals of at least 1 week. 1

Evidence Supporting 20 mg Starting Dose

• A large randomized controlled trial (N=551) demonstrated that both 20 mg/day and 40 mg/day paroxetine were significantly more effective than placebo for chronic PTSD, with no clear advantage for the higher dose. 2
• Both doses showed statistically significant improvement on all three PTSD symptom clusters (reexperiencing, avoidance/numbing, and hyperarousal) compared to placebo. 2
• Treatment response did not vary by trauma type, time since trauma, or severity of baseline symptoms, supporting a standard 20 mg starting dose across patient populations. 2
• Multiple studies confirm paroxetine 20-60 mg/day is effective for PTSD after 8-12 weeks of treatment. 3, 4, 5

Special Considerations for Patients Previously on Sertraline

• Allow at least 14 days washout period after discontinuing sertraline before starting paroxetine to minimize risk of serotonin syndrome. 1
• Sertraline should be tapered gradually over a minimum of 2-4 weeks (or longer for long-term therapy) to avoid discontinuation syndrome before switching. 6
• The patient's previous SSRI experience does not change the paroxetine starting dose—still begin at 20 mg/day. 1

Critical Pharmacokinetic Warnings

• Paroxetine exhibits nonlinear pharmacokinetics due to CYP2D6 saturation, meaning dose increases above 20 mg can lead to disproportionate plasma concentration increases. 7
• Paroxetine itself inhibits CYP2D6, with long-term use converting approximately 43% of extensive metabolizers to functional poor metabolizers. 7
• CYP2D6 poor metabolizers may have plasma concentrations up to 7-fold higher than extensive metabolizers, though this does not typically require dose adjustment at initiation. 7

Monitoring and Titration Strategy

• Monitor closely for suicidal thinking and behavior, especially in the first months of treatment and following any dose adjustments. 1
• Most adverse effects (nausea, sexual dysfunction, somnolence, headache, dizziness) emerge within the first few weeks and are dose-related. 4, 5
• If 20 mg/day is insufficient after at least 1 week, increase to 30 mg/day, then 40 mg/day if needed, with increases at minimum 1-week intervals. 1
• The maximum dose should not exceed 60 mg/day, though there is insufficient evidence that doses above 20 mg/day provide additional benefit for PTSD. 1

Special Population Adjustments

• For elderly patients, debilitated patients, or those with severe renal or hepatic impairment, start at 10 mg/day instead of 20 mg/day. 1
• In these populations, increases may be made if indicated, but dosage should not exceed 40 mg/day. 1

Common Pitfalls to Avoid

• Never start at doses higher than 20 mg/day—this increases adverse effects without improving efficacy for PTSD. 1, 2
• Never combine with MAOIs or start within 14 days of MAOI discontinuation due to risk of serotonin syndrome or NMS-like reactions. 1
• Never abruptly discontinue paroxetine—it has the highest risk of discontinuation syndrome among SSRIs and requires gradual tapering. 7
• Do not increase the dose too quickly—allow at least 1 week at each dose level before escalating. 1
• Be vigilant for drug interactions with other CYP2D6 substrates (risperidone, atomoxetine, tricyclic antidepressants) which may require dose adjustments. 7

Expected Timeline for Response

• Clinical trials demonstrated efficacy after 12 weeks of treatment at fixed doses. 2
• Improvement should be evident by 8-12 weeks; if no response by this time, reassess diagnosis and consider alternative treatments. 3, 4
• PTSD is a chronic condition, and continuation treatment for 6-12 months decreases relapse rates in responding patients. 3