What is the starting dose and titration schedule for Paroxetine (Selective Serotonin Reuptake Inhibitor) ER 25 mg?

Paroxetine ER 25 mg Dosing

Paroxetine ER 25 mg is typically used as a starting dose for major depressive disorder and most anxiety disorders, with titration upward in 12.5 mg increments at weekly intervals if needed, up to a maximum of 62.5 mg/day. 1

Starting Dose by Indication

For Major Depressive Disorder:

• Start with 25 mg once daily, preferably in the morning 1
• This is the standard initial dose for most adult patients 1

For Panic Disorder:

• Start with 12.5 mg once daily (lower than the 25 mg you're asking about) 1
• The lower starting dose reduces initial anxiety exacerbation that can occur with SSRIs in panic disorder 1

For Social Anxiety Disorder, Generalized Anxiety Disorder, and PTSD:

• Start with 25 mg once daily 1

Titration Schedule

If response is inadequate after 1-3 weeks:

• Increase by 12.5 mg increments 1
• Wait at least 1 week between dose increases 1, 2
• Maximum dose: 62.5 mg/day for most indications 1

Important caveat: Paroxetine exhibits nonlinear pharmacokinetics due to CYP2D6 enzyme saturation, meaning plasma concentrations can increase disproportionately with dose escalation 2. This makes cautious titration particularly important.

Special Population Adjustments

Elderly or debilitated patients:

• Start with 12.5 mg/day (not the 25 mg standard dose) 1
• Maximum dose should not exceed 50 mg/day 1
• Paroxetine's anticholinergic effects make it less ideal for older adults 2

Severe renal or hepatic impairment:

• Start with 12.5 mg/day 1
• Maximum dose: 50 mg/day 1

CYP2D6 poor metabolizers:

• May have plasma concentrations up to 7-fold higher than extensive metabolizers 2
• Consider genetic testing if poor tolerance occurs at standard doses 2
• May require lower starting doses or slower titration 2

Critical Monitoring Points

Within 24-48 hours after starting or increasing dose:

• Monitor for emergence or worsening of adverse effects 2
• Watch for serotonin syndrome symptoms (confusion, agitation, tremors, hyperreflexia, autonomic instability) 2

Ongoing monitoring:

• Higher doses are associated with increased dropout rates due to adverse effects 2
• Be vigilant for drug interactions with CYP2D6-metabolized medications (risperidone, atomoxetine, tricyclic antidepressants) 2
• Consider ECG monitoring in patients with cardiac risk factors due to potential QT prolongation 2

Common Pitfalls to Avoid

Discontinuation syndrome risk:

• Paroxetine has the highest risk among SSRIs for discontinuation syndrome 2
• When stopping, taper gradually over 10-14 days minimum 2
• Higher doses increase this risk 2

Drug interactions:

• Paroxetine inhibits CYP2D6, converting approximately 43% of extensive metabolizers to functional poor metabolizers with chronic use 2
• This can affect metabolism of other medications even after paroxetine is established 2

Pregnancy considerations:

• If treating during third trimester, carefully weigh risks versus benefits 1
• Consider tapering in the third trimester due to neonatal complications 1

Maintenance Therapy Duration

First episode of major depression:

• Continue for 4-12 months after remission 2

Recurrent depression:

• Prolonged treatment is beneficial 2
• Efficacy maintained for up to 1 year at average doses of 30 mg (immediate release equivalent) 1