Sertraline vs. Paroxetine Titration Protocols
Sertraline should be initiated at 25-50mg daily with increases of 50mg at weekly intervals as needed (up to 200mg daily), while paroxetine should start at 10-12.5mg daily with more cautious titration due to its stronger side effect profile and CYP2D6 inhibition. 1, 2
Initial Dosing
Sertraline
- Starting dose: 25-50mg daily 1, 2
- Usually effective therapeutic dose: 50mg daily 2
- Can be administered at any time of day as a single dose 2
- No need for altered dosing in elderly patients 2
Paroxetine
- Starting dose: 10-12.5mg daily 1
- More cautious titration required due to stronger side effect profile
- Higher risk of discontinuation symptoms compared to sertraline
- Strong CYP2D6 inhibitor - important consideration when used with other medications 1
Titration Approach
Sertraline
- Can increase in 50mg increments at weekly intervals if needed 2
- Maximum recommended dose: 200mg daily 2
- Evidence suggests that continuing at 50mg may be as effective as dose escalation for many patients 3
- Rapid titration (to 150mg within 5 days) has been studied for OCD with good tolerability 4
Paroxetine
- More gradual titration recommended due to higher side effect burden
- Doses of 12.5mg and 25mg show similar efficacy with fewer side effects at lower dose 5
- 20mg dose associated with higher rates of nausea compared to lower doses 5
- Requires more careful monitoring during dose changes
Side Effect Considerations
Sertraline
- Generally better tolerated with fewer discontinuations due to side effects
- Common side effects: gastrointestinal disturbances (nausea, diarrhea), sexual dysfunction 6
- Side effects typically mild and transient, decreasing with continued treatment 6
- Less anticholinergic activity and cardiovascular effects than tricyclics 6
Paroxetine
- Higher incidence of side effects including:
- Nausea, decreased appetite, constipation, dry mouth
- Somnolence, dizziness, headache, tremor
- Sexual dysfunction 1
- Strong CYP2D6 inhibitor - important consideration with tamoxifen and other medications 5
- Higher risk of discontinuation syndrome due to shorter half-life
Special Populations
Elderly Patients
- Sertraline: No specific dose adjustment needed 2
- Paroxetine: Lower starting doses recommended due to higher concentrations and more side effects 1
Patients with Hepatic/Renal Impairment
- Both medications may require dose adjustments 1
- Paroxetine typically requires more significant adjustments
Clinical Pearls
- Unlike tricyclic antidepressants, SSRIs typically don't require extensive dose titration as many patients find the initial dose effective 7
- Paroxetine should be avoided in patients taking tamoxifen due to CYP2D6 inhibition reducing tamoxifen's effectiveness 5
- When switching between these medications, consider their different half-lives and potential for discontinuation symptoms (paroxetine has higher risk)
- For both medications, taking with food can help reduce gastrointestinal side effects 1
- Morning dosing is preferred if the medication causes activation/insomnia, evening dosing if sedation occurs 1
Monitoring Recommendations
- Weekly assessments during initial therapy to monitor for side effects and therapeutic response 1
- Regular monitoring for sexual dysfunction, which may be underreported
- Watch for signs of serotonin syndrome when combining with other serotonergic medications
- ECG monitoring may be warranted in patients with cardiac risk factors, especially with paroxetine 1