Zoloft (Sertraline) Provider Cheat Sheet
Standard Dosing
Start sertraline at 50 mg once daily in the morning, which is both the starting dose and the optimal therapeutic dose for most patients with depression, and avoid routine dose escalation as higher doses do not enhance efficacy. 1, 2
Initial Dosing Strategy
- Depression/Anxiety: 50 mg once daily 1, 2
- OCD (adults): 50 mg once daily, may increase to 200 mg/day based on response 1
- OCD (pediatric 6-12 years): 25 mg once daily 1
- OCD (adolescents 13-18 years): 50 mg once daily 1
- Morning administration preferred to minimize insomnia risk 1
Titration Schedule
- If dose adjustment needed, increase in 25-50 mg increments at weekly intervals minimum 1, 2
- Maximum dose: 200 mg/day 1, 2
- Critical evidence: Patients who failed to respond at 50 mg after 3 weeks showed no additional benefit from escalation to 150 mg compared to continuing 50 mg (40% remission rate in both groups) 3
Special Populations
Hepatic Impairment
Use lower or less frequent dosing in any degree of liver impairment—sertraline clearance is reduced 3-fold in mild hepatic impairment (Child-Pugh 5-8), resulting in significantly elevated drug levels. 1
- Mild hepatic impairment: ~3-fold increase in sertraline exposure 1
- Desmethylsertraline exposure: ~2-fold increase 1
- Start with reduced dose or alternate-day dosing 1
- Moderate to severe hepatic impairment: Not studied, use extreme caution 1
Renal Impairment
- No dose adjustment needed for any degree of renal impairment, including hemodialysis 1
- Sertraline pharmacokinetics and protein binding unchanged in CKR 10-60 mL/min 1
- Extensive hepatic metabolism makes renal excretion a minor elimination route 1
Elderly Patients (>65 years)
- Sertraline clearance approximately 40% lower than younger adults 1
- Steady-state achieved after 2-3 weeks (vs. 1-2 weeks in younger patients) 1
- No routine dose adjustment recommended despite pharmacokinetic differences 2
- Monitor more closely for adverse effects 1
Pediatric Patients
- Higher weight-adjusted plasma levels in children 6-12 years vs. adolescents and adults 1
- Approximately 22% lower AUC and Cmax when adjusted for weight 1
- Monitor weight closely: ~7% of children experienced >7% body weight loss vs. 0% on placebo 1
- Mean weight loss ~0.5 kg in first 8 weeks, with weight gain resuming by week 12 1
- Regular weight and growth monitoring required for long-term treatment 1
Bipolar Disorder Considerations
Sertraline and all SSRIs carry significant risk of precipitating manic episodes in bipolar disorder—use only with concurrent mood stabilizer coverage and close monitoring. 1
- Not FDA-approved for bipolar depression 1
- Risk of treatment-emergent mania/hypomania with antidepressant monotherapy
- Requires mood stabilizer (lithium, valproate, or atypical antipsychotic) as foundation
- Monitor weekly during initiation for activation, agitation, or mood elevation
Drug Interactions with Blood Thinners
Sertraline increases bleeding risk when combined with anticoagulants or antiplatelet agents through serotonergic effects on platelet function—monitor INR closely and watch for bleeding signs. 1
Warfarin Interaction
- Sertraline may potentiate warfarin effect 1
- Monitor INR more frequently when initiating or adjusting sertraline 1
- Consider more frequent INR checks during first 4 weeks
Other Anticoagulants/Antiplatelets
- Increased bleeding risk with aspirin, NSAIDs, other antiplatelet agents 1
- SSRIs impair platelet aggregation through serotonin depletion 1
- Counsel patients on bleeding precautions 1
Therapeutic Drug Monitoring
Therapeutic drug monitoring is "probably useful" for sertraline, with expected plasma levels of 12-31 ng/mL at 50-200 mg/day doses. 4
When to Consider TDM
- Suspected non-compliance 4
- Lack of response despite adequate dosing 4
- Adverse effects at standard doses 4
- Suspected drug interactions 4
- Hepatic impairment 4
- Elderly patients 4
- Switching between brand and generic formulations 4
Expected Plasma Concentrations
- 50 mg/day: 12±8 ng/mL (geometric mean) 4
- 100 mg/day: 19±18 ng/mL 4
- 150 mg/day: 31±29 ng/mL 4
- 200 mg/day: 29±18 ng/mL 4
- Active metabolite (norsertraline) levels 2-3 times higher than parent compound 4
Onset of Action and Response
- Initial improvement: 1-2 weeks 5, 2
- Full therapeutic effect: 4-6 weeks 2
- Assess response at 2-4 weeks before considering dose adjustment 2
- Steady-state: 1 week in adults, 2-3 weeks in elderly 1
Common Adverse Effects
Nausea/vomiting (22.7%) and diarrhea (13.4%) are the most common adverse effects, typically self-limited within the first weeks of treatment. 6
Gastrointestinal
- Nausea/vomiting: 22.7% vs. 10.4% placebo 6
- Diarrhea: 13.4% vs. 3.1% placebo 6
- Dry mouth 5
- Constipation 5
CNS Effects
Other
Critical Safety Warnings
Pregnancy and Lactation
- Possible association with persistent pulmonary hypertension of newborn (PPHN): 1-2 per 1000 live births 1
- Women discontinuing antidepressants during pregnancy show significantly increased relapse risk 1
- Risk-benefit assessment required on case-by-case basis 1
- Unknown excretion in breast milk—exercise caution 1
Serotonin Syndrome Risk
- Monitor when combining with other serotonergic agents 1
- Symptoms: agitation, confusion, tachycardia, hyperthermia, hyperreflexia, myoclonus 1
Suicidality Monitoring
- Increased risk in children, adolescents, and young adults <24 years 1
- Monitor closely during initial weeks and dose changes 1
- Weekly monitoring recommended during first month 1
Practical Prescribing Algorithm
- Start 50 mg once daily in morning (25 mg for children 6-12 years) 1, 2
- Assess response at 3-4 weeks 2, 3
- If inadequate response: Continue 50 mg for additional 5 weeks rather than escalating dose (equivalent efficacy) 3
- If dose escalation deemed necessary: Increase by 50 mg at weekly intervals, maximum 200 mg/day 1, 2
- Hepatic impairment: Reduce dose or frequency from initiation 1
- Renal impairment: No adjustment needed 1
- Elderly: Standard dosing acceptable, monitor closely 1, 2