Which selective serotonin reuptake inhibitor (SSRI) to start as a basic treatment?

Which SSRI to Start as Basic Treatment

Start with sertraline 50 mg once daily or escitalopram as first-line SSRI therapy for most adult patients with depression or anxiety disorders. 1, 2

Rationale for Sertraline or Escitalopram as First-Line

No Efficacy Differences Between SSRIs

• All second-generation antidepressants, including SSRIs, show equivalent efficacy for treating major depressive disorder, with no justification for choosing one over another based on effectiveness alone 1
• The American College of Physicians recommends selecting SSRIs based on adverse effect profiles, cost, and patient preferences rather than efficacy differences 1
• For anxiety disorders, the SSRI class as a whole demonstrates effectiveness, with choice governed by pharmacokinetics, pharmacodynamics, tolerability, cost, and formulary considerations 1

Why Sertraline Stands Out

• Lowest drug interaction potential: Sertraline has minimal effect on cytochrome P450 isoenzymes compared to other SSRIs, resulting in fewer drug-drug interactions 1, 3, 4
• Favorable tolerability profile: Head-to-head comparisons show sertraline is at least as well-tolerated as other SSRIs and may have advantages in side effect profile 3, 5
• Lower sexual dysfunction rates: While all SSRIs can cause sexual side effects, paroxetine has higher rates of sexual dysfunction than sertraline 1
• No QT prolongation concerns: Unlike citalopram, sertraline does not carry warnings about QT prolongation and Torsade de Pointes 1
• Lower discontinuation syndrome risk: Compared to paroxetine and fluvoxamine, sertraline has less association with discontinuation syndrome 1

Why Escitalopram is Also Appropriate

• International guidelines (NICE, Japanese Society) list escitalopram alongside sertraline as first-line options 1
• Escitalopram has the least effect on CYP450 isoenzymes among SSRIs, similar to sertraline's low interaction profile 1

SSRIs to Avoid as First-Line

Paroxetine

• Higher rates of sexual dysfunction compared to other SSRIs 1
• Strong association with discontinuation syndrome 1
• Increased risk of suicidal thinking/behavior compared to other SSRIs 1
• Designated as second-line by NICE guidelines due to side effects and discontinuation symptoms 1

Fluvoxamine

• Greater potential for drug-drug interactions (affects CYP1A2, CYP2C19, CYP2C9, CYP3A4, and CYP2D6) 1
• May require twice-daily dosing at any dose, reducing convenience 1
• Designated as second-line by NICE guidelines 1

Citalopram

• Risk of QT prolongation, Torsade de Pointes, and sudden death at doses exceeding 40 mg/day 1
• Contraindicated in patients with long QT syndrome 1

Practical Dosing Algorithm

For Adults with Depression or Anxiety

1. Start sertraline 50 mg once daily (morning or evening) 2
2. For panic disorder, PTSD, or social anxiety disorder specifically, consider starting at 25 mg daily for one week, then increase to 50 mg daily 2
3. If inadequate response after 6-8 weeks at 50 mg, increase by 50 mg increments weekly up to maximum 200 mg/day 1, 2
4. Monitor response within 1-2 weeks of initiation and regularly thereafter 1

For Pediatric Patients (OCD)

• Ages 6-12: Start 25 mg once daily 2
• Ages 13-17: Start 50 mg once daily 2
• Titrate slowly given lower body weights; maximum 200 mg/day 2

Critical Monitoring Points

Suicidality Monitoring

• All SSRIs carry boxed warnings for suicidal thinking/behavior through age 24 1
• Monitor closely within first 1-2 weeks of initiation and after dose changes 1
• Risk is highest during first 1-2 months of treatment 1

Common Side Effects to Counsel About

• Nausea, diarrhea, headache, insomnia, somnolence, dizziness, sweating, sexual dysfunction 1, 6
• Most adverse effects emerge within first few weeks and often diminish with continued treatment 1
• Prepare patients for sexual side effects to prevent non-adherence 6

Drug Interactions to Avoid

• Never combine with MAOIs due to serotonin syndrome risk 1
• Exercise caution when combining with other serotonergic drugs (tramadol, dextromethorphan, other antidepressants) 1
• Space sertraline at least 4 hours away from bile acid resins if co-prescribed 1

Common Pitfalls

Discontinuation

• Never stop abruptly—taper gradually to avoid withdrawal symptoms (dizziness, nausea, paresthesias, anxiety) 1, 6
• While sertraline has lower discontinuation syndrome risk than paroxetine, tapering remains essential 1

Inadequate Trial Duration

• Clinical improvement may not be evident until 6 weeks, with maximal improvement by 12 weeks 1
• Modify treatment only if inadequate response after 6-8 weeks at therapeutic dose 1

Dose Escalation Errors

• Do not increase doses more frequently than weekly intervals given 24-hour elimination half-life 2
• Avoid exceeding optimal dose through overly rapid titration 1