What is the recommended starting dose and treatment approach for patients initiating Selective Serotonin Reuptake Inhibitor (SSRI) therapy?

SSRI Starting Dose and Treatment Approach

Start SSRIs at low doses (e.g., fluoxetine 10-20 mg, sertraline 25-50 mg) and titrate slowly over 3-4 week intervals, as clinical improvement typically occurs by week 6 with maximal benefit by week 12 or later. 1, 2

Initial Dosing Strategy

Standard Starting Doses

• Fluoxetine: 20 mg daily (morning) for adults; 10 mg daily for children/adolescents, increasing to 20 mg after 1 week 3
• Sertraline: 50 mg daily for most indications; 25-50 mg for special populations (elderly, Alzheimer's disease) 4
• Citalopram: 20 mg daily, with increases to 40 mg after 2-4 weeks 1
• Paroxetine: 10 mg daily with gradual increases 1

Low-Dose Initiation Approach

• Consider starting at subtherapeutic doses (e.g., fluoxetine 5-10 mg, sertraline 25 mg) in patients prone to anxiety, agitation, or panic disorder, as 28% of patients cannot tolerate standard starting doses 1, 2, 5
• Use small increments (5-10 mg increases) when titrating to prevent dose-related adverse effects, particularly behavioral activation 2

Titration Timeline

Dose Adjustment Intervals

• For shorter half-life SSRIs (sertraline, paroxetine, citalopram): Adjust doses at 1-2 week intervals 4, 2
• For fluoxetine: Wait 3-4 weeks between dose adjustments due to its long half-life (1-3 days for parent drug, 4-16 days for active metabolite norfluoxetine) 2, 3
• Increase doses only after 2-4 weeks if insufficient clinical improvement is observed 3

Response Timeline

• Statistically significant improvement: May occur within 2 weeks 1, 2
• Clinically meaningful improvement: Typically by week 6 1, 2
• Maximal therapeutic effect: Week 12 or later; full effect may be delayed until 4-5 weeks of treatment 1, 3

Dosing Frequency Considerations

• Once-daily dosing: Most SSRIs permit single daily dosing due to long elimination half-lives, particularly fluoxetine 1, 2
• Twice-daily dosing required: Sertraline at low doses and fluvoxamine at any dose in children/adolescents 1, 4, 2
• Timing flexibility: Sertraline can be administered morning or evening 4

Critical Safety Monitoring

Suicidality Risk

• All SSRIs carry a boxed warning for suicidal thinking and behavior through age 24 years 1, 2
• Absolute risk: 1% with antidepressants vs. 0.2% with placebo (NNH=143 vs. NNT=3 for response) 1, 2
• Monitor closely during the first months of treatment and following all dosage adjustments 1, 4, 2

Behavioral Activation/Agitation

• More common in younger children than adolescents and in anxiety disorders compared to depressive disorders 1
• Occurs early in treatment (first month), with dose increases, or with concomitant drugs that inhibit SSRI metabolism 1
• If increased anxiety occurs after dose escalation, immediately reduce back to the previous tolerated dose 2
• Usually improves quickly after dose decrease or discontinuation, unlike mania which may persist 1

Other Serious Adverse Effects

• Serotonin syndrome: Avoid combining with MAOIs (contraindicated); allow 14 days after stopping MAOI before starting SSRI, and 5 weeks after stopping fluoxetine before starting MAOI 3
• Monitor for hypomania/mania, seizures (use cautiously in seizure history), abnormal bleeding (especially with NSAIDs/aspirin), and sexual dysfunction 1

Common Adverse Effects

• Emerge within first few weeks: Nausea, insomnia, dizziness, headache, dry mouth, diarrhea, sweating, tremors, nervousness, changes in appetite, weight changes, fatigue 1, 4
• Dose-related: Higher doses (e.g., 60 mg fluoxetine) associated with significantly more nausea, anxiety, dizziness, and insomnia compared to 20 mg 6
• Discontinuation due to adverse events: 9.8% at usual starting doses vs. 16.5% at higher starting doses 7

Special Population Adjustments

Children and Adolescents

• Start fluoxetine at 10 mg daily (especially in lower weight children), increase to 20 mg after 1 week 3
• Parental oversight of medication regimens is paramount 1, 4
• Behavioral activation more common in younger children 1

Elderly and Hepatic Impairment

• Use lower or less frequent dosing 3
• Consider starting sertraline at 25 mg daily 4

Renal Impairment

• Dosage adjustments not routinely necessary 3

Monitoring and Assessment

• Use standardized symptom rating scales to systematically assess treatment response 4, 2
• Monitor weekly during dose adjustments 2
• Assess for treatment response after 2-4 weeks at current dose before increasing 4, 3

Common Pitfalls to Avoid

• Do not increase fluoxetine doses at 1-2 week intervals—its long half-life requires 3-4 week intervals to assess true response 2
• Do not abruptly discontinue, particularly sertraline—taper gradually to avoid discontinuation syndrome (dizziness, fatigue, myalgias, headaches, nausea, insomnia, sensory disturbances) 4, 2
• Do not automatically escalate doses—consider adding CBT to current tolerated SSRI dose rather than escalating medication, as combination therapy shows superior outcomes 2
• Avoid combining with MAOIs or other serotonergic drugs due to serotonin syndrome risk 1, 4, 3

Context-Specific Considerations

For Panic Disorder

• Start fluoxetine at 10 mg daily, increase to 20 mg after 1 week 3
• Patients with panic disorder are particularly intolerant of standard 20 mg doses; low-dose initiation (5 mg) with gradual titration is beneficial 5

For IBS

• SSRIs are not recommended for IBS treatment—AGA suggests against their use due to lack of significant improvement in global symptoms or abdominal pain (low certainty evidence) 1

Drug Interaction Considerations

• Sertraline has minimal effects on cytochrome P450 enzymes, resulting in fewer drug-drug interactions compared to other SSRIs 4