What is the typical starting dose for Selective Serotonin Reuptake Inhibitors (SSRIs)?

SSRI Starting Doses

For adults with depression, start fluoxetine at 20 mg daily, sertraline at 50 mg daily, or paroxetine at 20 mg daily—these are the FDA-approved initial doses that serve as both the starting and typically effective therapeutic doses for most patients. 1

Adult Starting Doses by Medication

Fluoxetine (Prozac)

• Start at 20 mg once daily in the morning 1
• This dose is sufficient to obtain satisfactory response in most cases of major depressive disorder 1
• Maximum dose: 80 mg/day 1
• Dose increases should only be considered after several weeks if insufficient clinical improvement is observed 1

Sertraline (Zoloft)

• Start at 50 mg once daily (morning or evening) 2, 3
• 50 mg/day is both the starting dose and the usually effective therapeutic dose 3
• Therapeutic range: 50-200 mg/day 2
• If inadequate response after 2-4 weeks, increase in 50 mg increments at weekly intervals 2, 3

Paroxetine (Paxil)

• Start at 20 mg once daily in the morning 4, 5
• 20 mg/day is both the minimal effective dose and optimal dose for most patients 4
• For non-responders after 1-3 weeks, increase in 10 mg increments weekly to maximum 50 mg/day 4
• In elderly patients, therapeutic range is 20-40 mg/day 4

Other SSRIs

• Citalopram: Maximum 40 mg/day (20 mg/day if >60 years old due to QT prolongation risk) 6
• Escitalopram: Associated with QT prolongation risk 6
• Fluvoxamine: May be ineffective for some indications 6

Pediatric Starting Doses (Children and Adolescents)

Critical Dosing Differences

• Fluoxetine: Start at 10 mg/day, increase to 20 mg after 1 week 1
• Lower weight children may require 10 mg/day as both starting and target dose due to higher plasma levels 1
• Sertraline and fluvoxamine require twice-daily dosing at low doses or any dose (respectively) in youth 6, 7, 2

Titration Principles for Pediatrics

• Use slow up-titration with 3-4 week intervals between dose increases 7
• Small increments (5-10 mg increases) prevent dose-related adverse effects, particularly behavioral activation 7
• Shorter half-life SSRIs like sertraline can be adjusted at 1-2 week intervals 2

Timeline for Clinical Response

Expected Response Pattern

• Statistically significant improvement: 2 weeks 7, 2
• Clinically meaningful improvement: 6 weeks 7, 2
• Maximal benefit: 12+ weeks 6, 7
• Full effect may be delayed until 4 weeks of treatment or longer 1

This logarithmic response model supports the rationale for slow up-titration to avoid exceeding the optimal dose 6, 7

Critical Safety Monitoring

Suicidality Risk

• All SSRIs carry boxed warning for suicidal thinking/behavior through age 24 years 6, 7
• Absolute risk: 1% with antidepressants vs 0.2% with placebo (NNH=143 vs NNT=3 for response) 6, 7, 2
• Monitor closely during first months and after all dosage adjustments 6, 7

Behavioral Activation/Agitation

• More common in younger children than adolescents 6
• Occurs early in treatment, with dose increases, or with drug interactions 6
• If increased anxiety occurs after dose escalation, immediately reduce to previous tolerated dose 7

Common Adverse Effects

• Emerge within first few weeks: dry mouth, nausea, diarrhea, headache, insomnia, dizziness, sexual dysfunction 6, 2
• Sexual dysfunction: weighted mean incidence 40% across observational studies 6
• Sertraline-specific: sweating, tremors, nervousness, GI disturbances 2

Common Pitfalls to Avoid

Fluoxetine-Specific Caution

• Do not increase doses at 1-2 week intervals for fluoxetine 7
• Long half-life (1-3 days for parent drug, 4-16 days for norfluoxetine) requires 3-4 week intervals to assess true response 7

Discontinuation Syndrome

• Avoid abrupt cessation, particularly with sertraline 7, 2
• Symptoms include dizziness, fatigue, myalgias, headaches, nausea, insomnia, sensory disturbances 2
• Taper gradually when discontinuing 2

Drug Interactions

• Sertraline has minimal cytochrome P450 effects, resulting in fewer drug-drug interactions 2
• Fluoxetine inhibits CYP2D6 and other enzymes, increasing interaction potential 8
• All SSRIs contraindicated with MAOIs due to serotonin syndrome risk 2

Special Population Considerations

Hepatic/Renal Impairment

• Use lower or less frequent dosing in hepatic impairment 1
• Dosage adjustments for renal impairment not routinely necessary 1

Elderly Patients

• Consider lower or less frequent dosing 1
• Citalopram maximum 20 mg/day if >60 years due to QT prolongation 6
• Paroxetine therapeutic range 20-40 mg/day in elderly 4
• Sertraline requires no altered dose recommendations in elderly 3

Concurrent Medications

• Consider lower dosing with multiple concomitant medications 1
• Monitor for drug interactions, particularly with fluoxetine 8

Monitoring Strategy

• Use standardized symptom rating scales to systematically assess response 7
• Monitor weekly during dose adjustments 7
• Ensure parental oversight of medication regimens in children and adolescents 7, 2
• Consider adding CBT to current tolerated SSRI dose rather than escalating medication, as combination therapy shows superior outcomes 7