What is the best Selective Serotonin Reuptake Inhibitor (SSRI) for treating depression, anxiety, and panic attacks?

Best SSRI for Depression, Anxiety, and Panic Attacks

For adults with comorbid depression, anxiety, and panic disorder, sertraline is the optimal first-line SSRI choice, as it is FDA-approved for all three conditions (major depressive disorder, panic disorder, and multiple anxiety disorders) and has the most comprehensive evidence base across this symptom triad. 1

Primary Recommendation: Sertraline

Sertraline stands alone as the only SSRI with FDA approval spanning major depressive disorder, panic disorder, PTSD, social anxiety disorder, and OCD, making it uniquely positioned for patients presenting with overlapping depression and anxiety symptoms 1. The FDA label explicitly indicates sertraline for panic disorder with or without agoraphobia, major depressive disorder, and multiple anxiety spectrum conditions 1.

Dosing Strategy

• Start sertraline at 25-50 mg daily for panic disorder (lower than the typical 50 mg depression starting dose) to minimize initial anxiety activation, which is more common in anxiety disorders 1, 2
• Titrate to 50-200 mg daily based on response, recognizing that anxiety disorders often require higher doses than depression (though panic disorder may respond at lower doses than OCD) 3, 2
• Expect slower onset in anxiety compared to depression—while depressive symptoms may improve by week 2-6, panic and anxiety symptoms typically require 6-12 weeks for maximal benefit 4, 2

Evidence Supporting Sertraline

• Sertraline demonstrated efficacy in 6-8 week controlled trials for major depression and 10-12 week trials for panic disorder, with maintenance of response documented up to 52 weeks 1
• The drug is well-tolerated in adults with a favorable side effect profile: most common adverse events include nausea (26% vs 11% placebo), diarrhea (20% vs 10%), insomnia (21% vs 11%), and sexual dysfunction (17% vs <1% in men) 1
• Sertraline has low potential for drug interactions via cytochrome P450 enzymes, making it safer in patients on multiple medications 5

Alternative First-Line Options

Escitalopram as Second Choice

If sertraline is not tolerated or contraindicated, escitalopram 10-20 mg daily is the next best option, with demonstrated efficacy across panic disorder, generalized anxiety disorder, social anxiety disorder, and depression 6. Escitalopram showed faster onset of action than citalopram in panic disorder (50% panic-free vs 38% placebo) and superior relapse prevention in GAD (4.04 times lower relapse risk than placebo) 6.

Fluoxetine for Specific Populations

Fluoxetine is the only SSRI FDA-approved for depression in children/adolescents aged 8+ years and should be considered if the patient is under 18 3. However, fluoxetine has a longer half-life and more drug interactions via CYP2D6 inhibition compared to sertraline 3.

Critical Monitoring Requirements

Early Treatment Phase (Weeks 0-6)

• Assess for suicidal ideation at every visit, especially in patients under age 24, as all SSRIs carry a black box warning for treatment-emergent suicidality 3
• Monitor for behavioral activation/agitation in the first 2-4 weeks, which occurs more frequently in anxiety disorders than depression and may require dose reduction 3, 7
• Watch for paradoxical worsening of panic attacks in the first 1-2 weeks—this has been reported with SSRIs including citalopram and fluvoxamine, though rare 7, 8

Response Assessment Timeline

• Administer GAD-7 and PHQ-9 at baseline, week 2, week 6, and week 12 to objectively track response 4
• Define response as ≥50% reduction in baseline PHQ-9 or GAD-7 scores by week 6-12 4
• Define remission as PHQ-9 <5 and GAD-7 <5, which should be the treatment target 4

Agents to Avoid

Paroxetine and Fluoxetine in Older Adults

Avoid paroxetine and fluoxetine in patients over 60 years due to higher rates of adverse effects in this population; prefer sertraline, escitalopram, or citalopram instead 3. Paroxetine has significant anticholinergic effects and fluoxetine has a prolonged half-life that increases drug interaction risk 3, 5.

Citalopram Cautions

Citalopram carries QTc prolongation risk and has a maximum dose restriction of 40 mg daily (20 mg in patients >60 years), making it less flexible for dose optimization in anxiety disorders that may require higher dosing 3. Additionally, isolated case reports document citalopram-induced panic attacks 8.

Treatment Duration

• Continue treatment for at least 4-9 months after achieving remission for first-episode depression 3
• For panic disorder, maintain treatment for 12-24 months after symptom resolution to prevent relapse, as demonstrated in sertraline maintenance trials 1
• Patients with ≥2 prior depressive episodes benefit from indefinite maintenance therapy 3

Common Pitfalls to Avoid

• Do not start at full antidepressant doses in panic disorder—initial anxiety activation can cause treatment discontinuation; start low (25 mg sertraline) and titrate slowly 1, 2
• Do not switch SSRIs before allowing 8-12 weeks at therapeutic dose—anxiety disorders have slower onset than depression 2
• Do not assume treatment failure if depressive symptoms improve but anxiety persists—anxiety often requires longer treatment duration and sometimes higher doses 2
• Do not overlook pharmacogenetic considerations in treatment-resistant cases—CYP2D6 and CYP2C19 poor metabolizers may have altered response to SSRIs metabolized by these pathways (fluoxetine, paroxetine) 3