What selective serotonin reuptake inhibitor (SSRI) is most effective for treating panic attacks in a patient with a history of panic disorder?

Best SSRI for Panic Disorder

Sertraline is the preferred SSRI for panic disorder, with the strongest evidence for both acute treatment efficacy and long-term relapse prevention, typically dosed at 50-200 mg daily. 1, 2

Evidence Supporting Sertraline as First Choice

The American College of Neuropsychopharmacology specifically identifies sertraline as having particularly strong evidence among SSRIs for panic disorder treatment and relapse prevention. 1 This recommendation is supported by FDA approval for panic disorder based on three large controlled trials demonstrating that 51-76% of sertraline-treated patients became panic-attack free compared to 32-44% on placebo. 2, 3

Key Efficacy Data

• Sertraline demonstrated superior efficacy across multiple outcome measures: panic attack frequency reduction (79-80% mean reduction), Clinical Global Impression scores, quality of life measures, and high end-state functioning. 4, 3
• Long-term relapse prevention was proven in controlled trials: patients continuing sertraline after initial response showed significantly lower relapse rates during 28-week follow-up compared to those switched to placebo. 2, 5
• Sertraline maintains efficacy regardless of prior benzodiazepine exposure: unlike some other anxiolytics, prior benzodiazepine treatment does not diminish sertraline's effectiveness (79% vs 80% panic attack reduction in those with vs without prior benzodiazepine use). 4

Practical Dosing Considerations

Start sertraline at 25-50 mg daily for the first week to minimize initial anxiety or agitation, then increase to 50 mg daily, with a therapeutic target range of 50-200 mg/day. 6, 2 Single daily dosing is appropriate at therapeutic doses due to sertraline's adequate half-life, though at very low doses (<50 mg) twice-daily dosing may be needed. 7

Expected Timeline

• Statistically significant improvement may begin by week 2, but clinically meaningful improvement typically occurs by week 6, with maximal benefit at week 12 or later. 7, 6 This logarithmic response pattern supports slow dose titration and patience before declaring treatment failure.
• Allow a full 12-week trial at therapeutic doses before considering the treatment unsuccessful. 6

Alternative SSRIs

While sertraline has the strongest evidence, paroxetine is FDA-approved for panic disorder and demonstrated 51-85% responder rates in controlled trials. 8 However, paroxetine carries higher risks: increased discontinuation syndrome, potentially elevated suicidal thinking compared to other SSRIs, and more drug-drug interactions via CYP2D6 inhibition. 7, 6

Fluoxetine, fluvoxamine, and escitalopram are reasonable alternatives if sertraline is not tolerated, though they lack the specific panic disorder evidence base that sertraline possesses. 7 The American Academy of Child and Adolescent Psychiatry notes that choice among SSRIs should be governed by pharmacokinetics, tolerability, and cost when class-level evidence is similar. 7

Critical Safety Monitoring

All SSRIs carry a boxed warning for suicidal thinking and behavior through age 24, with pooled rates of 1% on antidepressants vs 0.2% on placebo (NNH=143). 7, 6 Close monitoring is essential during the first months of treatment and following dose adjustments. 7

Common Pitfalls to Avoid

• Do not escalate doses too rapidly: behavioral activation/agitation can occur early in treatment, particularly in younger patients, supporting slow up-titration over 1-2 weeks between increases. 7, 6
• Do not discontinue abruptly: sertraline requires gradual tapering to avoid discontinuation syndrome, though it has lower risk than paroxetine or fluvoxamine. 7, 6
• Do not combine with other serotonergic agents without caution: risk of serotonin syndrome increases when combining SSRIs with MAOIs (contraindicated), tramadol, dextromethorphan, or other serotonergic drugs. 7, 6

Combination Treatment Strategy

Combining sertraline with cognitive behavioral therapy (CBT) provides superior outcomes to either treatment alone, with individual CBT preferred over group therapy. 1, 6 A structured course of 12-20 CBT sessions targeting panic-specific cognitive distortions and exposure techniques is recommended. 6

Long-Term Management

Continue sertraline for a minimum of 9-12 months after achieving remission to prevent relapse, as medication discontinuation carries higher relapse risk than CBT discontinuation. 1, 6 The physician should periodically re-evaluate long-term usefulness, but premature discontinuation significantly increases relapse probability. 2