What are the treatment options for panic disorder?

Treatment of Panic Disorder

Start with an SSRI (sertraline 25-50 mg daily or escitalopram 10-20 mg daily) combined with cognitive behavioral therapy (CBT) for optimal outcomes in panic disorder. 1, 2

First-Line Pharmacotherapy: SSRIs

Sertraline and escitalopram are the preferred initial SSRIs due to superior evidence for efficacy, tolerability, and lower risk of discontinuation syndrome compared to paroxetine or fluvoxamine. 1, 2

Sertraline Dosing Protocol

• Start with 25 mg daily for the first week as a "test dose" to minimize initial anxiety or agitation that commonly occurs with SSRI initiation in panic disorder patients who are hypersensitive to physical sensations. 1, 2
• Increase to 50 mg daily after week 1, then titrate by 25-50 mg every 1-2 weeks as tolerated. 1, 2
• Target therapeutic dose: 50-200 mg/day with single daily dosing. 1, 2, 3

Escitalopram Dosing Protocol

• Start with 5-10 mg daily, titrate by 5-10 mg every 1-2 weeks. 1
• Target dose: 10-20 mg/day. 1, 2

Expected Timeline for Response

• Statistically significant improvement may begin by week 2. 1, 2
• Clinically significant improvement expected by week 4-6. 1, 2
• Maximal therapeutic benefit achieved by week 12 or later—do not abandon treatment prematurely. 1, 2

Critical Monitoring Requirements

• Monitor for suicidal thinking and behavior, especially in the first months and after dose adjustments (pooled risk 1% vs 0.2% placebo; number needed to harm = 143). 1, 2
• Assess treatment response at 4-6 weeks using standardized symptom rating scales. 1
• Monitor for serotonin syndrome, behavioral activation/agitation, and hypomania/mania. 1

Acute Management: Short-Term Benzodiazepines

Administer a benzodiazepine (alprazolam 0.5 mg three times daily) for rapid symptom relief during the first few weeks while waiting for SSRI onset of action, then taper and discontinue. 1, 4

Alprazolam Dosing for Panic Disorder

• Initial dose: 0.5 mg three times daily. 4
• Titrate at 3-4 day intervals in increments of no more than 1 mg per day. 4
• Typical effective dose range: 1-10 mg daily (mean 5-6 mg/day in controlled trials). 4
• Maximum dose: 4 mg/day for most patients, though some may require up to 10 mg/day. 4

Critical Benzodiazepine Precautions

• Use only short-term (first few weeks), then taper gradually. 1
• Avoid entirely in patients with substance use history, respiratory disorders, or elderly patients due to risks of dependence, tolerance, and withdrawal. 1
• Taper by no more than 0.5 mg every 3 days when discontinuing to avoid withdrawal syndrome. 4

First-Line Psychotherapy: Cognitive Behavioral Therapy

CBT should be offered as monotherapy or combined with medication, with combination treatment (CBT plus SSRI) showing superior response rates and remission compared to either treatment alone. 5, 1, 2

CBT Structure and Components

• 12-20 structured sessions over approximately 3-4 months, with individual sessions lasting 60-90 minutes. 5, 1, 2
• Individual CBT is prioritized over group therapy due to superior clinical effectiveness. 5, 1
• Core elements include: education about anxiety, cognitive restructuring (challenging catastrophizing, over-generalization, negative prediction, all-or-nothing thinking), relaxation techniques (deep breathing, progressive muscle relaxation, guided imagery), and graduated exposure to feared stimuli. 5, 1

Evidence for Combination Treatment

Combination CBT plus sertraline improved primary anxiety, global function, response to treatment, and remission of disorder compared to either treatment alone (moderate strength of evidence). 5

Second-Line Options

Alternative SSRIs

• Switch to fluoxetine 20-40 mg/day if sertraline or escitalopram not tolerated. 2
• Avoid paroxetine due to higher discontinuation syndrome risk and potentially increased suicidal thinking compared to other SSRIs. 5, 2, 6
• Avoid fluvoxamine due to greater potential for drug-drug interactions (CYP1A2, CYP2C19, CYP2C9, CYP3A4, CYP2D6). 5

SNRIs as Alternative First-Line

Consider venlafaxine extended-release 75-225 mg/day for patients who fail or cannot tolerate SSRIs. 5, 1

• Venlafaxine requires blood pressure monitoring due to risk of sustained hypertension and increased pulse. 5, 1
• Duloxetine is FDA-approved for generalized anxiety disorder in children and adolescents aged 7 years and older, though evidence for panic disorder specifically is more limited. 5

Treatment Duration and Discontinuation

Continue treatment for 9-12 months after recovery to prevent relapse. 1

Tapering Protocol

• Taper gradually when discontinuing to avoid discontinuation syndrome (dizziness, fatigue, nausea, sensory disturbances, anxiety, irritability). 5, 1, 2
• For shorter half-life SSRIs (sertraline, paroxetine): decrease by no more than 25-50% every 1-2 weeks. 1, 2
• For longer half-life SSRIs (fluoxetine): taper at 3-4 week intervals. 5
• Paroxetine, fluvoxamine, and sertraline have highest risk of discontinuation syndrome. 5

Medications to Avoid

• Tricyclic antidepressants should be avoided despite equal efficacy due to unfavorable risk-benefit profile, particularly cardiac toxicity. 1, 7, 8
• Beta-blockers have limited evidence for panic disorder and should be reserved for performance anxiety only. 1
• Long-term benzodiazepines carry significant risks of dependence, tolerance, and withdrawal. 1, 7, 8

Common Pitfalls to Avoid

• Do not escalate SSRI doses too quickly—allow 1-2 weeks between increases to assess tolerability and avoid overshooting the therapeutic window. 5, 2
• Do not start with full therapeutic doses—begin with subtherapeutic "test" doses to minimize initial anxiety/agitation that is common in panic disorder patients. 5, 1, 2
• Do not abandon treatment before 12 weeks—full response requires patience due to the logarithmic response curve of SSRIs. 1, 2
• Do not discontinue SSRIs abruptly—always taper gradually to avoid withdrawal symptoms. 5, 1, 2
• Do not use benzodiazepines long-term—reserve for acute management only during the first few weeks. 1