What is the first‑line treatment for an adult patient with panic disorder?

First-Line Treatment for Panic Disorder in Adults

Cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs)—specifically escitalopram, paroxetine, or sertraline—constitute equally effective first-line treatments for panic disorder, with the choice guided by patient preference, symptom severity, and treatment availability. 1

Pharmacologic First-Line Options

SSRIs represent the strongest evidence-based pharmacologic choice for panic disorder due to superior tolerability compared to older antidepressants, despite all antidepressant classes showing similar efficacy. 1, 2, 3

Preferred SSRI Agents

• Sertraline, escitalopram, and paroxetine are the recommended first-line SSRIs, with FDA approval for panic disorder (sertraline and paroxetine). 1, 4, 3
• Sertraline dosing: Start at 25 mg/day for week 1, then titrate to 50-200 mg/day based on response; mean effective dose in clinical trials was 131-151 mg/day. 4
• Venlafaxine extended-release (SNRI) serves as an equally effective alternative, particularly when comorbid generalized anxiety is present. 1

Expected Response Timeline

• Initial symptom reduction typically occurs within 2-4 weeks of starting treatment. 1
• Full therapeutic effect requires 8-12 weeks of continuous treatment at an adequate dose. 1
• Continue treatment for 9-12 months minimum after achieving remission to prevent relapse. 1

Efficacy Data

• Antidepressants as a class show a Number Needed to Treat (NNTB) of 7 compared to placebo—meaning seven patients must be treated for one additional patient to respond. 5
• Sertraline demonstrated approximately 2 fewer panic attacks per week compared to placebo in controlled trials. 4

Psychotherapy First-Line Option

Cognitive-behavioral therapy is the psychological treatment of first choice and should be offered as monotherapy or combined with pharmacotherapy. 1, 6, 2, 7, 8

CBT Structure and Components

• Deliver as 12-20 structured sessions over 3-4 months, with each session lasting 60-90 minutes. 6
• Core components include:
  • Psychoeducation about panic physiology and the cognitive-behavioral model 6
  • Cognitive restructuring to challenge catastrophic misinterpretations of bodily sensations 6, 7
  • Interoceptive exposure (deliberately inducing feared physical sensations) 7
  • In vivo exposure to agoraphobic situations using a graduated fear hierarchy 6
  • Breathing retraining and relaxation techniques 6
  • Elimination of safety behaviors and avoidance patterns 7

CBT Delivery Format

• Individual face-to-face therapy is superior to group therapy for both clinical effectiveness and cost-effectiveness. 6
• Brief CBT adapted for primary care (6 or fewer sessions of 15-30 minutes) can be effective when traditional longer-format therapy is not feasible. 6
• Guided self-help based on CBT principles represents a second-line option when face-to-face therapy is unavailable, requiring approximately 9 sessions over 3-4 months with minimal therapist support (3 hours total). 9, 6

CBT Efficacy

• CBT produces large effect sizes for panic disorder (Hedges g = 0.39 compared to placebo). 6
• Between-session homework completion is the most robust predictor of both short-term and long-term treatment success. 6
• Treatment gains are maintained at follow-up in 77.8% of cases. 6

Combined Treatment Approach

Initiate CBT concurrently with pharmacotherapy rather than sequentially, as this approach addresses both immediate symptom relief and underlying cognitive-behavioral patterns. 1

• Most primary care patients prefer psychological treatment over medication alone, making combined treatment particularly acceptable. 9, 6
• The collaborative format of CBT and focus on eliminating core fears may enhance longer-term outcomes beyond medication discontinuation. 7

Management of Benzodiazepines (If Currently Prescribed)

Benzodiazepines provide only short-term symptomatic relief and do not address the underlying pathology of panic disorder. 1

Discontinuation Protocol

• Implement a gradual taper: Reduce the current dose by 10-25% every 1-2 weeks, aiming for complete discontinuation over 6-12 months minimum. 1
• Never abruptly discontinue benzodiazepines—this can precipitate seizures and potentially fatal outcomes. 1
• Deliver CBT during the benzodiazepine taper, as this markedly improves taper success rates. 1
• Approximately 50% of patients continuously exposed to benzodiazepines for 12 months develop physiological dependence. 1

Short-Term Bridging Strategy

• Benzodiazepines may be used for 2-4 weeks during SSRI/SNRI initiation to provide immediate symptom relief while awaiting antidepressant onset of action. 2
• Reserve benzodiazepines for treatment-resistant patients without a history of dependence. 2

Adjunctive Symptomatic Management

Beta-blocker atenolol (25 mg twice daily) may be used short-term to control peripheral somatic symptoms such as palpitations and tremor during the first 8-12 weeks of SSRI/SNRI titration, then reassess and discontinue if core panic symptoms are controlled. 1

Safety Monitoring

Antidepressant Monitoring

• Screen for emergent suicidal thoughts/behaviors in patients ≤24 years old. 1
• Watch for behavioral activation, hypomania/mania, especially in patients with undiagnosed bipolar disorder. 1
• Monitor for serotonin syndrome if combining serotonergic agents. 1
• Check blood pressure regularly with SNRIs due to risk of sustained hypertension. 1

Tolerability Profile

• Antidepressants as a class cause more dropouts due to adverse effects compared to placebo, though they have fewer total dropouts overall (NNTB = 27 for preventing one dropout). 5
• TCAs and SSRIs produce more adverse-effect-related dropouts than placebo, while SNRIs show a more favorable tolerability profile. 5

Common Pitfalls and How to Avoid Them

• Inadequate SSRI dosing: Anxiety disorders typically require higher SSRI doses than depression, though this increases dropout risk—titrate gradually to balance efficacy and tolerability. 6
• Premature discontinuation: Continue antidepressants for at least 9-12 months after remission; early discontinuation substantially increases relapse risk. 1
• Exposure avoidance in CBT: Patients commonly resist confronting feared situations—start with lower-intensity exposures to build confidence before progressing. 6
• Neglecting homework assignments: Emphasize that between-session practice is essential for treatment success. 6
• Relying on exposure alone: Integration of cognitive restructuring with exposure makes treatment less aversive and enhances effectiveness. 6

When to Escalate Treatment

Add an SSRI/SNRI if CBT monotherapy produces insufficient improvement after 12-20 sessions, or add CBT if pharmacotherapy alone is inadequate after 8-12 weeks at therapeutic doses. 6