What is the recommended first-line treatment for anxiety?

First-Line Treatment for Anxiety Disorders

The recommended first-line treatment for anxiety is either an SSRI (escitalopram, paroxetine, or sertraline) or SNRI (venlafaxine), combined with or as an alternative to cognitive behavioral therapy (CBT), with individual CBT preferred over group therapy when available. 1, 2

Pharmacological First-Line Options

SSRIs as Primary Agents

• Escitalopram, paroxetine, sertraline, and fluvoxamine are established first-line SSRIs for anxiety disorders based on multiple international guidelines. 1
• Sertraline demonstrates efficacy across multiple anxiety disorder subtypes including social anxiety disorder, panic disorder, and PTSD, with FDA approval for these indications. 3, 4
• Paroxetine is effective at doses of 20-50 mg daily for social anxiety disorder and generalized anxiety disorder, with 20 mg often sufficient as demonstrated in controlled trials. 5
• These agents show small to medium effect sizes compared to placebo (standardized mean differences ranging from -0.30 to -0.67 depending on the specific anxiety disorder). 4

SNRIs as Equally Valid First-Line Agents

• Venlafaxine extended release is a first-line SNRI option, particularly effective when SSRIs are not tolerated or ineffective. 1, 2
• SNRIs demonstrate comparable efficacy to SSRIs across anxiety disorder subtypes. 6, 4

Alternative First-Line Pharmacotherapy

• Pregabalin is listed as a first-line option in Canadian guidelines, particularly for generalized anxiety disorder. 1, 2

Psychological First-Line Treatment

Cognitive Behavioral Therapy Structure

• CBT is strongly recommended as first-line treatment, either as monotherapy or combined with pharmacotherapy. 2, 6
• Individual CBT should consist of approximately 14 sessions over 4 months, with each session lasting 60-90 minutes. 1
• Individual therapy is prioritized over group therapy due to superior clinical and cost-effectiveness outcomes. 1
• CBT demonstrates large effect sizes for generalized anxiety disorder (Hedges g = 1.01) and small to medium effects for social anxiety disorder and panic disorder (Hedges g = 0.39-0.41). 4

CBT Models for Anxiety

• Structured CBT should follow either the Clark and Wells model or Heimberg model, which include psychoeducation, cognitive restructuring, gradual exposure to feared situations, and relapse prevention. 1
• For patients unable or unwilling to attend face-to-face CBT, self-help with therapist support based on CBT principles is a viable alternative, typically delivered over approximately 9 sessions across 3-4 months. 1

Treatment Algorithm

Initial Management Steps

1. Initiate an SSRI (sertraline 50-200 mg, paroxetine 20-50 mg, or escitalopram) or SNRI (venlafaxine extended release) as pharmacological first-line. 1, 2, 4
2. Concurrently refer for individual CBT with a skilled therapist trained in anxiety-specific protocols. 1, 2
3. Monitor treatment response using standardized instruments at regular intervals. 2

Management of Inadequate Response

• If medication shows inadequate response after 8 weeks of adequate dosing and adherence, switch to another SSRI or SNRI rather than continuing ineffective treatment. 1, 2
• Add or intensify CBT if not already implemented as part of the treatment plan. 2, 7
• Combination therapy (medication plus CBT) often yields superior results to either approach alone. 7

Critical Pitfalls to Avoid

Common Treatment Errors

• Do not use benzodiazepines as first-line treatment—they are relegated to second-line status due to dependence potential and should only be considered for acute, short-term relief while first-line treatments take effect. 1, 6
• Avoid beta-blockers (atenolol, propranolol) as they have negative evidence for efficacy in anxiety disorders. 1
• Do not use quetiapine as first-line treatment; it has negative evidence specifically in social anxiety disorder. 1, 7
• Underutilizing CBT is a major pitfall—psychological interventions have strong evidence and should be offered alongside or instead of pharmacotherapy based on patient preference. 2, 7

Medication-Specific Considerations

• Sertraline has low potential for cytochrome P450 drug interactions compared to fluoxetine, fluvoxamine, and paroxetine, making it advantageous in patients on multiple medications. 8
• Common SSRI/SNRI adverse effects include gastrointestinal symptoms (diarrhea, nausea), sexual dysfunction, headache, and initial anxiety worsening, which should be discussed with patients upfront. 1
• Continue medications for 6-12 months after remission to prevent relapse, as anxiety disorders are chronic conditions. 6, 9

Special Population Adjustments

• Reduce doses or use less frequent dosing in elderly patients, those with hepatic impairment, or patients on multiple concomitant medications. 5, 10
• Renal impairment does not routinely require dosage adjustments for SSRIs/SNRIs. 5, 10