What are the recommended medications for treating chronic anxiety?

Medication for Chronic Anxiety

SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors) are the recommended first-line medications for chronic anxiety disorders, with escitalopram and sertraline being the preferred initial choices due to their superior efficacy and lower discontinuation rates. 1

First-Line Medication Selection

Preferred SSRIs

• Escitalopram (10-20 mg/day) or sertraline (50-200 mg/day) should be your initial choice for generalized anxiety disorder, social anxiety disorder, and panic disorder 2, 1
• Start escitalopram at 5-10 mg daily and titrate by 5-10 mg increments every 1-2 weeks 1
• Start sertraline at 25-50 mg daily and titrate by 25-50 mg increments every 1-2 weeks as tolerated 1
• These agents demonstrate high treatment response rates (NNT = 4.70 for SSRIs) with dropout rates similar to placebo 2

Alternative SSRIs (Second-Tier)

• Paroxetine and fluvoxamine are equally effective but should be reserved for when first-tier SSRIs fail due to higher risks of discontinuation symptoms 2, 1
• Fluoxetine (20-40 mg/day) can be considered, particularly for patients who occasionally miss doses due to its longer half-life 1
• Start fluoxetine at 5-10 mg daily and increase by 5-10 mg increments every 1-2 weeks 1

SNRIs as First-Line Alternatives

• Duloxetine (60-120 mg/day) is particularly beneficial for patients with comorbid pain conditions 1
• Start duloxetine at 30 mg daily for one week to reduce nausea, then increase to 60 mg 1
• Venlafaxine extended-release (75-225 mg/day) is effective across all anxiety disorders but requires blood pressure monitoring due to risk of sustained hypertension 1, 3
• The response rate for SNRIs is NNT = 4.94, comparable to SSRIs 2

Treatment Timeline and Monitoring

Expected Response Pattern

• Statistically significant improvement begins by week 2, clinically significant improvement by week 6, and maximal benefit by week 12 or later 1
• Do not abandon treatment prematurely—full response may require 12+ weeks 1
• Allow 1-2 weeks between dose increases to assess tolerability and avoid overshooting the therapeutic window 1

Critical Monitoring Requirements

• Monitor closely for suicidal thinking and behavior, especially in the first months and following dose adjustments (pooled risk difference 0.7% vs placebo, NNH = 143) 1, 4
• Assess response using standardized anxiety rating scales such as HAM-A 1
• Monitor for common side effects: nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, somnolence, and dizziness 1
• Most adverse effects emerge within the first few weeks and typically resolve with continued treatment 1

Treatment Algorithm for Inadequate Response

If First SSRI Fails After 8-12 Weeks

• Switch to a different SSRI (e.g., sertraline to escitalopram or vice versa) rather than increasing to supramaximal doses 1
• Consider adding cognitive behavioral therapy if not already implemented 1
• Switching to another standard drug within the SSRI/SNRI class is recommended by international guidelines 2

Second-Line Medication Options

• Pregabalin can be considered when first-line treatments are ineffective or not tolerated, particularly for patients with comorbid pain conditions 1
• Gabapentin is also listed as a second-line option in Canadian guidelines 2

Combination with Psychotherapy

Combining medication with cognitive behavioral therapy (CBT) provides superior outcomes compared to either treatment alone 1, 3

• Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness 1
• CBT demonstrates large effect sizes for generalized anxiety disorder (Hedges g = 1.01) 1, 3
• Meta-analyses suggest combining an antidepressant with exposure therapy produces the greatest treatment gains 5

Treatment Duration

• Continue medications for 6-12 months after remission 6
• Discontinue medication gradually to avoid withdrawal symptoms, particularly with shorter half-life SSRIs like paroxetine 1, 6

Critical Warnings and Pitfalls to Avoid

Medications to Avoid

• Benzodiazepines are not recommended for routine use in chronic anxiety despite their rapid onset 6
• Tricyclic antidepressants should be avoided due to unfavorable risk-benefit profile, particularly cardiac toxicity 1
• Beta blockers (atenolol, propranolol) are deprecated based on negative evidence 2

Drug Interactions

• Caution with concomitant use of NSAIDs, aspirin, or warfarin due to increased bleeding risk 4
• Avoid combining with other serotonergic agents (triptans, tramadol) due to serotonin syndrome risk 4
• Fluoxetine inhibits CYP2D6 and may require dose adjustments of medications metabolized by this pathway 4

Initial Activation Syndrome

• Start with low doses to minimize initial anxiety/agitation that can occur with SSRIs in the first few weeks 1
• Gradual up-titration prevents unintentionally exceeding the optimal dose, as SSRI response follows a logarithmic model with diminishing returns at higher doses 1

Quality of Evidence

The certainty of evidence for SSRIs and SNRIs in anxiety disorders is rated as "low" according to GRADE methodology due to risk of bias, inconsistency, and imprecision across studies 2. However, the overall benefit (improvements in treatment response and anxiety symptoms) substantially outweighs harm (dropout from treatment), with dropout rates similar to placebo 2. Meta-analyses demonstrate small to medium effect sizes for SSRIs/SNRIs compared with placebo across anxiety disorders (SMD ranging from -0.30 to -0.67) 3.