First-Line Medication for Chronic Anxiety
Start with either escitalopram (5-10 mg daily) or sertraline (25-50 mg daily) as your first-line medication for chronic anxiety, as these SSRIs have the strongest evidence for efficacy, favorable side effect profiles, and lowest risk of discontinuation symptoms. 1
Preferred SSRI Options
Escitalopram is the top-tier choice due to:
- Minimal drug interactions (least effect on CYP450 enzymes) 2
- Start at 5-10 mg daily, titrate by 5-10 mg increments every 1-2 weeks 1
- Target dose: 10-20 mg/day 1
Sertraline is equally preferred because:
- Extensive evidence base across all anxiety disorders 3, 4
- Start at 25-50 mg daily, titrate by 25-50 mg increments every 1-2 weeks 1
- Target dose: 50-200 mg/day 1
- FDA-approved for panic disorder, PTSD, and social anxiety disorder 3
Critical Timeline Expectations
Set realistic expectations with patients about response patterns 1:
- Week 2: Statistically significant improvement may begin
- Week 6: Clinically meaningful improvement expected
- Week 12 or later: Maximal therapeutic benefit achieved
Do not abandon treatment prematurely or escalate doses too quickly—allow 1-2 weeks between dose increases to assess tolerability and avoid overshooting the therapeutic window. 1
Alternative First-Line: SNRIs
If SSRIs are contraindicated or patient preference dictates, use:
Venlafaxine extended-release (75-225 mg/day):
- Effective for generalized anxiety disorder, panic disorder, and social anxiety disorder 1
- Requires blood pressure monitoring due to risk of sustained hypertension 1
Duloxetine (60-120 mg/day):
- Particularly beneficial when comorbid pain conditions exist 1
- Start at 30 mg daily for one week to reduce nausea 1
Common Side Effects to Monitor
Most adverse effects emerge within the first few weeks and typically resolve with continued treatment 1:
- Nausea, diarrhea, dry mouth, heartburn
- Headache, dizziness
- Insomnia or somnolence
- Sexual dysfunction
- Nervousness, tremor
Critical Safety Warning
All SSRIs carry a boxed warning for suicidal thinking and behavior (pooled absolute rates: 1% vs 0.2% for placebo; NNH=143). 1 Monitor closely, especially during the first months and following any dose adjustments. 1
If First SSRI Fails
After 8-12 weeks at therapeutic doses with inadequate response 1:
- Switch to a different SSRI (e.g., sertraline to escitalopram or vice versa)
- Consider switching to an SNRI (venlafaxine or duloxetine)
- Add cognitive behavioral therapy if not already implemented
Essential Combination Treatment
Combining medication with cognitive behavioral therapy (CBT) provides superior outcomes compared to either treatment alone. 1 Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness. 1
CBT should include 2:
- Education on anxiety mechanisms
- Cognitive restructuring to challenge distortions
- Relaxation techniques
- Gradual exposure when appropriate
Medications to Avoid
Benzodiazepines should NOT be used as first-line treatment—reserve only for short-term use due to risks of dependence, tolerance, and withdrawal. 1 They do not address the underlying anxiety disorder. 2
Avoid paroxetine and fluvoxamine as initial choices due to higher risk of discontinuation symptoms, though they remain effective if first-tier SSRIs fail. 1
Tricyclic antidepressants should be avoided due to unfavorable risk-benefit profile, particularly cardiac toxicity. 1
Treatment Duration
Continue medication for 6-12 months after remission to prevent relapse. 5 When discontinuing, taper gradually to avoid withdrawal symptoms, particularly with shorter half-life SSRIs. 1