Best Antidepressant for Anxiety
Escitalopram or sertraline are the first-line antidepressants for anxiety in otherwise healthy adults, with escitalopram preferred due to its superior efficacy profile, lowest drug-interaction potential, and minimal discontinuation symptoms. 1, 2
Primary Medication Recommendations
Start with escitalopram 5–10 mg daily, titrating by 5–10 mg increments every 1–2 weeks to a target dose of 10–20 mg/day. 1, 2 This SSRI demonstrates the most favorable balance of efficacy and tolerability among all anxiety medications, with the lowest risk of drug-drug interactions and discontinuation symptoms compared to other SSRIs. 1
Sertraline is an equally valid first-line choice, starting at 25–50 mg daily and increasing by 25–50 mg increments every 1–2 weeks to a target dose of 50–200 mg/day. 1, 2 Both agents have FDA approval for generalized anxiety disorder and demonstrate robust efficacy across all anxiety subtypes (panic disorder, social anxiety, GAD). 3, 1
The number needed to treat (NNT) for SSRIs in anxiety disorders is approximately 4.7, meaning one in five patients will respond to SSRIs who would not have responded to placebo. 1
Expected Timeline and Response Monitoring
Statistically significant improvement begins by week 2, clinically meaningful improvement appears by week 6, and maximal therapeutic benefit is achieved by week 12 or later. 1, 2 This logarithmic response pattern means early improvement (by week 4) predicts eventual success, but treatment should not be abandoned before 8–12 weeks at therapeutic doses. 1
Monitor using standardized scales (GAD-7 or HAM-A) at baseline, week 2, week 6, and week 12. 1 Schedule follow-up within 1–2 weeks after initiating treatment to assess for adverse effects and initial response. 2
Common Adverse Effects
Nausea is the most frequent side effect leading to discontinuation; counsel patients that it typically emerges within the first few weeks and resolves with continued treatment. 2 Other common effects include sexual dysfunction, headache, insomnia, dry mouth, diarrhea, and dizziness. 1
All SSRIs carry an FDA boxed warning for increased suicidal thinking and behavior (pooled absolute rate 1% vs 0.2% placebo), requiring close monitoring especially in the first months and following dose adjustments. 1, 2
Second-Tier SSRI Options
Paroxetine (20–60 mg/day) and fluvoxamine are equally effective but should be reserved for when first-tier SSRIs fail due to higher discontinuation symptoms and greater drug-interaction potential. 1, 2 Paroxetine has specific FDA approval for social anxiety disorder but carries the highest risk of withdrawal syndrome among SSRIs. 1
SNRI Alternatives When SSRIs Fail
If inadequate response after 8–12 weeks at therapeutic SSRI doses, switch to venlafaxine extended-release 75–225 mg/day or duloxetine 60–120 mg/day. 1, 2 Venlafaxine demonstrates comparable efficacy to SSRIs (NNT 4.94 vs 4.70) and is effective across all anxiety disorders. 1, 4, 5
Venlafaxine requires blood pressure monitoring due to risk of sustained hypertension, particularly at doses above 150 mg/day. 1 Start at 37.5–75 mg daily and increase by 37.5–75 mg increments every 1–2 weeks. 1
Duloxetine is particularly beneficial for patients with comorbid pain conditions. 1, 2 Start at 30 mg daily for one week to minimize nausea, then increase to 60 mg/day. 1
Combination with Cognitive-Behavioral Therapy
Combining an SSRI or SNRI with individual cognitive-behavioral therapy (12–20 sessions) provides superior outcomes compared to either treatment alone, particularly for moderate to severe anxiety. 1, 2 Individual CBT is more clinically effective and cost-effective than group therapy. 1
When face-to-face CBT is unavailable, self-help CBT with professional support offers a viable evidence-based alternative. 1
Medications to Avoid
Benzodiazepines should be reserved for short-term use only (days to a few weeks) due to high risks of dependence, tolerance, cognitive impairment, and withdrawal. 1, 2 They are not recommended as first-line or long-term therapy for anxiety disorders. 1
Beta-blockers (atenolol, propranolol) are deprecated by Canadian guidelines for generalized anxiety disorder and social anxiety disorder due to lack of therapeutic benefit. 1
Bupropion is contraindicated for anxiety disorders because it is activating and can exacerbate anxiety symptoms, agitation, and nervousness. 1, 2
Tricyclic antidepressants should be avoided due to unfavorable risk-benefit profile, particularly cardiac toxicity. 1
Treatment Duration and Maintenance
Continue effective medication for a minimum of 9–12 months after achieving remission to prevent relapse. 1, 2 For recurrent episodes, long-term or indefinite maintenance therapy is advised. 2
Taper gradually when discontinuing to avoid withdrawal symptoms, particularly with shorter half-life SSRIs like sertraline and paroxetine. 1, 2 Escitalopram's longer half-life provides some protection against discontinuation syndrome. 1
Clinical Algorithm for Treatment-Resistant Cases
If no improvement after 8–12 weeks at therapeutic doses:
Switch to a different SSRI (escitalopram ↔ sertraline) — approximately 25% of patients achieve remission after switching within the SSRI class. 2
Switch to an SNRI (venlafaxine XR or duloxetine) if two SSRI trials have failed. 1, 2
Add individual CBT if not already implemented — psychotherapy augmentation produces larger effect sizes than adding a second medication. 1
Consider pregabalin or gabapentin for patients with comorbid pain or when first-line treatments are ineffective. 1, 6
Special Considerations for Comorbid Depression
Approximately 50–60% of adults with major depressive disorder also meet criteria for an anxiety disorder. 4 SSRIs (escitalopram or sertraline) effectively address both depressive and anxiety symptoms simultaneously, making them optimal first-line agents for co-occurring conditions. 4, 7, 8
When depression and anxiety occur together, they are associated with more severe symptoms, increased impairment, more chronic course, and higher suicide risk. 4 Venlafaxine has demonstrated significant efficacy in patients with depression and concomitant anxiety in prospective trials. 4