What are the recommended medications for treating anxiety?

Recommended Medications for Anxiety

Start with an SSRI—specifically sertraline (50-200 mg/day) or escitalopram (10-20 mg/day)—as first-line pharmacotherapy for anxiety disorders, as these agents demonstrate the highest efficacy and tolerability with treatment response rates of NNT = 4.70 and dropout rates similar to placebo. 1, 2

First-Line Medication Selection

Preferred SSRIs

• Sertraline is the top choice: start at 25 mg daily for the first week to minimize initial anxiety or agitation, then increase to 50 mg daily after week 1, with a target therapeutic dose of 50-200 mg/day 3, 2, 4
• Escitalopram is an equally strong alternative: start at 5-10 mg daily and titrate by 5-10 mg increments every 1-2 weeks to a target of 10-20 mg/day 1, 2
• Both medications are recommended by NICE, German S3, and Canadian guidelines as first-line agents 1

Alternative First-Line SSRIs

• Fluoxetine (20-40 mg/day) can be considered, particularly for patients who occasionally miss doses due to its longer half-life: start at 5-10 mg daily and increase by 5-10 mg increments every 1-2 weeks 3, 2, 5
• Paroxetine and fluvoxamine should be reserved as second-tier SSRIs when first choices fail, due to higher discontinuation syndrome risk and potentially increased suicidal thinking 1, 3

SNRIs as First-Line Alternatives

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

Treatment Timeline and Dosing Strategy

Expected Response Curve

• Statistically significant improvement may begin by week 2, with clinically significant improvement expected by week 6, and maximal therapeutic benefit achieved by week 12 or later 3, 2
• Do not abandon treatment before 12 weeks—full response requires patience due to the logarithmic response curve of SSRIs 3, 6

Dose Titration Principles

• Allow 1-2 weeks between dose increases to assess tolerability and avoid overshooting the therapeutic window 3, 2
• Higher doses of SSRIs within the therapeutic range are associated with greater treatment benefit, whereas higher doses of SNRIs are not 6
• Start with low doses to minimize initial anxiety/agitation that can occur with SSRIs in the first few weeks 3, 2

Critical Monitoring Requirements

Suicidality Surveillance

• Monitor closely for suicidal thinking and behavior, especially in the first months and following dose adjustments, with a pooled risk difference of 0.7% vs placebo (NNH = 143) 3, 2, 5
• Watch for emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, or worsening depression 5

Common Side Effects

• Expect nausea, headache, insomnia, nervousness, initial anxiety/agitation, sexual dysfunction, dry mouth, diarrhea, somnolence, and dizziness 1, 3, 2
• Most adverse effects emerge within the first few weeks and typically resolve with continued treatment 3, 2

Treatment Algorithm for Inadequate Response

Sequential Steps

1. If first SSRI fails after 8-12 weeks at therapeutic doses, switch to a different SSRI (e.g., sertraline to escitalopram or vice versa) rather than increasing to supramaximal doses 2
2. If multiple SSRIs fail, consider switching to an SNRI (venlafaxine or duloxetine) 1, 3, 2
3. Add cognitive behavioral therapy if not already implemented—combination therapy provides superior outcomes to either treatment alone 1, 3, 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, 2
• Gabapentin is also listed as a second-line option in Canadian guidelines 1, 2

Combination with Psychotherapy

• Combining medication with cognitive behavioral therapy (CBT) provides superior outcomes compared to either treatment alone for panic disorder and generalized anxiety 1, 3, 2, 7
• Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness 1, 2
• A treatment course of 12-20 structured CBT sessions targeting anxiety-specific cognitive distortions and exposure techniques is recommended 3, 2
• CBT demonstrates large effect sizes for generalized anxiety disorder (Hedges g = 1.01) 2, 7

Maintenance and Discontinuation

Duration of Treatment

• Continue medication for at least 9-12 months after recovery to prevent relapse 3
• For social anxiety disorder, efficacy in maintaining response for up to 24 weeks following 20 weeks of treatment has been demonstrated 4

Discontinuation Strategy

• Never discontinue SSRIs/SNRIs abruptly—taper gradually to avoid withdrawal symptoms, particularly with shorter half-life agents like sertraline and paroxetine 3, 2

Critical Pitfalls to Avoid

Medications to Avoid

• Tricyclic antidepressants should be avoided due to unfavorable risk-benefit profile, particularly cardiac toxicity 2
• Beta blockers (atenolol, propranolol) are deprecated based on negative evidence 1, 2
• Benzodiazepines are not recommended for routine use despite their efficacy, due to dependence risk and should only be considered as second-line agents 1, 8, 9

Common Prescribing Errors

• Do not escalate doses too quickly—this increases side effects without improving efficacy 3, 2
• Do not use paroxetine or fluvoxamine as first-choice SSRIs due to higher discontinuation syndrome risk 1, 3
• Do not forget to monitor blood pressure with venlafaxine 2
• Do not combine SSRIs/SNRIs with NSAIDs, aspirin, or warfarin without counseling patients about increased bleeding risk 5

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 1, 2
• However, the overall benefit (improvements in treatment response and anxiety symptoms) substantially outweighs harm (dropout from treatment), with dropout rates similar to placebo 1, 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) 7