What medications are used to treat anxiety?

Medications for Anxiety

SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors) are the first-line pharmacological treatments for anxiety disorders, with escitalopram and sertraline being the preferred initial choices due to their established efficacy, favorable side effect profiles, and lower risk of drug interactions. 1

First-Line Medication Options

Preferred SSRIs

• Escitalopram (5-10 mg daily initially, target 10-20 mg/day) and sertraline (25-50 mg daily initially, target 50-200 mg/day) are the top-tier first-line agents 1, 2
• Start with low doses and titrate by 5-10 mg (escitalopram) or 25-50 mg (sertraline) every 1-2 weeks to minimize initial anxiety/agitation that can occur early in treatment 1
• Fluoxetine (5-10 mg initially, target 20-40 mg/day) has a longer half-life which may benefit patients who occasionally miss doses 1
• Citalopram and escitalopram have the least effect on CYP450 enzymes and therefore lower propensity for drug-drug interactions 3, 2

Alternative SSRIs (Second-Tier)

• Paroxetine and fluvoxamine are equally effective but carry higher risks of discontinuation symptoms and should be reserved for when first-tier SSRIs fail 1, 2
• Paroxetine has been associated with increased risk of suicidal thinking compared to other SSRIs 3, 2
• Fluvoxamine has greater potential for drug-drug interactions through multiple CYP450 pathways 3, 2

SNRIs as First-Line Alternatives

• Venlafaxine extended-release (75-225 mg/day) is effective for generalized anxiety disorder, social anxiety disorder, and panic disorder 1, 2
• Requires blood pressure monitoring due to risk of sustained hypertension 1
• Duloxetine (60-120 mg/day) has demonstrated efficacy in GAD and provides additional benefits 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

Expected Timeline and Response

• 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 1
• Full response may take 12+ weeks; treatment should not be abandoned prematurely 1
• Allow 1-2 weeks between dose increases for shorter half-life SSRIs (sertraline, citalopram, escitalopram) and 3-4 weeks for longer half-life SSRIs (fluoxetine) to assess tolerability 2

Second-Line Medications

If first-line SSRIs/SNRIs are ineffective or not tolerated after 8-12 weeks at therapeutic doses:

• Switch to a different SSRI or SNRI (e.g., sertraline to escitalopram or vice versa) 1
• Pregabalin/Gabapentin can be considered, particularly for patients with comorbid pain conditions 1

Benzodiazepines: Limited Role

• Alprazolam is FDA-approved for anxiety disorders and panic disorder 4
• However, benzodiazepines are not recommended for routine use in anxiety disorders due to risk of rebound anxiety after >4 weeks, withdrawal symptoms, and dependence 5, 6
• When prescribed, effectiveness is limited to 4 months for anxiety disorder and 4-10 weeks for panic disorder 4

Common Side Effects to Monitor

• Nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, heartburn, somnolence, dizziness, and vivid dreams 1
• Most adverse effects emerge within the first few weeks and typically resolve with continued treatment 1
• Behavioral activation/agitation may occur early in treatment (first month) or with dose increases, particularly in younger patients 3

Critical Safety Warnings

Serotonin Syndrome Risk

• Concomitant administration of SSRIs with MAOIs is contraindicated due to risk of serotonin syndrome 3, 2
• Exercise caution when combining two or more serotonergic drugs (SSRIs, SNRIs, tramadol, dextromethorphan, St. John's wort) 3
• Symptoms include mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity, typically arising within 24-48 hours after combining medications 3

Discontinuation Syndrome

• Paroxetine, fluvoxamine, and sertraline have been associated with discontinuation syndrome 3, 2
• Symptoms include dizziness, fatigue, headaches, nausea, insomnia, and anxiety 2
• Taper medications gradually to avoid withdrawal symptoms, particularly with shorter half-life SSRIs 1

Other Warnings

• Monitor for suicidal thinking and behavior, especially in the first months and following dose adjustments (pooled risk difference 0.7% vs placebo, NNH=143) 1
• Citalopram may cause QT prolongation at doses exceeding 40 mg/day and should be avoided in patients with long QT syndrome 3, 2

Combination with Psychotherapy

Combining medication with cognitive behavioral therapy (CBT) provides optimal outcomes and is the preferred approach over monotherapy. 1, 2

• Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness, with large effect sizes for GAD (Hedges g = 1.01) 1
• CBT elements should include education on anxiety, cognitive restructuring, relaxation techniques, and gradual exposure when appropriate 1
• A structured duration of 12-20 CBT sessions is recommended to achieve significant symptomatic and functional improvement 1

Treatment Duration

• After remission, medications should be continued for 6-12 months 5
• Medication tapering and discontinuation are facilitated by CBT 3
• Long-term medication may be indicated for severe or refractory anxiety or chronic comorbid illness 3

Medications to Avoid

• Tricyclic antidepressants (TCAs) should be avoided due to unfavorable risk-benefit profile, particularly cardiac toxicity 1
• Beta blockers (atenolol, propranolol) are not recommended for social anxiety disorder based on negative evidence 1
• Over-the-counter antihistamines and herbal substances (valerian, melatonin) are not recommended due to lack of efficacy and safety data 3
• Barbiturates, barbiturate-type drugs, and chloral hydrate are not recommended 3