What medications are used to treat anxiety?

Medications for Anxiety Disorders

Start with escitalopram (10-20 mg/day) or sertraline (50-200 mg/day) as first-line pharmacotherapy for anxiety disorders, as these SSRIs have the strongest evidence for efficacy with the most favorable side effect profiles and lowest discontinuation symptoms. 1, 2

First-Line Pharmacotherapy: SSRIs and SNRIs

Preferred First-Line Agents

• Escitalopram and sertraline are the top-tier first-line medications due to established efficacy, favorable tolerability, and lower risk of discontinuation symptoms compared to other SSRIs 1, 2
• Begin sertraline at 25-50 mg daily or escitalopram at 5-10 mg daily to minimize initial anxiety/agitation that can occur early in SSRI treatment 2
• Titrate sertraline by 25-50 mg increments every 1-2 weeks as tolerated, targeting 50-200 mg/day 2
• Titrate escitalopram by 5-10 mg increments, targeting 10-20 mg/day 2

Alternative First-Line SSRIs

• Fluoxetine and fluvoxamine are effective alternatives, with fluoxetine having a longer half-life that may benefit patients who occasionally miss doses 2
• Paroxetine and fluvoxamine should be reserved for second-line use due to higher risks of discontinuation symptoms, despite equal efficacy 1
• Paroxetine carries additional concern for potentially increased suicidal thinking compared to other SSRIs 1, 2

SNRIs as First-Line Options

• Venlafaxine extended-release (75-225 mg/day) and duloxetine (60-120 mg/day) are effective first-line alternatives to SSRIs 1, 2
• Venlafaxine requires blood pressure monitoring due to risk of sustained hypertension 2
• Duloxetine offers additional benefits for patients with comorbid pain conditions; start at 30 mg daily for one week to reduce nausea, then increase to 60-120 mg/day 2

Timeline and Monitoring

Expected Response Pattern

• Statistically significant improvement typically occurs within 2 weeks of starting SSRIs 2
• Clinically significant improvement emerges by week 6 2
• Maximal improvement occurs by week 12 or later 2
• Allow 8-12 weeks at therapeutic doses before concluding inadequate response 2

Critical Monitoring Points

• Assess response using standardized anxiety rating scales (e.g., HAM-A, GAD-7) 2
• Monitor closely for behavioral activation/agitation, particularly in the first month or with dose increases 1
• Watch for emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, or suicidal ideation, especially early in treatment 3
• Most adverse effects emerge within the first few weeks of treatment 2

Common Side Effects to Anticipate

• Nausea, sexual dysfunction (erectile dysfunction, delayed ejaculation, anorgasmia), headache, insomnia, dry mouth, diarrhea, heartburn, somnolence, dizziness, and vivid dreams are common with SSRIs/SNRIs 1, 2, 3
• Abnormal bleeding risk increases, particularly with concomitant NSAIDs, aspirin, or anticoagulants 1, 3
• Hyponatremia may occur, especially in elderly patients or those taking diuretics 3
• Seizures have been observed; use cautiously in patients with seizure history 1

Critical Drug Interactions and Warnings

Serotonin Syndrome Risk

• Never combine SSRIs/SNRIs with MAOIs (phenelzine, isocarboxazid, moclobemide, isoniazid, linezolid) due to severe serotonin syndrome risk 1
• Exercise caution when combining with other serotonergic drugs including tramadol, meperidine, methadone, fentanyl, dextromethorphan, amphetamines, St. John's wort, and L-tryptophan 1
• Serotonin syndrome symptoms include mental status changes, neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis) within 24-48 hours of combining medications 1

CYP450 Interactions

• Fluoxetine, paroxetine, and sertraline inhibit CYP2D6 and may interact with TCAs, antipsychotics (phenothiazines), and antiarrhythmics (propafenone, flecainide) 1, 3
• Fluvoxamine has the greatest potential for drug-drug interactions, affecting CYP1A2, CYP2C19, CYP2C9, CYP3A4, and CYP2D6 1
• Citalopram/escitalopram have the least effect on CYP450 enzymes, making them preferable when drug interactions are a concern 1

Specific SSRI Warnings

• Citalopram may cause QT prolongation at doses exceeding 40 mg/day; avoid in patients with long QT syndrome 1
• Paroxetine, fluvoxamine, and sertraline are associated with discontinuation syndrome; taper gradually when stopping 1, 2

Algorithm for Treatment Failure

If First SSRI Inadequate After 8-12 Weeks

1. Switch to a different SSRI (e.g., sertraline to escitalopram or vice versa) 2
2. Consider switching to an SNRI (venlafaxine or duloxetine) 2
3. Add cognitive behavioral therapy if not already implemented 2

Second-Line Pharmacological Options

• Pregabalin (300-600 mg/day in 2-3 divided doses) when first-line treatments fail, particularly beneficial for comorbid pain conditions 1, 4
• Gabapentin (900-3600 mg/day in 3 divided doses) as second-line option 1, 4
• Benzodiazepines (alprazolam 0.25-4 mg/day, clonazepam 0.5-4 mg/day, bromazepam 6-18 mg/day) for rapid relief while titrating other agents, but limit duration due to dependence risk 1, 4

Medications to Avoid

• Tricyclic antidepressants should be avoided due to unfavorable risk-benefit profile, particularly cardiac toxicity 2
• Beta blockers (atenolol, propranolol) are not recommended based on negative evidence for social anxiety disorder 1
• Quetiapine, levetiracetam, and imipramine are deprecated based on negative evidence 1

Treatment Duration and Discontinuation

• Continue medications for 6-12 months after remission 5, 6
• Discontinue gradually to avoid withdrawal symptoms, particularly with shorter half-life SSRIs like paroxetine, fluvoxamine, and sertraline 1, 2
• Behavioral activation usually improves quickly after SSRI dose decrease, whereas mania/hypomania may persist and require active intervention 1

Integration with Psychotherapy

• Combining medication with cognitive behavioral therapy provides optimal outcomes 2, 4
• CBT demonstrates large effect sizes for generalized anxiety disorder (Hedges g = 1.01) and small to medium effects for social anxiety disorder and panic disorder 2, 6
• Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness 2

Common Pitfalls to Avoid

• Premature switching before allowing 8-12 weeks at therapeutic doses is a frequent error 2, 4
• Starting at too high a dose can worsen initial anxiety; always start low and titrate slowly 2
• Failing to educate patients about potential behavioral activation in the first month leads to premature discontinuation 1
• Not monitoring for suicidal ideation, especially in younger patients during the first weeks of treatment 3
• Polypharmacy without adequate trials of first-line agents 4
• Abrupt discontinuation rather than gradual taper, particularly with paroxetine, fluvoxamine, and sertraline 1, 2