What is the best antidepressant for anxiety?

Best Antidepressants for Anxiety

SSRIs and SNRIs are the first-line antidepressant treatments for anxiety disorders, with SSRIs generally preferred due to their established efficacy and favorable safety profile. 1

First-Line Medications

SSRIs (Selective Serotonin Reuptake Inhibitors)

• SSRIs are considered first-line pharmacotherapy for anxiety disorders with a high response rate (NNT = 4.70) and similar discontinuation rates to placebo 1
• SSRIs work by inhibiting the presynaptic reuptake of serotonin, increasing its availability at the synaptic cleft 1
• Commonly used SSRIs for anxiety include:
  • Paroxetine - Demonstrated efficacy in social anxiety disorder, generalized anxiety disorder, and PTSD 2
  • Sertraline - Effective for panic disorder and other anxiety disorders 3, 4
  • Escitalopram - Recommended as first-line in some guidelines 1
  • Fluvoxamine - Effective but may have more drug interactions 1
• Clinical improvement typically begins within 2-6 weeks, with maximal improvement by week 12 1

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

• SNRIs are also effective first-line options with response rates similar to SSRIs (NNT = 4.94) 1, 4
• Venlafaxine is the most studied SNRI for anxiety disorders 1
• SNRIs inhibit the reuptake of both serotonin and norepinephrine 5
• Duloxetine is FDA-approved for generalized anxiety disorder in children and adolescents 7 years and older 1
• SNRIs may cause dose-dependent increases in blood pressure and pulse 1, 5

Medication Selection Considerations

Efficacy Considerations

• Both SSRIs and SNRIs show small to medium effect sizes compared to placebo for anxiety disorders 4
• Combination treatment with cognitive behavioral therapy (CBT) and an SSRI may be more effective than either treatment alone 1
• For social anxiety disorder specifically, both SSRIs and SNRIs demonstrate significant improvements compared to placebo 1

Safety and Tolerability

• Common side effects of SSRIs include nausea, diarrhea, headache, insomnia, sexual dysfunction, and initial anxiety/agitation 1
• SNRIs may additionally cause hypertension, diaphoresis, and tachycardia, especially at higher doses 1, 5
• Paroxetine, fluvoxamine, and sertraline have been associated with discontinuation syndrome 1
• Citalopram may cause QT prolongation at doses exceeding 40 mg/day 1
• Paroxetine has been associated with increased risk of suicidal thinking compared to other SSRIs 1

Drug Interactions

• All SSRIs and SNRIs are contraindicated with MAOIs due to risk of serotonin syndrome 1
• Fluvoxamine has greater potential for drug-drug interactions (affects multiple CYP enzymes) 1
• Citalopram/escitalopram may have fewer CYP450 interactions compared to other SSRIs 1
• Venlafaxine and desvenlafaxine have favorable drug-drug interaction profiles 5

Implementation Recommendations

Dosing Strategy

• Start with a low dose, especially with SSRIs, as initial anxiety/agitation can occur 1
• Titrate doses gradually:
  • For shorter half-life SSRIs (sertraline, citalopram): increase at 1-2 week intervals 1
  • For longer half-life SSRIs (fluoxetine): increase at 3-4 week intervals 1
• Higher doses may not necessarily provide greater efficacy but can increase adverse effects 1

Monitoring

• Monitor closely for suicidality, especially in the first months of treatment and following dose adjustments 1
• Watch for behavioral activation/agitation, particularly in younger patients 1
• Assess treatment response using standardized symptom rating scales 1

Special Considerations

Treatment-Resistant Anxiety

• For OCD specifically, antipsychotic augmentation of SSRIs has shown efficacy 6
• Limited evidence exists for augmentation strategies in treatment-resistant generalized anxiety disorder 6
• For PTSD, adjunctive risperidone or prazosin may be beneficial in some cases 6

Discontinuation

• Taper medications slowly, particularly paroxetine, fluvoxamine, and sertraline, to avoid discontinuation syndrome 1
• Discontinuation symptoms may include dizziness, fatigue, headaches, nausea, sensory disturbances, and anxiety 1

In conclusion, while both SSRIs and SNRIs are effective for anxiety disorders, SSRIs are typically preferred as first-line treatment due to their established efficacy and favorable safety profile. The specific choice among SSRIs should consider individual factors such as side effect profile, potential drug interactions, and prior treatment response.