What is the first-line SSRI (Selective Serotonin Reuptake Inhibitor) for anxiety?

First-Line SSRI for Anxiety Disorders

Sertraline is the recommended first-line SSRI for anxiety disorders due to its strong efficacy profile, favorable tolerability, and low potential for pharmacokinetic drug interactions. 1

Evidence-Based Selection of SSRIs for Anxiety

• SSRIs are suggested as first-line pharmacotherapy for anxiety disorders, with strong evidence supporting their efficacy across various anxiety conditions including social anxiety disorder, generalized anxiety, separation anxiety, and panic disorders 2
• Sertraline has demonstrated efficacy in multiple anxiety disorders including social anxiety disorder, panic disorder, and PTSD, as confirmed by FDA approval for these conditions 3
• Sertraline has shown to be at least as well-tolerated as other SSRIs and may have a more favorable side effect profile in head-to-head comparisons 1
• The National Institute for Health and Care Excellence (NICE) in the United Kingdom specifically lists sertraline along with escitalopram as first-line pharmacotherapy for anxiety disorders 2

Mechanism of Action

• SSRIs inhibit the presynaptic reuptake of serotonin in the brain, increasing serotonin availability at the synaptic cleft 2
• This blockade leads to downregulation of inhibitory serotonin autoreceptors over time, which eventually heightens serotonergic neuronal firing rate and increases serotonin release 4
• The multistep process explains the delayed onset of therapeutic effect typically seen with SSRI treatment 2

Dosing and Administration Guidelines

• Start with a lower dose to minimize initial anxiety or agitation that can sometimes occur with SSRI initiation 5
• Sertraline may require twice-daily dosing at low doses due to its shorter half-life compared to some other SSRIs 5
• Full therapeutic effect may take 8-12 weeks to develop, though some improvement may be seen earlier 2, 5
• Slow up-titration is recommended to avoid unintentionally exceeding the optimal medication dose 2

Advantages of Sertraline Over Other SSRIs

• Low potential for pharmacokinetic drug interactions as sertraline is not a potent inhibitor of any cytochrome P450 isoenzyme systems, unlike fluoxetine, fluvoxamine, and paroxetine 1
• Sertraline has demonstrated efficacy across multiple anxiety disorders with FDA approval for panic disorder, PTSD, and social anxiety disorder 3
• The best-fitting model for SSRI response may be logarithmic, with clinically significant improvement by week 6 and maximal improvement by week 12 or later 2

Common Side Effects and Management

• Most adverse effects emerge within the first few weeks of treatment and can include dry mouth, nausea, diarrhea, heartburn, headache, somnolence, insomnia, and dizziness 2
• Potentially serious adverse effects include suicidal thinking and behavior (particularly in young adults), behavioral activation/agitation, hypomania, mania, sexual dysfunction, and serotonin syndrome 2
• All SSRIs carry a boxed warning for suicidal thinking and behavior through age 24 years, with monitoring particularly important in the first months of treatment 2, 5

Treatment Duration and Discontinuation

• Long-term usefulness of SSRIs should be periodically reevaluated for the individual patient 3
• If discontinuation is planned, gradual tapering is recommended to minimize discontinuation symptoms 5
• Studies suggest relapse is more common after discontinuation of medication compared to after completion of cognitive behavioral therapy (CBT) 5

Special Considerations

• Exercise caution when combining sertraline with other serotonergic medications due to the risk of serotonin syndrome 5
• Consider combining sertraline with CBT for potentially superior outcomes compared to either treatment alone 5
• For social anxiety disorder specifically, both sertraline and paroxetine have demonstrated efficacy, with paroxetine showing response rates of 51-85% in clinical studies 6