What is the best initial medication for treating anxiety disorders, specifically selective serotonin reuptake inhibitors (SSRIs)?

Best Initial Medication for Anxiety Disorders

SSRIs are the best first-line medication for anxiety disorders, with escitalopram and sertraline being the preferred agents due to their superior efficacy, favorable side effect profiles, and lower drug interaction potential. 1, 2, 3

Primary Recommendation: SSRIs as First-Line Treatment

Start with either escitalopram 10 mg daily or sertraline 50 mg daily as your initial pharmacotherapy for anxiety disorders. 1, 4, 5

Why SSRIs Are Superior

• High treatment response rates: SSRIs demonstrate a number needed to treat (NNT) of 4.70 for social anxiety disorder, meaning approximately 1 in 5 patients will respond who wouldn't have responded to placebo 1
• Excellent safety profile: Dropout rates are similar to placebo, indicating good tolerability 1
• Broad spectrum efficacy: Effective across generalized anxiety disorder, social anxiety disorder, and panic disorder 5
• Treat comorbid conditions: Particularly valuable since anxiety disorders frequently co-occur with depression 6, 5

Choosing Between Specific SSRIs

Escitalopram (Preferred for Most Patients)

• Lowest drug interaction potential: Has the least effect on CYP450 isoenzymes compared to other SSRIs 2
• Once-daily dosing: Can be taken morning or evening, with or without food 4
• Dosing: Start 10 mg daily; can increase to 20 mg after minimum 1 week if needed 4
• Special populations: Use 10 mg daily in elderly patients and those with hepatic impairment 4

Sertraline (Alternative First Choice)

• Particularly strong evidence for panic disorder: Superior data for both acute treatment and relapse prevention in panic disorder specifically 3
• Dosing consideration: May require twice-daily dosing at low doses due to shorter half-life, which can affect adherence 2, 3
• Higher drug interaction risk: Interacts with drugs metabolized by CYP2D6 2

SNRIs as Alternative First-Line Option

SNRIs (particularly venlafaxine extended release) are equally effective alternatives to SSRIs with NNT of 4.94, nearly identical to SSRIs 1, 7

• Consider SNRIs when SSRIs have failed or when comorbid pain conditions exist 7
• Evidence base is more limited compared to SSRIs, with most data specific to venlafaxine 1

Critical Implementation Details

Starting Treatment

• Use a "test dose" initially: Start with subtherapeutic dose to minimize initial anxiety or agitation that can occur with SSRI initiation 2, 3
• Screen for bipolar disorder: Prior to initiating any antidepressant, screen for personal or family history of bipolar disorder, mania, or hypomania 4
• Set expectations: Full therapeutic effect takes 8-12 weeks, though some improvement may occur earlier 3

Monitoring Requirements

• Suicidal ideation: Monitor closely, especially in first months of treatment and after dosage adjustments 2, 3, 4
• Behavioral activation: Watch for agitation particularly early in treatment 2
• Serotonin syndrome risk: Exercise caution when combining with other serotonergic medications 2, 3

Common Adverse Effects to Anticipate

• Neuropsychiatric: Somnolence, dizziness, initial anxiety/agitation 1
• Gastrointestinal: Nausea (most common early side effect) 1
• Serious but rare: Serotonin syndrome, neuroleptic malignant syndrome 1

Discontinuation Strategy

Never stop SSRIs abruptly - gradual tapering is essential 4

• Allow at least 14 days between discontinuing SSRI and starting MAOI, and vice versa 4
• Sertraline has higher risk of discontinuation syndrome with missed doses or abrupt cessation 2
• If intolerable symptoms occur during taper, resume previous dose and decrease more gradually 4

Optimizing Treatment Response

Combination Therapy for Inadequate Response

Add cognitive behavioral therapy (CBT) to medication for superior outcomes 2, 3

• Combination treatment (SSRI plus CBT) demonstrates better results than either alone 2, 3
• CBT may provide more durable benefits after discontinuation compared to medication alone 3

Maintenance Treatment

• Generalized anxiety disorder: Efficacy beyond 8 weeks is established; periodically reassess need for continued treatment 4
• Major depression with anxiety: Several months or longer of sustained therapy required beyond acute response 4
• Relapse rates are lower with continued medication compared to discontinuation 3

Medications to Avoid as First-Line

The following have insufficient evidence or unfavorable risk-benefit profiles for initial treatment 1:

• Benzodiazepines (dependency risk, though may have role as adjunct)
• Beta blockers (limited to performance anxiety only) 6
• Antipsychotics, anticonvulsants, MAOIs (insufficient evidence or higher risk profiles)