What is the first-line treatment for anxiety and depression?

First-Line Treatment for Anxiety and Depression

For patients with comorbid anxiety and depression, cognitive behavioral therapy (CBT) or interpersonal therapy should be offered as first-line treatment, with SSRIs (particularly sertraline, escitalopram, or fluoxetine) as the preferred pharmacologic option when psychotherapy is unavailable, not preferred by the patient, or symptoms are severe. 1, 2

Treatment Prioritization When Both Conditions Present

When patients have symptoms of both depression and anxiety, treat the depressive symptoms first, or use a unified protocol combining CBT treatments for both conditions. 1 This recommendation is based on high-quality evidence showing that addressing depression often improves comorbid anxiety symptoms 1.

Psychological Interventions as First-Line

• Cognitive behavioral therapy (CBT) or interpersonal therapy are the recommended first-line treatments for moderate to severe depression and anxiety. 1
• These psychological interventions should be culturally informed and linguistically appropriate 1
• Mental health professionals should assess treatment response regularly at pretreatment, 4 weeks, 8 weeks, and end of treatment 1

When to Initiate Pharmacotherapy

Offer pharmacologic treatment (SSRIs) for patients who:

• Lack access to first-line psychological treatment 1
• Express preference for medication 1
• Do not improve following first-line psychological management 1
• Have severe symptoms or accompanying psychotic features 1
• Have a history of positive response to medications 1

Specific SSRI Selection

All SSRIs demonstrate equivalent efficacy for treating depression and anxiety, but selection should consider specific factors: 2

• Sertraline, escitalopram, or fluoxetine are preferred first-line SSRIs 2
• Escitalopram and citalopram have the least drug-drug interactions via CYP450 enzymes 2
• Fluoxetine is FDA-approved for the broadest range of conditions including major depression, OCD, panic disorder, and is the only antidepressant approved for pediatric depression 2
• Paroxetine is FDA-approved for the widest range of anxiety disorders (GAD, panic disorder, social anxiety disorder, PTSD) but has higher discontinuation syndrome risk 2

Dosing Strategy

• Start with standard SSRI doses and allow 6-8 weeks for adequate trial 2
• For anxiety disorders specifically, higher doses may be required (e.g., fluoxetine 60-80 mg for OCD) 2, 3
• Assess response regularly at 4 and 8 weeks using standardized validated instruments 1

Critical Monitoring Requirements

• Monitor for treatment-emergent suicidality, particularly in the first 1-2 weeks after initiation or dose changes 1, 2
• All SSRIs carry FDA black box warnings for suicidality in adolescents and young adults 2
• Assess for symptom relief, side effects, and patient satisfaction at 4 and 8 weeks 1

When Initial Treatment Fails

If there is little improvement after 8 weeks despite good adherence, adjust the regimen by: 1

• Adding a psychological intervention to pharmacotherapy (or vice versa) 1
• Switching to a different SSRI or SNRI 1, 2
• Changing from group to individual therapy if applicable 1

Approximately 38% of patients do not achieve treatment response during 6-12 weeks, and 54% do not achieve remission, making treatment adjustment common 2

Treatment Duration

Continue SSRI treatment for 4-9 months after satisfactory response for first-episode depression; longer duration (≥1 year) for patients with recurrent episodes. 1, 2 This reduces relapse risk during the continuation and maintenance phases 2

Common Pitfalls to Avoid

• Do not discontinue SSRIs abruptly - taper to avoid discontinuation syndrome with dizziness, nausea, and sensory disturbances 2
• Do not combine SSRIs with MAOIs due to serotonin syndrome risk 2
• Do not switch medications prematurely - full response may take 6-8 weeks; partial response at 4 weeks warrants continued treatment 2
• Do not use SSRIs as first-line for IBS with comorbid anxiety/depression - they lack significant benefit for GI symptoms 2
• Recognize that initial anxiety or agitation in the first week is common and typically resolves with continued treatment 2, 4

Special Populations

• For patients with severe depression, antidepressants show greater benefit compared to placebo than in mild-to-moderate depression 1
• Patients with anxious depression may require lower starting doses, more gradual dose escalations, higher endpoint doses, and longer treatment duration 4
• Consider genetic testing for CYP2D6 and CYP2C19 to guide dosing of fluoxetine and paroxetine 2