What is the first line treatment for an adult with depression and anxiety?

First-Line Treatment for Depression and Anxiety in Adults

For adults with comorbid depression and anxiety, Cognitive Behavioral Therapy (CBT) is the first-line treatment, with SSRIs (such as sertraline 50 mg daily) as the preferred pharmacologic option for those without access to CBT, those preferring medication, or those who fail psychological treatment. 1, 2

Treatment Algorithm

Step 1: Initial Treatment Selection

• Start with CBT as monotherapy delivered by a trained therapist using manualized, structured protocols for patients with moderate symptoms 1, 2
• CBT demonstrates similar efficacy to second-generation antidepressants for depression, with the critical advantage of significantly fewer adverse events and lower treatment discontinuation rates 1
• Prioritize treating depressive symptoms first, as evidence shows that successfully treating depression often concurrently improves anxiety symptoms 1, 2, 3

Step 2: When to Use Pharmacotherapy

Offer SSRIs as first-line pharmacologic treatment in these specific situations: 1, 2, 4

• Patient lacks access to qualified CBT providers
• Patient expresses clear preference for medication over psychotherapy
• Patient has severe symptoms requiring immediate intervention
• Patient has history of positive response to antidepressants
• Patient fails to improve after 8 weeks of adequate CBT

Step 3: SSRI Selection and Dosing

Sertraline is the prototypical first-line SSRI: 4

• Start at 50 mg once daily (either morning or evening) for depression 4
• Start at 25 mg once daily for one week, then increase to 50 mg daily for anxiety disorders (panic disorder, social anxiety disorder) 4
• Patients not responding to 50 mg may benefit from dose increases up to maximum 200 mg/day 4
• Do not change doses more frequently than weekly intervals due to sertraline's 24-hour elimination half-life 4

Treatment Monitoring

Assess treatment response at 4 weeks and 8 weeks using standardized instruments (PHQ-9 for depression, GAD-7 for anxiety) 2, 5

If symptoms are stable or worsening after 8 weeks despite good adherence, immediately adjust the treatment plan: 1, 2, 5

• Add pharmacotherapy to ongoing CBT, or add CBT to ongoing SSRI
• Switch to a different SSRI
• Consider augmentation with bupropion or cognitive therapy (evidence from STAR*D trial shows similar efficacy) 1

Combined Treatment Considerations

Combined CBT plus SSRI from treatment initiation may be optimal for severe symptoms (PHQ-9 ≥15, GAD-7 ≥15), as meta-analytic evidence shows combined treatment produces effects approximately twice as large as medication alone 5, 6

• The number needed to treat (NNT) for combined treatment versus medication alone is 4.20, indicating clinically meaningful benefit 6
• Effects of psychotherapy and pharmacotherapy appear largely independent, with both contributing equally to combined treatment outcomes 6
• Combined treatment superiority is well-established specifically for major depression, panic disorder, and OCD 6

Adjunctive Interventions

Structured physical activity and exercise provide moderate to large reductions in depression and may reduce anxiety; recommend as supplement to primary treatment 2, 5

Mindfulness-Based Stress Reduction (MBSR) demonstrates statistically significant improvements in both depression and anxiety in short and medium term 2

Critical Pitfalls to Avoid

Do not wait beyond 8 weeks to adjust ineffective treatment, as prolonged inadequate response worsens outcomes and increases chronicity 2, 5

Do not use antidepressant monotherapy in patients with undiagnosed bipolar disorder, as this can trigger manic episodes; screen for history of manic/hypomanic episodes before initiating SSRIs 2

Do not neglect comorbid substance use, which occurs frequently and complicates both diagnosis and treatment response in patients with depression and anxiety 2

Do not assume treatment adherence—assess follow-through with referrals and medication compliance at every visit, as patients with depression often lack motivation to follow through on treatment recommendations 1

Do not use benzodiazepines as first-line treatment—while they may help with insomnia and acute anxiety, they do not treat depression, carry dependency risks, and increase fall risk in older adults 7

Evidence Quality Note

The strongest evidence supports CBT versus antidepressants as first-step treatment (moderate certainty evidence from multiple trials), and various pharmacologic switch and augmentation strategies as second-step treatments (moderate certainty evidence) 1. The evidence base shows that approximately 85% of patients with depression have significant anxiety, and 90% of patients with anxiety have depression, supporting the unified treatment approach 7.