What medication is suitable for a patient with depression and anxiety?

First-Line Medication for Depression and Anxiety

For patients with both depression and anxiety, start with an SSRI—specifically sertraline (50 mg daily, titrating to 100-200 mg) or escitalopram—as these demonstrate equivalent efficacy for both conditions with favorable tolerability profiles. 1

Why SSRIs Are the Clear Choice

All second-generation antidepressants (SSRIs and SNRIs) show no significant differences in overall efficacy for treating major depression with anxiety symptoms. 1 Multiple head-to-head trials comparing fluoxetine, paroxetine, sertraline, bupropion, and venlafaxine demonstrated similar antidepressive efficacy in patients with comorbid anxiety. 1

However, sertraline and escitalopram emerge as preferred first-line options based on international guidelines:

• The NICE guideline lists escitalopram and sertraline as first-line pharmacotherapy, relegating fluvoxamine, paroxetine, and venlafaxine to second-line due to side effects or discontinuation symptoms despite equal effectiveness. 1
• Sertraline has superior tolerability compared to other SSRIs, with evidence showing better acceptability than amitriptyline, imipramine, paroxetine, and mirtazapine. 2
• Escitalopram and citalopram have the least effect on CYP450 enzymes and the lowest propensity for drug interactions, making them safer in patients on multiple medications. 3

Practical Dosing Strategy

Start sertraline at 50 mg daily (or 25 mg if the patient is particularly anxious or sensitive to initial activation effects). 3

• Increase in 50 mg increments at 1-2 week intervals if response is inadequate, up to a maximum of 200 mg daily. 3
• Allow 6-8 weeks for an adequate trial, including at least 2 weeks at the maximum tolerated dose before declaring treatment failure. 3
• Approximately 38% of patients will not achieve response during the initial 6-12 weeks, and 54% will not achieve remission—this is expected and does not indicate treatment failure if improvement is occurring. 1, 3

Expected Timeline and Monitoring

Assess treatment response at 4 weeks and 8 weeks, evaluating for symptom relief, side effects, adherence, and patient satisfaction. 3

• Partial response at 4 weeks warrants continued treatment, not switching—full therapeutic effects may take up to 12 weeks. 3
• Monitor closely for treatment-emergent suicidality, especially in patients under age 24 during the first 1-2 weeks after initiation or dose changes. 3

When Initial Treatment Fails

If there is minimal improvement after 8 weeks at therapeutic doses despite good adherence, implement one of these strategies: 3

1. Switch to another SSRI (escitalopram, fluoxetine) or an SNRI (venlafaxine)—one in four patients becomes symptom-free after switching medications. 1, 3
2. Add cognitive behavioral therapy to ongoing pharmacotherapy—combination treatment is superior to either alone for anxiety disorders. 3
3. Consider venlafaxine specifically if anxiety symptoms are particularly prominent, as limited evidence suggests statistically better response rates than fluoxetine for depression with severe anxiety. 1, 3

Critical Safety Considerations

All SSRIs carry FDA black box warnings for treatment-emergent suicidality, particularly in adolescents and young adults—close monitoring is mandatory. 3

Avoid abrupt discontinuation of sertraline, as it can cause discontinuation syndrome with dizziness, nausea, and sensory disturbances—always taper when stopping. 3

Never combine SSRIs with MAOIs due to serotonin syndrome risk; ensure a 14-day washout period. 3, 4

Sertraline inhibits CYP2D6 and can increase plasma concentrations of co-administered drugs metabolized by this enzyme (tricyclic antidepressants, Type 1C antiarrhythmics like propafenone and flecainide). 4

Monitor patients on warfarin carefully when initiating or discontinuing sertraline, as altered anticoagulant effects and increased bleeding have been reported. 4

Treatment Duration

Continue SSRI treatment for 4-9 months after satisfactory response for first-episode depression; longer duration (≥1 year) is necessary for patients with recurrent episodes to reduce relapse risk. 1, 3

Meta-analysis of 31 trials supports continuation therapy to prevent relapse during the continuation and maintenance phases. 1

Common Pitfalls to Avoid

Do not discontinue prematurely—full response may take 6-8 weeks, and partial response at 4 weeks indicates the medication is working. 3

Do not start with excessively high doses in anxious patients—initial activation or agitation can occur but typically resolves with continued treatment; starting at 25 mg can improve tolerability. 3

Do not ignore the role of psychotherapy—cognitive behavioral therapy or interpersonal therapy should be offered as first-line treatment when available, with SSRIs reserved for patients who lack access, prefer medication, have severe symptoms, or fail psychological interventions. 3

Do not use benzodiazepines as monotherapy—while they may help alleviate insomnia and anxiety acutely, they do not treat depression and carry dependency, withdrawal, and fall risks. 5