When starting an antidepressant, should anxiety symptoms or depressive symptoms be prioritized first in a patient with both anxiety and depressive symptoms?

Treatment Priority: Depression First When Starting Antidepressants

When initiating antidepressant therapy in patients with both anxiety and depressive symptoms, treat the depressive symptoms first, as addressing depression often improves comorbid anxiety symptoms. 1

Evidence-Based Rationale

The American Society of Clinical Oncology guidelines explicitly recommend treating depressive symptoms first when patients present with both conditions, based on high-quality evidence showing that addressing depression frequently resolves comorbid anxiety without requiring separate interventions. 1 This approach is supported by the observation that 50-60% of individuals with diagnosed depressive disorder have comorbid anxiety, making it the most common presentation rather than the exception. 1

Why Depression Takes Priority

Treating depression first is more effective because:

• Anxiety symptoms in depression often represent a manifestation of the underlying depressive disorder rather than a separate condition requiring distinct treatment. 1
• When generalized anxiety disorder accompanies depression, it delays recovery from depression, delays functional recovery, and reduces overall social functioning—making depression treatment the critical first step. 1
• SSRIs effectively treat both conditions simultaneously, eliminating the need to prioritize one symptom cluster over another in most cases. 2, 3

First-Line Medication Selection

Start with sertraline 50 mg daily as the preferred SSRI, as it demonstrates optimal efficacy for both depression and anxiety with superior tolerability compared to other options. 2 Alternative first-line choices include escitalopram or fluoxetine if sertraline is contraindicated or not tolerated. 2

Key Prescribing Details:

• Begin at 50 mg daily (or 25 mg as a "test dose" in highly anxious patients to minimize initial activation). 2
• Increase in 50 mg increments at 1-2 week intervals if response is inadequate, up to maximum 200 mg daily. 2
• Allow 6-8 weeks for adequate trial, including at least 2 weeks at maximum tolerated dose. 2
• Monitor for treatment-emergent suicidality closely during the first 1-2 weeks after initiation or dose changes. 2

Expected Treatment Response

Approximately 38% of patients do not achieve response during the initial 6-12 weeks of SSRI treatment, and 54% do not achieve remission. 2 However, SSRIs are significantly more effective than placebo in treating both anxious and nonanxious major depression, with comparable efficacy across all second-generation antidepressants. 3, 2

The presence of anxiety does not affect antidepressant response rates—fluoxetine demonstrated equivalent efficacy in both anxious and nonanxious depressed patients in meta-analysis of 19 trials involving 3,183 patients. 3

Treatment Duration

Continue SSRI treatment for minimum 4-9 months after satisfactory response for first-episode depression. 2 For patients with recurrent episodes, consider longer duration of ≥1 year or indefinite maintenance therapy, as recurrence probability increases to 50% after first episode, 70% after two episodes, and 90% after three episodes. 2

When to Adjust Strategy

If inadequate response after 6-8 weeks at therapeutic doses (100-200 mg sertraline):

• Switch to venlafaxine extended-release (SNRI), which demonstrated statistically significantly better response rates than fluoxetine specifically for depression with prominent anxiety symptoms. 2, 4
• Add cognitive behavioral therapy, as combination treatment (CBT + SSRI) is superior to either alone for anxiety disorders. 2

Critical Safety Monitoring

• Monitor for suicidality particularly in patients under age 24, as SSRIs carry FDA black box warnings for treatment-emergent suicidal thinking (14 additional cases per 1000 patients treated compared to placebo). 2
• Never combine with MAOIs due to serotonin syndrome risk; allow at least 2 weeks washout when switching. 2
• Taper gradually when discontinuing to minimize discontinuation syndrome, though sertraline has lower risk than paroxetine. 2

Common Pitfalls to Avoid

Do not switch medications prematurely—full response may take 6-8 weeks, and partial response at 4 weeks warrants continued treatment rather than switching. 2 The traditional concept of selecting "activating" versus "sedating" antidepressants based on anxiety presence has little scientific support and should not guide medication selection. 3

Do not prescribe tricyclic antidepressants to patients with suicidal ideation due to high lethality in overdose. 2