What can be added to Lexapro (escitalopram) 20mg for a patient with anxiety and depression who is not responding to treatment?

Treatment Options for Inadequate Response to Lexapro 20mg in Anxiety and Depression

Add cognitive-behavioral therapy (CBT) to the current Lexapro regimen, as combination therapy demonstrates superior efficacy compared to medication alone and should be the first-line augmentation strategy. 1, 2

Primary Recommendation: Add Psychotherapy

• Augmenting escitalopram with CBT produces larger effect sizes than pharmacological augmentation strategies and addresses both neurobiological and psychological components of anxiety and depression simultaneously. 1
• The American College of Physicians recommends either switching to or augmenting with CBT as a first-line option for patients who fail initial SSRI treatment at adequate doses. 2
• Combination therapy achieves remission rates of approximately 50% compared to 30% with SSRI monotherapy alone. 1
• Allow 8-12 weeks to evaluate response to the combined treatment before considering alternative strategies. 1

If CBT Is Not Available or Feasible: Pharmacological Options

Option 1: Add Bupropion SR (Preferred Pharmacological Augmentation)

• Bupropion SR 150-400mg daily as augmentation therapy is the preferred pharmacological strategy, with similar efficacy to buspirone but significantly lower discontinuation rates due to adverse events (12.5% vs 20.6%, p<0.001). 3, 1
• Bupropion has the additional advantage of lower sexual dysfunction rates compared to continuing SSRI monotherapy. 3
• The STAR*D trial demonstrated that bupropion augmentation achieved similar remission rates to cognitive therapy augmentation. 1

Option 2: Switch to an SNRI

• Switch to venlafaxine extended-release (37.5-225mg daily) or duloxetine (40-120mg daily) if augmentation strategies fail, as SNRIs demonstrate statistically significantly better response and remission rates than SSRIs in treatment-resistant cases. 1, 2
• Venlafaxine addresses both serotonin and norepinephrine reuptake, which may provide greater efficacy for combined anxiety and depression symptoms. 1
• Be aware that SNRIs have higher rates of nausea and vomiting compared to SSRIs. 1

Option 3: Add Buspirone (Alternative Augmentation)

• Buspirone 20mg three times daily (titrated from 5mg twice daily over 2-4 weeks) can be added to escitalopram, though it has higher discontinuation rates than bupropion. 3, 1
• The STAR*D trial showed no significant difference in response or remission between buspirone and bupropion augmentation, but buspirone had significantly more adverse events. 3

Critical Timing and Monitoring Requirements

• Ensure the patient has been on escitalopram 20mg for at least 8-12 weeks before declaring treatment failure, as this is the optimal duration to determine SSRI efficacy. 3, 1
• Assess treatment response every 2-4 weeks using standardized anxiety and depression rating scales (GAD-7, PHQ-9, HAM-A, or MADRS). 1
• Monitor closely for suicidal ideation during the first 1-2 months after any treatment change, as suicide risk is greatest during this period. 3, 1
• Watch for behavioral activation, agitation, or unusual changes in behavior, particularly when adding medications. 1

Bridging Strategy: Consider Short-Term Hydroxyzine

• Hydroxyzine 25-50mg as needed can provide rapid anxiolytic relief during the 4-8 week period required for augmentation strategies to reach full effect, avoiding benzodiazepine-related dependency and cognitive impairment risks. 4
• This is particularly valuable if increasing anxiety occurs when initiating augmentation therapy. 4

Common Pitfalls to Avoid

• Do not switch medications before allowing adequate trial duration (8-12 weeks at 20mg), as premature switching leads to missed opportunities for response. 1
• Do not exceed escitalopram 20mg daily, as higher doses increase QT prolongation risk without additional therapeutic benefit. 1, 5
• Do not combine escitalopram with MAOIs or multiple serotonergic agents beyond the recommended augmentation strategies due to serotonin syndrome risk. 1, 5
• Do not assume combination therapy is needed if the patient has only been on 20mg for less than 8 weeks. 3, 1

Alternative Switching Strategy (If Augmentation Fails)

• The American College of Physicians found no significant difference between switching versus augmenting strategies overall. 3, 1
• If switching is chosen, sertraline, paroxetine, or another SSRI shows similar efficacy, with approximately 25% of treatment-resistant patients becoming symptom-free after switching. 1

Duration of Continuation Therapy

• Continue successful treatment for at least 4-9 months after first episode of major depression. 1
• For recurrent depression (2+ episodes) or chronic anxiety, consider years to lifelong maintenance therapy. 1