What alternative treatment options are available for a patient with anxiety and depression who has failed to respond to Lexapro (escitalopram)?

Treatment Options After Lexapro Failure in Anxiety and Depression

For a patient who has failed Lexapro with comorbid anxiety and depression, switch to mirtazapine 15-45mg at bedtime as the first-line option, or alternatively switch to venlafaxine 75-225mg daily if insomnia is not prominent. 1

Primary Switching Strategies

Mirtazapine as Preferred Switch

• Mirtazapine provides statistically significantly faster symptom relief compared to SSRIs and simultaneously addresses anxiety, depression, and insomnia through its sedating properties. 1
• This agent demonstrates faster onset of action than citalopram, fluoxetine, paroxetine, or sertraline, with most response rates becoming similar after 4 weeks of treatment. 2
• Start at 15mg at bedtime and titrate to 45mg based on response. 1

Venlafaxine as Alternative Switch

• Venlafaxine (SNRI) is the alternative switch option when anxiety symptoms are prominent, as it demonstrates superior efficacy compared to fluoxetine for treating anxiety symptoms in patients with depression and comorbid anxiety. 1
• Dose range: 75-225mg daily. 1
• Moderate-quality evidence shows no significant difference in response rates when switching between bupropion, sertraline, or venlafaxine, so the choice should be guided by the patient's specific symptom profile. 2

Augmentation Strategy (If Partial Response to Lexapro)

Bupropion Augmentation

• If the patient had any partial response to Lexapro, augment with bupropion 150-300mg daily rather than switching, as it decreases depression severity more than buspirone and has lower discontinuation rates due to adverse events. 1
• Low-quality evidence shows no difference in response or remission between bupropion and buspirone augmentation of citalopram (Lexapro's parent compound), but bupropion demonstrates superior reduction in depression severity. 2
• Moderate-quality evidence shows discontinuation due to adverse events was lower with bupropion than buspirone. 2

Cognitive Behavioral Therapy Integration

• Add cognitive behavioral therapy (CBT) regardless of medication choice, as low-quality evidence shows no difference between switching to another antidepressant versus switching to cognitive therapy alone. 1
• This equivalence suggests CBT provides comparable efficacy to medication switches and should be offered concurrently. 2

Second-Line Augmentation Options

Atypical Antipsychotic Augmentation

• Consider augmentation with aripiprazole 2-15mg or quetiapine 150-300mg if multiple first-line strategies fail. 1
• This approach is typically reserved after trying switching or bupropion augmentation first. 1

Lithium Augmentation

• Lithium augmentation remains one of the best-documented treatments for treatment-resistant depression, but requires careful monitoring of blood levels and thyroid/renal function. 1

Critical Treatment Verification

Before proceeding, verify that Lexapro was tried at therapeutic doses (10-20mg daily) for a minimum of 4 weeks before declaring treatment failure. 1

• An adequate antidepressant trial requires at least 4 weeks at a licensed dosage. 1
• If previous trials with Cymbalta (duloxetine) and Celexa (citalopram) occurred, confirm each was at therapeutic doses for sufficient duration. 1

Common Pitfalls to Avoid

• Do not add benzodiazepines as a long-term solution—they should be avoided or used only for short duration when absolutely necessary, with preference for slower-onset, longer-acting agents if required. 3
• Do not switch medications prematurely—ensure adequate trial duration and dosing before declaring failure. 1
• Do not overlook psychotherapy—evidence shows switching to cognitive therapy is as effective as switching medications, making combined treatment optimal. 2

Treatment Algorithm Summary

1. If anxiety + insomnia prominent: Switch to mirtazapine 15-45mg at bedtime 1
2. If anxiety without significant insomnia: Switch to venlafaxine 75-225mg daily 1
3. If partial response to Lexapro: Augment with bupropion 150-300mg daily 1
4. All patients: Add cognitive behavioral therapy 1
5. If multiple strategies fail: Consider atypical antipsychotic augmentation (aripiprazole or quetiapine) 1
6. If pharmacological approaches continue to fail: Consider electroconvulsive therapy 1