What is the next step for a patient experiencing significant side effects, including feelings of being flat and numb, after showing 50% improvement on 20mg of Lexapro (escitalopram)?

Management of Emotional Blunting on Escitalopram 20mg

For a patient experiencing emotional blunting ("flat and numb") despite 50% improvement on escitalopram 20mg after 11 weeks, the optimal next step is to add bupropion as augmentation therapy rather than switching medications, as this preserves the partial therapeutic benefit while directly addressing the emotional blunting side effect. 1

Rationale for Augmentation Strategy

• Bupropion augmentation is the preferred approach because it specifically addresses SSRI-induced emotional blunting and apathy while maintaining the anxiety/depression improvement already achieved 1
• The patient has demonstrated meaningful clinical response (50% improvement), making it preferable to augment rather than abandon this partial success 2
• Escitalopram has minimal effects on cytochrome P450 enzymes, resulting in low risk of drug interactions with bupropion, making this combination pharmacologically safe 1

Bupropion Augmentation Protocol

Starting and titration schedule:

• Start bupropion at 37.5 mg every morning 3
• Increase by 37.5 mg every 3 days as tolerated 3
• Target dose: 150 mg twice daily 1
• Critical timing consideration: Give the second dose before 3 PM to minimize insomnia risk 3, 1

Expected benefits:

• Resolution of emotional blunting and numbness 1
• Activating properties that can improve energy and reduce apathy 3
• Potential additional benefit for residual anxiety symptoms when combined with the SSRI 1

Monitoring and Timeline

• Assess response after 4-6 weeks of combined therapy using standardized assessment tools for both mood symptoms and emotional blunting 1
• Monitor for activation/agitation, particularly in the first few weeks after adding bupropion 4
• Watch for any worsening of anxiety symptoms, though the combination typically addresses this 1

Important Contraindications and Cautions

Bupropion is absolutely contraindicated in:

• Seizure disorders (bupropion lowers seizure threshold) 3, 1
• Patients with eating disorders (bulimia, anorexia nervosa) 3
• Those in acute alcohol or drug withdrawal 3

Additional monitoring considerations:

• Should not be used in highly agitated patients initially 3
• Monitor for potential insomnia (hence the timing of second dose) 3, 1

Alternative Approach: Mirtazapine Augmentation

If bupropion is contraindicated or not tolerated, mirtazapine represents a viable alternative:

• Start at 7.5 mg at bedtime, titrate up to 30 mg 1
• Lower rates of sexual dysfunction and emotional blunting compared to SSRIs 1
• Additional benefits for insomnia and anxiety symptoms 1
• May cause sedation and weight gain, which could be beneficial or problematic depending on the patient's profile 3

If Augmentation Fails After 8-12 Weeks

Consider switching to an SNRI (venlafaxine) or another SSRI:

• Venlafaxine demonstrates superior efficacy in treatment-resistant cases compared to continuing SSRI therapy 2
• SNRIs may have greater effect on both depression and anxiety due to dual serotonin-norepinephrine action 2
• Alternative SSRIs include sertraline or paroxetine, though these may have similar emotional blunting effects 2

Critical Pitfall to Avoid

Do not simply increase the escitalopram dose beyond 20mg - the patient is already at the FDA-approved maximum dose, and higher doses would increase side effects (including emotional blunting) without proportional therapeutic benefit 4. The 20mg dose has already demonstrated efficacy in clinical trials, and the issue here is a side effect profile rather than inadequate dosing 5, 6.

Discontinuation Considerations

If ultimately switching medications becomes necessary, taper escitalopram over 10-14 days to limit withdrawal symptoms including anxiety, irritability, dizziness, and electric shock-like sensations 3, 4. Do not stop abruptly 4.