What medication can be used for augmentation in a patient taking 600 mg of lithium (lithium) daily without increased anxiety?

Antidepressant Augmentation for Lithium-Treated Patient

For a 21-year-old patient on 600 mg lithium daily without increased anxiety, an SSRI (particularly sertraline 25-50 mg/day or citalopram 10 mg/day) represents the most appropriate augmentation strategy, as lithium is specifically indicated to augment antidepressant drugs and this combination is well-established for treatment-resistant depression. 1

Rationale for SSRI Selection

The evidence clearly supports that lithium can be used to augment antidepressant drugs 1, but the clinical scenario here is reversed—the patient is already on lithium, so we need to add an antidepressant to complete the therapeutic combination.

First-Line SSRI Options:

• Sertraline: Start 25-50 mg daily, well-tolerated with less effect on metabolism of other medications compared to other SSRIs 1

  • Maximum dose: 200 mg/day 1
  • Can be given morning or evening 1

• Citalopram: Start 10 mg daily, well-tolerated with some patients experiencing nausea and sleep disturbances 1

  • Maximum dose: 40 mg/day 1

Why SSRIs Are Preferred in This Context:

• The patient is not experiencing increased anxiety, which makes activating SSRIs appropriate 1
• SSRIs have favorable tolerability profiles in young adults 1
• The lithium-SSRI combination is supported by robust evidence for treatment-resistant depression 2, 3, 4, 5

Lithium Augmentation Evidence Base

The current lithium dose of 600 mg daily is appropriate for augmentation purposes:

• Therapeutic lithium levels for augmentation: 0.2-0.6 mEq/L are generally adequate 1
• Low-dose lithium augmentation (300-450 mg/day achieving plasma levels of 0.33±0.09 mEq/L) has shown 51% response rates in treatment-resistant depression 2
• The patient's 600 mg daily dose likely achieves appropriate augmentation levels without requiring the higher doses (900 mg/day, 0.5-0.8 mEq/L) traditionally used for mood stabilization 2, 5

Alternative Augmentation Options

If SSRIs are contraindicated or ineffective:

Second-Line Options:

• Bupropion: 37.5 mg every morning, increase by 37.5 mg every 3 days to maximum 150 mg twice daily 1

  • Activating with possible rapid improvement of energy level 1
  • Avoid if patient has seizure disorders 1
  • Give second dose before 3 PM to minimize insomnia risk 1

• Mirtazapine: 7.5 mg at bedtime, maximum 30 mg at bedtime 1

  • Potent and well-tolerated, promotes sleep and appetite 1
  • Useful if patient has comorbid insomnia or poor appetite 1

Critical Monitoring Considerations

For Lithium:

• Monitor lithium levels to maintain 0.2-0.6 mEq/L for augmentation 1
• Watch for neurotoxicity, particularly at higher doses 1

For SSRI Addition:

• Allow 4-8 weeks for full therapeutic trial of the antidepressant-lithium combination 1
• Monitor for serotonin syndrome when combining lithium with SSRIs 1
• Assess response using standardized scales 2

Common Pitfalls to Avoid

• Do not use nefazodone due to hepatotoxicity risk, despite its efficacy in anxiety 1
• Avoid fluvoxamine if patient takes benzodiazepines (alprazolam/triazolam) due to significant drug interactions 1
• Do not discontinue lithium prematurely—responders should maintain the combination for minimum 12 months 5
• Most responses to lithium augmentation occur within 2 weeks, with 76% showing rapid response (up to 7 days) 2

Duration of Treatment

• Minimum trial period: 4-8 weeks for adequate assessment 1
• Maintenance duration: If response achieved, continue combination for at least 12 months 5
• After 9 months, consider dose reduction to reassess need for continued medication 1