What medication should be added to a patient's current regimen of Abilify (aripiprazole) 15 mg, Lamictal (lamotrigine) 25 mg daily, and Naltrexone 50 mg daily, who has a history of multiple suicide attempts and continues to report severe depression?

Medication Management for Severe Depression with Suicidal History

For a patient on Abilify 15 mg, Lamictal 25 mg, and Naltrexone 50 mg daily who is reporting severe depression (10/10) with a history of multiple suicide attempts, I strongly recommend adding an SSRI antidepressant, specifically sertraline (Zoloft), starting at 50 mg daily and titrating up to 200 mg as needed based on response and tolerability.

Current Medication Analysis

The patient's current regimen includes:

• Abilify (aripiprazole) 15 mg - an atypical antipsychotic with partial dopamine agonist properties
• Lamictal (lamotrigine) 25 mg - a mood stabilizer, but at a subtherapeutic dose
• Naltrexone 50 mg - an opioid antagonist typically used for alcohol/opioid use disorders

Key Issues with Current Regimen:

1. Lamotrigine dose is subtherapeutic (therapeutic range typically 100-200 mg)
2. No dedicated antidepressant in the regimen
3. Continued severe depression despite current medications

Recommended Medication Adjustments

1. Add an SSRI Antidepressant

• First choice: Sertraline (Zoloft)
  • Starting dose: 50 mg daily
  • Target dose: 150-200 mg daily
  • Rationale: SSRIs are recommended as first-line agents for major depressive disorder 1

2. Optimize Lamotrigine Dosing

• Increase Lamictal to therapeutic levels (100-200 mg) through standard titration schedule:
  • Week 1-2: 25 mg daily (current dose)
  • Week 3-4: 50 mg daily
  • Week 5-6: 100 mg daily
  • Week 7+: 150-200 mg daily as needed
• Rationale: Subtherapeutic dosing may be contributing to treatment failure

Evidence Supporting This Approach

The American College of Physicians recommends second-generation antidepressants as a first-line treatment for major depressive disorder 1. For patients with severe depression and suicidal history, medication management is particularly important.

SSRIs have demonstrated efficacy in reducing suicidal ideation 1, with evidence suggesting they can significantly improve a wide range of depressive symptoms, including suicidality, within the first week of treatment 2.

While there has been controversy regarding SSRIs and suicidality, meta-analyses have not supported increased risk in adults 1. In fact, studies suggest that antidepressant treatment may reduce suicide risk in adults with major depression 3.

Monitoring and Follow-up

1. Close monitoring is essential:

   • Assess response within 1-2 weeks of starting treatment 1, 3
   • Monitor specifically for:
     • Changes in suicidal thoughts or behaviors
     • Emergence of agitation, irritability, or unusual behavior changes
     • Treatment response using standardized scales (e.g., PHQ-9)

2. Warning signs requiring immediate attention 1:

   • New or more frequent thoughts of wanting to die
   • Self-destructive behaviors
   • Increased anxiety, panic, agitation, or impulsivity
   • New onset of akathisia (restlessness)
   • Extreme elation or energy

Alternative Considerations

If the patient does not respond to an SSRI or experiences intolerable side effects:

1. Consider an SNRI such as venlafaxine or milnacipran, which has shown rapid improvement in depressive symptoms including suicidality in suicide attempters 2

2. Consider lithium augmentation for patients with recurrent suicidal behavior, as lithium has demonstrated specific antisuicidal properties 4

3. Consider ECT for severe, treatment-resistant depression with acute suicidal risk 5

Important Cautions

• Avoid tricyclic antidepressants due to their high lethality in overdose for patients with suicidal history 6
• Monitor closely during the first 1-2 months of treatment when suicide risk may be elevated 1
• Ensure the patient has adequate support and emergency resources

This treatment approach prioritizes both the immediate need to address severe depression and the long-term goal of reducing suicide risk, with careful attention to medication selection based on safety profile and efficacy evidence.