What is a suitable second medication to treat depression in an 81-year-old female patient with chronic kidney disease (CKD), one kidney, bipolar disorder, and a recent suicidal attempt, currently being treated with 10mg of Abilify (aripiprazole)?

Second-Line Antidepressant for Bipolar Depression in Elderly CKD Patient

Add lamotrigine as the second medication to treat depression in this 81-year-old patient with bipolar disorder, CKD, one kidney, and recent suicide attempt currently on aripiprazole 10mg. 1

Rationale for Lamotrigine Selection

Lamotrigine is FDA-approved for maintenance therapy in bipolar I disorder and is particularly effective for preventing depressive episodes, making it the optimal choice for targeting the depressive pole of bipolar disorder. 1 The American Academy of Child and Adolescent Psychiatry recognizes lamotrigine as a rational maintenance therapy option specifically for bipolar depression. 1

Critical Safety Advantages in This Patient

• Renal safety: Unlike many mood stabilizers, lamotrigine does not require dose adjustment in CKD and does not cause further renal impairment. 2
• Metabolic neutrality: Lamotrigine does not cause weight gain or metabolic disturbances, crucial for long-term tolerability in elderly patients. 3
• Minimal drug interactions: Lamotrigine has few significant drug interactions with aripiprazole, making it safe to combine with the current regimen. 1
• Low lethality in overdose: This is particularly important given the recent suicide attempt, as lamotrigine carries significantly lower overdose risk compared to lithium or tricyclic antidepressants. 1

Why NOT Other Options

Avoid SSRIs/SNRIs

• SSRIs are associated with increased risk for nonfatal suicide attempts compared to placebo in patients already at high suicide risk. 4
• Antidepressant monotherapy or inappropriate combination in bipolar disorder carries risk of mood destabilization, mania induction, and rapid cycling. 1
• Hyponatremia risk: SSRIs like citalopram can worsen preexisting hyponatremia in elderly patients, particularly dangerous with CKD. 5
• If an antidepressant is absolutely necessary later, it must always be combined with a mood stabilizer (which lamotrigine provides), with preference for SSRIs like fluoxetine or bupropion over others. 1

Avoid Lithium

• Lithium carries significant overdose risk and requires careful third-person supervision in patients with suicidal history, as lithium overdoses can be lethal. 1
• Renal toxicity: Lithium requires monitoring of renal function every 3-6 months and can worsen kidney function in a patient with only one kidney. 1
• While lithium reduces suicide attempts 8.6-fold and completed suicides 9-fold, the renal and overdose risks outweigh benefits in this specific patient. 1

Avoid Valproate

• Valproate requires hepatic monitoring and carries risk of hepatotoxicity. 4
• Sedation: Valproate is associated with sedation, which may worsen quality of life in elderly patients. 1

Lamotrigine Titration Protocol

CRITICAL: Slow titration is mandatory to minimize risk of Stevens-Johnson syndrome and serious rash. 1, 6

Standard Titration Schedule

• Weeks 1-2: 25mg daily
• Weeks 3-4: 50mg daily
• Weeks 5-6: 100mg daily
• Week 7+: 200mg daily (target maintenance dose) 1

If lamotrigine was discontinued for more than 5 days, restart with the full titration schedule rather than resuming the previous dose to minimize risk of serious rash. 1

Monitoring Requirements

Weekly Monitoring (First 8 Weeks)

• Monitor weekly for any signs of rash, particularly during the first 8 weeks of titration. 1
• Assess mood symptoms, suicidal ideation, and medication adherence at each visit. 1

Ongoing Monitoring

• Schedule follow-up visits every 1-2 weeks initially, then monthly once stable. 1
• Monitor for signs of depression worsening, emergence of manic symptoms, or behavioral changes. 1
• The American College of Physicians recommends assessing patient status, therapeutic response, and adverse effects on a regular basis beginning within 1-2 weeks of initiation of therapy. 4

Expected Timeline and Outcomes

• Adequate trial duration: Continue lamotrigine for at least 8 weeks at target dose (200mg) before concluding ineffectiveness. 1
• Maintenance therapy should continue for at least 12-24 months after mood stabilization; some patients require lifelong treatment. 1
• More than 90% of adolescents who were noncompliant with maintenance therapy relapsed, compared to 37.5% of compliant patients, emphasizing the importance of adherence. 1

Adjunctive Psychosocial Interventions

• Cognitive-behavioral therapy (CBT) has strong evidence for addressing both depression and anxiety components of bipolar disorder. 1
• Psychoeducation about symptoms, course of illness, treatment options, and importance of medication adherence should accompany pharmacotherapy. 1
• Family intervention helps with medication supervision, early warning sign identification, and reducing access to lethal means in patients with suicide risk. 1

Common Pitfalls to Avoid

• Never rapid-load lamotrigine - this dramatically increases risk of Stevens-Johnson syndrome, which can be fatal. 1
• Do not add an SSRI without a mood stabilizer in place first - this risks mood destabilization and mania induction. 1
• Inadequate duration of maintenance therapy leads to high relapse rates exceeding 90% in noncompliant patients. 1
• Failure to monitor for rash during titration can result in missing early signs of serious dermatologic reactions. 1