What can be added to Abilify (aripiprazole) and Cymbalta (duloxetine) for a patient with worsening anxiety and depression?

Adding Medication to Abilify and Cymbalta for Worsening Anxiety and Depression

Add lamotrigine (Lamictal) as the primary augmentation strategy for worsening depression, while considering low-dose buspirone or an SSRI for anxiety symptoms, always maintaining the existing mood stabilization with Abilify. 1

Primary Recommendation: Lamotrigine for Depression

Lamotrigine is the most evidence-based addition for patients with bipolar disorder experiencing persistent or worsening depressive symptoms despite treatment with an atypical antipsychotic like Abilify. 1 The American Academy of Child and Adolescent Psychiatry recognizes lamotrigine as FDA-approved maintenance therapy specifically targeting the depressive pole of bipolar disorder, making it superior to other augmentation strategies when depression predominates. 1

Lamotrigine Initiation Protocol

• Start lamotrigine at 25mg daily for weeks 1-2, then increase to 50mg daily for weeks 3-4, then 100mg daily for weeks 5-6, with a target maintenance dose of 200mg daily. 1
• Critical safety requirement: Slow titration is mandatory to minimize risk of Stevens-Johnson syndrome and serious rash—never rapid-load lamotrigine. 1
• If lamotrigine was previously discontinued for more than 5 days, restart with the full titration schedule rather than resuming the previous dose. 1
• Monitor weekly for any signs of rash, particularly during the first 8 weeks of titration. 1

Expected Timeline and Monitoring

• Expect initial response within 4-6 weeks of reaching therapeutic doses (100-200mg daily), with maximal benefit by 8-12 weeks. 1
• Schedule follow-up visits every 1-2 weeks initially during titration, then monthly once stable. 1
• Assess mood symptoms, suicidal ideation, and medication adherence at each visit. 1

Addressing Anxiety Symptoms

First-Line Anxiety Management: Buspirone

For mild-to-moderate anxiety without panic attacks, add buspirone 5mg twice daily, titrating to a maximum of 20mg three times daily. 1 Buspirone provides anxiolytic effects without risk of mood destabilization or dependence, though it requires 2-4 weeks to become effective. 1

Alternative: SSRI Augmentation for Severe Anxiety

If anxiety is severe or includes panic attacks, consider adding an SSRI (sertraline or escitalopram) always in combination with a mood stabilizer to prevent mood destabilization. 1

• Start sertraline 25mg daily or escitalopram 5mg daily as a test dose, increasing to sertraline 50mg or escitalopram 10mg after 3-7 days. 1
• Titrate sertraline by 25-50mg increments every 1-2 weeks to a target of 100-150mg daily, or escitalopram by 5mg increments every 2-3 weeks to a target of 10-20mg daily. 1
• Critical caveat: Antidepressant monotherapy is contraindicated in bipolar disorder due to risk of mood destabilization, mania induction, and rapid cycling—SSRIs must always be combined with Abilify or another mood stabilizer. 1
• Monitor for serotonin syndrome when combining SSRIs with Cymbalta, particularly within the first 24-48 hours after dosage changes, characterized by mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity. 1

PRN Anxiety Management

For breakthrough anxiety episodes, low-dose lorazepam (0.25-0.5mg PRN, maximum 2mg daily) can be used cautiously. 1 Benzodiazepines should be prescribed with clear instructions regarding maximum daily dosage and frequency limitations (not more than 2-3 times weekly for PRN use), with regular monitoring for tolerance or dependence. 1

Aripiprazole's Role in Anxiety

Aripiprazole itself has demonstrated anxiolytic properties through its 5-HT1A partial agonist activity. 2, 3 Open-label trials and retrospective studies show that aripiprazole augmentation of SSRIs produces improvement in anxiety symptoms, with 59% of patients achieving "much improved" or "very much improved" ratings at 15-30mg daily doses. 4 However, monitor carefully for akathisia, which affects approximately 18% of patients with mood disorders on aripiprazole and may paradoxically worsen anxiety. 5 Akathisia can present as increased anxiety, restlessness, or agitation and may be difficult to distinguish from worsening anxiety symptoms. 5

Combination Therapy Considerations

The combination of Abilify (aripiprazole) with lamotrigine provides complementary mechanisms: Abilify addresses acute symptoms and psychotic features while lamotrigine prevents depressive recurrence. 1 This combination has few significant drug interactions, making it a safe regimen. 1

If response remains inadequate after 8 weeks on lamotrigine 200mg plus optimized Abilify dosing, consider adding an SSRI to the mood stabilizer rather than increasing Abilify further. 1

Psychosocial Interventions

Cognitive-behavioral therapy (CBT) should accompany pharmacotherapy, as combination treatment is superior to either treatment alone for both anxiety and depression. 1 CBT has strong evidence for addressing emotional dysregulation, anxiety, and depression components of bipolar disorder. 1 Psychoeducation about symptoms, course of illness, treatment options, and medication adherence improves outcomes. 1

Common Pitfalls to Avoid

• Never add an antidepressant without maintaining adequate mood stabilization—this can trigger manic episodes or rapid cycling. 1
• Avoid rapid titration of lamotrigine, which dramatically increases Stevens-Johnson syndrome risk. 1
• Do not use high-dose benzodiazepines chronically, as this increases risk of tolerance, dependence, and paradoxical worsening of anxiety. 1
• Monitor for behavioral activation with SSRIs (motor restlessness, insomnia, impulsiveness, disinhibited behavior), which is more common in younger patients and can be difficult to distinguish from treatment-emergent mania. 1
• Ensure adequate trial duration (6-8 weeks at therapeutic doses) before concluding a medication is ineffective. 1

Maintenance Therapy

Once mood stabilization is achieved, continue combination therapy for at least 12-24 months, with some patients requiring lifelong treatment. 1 Withdrawal of maintenance therapy dramatically increases relapse risk, with over 90% of noncompliant patients relapsing versus 37.5% of compliant patients. 1