What is the recommended treatment plan for a 35-year-old male with a history of Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD), currently on Abilify (Aripiprazole) 5mg and Cymbalta (Duloxetine) 90mg?

Treatment Plan for 35-Year-Old Male with MDD and GAD on Abilify 5mg and Cymbalta 90mg

Current Regimen Assessment and Recommendation

Continue the current combination of duloxetine (Cymbalta) 90mg and aripiprazole (Abilify) 5mg, as this represents evidence-based augmentation therapy for treatment-resistant depression, and reassess response at 6-8 weeks from any recent dose adjustment. 1, 2

Rationale for Current Medications

Duloxetine 90mg for MDD and GAD

• Duloxetine is FDA-approved and guideline-recommended as first-line treatment for both MDD and GAD, making it an ideal choice for this patient with both conditions 3, 4
• The current dose of 90mg is within the therapeutic range (60-120mg daily), though the FDA label states there is no evidence that doses greater than 60mg/day confer additional benefits for MDD 3
• For GAD in adults under 65, duloxetine 60mg once daily is the recommended starting dose, with potential increases to 120mg if needed 3, 4
• Real-world evidence demonstrates significant improvement in illness severity, pain, and quality of life with duloxetine in both MDD and GAD patients 5

Aripiprazole 5mg as Augmentation

• Aripiprazole augmentation is appropriate for patients who have not achieved adequate response to antidepressant monotherapy 1, 2
• The 5mg dose is a reasonable starting point for augmentation, though typical augmentation doses range from 2-15mg daily
• This suggests the patient likely had inadequate response to duloxetine alone, warranting the augmentation strategy

Treatment Monitoring Algorithm

Step 1: Assess Current Response (Now)

• Evaluate treatment response using standardized measures (PHQ-9 or HAM-D scores) 2
• Determine if patient has achieved:
  • Response: ≥50% reduction in depressive symptoms 1
  • Remission: Average symptom scores reduced to minimal levels 1
• If inadequate response after 6-8 weeks at current doses, modification is required 1

Step 2: If Inadequate Response After 6-8 Weeks

Option A: Optimize Duloxetine Dose

• Consider increasing duloxetine to 120mg daily if tolerability allows 3, 4
• Monitor for dose-dependent side effects (nausea, dizziness, sedation) 4

Option B: Optimize Aripiprazole Dose

• Consider increasing aripiprazole dose incrementally (typical augmentation range 2-15mg)
• Monitor for akathisia, weight gain, and metabolic effects

Option C: Switch Strategies

• If no response after adequate trials, consider switching to alternative second-generation antidepressant (bupropion, sertraline, or venlafaxine) 2
• Moderate-quality evidence shows no difference between switching options 2

Step 3: If Adequate Response

• Continue current treatment for 4-9 months after achieving satisfactory response for first episode of MDD 1
• For patients with 2 or more depressive episodes, continue treatment for years to lifelong 1
• Continue monitoring for GAD symptoms, as duloxetine provides sustained long-term benefit 4, 6

Critical Monitoring Parameters

Adverse Effects to Monitor

• Nausea (most common with duloxetine, typically improves after initial weeks) 4
• Sexual dysfunction (common with SNRIs) 2
• Suicidal ideation (monitor closely, especially in first 1-2 months and at dose changes) 1
• Blood pressure (duloxetine can cause increases; use with caution in cardiac disease) 1
• Discontinuation syndrome (if stopping duloxetine, taper gradually) 4

Frequency of Monitoring

• Begin monitoring 1-2 weeks after any treatment change 1
• Assess for agitation, irritability, or unusual behavioral changes (may indicate worsening depression) 1
• Risk for suicide attempts is greatest during first 1-2 months of treatment 1

Common Pitfalls to Avoid

• Do not underdose: Ensure adequate trial of 6-8 weeks at therapeutic dose before declaring treatment failure 1, 2
• Do not abruptly discontinue duloxetine: Taper to prevent discontinuation-emergent adverse events (nausea, dizziness occur in up to one-third of patients) 4
• Do not ignore drug interactions: Duloxetine is metabolized by CYP1A2 and CYP2D6; avoid potent CYP1A2 inhibitors 4
• Do not overlook comorbid conditions: GAD has high comorbidity with MDD (62%), making duloxetine's dual indication particularly valuable 7

Adjunctive Treatment Considerations

Non-Pharmacological Options

• Consider adding Cognitive Behavioral Therapy (CBT), which has similar efficacy to antidepressants with fewer side effects and lower relapse rates 8, 2
• Structured exercise programs show no difference in remission rates compared to sertraline monotherapy and can be added to current regimen 8
• CBT combined with pharmacotherapy may provide broader benefits for moderate to severe depression 8

If Treatment Resistance Persists

• After failure of two adequate trials, consider specialized approaches including alternative augmentation strategies or referral to psychiatry 2
• Psychotherapy (CBT, interpersonal therapy) combined with medication may be beneficial 1, 8