Management of GAD and MDD on Cymbalta 90mg and Abilify 5mg
Direct Recommendation
Assess therapeutic response at this 1-month mark; if inadequate response persists at 6-8 weeks, consider switching to a different second-generation antidepressant (such as bupropion, sertraline, or venlafaxine) or augmenting with cognitive behavioral therapy, as there is no evidence that doses above 60mg duloxetine provide additional benefit for GAD or MDD. 1, 2
Assessment Timeline and Next Steps
Immediate Actions (1-2 Week Intervals)
- Monitor closely for therapeutic response, adverse effects, suicidal ideation, agitation, irritability, or unusual behavioral changes at 1-2 week intervals, as the risk for suicide attempts is greatest during the first 1-2 months of treatment 1
- The current duloxetine dose of 90mg exceeds the evidence-based maximum effective dose of 60mg once daily for both GAD and MDD 2, 3
- There is no evidence that duloxetine doses greater than 60mg/day confer additional benefits, even in non-responders, and higher doses are associated with increased adverse reactions 2
Decision Point at 6-8 Weeks
If inadequate response after 6-8 weeks of treatment, modify the regimen as this represents an adequate treatment trial 1
The response rate to initial antidepressant therapy may be as low as 50%, and approximately 38% of patients do not achieve treatment response during 6-12 weeks, with 54% not achieving remission 1
Treatment Modification Options
Option 1: Switch Antidepressants (Preferred Strategy)
Switch from duloxetine to an alternative second-generation antidepressant such as:
- Bupropion sustained-release
- Sertraline
- Venlafaxine extended-release
Moderate-quality evidence shows no difference in response rates when switching between these agents (bupropion vs. sertraline vs. venlafaxine), with approximately 1 in 4 patients becoming symptom-free after switching 1
Option 2: Augment with Psychotherapy
Add cognitive behavioral therapy (CBT) to the current medication regimen 1
- Moderate-quality evidence shows SGAs plus CBT combination therapy is as effective as monotherapy for response and remission 1
- Some evidence suggests combination therapy may improve work-functioning measures compared to medication alone 1
Option 3: Continue Current Regimen with Dose Adjustment
Reduce duloxetine from 90mg to 60mg once daily while maintaining aripiprazole 5mg 2
- The FDA-approved dosing for GAD is 60mg once daily (may start at 30mg for 1 week) 2
- For MDD, the recommended dose is 40-60mg/day, with no evidence that 120mg/day provides additional benefit beyond 60mg/day 2
- The current aripiprazole 5mg dose is appropriate as adjunctive therapy for MDD 4
Regarding the Aripiprazole Component
The aripiprazole 5mg is appropriately dosed as adjunctive therapy for MDD 4
- Aripiprazole as adjunctive therapy to antidepressants demonstrated clinically meaningful efficacy in three large-scale trials for MDD 4
- The medication is safe and well tolerated, with minimal weight gain trend over 6 weeks 4
- Akathisia incidence is higher than in schizophrenia trials but most cases are mild to moderate 4
Common Pitfalls to Avoid
Do not continue escalating duloxetine beyond 60mg expecting additional benefit, as this only increases adverse effects without improving efficacy 2, 3
Do not wait beyond 8 weeks to modify treatment if response is inadequate, as prolonged inadequate treatment delays recovery 1
Do not abruptly discontinue duloxetine if switching medications; taper appropriately to minimize discontinuation-emergent adverse events (nausea, dizziness) 3
Duration of Successful Treatment
Once adequate response is achieved, continue treatment for 4-9 months minimum for a first episode of MDD 1
For patients with 2 or more previous depressive episodes, consider years to lifelong maintenance therapy to prevent relapse and recurrence 1