Duloxetine Dose Escalation and Aripiprazole Initiation

Increasing Cymbalta (Duloxetine)

Start duloxetine at 30 mg once daily for one week to minimize nausea, then increase to the standard therapeutic dose of 60 mg once daily. 1

Initial dose: 30 mg once daily for 7 days to reduce the risk of nausea, which is the most common side effect 1
Target dose: 60 mg once daily after the first week, which is the standard therapeutic dose for depression and anxiety 2, 1
Maximum dose: Can be increased to 120 mg daily (either 60 mg twice daily or 120 mg once daily) if clinically indicated and the patient tolerates the 60 mg dose 2, 1

If escalating beyond 60 mg once daily, increase to 90 mg once daily for one week, then to 120 mg once daily if needed 3
The majority of adverse events occur during the first week at 60 mg; subsequent dose increases produce few additional side effects 3
Weekly escalation from 60 mg → 90 mg → 120 mg has been shown to be safe and tolerable 3

Monitor blood pressure and pulse regularly, as duloxetine can cause increases in both parameters 1
Common side effects include nausea, dry mouth, headache, constipation, dizziness, fatigue, diaphoresis, and insomnia 2, 1
Gastrointestinal disturbance typically worsens in the first week but improves with continued treatment even as doses increase 3

Elderly or frail patients: Use a slower escalation schedule with a lower initial dose (e.g., 20 mg) 1
Renal insufficiency: Dosage adjustment may be required 2
Hepatic failure: Use with caution 2

Initiate aripiprazole at 2.5-5 mg once daily and titrate slowly based on the clinical indication and patient tolerability.

For augmentation of antidepressants (including duloxetine):

Starting dose: 2.5 mg once daily 4
Target dose: Titrate to 5 mg once daily within 1-2 weeks 4
Maintenance: Most patients respond to 5-10 mg daily for augmentation 5
Aripiprazole augmentation is effective regardless of the primary antidepressant used (including duloxetine, paroxetine, sertraline, escitalopram, mirtazapine) 5

For schizophrenia or bipolar disorder:

Two strategies exist based on symptom severity 6:

Rapid titration/high-dose strategy: For patients with severe, acute symptoms requiring faster control 6
Slow titration/low-dose strategy: For patients with less severe symptoms or those sensitive to side effects 6

Combining aripiprazole with clozapine may reduce clozapine dose requirements, treatment side effects, and residual symptoms 2
Aripiprazole augmentation can be considered for persistent positive or negative symptoms on clozapine 2
For negative symptoms specifically, aripiprazole augmentation is a suitable option in patients not already on a D2 partial agonist 2

Aripiprazole is generally safe and well tolerated 6
Can effectively reduce antipsychotic-induced hyperprolactinemia and has been shown to reduce duloxetine-induced hyperprolactinemia 4
When used with duloxetine at 60 mg once daily plus aripiprazole 5 mg daily, prolactin levels normalized within 8 weeks 4

Aripiprazole can be added to duloxetine after the duloxetine dose has been stabilized at 60 mg once daily 4
If starting both medications, establish duloxetine at 60 mg daily first (after the initial 30 mg week), then add aripiprazole 2.5-5 mg daily 1, 4
Earlier initiation of aripiprazole augmentation (<176 days from depression episode onset) increases likelihood of achieving remission 5

Do not start duloxetine at 60 mg: This significantly increases nausea risk; always start at 30 mg for one week 1
Do not rush aripiprazole titration: Start low (2.5-5 mg) to assess tolerability before increasing 6, 4
Monitor for serotonin syndrome: Duloxetine carries risk, particularly with other serotonergic agents 2
Assess anticholinergic burden: If using aripiprazole for schizophrenia with cognitive symptoms, minimize anticholinergic medications 2