Can You Increase Both Abilify and Zoloft at the Same Time?
Yes, you can increase both aripiprazole (Abilify) and sertraline (Zoloft) simultaneously, but this should be done cautiously with close monitoring, particularly in the first 24-48 hours after dosage changes. 1
Safety Considerations for Concurrent Dose Increases
When combining two serotonergic medications, caution is essential. The American Academy of Child and Adolescent Psychiatry guidelines specifically address combining non-MAOI serotonergic drugs and recommend starting the second drug at a low dose, increasing slowly, and monitoring for symptoms especially in the first 24-48 hours after dosage changes 1. While this guidance addresses initiation, the same principle applies to dose adjustments of both medications simultaneously.
Key Monitoring Points:
Watch for serotonin syndrome symptoms within 24-48 hours of dose changes, including mental status changes (confusion, agitation, anxiety), neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 1
Monitor for akathisia and sedation, as aripiprazole can cause akathisia particularly at higher doses 2, 3
Assess blood pressure, as aripiprazole has alpha-adrenergic antagonism that can enhance antihypertensive effects 4
Drug Interaction Profile
The FDA label for aripiprazole explicitly states that no dosage adjustment is necessary for sertraline when co-administered with aripiprazole 4. This indicates these medications can be safely combined without significant pharmacokinetic interactions. Sertraline may interact with drugs metabolized by CYP2D6, but aripiprazole's metabolism is not significantly affected by this pathway in a clinically meaningful way when combined with sertraline 4.
Evidence for Combination Therapy
Aripiprazole augmentation of sertraline is well-established and effective for major depressive disorder. A randomized, double-blind study of 412 patients showed that aripiprazole/sertraline combination (3-12 mg/day aripiprazole with 100 mg/day sertraline) was significantly more efficacious than sertraline alone, with treatment-emergent adverse events being mild to moderate in severity 2. The discontinuation rate due to adverse events was low (1.9% for combination vs 1.5% for sertraline alone) 2.
Low-dose aripiprazole (2.5-5 mg) may be optimal. Meta-analysis evidence suggests the dose-efficacy curve for aripiprazole augmentation shows maximum benefit between 2-5 mg daily, with no additional efficacy at higher doses up to 20 mg 5. Starting with lower doses (2.5 mg) significantly reduced akathisia-related discontinuation compared to starting at 10 mg 6.
Practical Titration Strategy
For sertraline: Increase in the smallest available increments at approximately 1-2 week intervals (as it is a shorter half-life SSRI), monitoring tolerability and response 1
For aripiprazole: If not already at optimal dose, consider increasing gradually while monitoring for akathisia and sedation. The evidence suggests 2-5 mg may be sufficient for augmentation 5, 3
Simultaneous increases: Can be done but require heightened vigilance for the first 24-48 hours, with particular attention to serotonin syndrome symptoms, akathisia, sedation, and blood pressure changes 1, 4
Important Caveats
Avoid this approach if: The patient has a history of serotonin syndrome, is taking MAOIs (contraindicated), has long QT syndrome (sertraline can prolong QT interval), or has demonstrated poor tolerance to either medication previously 1
Consider sequential titration instead if the patient is particularly sensitive to medication changes, has multiple comorbidities, or if you want to clearly attribute any adverse effects to a specific medication change 1