Can You Increase Mirtazapine and Abilify at the Same Time?
Yes, it is generally safe to increase both mirtazapine and aripiprazole (Abilify) simultaneously, but you should wait at least one week between dose adjustments for aripiprazole when used for depression augmentation, and monitor closely for side effects. 1
Dosing Guidelines for Combined Use
For Aripiprazole (Abilify) in Depression Augmentation:
- Start at 2-5 mg/day when adding to an existing antidepressant
- Increase gradually in 5 mg increments
- Wait at least one week between dose adjustments
- Target range: 2-15 mg/day 1
The FDA labeling explicitly states that "dosage adjustments of up to 5 mg/day should occur gradually, at intervals of no less than one week" for major depressive disorder augmentation 1. This is your primary constraint when adjusting aripiprazole.
For Mirtazapine:
While specific FDA guidance on dose adjustment timing for mirtazapine isn't provided in the evidence, standard practice allows for adjustments every 1-2 weeks after assessing response.
Evidence Supporting Combined Use
The combination of mirtazapine and aripiprazole is well-studied and safe. A 2007 open-label study directly examined this combination (mirtazapine 45 mg/day plus aripiprazole 15 mg/day) and found:
- Comparable antidepressant effects to monotherapy
- Accelerated onset of antidepressant action in treatment-resistant depression
- Aripiprazole reduced mirtazapine-induced weight gain
- Mirtazapine had favorable effects on aripiprazole-induced akathisia
- No significant extrapyramidal side effects 2
Additional research confirms that low-dose mirtazapine (15 mg/day) effectively treats aripiprazole-induced akathisia, with significant reductions in subjective distress 3.
Practical Approach to Simultaneous Dose Increases
If Both Medications Need Adjustment:
Prioritize which medication to adjust first based on clinical presentation:
- If akathisia or restlessness is prominent → increase mirtazapine first
- If inadequate antidepressant response → consider increasing aripiprazole first
If adjusting both simultaneously:
- Increase mirtazapine by standard increments (typically 15 mg)
- Increase aripiprazole by no more than 5 mg
- Wait at least one week before making any further adjustments 1
- Monitor closely for sedation, akathisia, and metabolic effects
Optimal dosing based on recent meta-analysis:
- Aripiprazole shows optimal efficacy at 2-5 mg/day for depression augmentation, with diminishing returns at higher doses 4
- Consider that doses above 5 mg may not provide additional benefit while increasing side effect burden
Important Drug Interaction Considerations
Be aware of CYP450 interactions. If the patient is taking other medications that inhibit CYP2D6 (like fluoxetine, paroxetine) or CYP3A4 (like clarithromycin), aripiprazole levels will be significantly elevated, requiring dose reduction 1. The FDA recommends reducing aripiprazole dose by 50% when combined with strong CYP2D6 or CYP3A4 inhibitors 1.
Monitoring Parameters
Watch for:
- Akathisia (restlessness, inability to sit still) - most common with aripiprazole
- Sedation - additive effect from both medications
- Weight gain - mirtazapine effect, partially offset by aripiprazole 2
- Metabolic changes - blood glucose, lipids
- Orthostatic hypotension - both medications can contribute 1
Common Pitfalls to Avoid
- Don't increase aripiprazole more frequently than weekly - violates FDA dosing recommendations 1
- Don't assume higher aripiprazole doses are better - evidence suggests 2-5 mg may be optimal for depression 4
- Don't ignore akathisia symptoms - this is the most common reason for discontinuation and can be mistaken for worsening anxiety
- Don't forget that aripiprazole takes 2 weeks to reach steady state - premature dose increases may lead to excessive levels 1
The combination is evidence-based and generally well-tolerated, with potential synergistic benefits including mirtazapine's mitigation of aripiprazole-induced akathisia and aripiprazole's reduction of mirtazapine-induced weight gain 2, 3.