Safety of Using Strattera (Atomoxetine) and Remeron (Mirtazapine) Together
The combination of Strattera (atomoxetine) and Remeron (mirtazapine) is generally safe when used together, as they work on different neurotransmitter systems with minimal interaction potential.
Mechanism of Action and Potential Interactions
- Strattera (atomoxetine) is a selective norepinephrine reuptake inhibitor that primarily affects norepinephrine neurotransmission with minimal effect on serotonin 1, 2
- Remeron (mirtazapine) is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA) that enhances both noradrenergic and serotonergic neurotransmission 1, 3
- Unlike many antidepressant combinations that might increase risk of serotonin syndrome, this particular combination has a lower risk profile due to mirtazapine's unique mechanism as a 5-HT2 and 5-HT3 antagonist rather than a reuptake inhibitor 3
Metabolism Considerations
- Atomoxetine is primarily metabolized by CYP2D6, with significant differences in metabolism between CYP2D6 extensive metabolizers and poor metabolizers 4, 5
- Mirtazapine is extensively metabolized by the hepatic cytochrome P450 system and excreted mainly in urine 3
- In vitro studies suggest atomoxetine does not significantly inhibit or induce major CYP enzymes at therapeutic doses, reducing the risk of pharmacokinetic interactions 5
- Mirtazapine is unlikely to inhibit the metabolism of coadministered drugs metabolized by CYP1A2, CYP2D6, or CYP3A4 3
Safety Profile
- Both medications individually have favorable safety profiles with different side effect patterns 2, 3
- Atomoxetine may cause slight increases in heart rate and blood pressure, but these changes are generally not clinically significant 2
- Mirtazapine is well-tolerated with its primary side effects being sedation (especially at lower doses) and potential weight gain 1, 3
- Mirtazapine overdoses are generally well-tolerated with drowsiness being the most common symptom 6
Monitoring Recommendations
- Monitor for potential additive effects on noradrenergic symptoms such as increased heart rate, blood pressure changes, or insomnia 2, 3
- Be aware that mirtazapine's sedative effects (particularly at lower doses) may counteract any activating effects of atomoxetine 1, 3
- Patients with hepatic or renal impairment may require dose adjustments as both medications are metabolized by the liver and excreted through the kidneys 4, 3
Common Pitfalls and Caveats
- Avoid combining either medication with monoamine oxidase inhibitors (MAOIs) as this could lead to serious adverse effects 1
- Unlike some other antidepressant combinations, this particular combination does not carry a significant risk of serotonin syndrome 3
- Atomoxetine carries a black box warning for suicidal ideation, so monitor for changes in mood or behavior, especially when initiating treatment 2
- Mirtazapine has historically been associated with rare cases of neutropenia, though post-marketing surveillance has shown this to be extremely uncommon 3