What medications can be used in conjunction with mirtazapine (Remeron)?

From the Guidelines

Mirtazapine is most effectively combined with selective serotonin reuptake inhibitors (SSRIs) like sertraline or escitalopram, or serotonin-norepinephrine reuptake inhibitors (SNRIs) like venlafaxine, to enhance treatment outcomes for depression and anxiety disorders. When considering combinations, it's crucial to start with low doses and gradually increase them while monitoring for potential side effects such as increased sedation, weight gain, or serotonin syndrome 1. The choice of medication to combine with mirtazapine should be based on the patient's specific symptoms, medical history, and potential drug interactions. For example, SSRIs like sertraline (50-200mg daily) or escitalopram (10-20mg daily) can provide complementary antidepressant effects through different mechanisms. SNRIs such as venlafaxine (75-225mg daily) are also effective combinations, especially for patients with both depression and pain symptoms.

Key Considerations for Combination Therapy

• Monitor for side effects: Regularly assess patients for increased sedation, weight gain, or signs of serotonin syndrome when combining mirtazapine with other medications.
• Start with low doses: Gradually increase doses of the combined medications to minimize the risk of adverse effects.
• Consider patient preferences and medical history: Choose medications that align with the patient's specific needs and health status.
• Regular follow-up: Assess patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis, beginning within 1 to 2 weeks of initiation of therapy 1.

Medication Options for Combination Therapy

• SSRIs: sertraline (50-200mg daily), escitalopram (10-20mg daily)
• SNRIs: venlafaxine (75-225mg daily)
• Other options: bupropion (150-300mg daily) for treatment-resistant depression, or low-dose antipsychotics like quetiapine (25-300mg daily) or aripiprazole (2-15mg daily) for augmentation. Always consult with a healthcare provider before combining medications, considering individual factors like medical history and potential drug interactions 1.

From the FDA Drug Label

Patients should be made aware of a potential increased risk for serotonin syndrome if concomitant use of mirtazapine with other serotonergic drugs, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John's wort, is clinically warranted, particularly during treatment initiation and dose increases If concomitant use of mirtazapine with other serotonergic drugs, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John's wort, is clinically warranted, be aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases

Medications to Avoid or Use with Caution:

• Serotonergic drugs: triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John's wort, due to the risk of serotonin syndrome 2
• Monoamine Oxidase Inhibitors (MAOIs): contraindicated due to the risk of serotonin syndrome 2
• CYP Enzyme Inducers: phenytoin, carbamazepine, and rifampicin, may require an increase in mirtazapine dose 2
• CYP Enzyme Inhibitors: cimetidine, may require a decrease in mirtazapine dose 2

From the Research

Medications to Use in Conjunction with Mirtazapine

• Bupropion: This medication can be used in conjunction with mirtazapine, as it has a different mechanism of action, targeting the norepinephrine and dopamine neurotransmitters 3.
• Trazodone: Trazodone can be used in combination with mirtazapine, as it has a different pharmacological profile, with antagonistic effects on the 5-HT2A and 5-HT2C receptors 3, 4.
• Vortioxetine: This medication can be used in conjunction with mirtazapine, as it has a unique mechanism of action, targeting the serotonin transporter and 5-HT1A receptor 3.
• Vilazodone: Vilazodone can be used in combination with mirtazapine, as it has a different pharmacological profile, with selective serotonin reuptake inhibition and 5-HT1A receptor partial agonism 3.
• Lithium: Lithium can be used as an augmentation strategy for patients with major depressive disorder who do not respond to first-line treatment, including mirtazapine 5.
• Atypical antipsychotics: Atypical antipsychotics, such as olanzapine, quetiapine, aripiprazole, and risperidone, can be used as an augmentation strategy for patients with major depressive disorder who do not respond to first-line treatment, including mirtazapine 5.

Considerations for Combination Therapy

• The combination of mirtazapine with other antidepressants may significantly lessen the drawbacks of delayed therapeutic response and persistence of depressive symptoms 6.
• The side effects of mirtazapine can be partially neutralized by the pharmacodynamic activity of other antidepressants, while mirtazapine can ameliorate the serious adverse effects of other medications 6.
• The choice of medication to use in conjunction with mirtazapine should be based on the individual patient's needs and medical history, as well as the potential benefits and risks of combination therapy 3, 4, 7, 6, 5.