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

From the Guidelines

Mirtazapine is most effectively combined with SSRIs like sertraline or SNRIs like venlafaxine to enhance treatment effectiveness for depression or anxiety disorders. When considering medications to use in conjunction with mirtazapine, it's essential to prioritize combinations that have shown efficacy and safety in clinical practice.

Medication Combinations

• SSRIs like sertraline (50-200mg daily) or fluoxetine (20-60mg daily) can provide complementary antidepressant effects when used alongside mirtazapine, as evidenced by studies showing similar response rates among different second-generation antidepressants 1.
• SNRIs such as venlafaxine (75-225mg daily) are also effective combinations, with some studies suggesting greater response rates with venlafaxine than with other second-generation antidepressants 1.
• For patients with treatment-resistant depression, adding bupropion (150-300mg daily) can be beneficial as it works through different neurotransmitter systems.

Considerations for Combination Therapy

When combining medications, it's crucial to start with lower doses and gradually increase while monitoring for side effects, particularly serotonin syndrome when combining with other serotonergic agents. Regular follow-up appointments are essential to assess effectiveness and manage any adverse effects. The choice of a specific pharmacological agent should be directed by symptom pattern, treatment goals, past treatment responses, patient preference, cost, availability of other treatments, comorbid conditions, contraindications, concurrent medication interactions, and side effects 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 increased mirtazapine dose 2
• CYP Enzyme Inhibitors: cimetidine and ketoconazole, may require decreased mirtazapine dose 2

From the Research

Medications to Use in Conjunction with Mirtazapine

• Mirtazapine can be combined with selective serotonin reuptake inhibitors (SSRIs) or serotonin-noradrenaline reuptake inhibitors (SNRIs) for treatment-resistant depression, as seen in the MIR RCT study 3.
• The combination of mirtazapine and venlafaxine has been suggested as a treatment option for difficult to treat depressive illness, with clinical response rates of 44% at 4 weeks and 50% at 8 weeks 4.
• A systematic review and dose-response meta-analysis found that the lower range of the licensed dose of SSRIs, venlafaxine, and mirtazapine achieves the optimal balance between efficacy, tolerability, and acceptability in the acute treatment of major depression 5.
• An umbrella review on systematic reviews found that escitalopram was more effective than other defined SSRIs in terms of response rate, remission rate, and withdrawal rate 6.
• A study on the antinociceptive activity of SSRIs and atypical antidepressants found that fluoxetine, mirtazapine, and venlafaxine have antinociceptive activity, whereas escitalopram does not, and their site of action seems to be the same as that of opioid analgesics 7.

Potential Combinations

• Mirtazapine and SSRIs (e.g. escitalopram, fluoxetine) 3, 5, 6
• Mirtazapine and SNRIs (e.g. venlafaxine) 3, 4, 5
• Mirtazapine and atypical antidepressants (e.g. venlafaxine, fluoxetine) 4, 5, 7

Considerations

• The efficacy and tolerability of combining mirtazapine with other medications should be carefully evaluated, as the evidence is not always conclusive 3, 5.
• The optimal dose of mirtazapine and other medications should be determined based on individual patient needs and response 5.
• The potential for adverse effects and interactions should be carefully monitored when combining mirtazapine with other medications 3, 4, 7.