Can mirtazapine and sertraline be given together?

From the Guidelines

Yes, mirtazapine and sertraline can be given together, and this combination is sometimes prescribed for patients with depression who haven't responded adequately to a single antidepressant. This approach, known as antidepressant augmentation or combination therapy, takes advantage of the different mechanisms of action of these medications. Sertraline is a selective serotonin reuptake inhibitor (SSRI) that primarily increases serotonin levels, while mirtazapine works differently by affecting both serotonin and norepinephrine systems through different receptors. When used together, typical dosing might include sertraline 50-200 mg daily and mirtazapine 15-45 mg at bedtime. Patients should be aware that this combination may increase the risk of serotonin syndrome, though this is relatively uncommon at standard doses. Side effects to watch for include increased sedation (particularly from mirtazapine), weight gain, dry mouth, and dizziness. This combination should always be initiated and monitored by a healthcare provider who can adjust doses based on response and tolerability, and patients should report any unusual symptoms promptly.

Some key points to consider when prescribing this combination include:

• Monitoring for signs of serotonin syndrome, such as agitation, confusion, rapid heart rate, and changes in blood pressure 1
• Adjusting doses based on response and tolerability, as some patients may experience increased side effects 1
• Being aware of the potential for increased sedation, particularly when combining mirtazapine with other sedating medications 1
• Considering the potential benefits of combination therapy, including improved response rates and reduced symptoms of depression 1

Overall, the combination of mirtazapine and sertraline can be a useful treatment option for patients with depression who have not responded to single antidepressant therapy. However, it is essential to carefully monitor patients for potential side effects and adjust treatment as needed to ensure optimal outcomes.

From the FDA Drug Label

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including mirtazapine, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St John's wort), and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). 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

Mirtazapine and sertraline can be given together, but with caution due to the potential increased risk of serotonin syndrome. Patients should be monitored for the emergence of serotonin syndrome, and treatment with mirtazapine and sertraline should be discontinued immediately if symptoms occur 2.

From the Research

Combination of Mirtazapine and Sertraline

• The combination of mirtazapine and sertraline has not been directly studied in the provided evidence for its safety or efficacy.
• However, both mirtazapine and sertraline are known to affect serotonin levels in the body, with mirtazapine acting as a serotonin antagonist and sertraline as a selective serotonin reuptake inhibitor (SSRI) 3, 4.
• The risk of serotonin syndrome, a potentially fatal condition, is a concern when combining serotonergic agents, as seen in cases involving SSRIs and other medications that increase serotonin activity 3, 5, 6, 7, 4.

Serotonin Syndrome Risk

• Serotonin syndrome has been reported in cases where SSRIs, such as sertraline, were combined with other medications that affect serotonin levels, including monoamine oxidase inhibitors, bupropion, metoclopramide, and tramadol 3, 5, 6, 7, 4.
• Mirtazapine, when combined with other serotonergic agents like venlafaxine and tramadol, has also been implicated in cases of serotonin syndrome 4.
• The combination of mirtazapine and sertraline may pose a similar risk, although direct evidence is not provided in the studies referenced 3, 5, 6, 7, 4.

Clinical Considerations

• Clinicians should be aware of the potential risk of serotonin syndrome when considering the combination of mirtazapine and sertraline, or when adding either medication to a regimen that includes other serotonergic agents 3, 5, 6, 7, 4.
• Careful monitoring of patients for signs of serotonin syndrome, such as agitation, confusion, myoclonus, hyperreflexia, and changes in vital signs, is essential when combining these medications 3, 5, 6, 7, 4.