What is the interaction between Sertraline (Zoloft), Mirtazapine (Remeron), and Metoclopramide (Reglan)?

From the Guidelines

Zoloft (sertraline), mirtazapine, and Reglan (metoclopramide) should be used together with caution due to the potential for serotonin syndrome, and their combination requires careful monitoring, especially in the first 24 to 48 hours after dosage changes, as noted in the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1. When prescribing these medications together, it is essential to start with low doses and gradually increase them, monitoring for symptoms of serotonin syndrome, such as anxiety, agitation, or changes in mental status.

• Zoloft is an SSRI antidepressant typically started at 25-50mg daily and gradually increased to an effective dose of 50-200mg daily.
• Mirtazapine is another antidepressant often given at 15-45mg at bedtime, which can help with sleep and appetite issues, as described in guidelines for managing Alzheimer's disease 1.
• Reglan is primarily used for gastrointestinal motility disorders and nausea, usually dosed at 5-10mg up to four times daily before meals and at bedtime. The combination of these medications may enhance sedation, as both Zoloft and mirtazapine can cause sedation, and Reglan should generally be used for the shortest duration possible (typically less than 12 weeks) due to the risk of tardive dyskinesia, as mentioned in the guideline for using second-generation antidepressants to treat depressive disorders 1. These medications should only be taken under medical supervision, with regular follow-up to assess effectiveness and monitor for side effects, such as discontinuation syndrome, which has been reported with SSRIs, including sertraline, as noted in the clinical practice guideline 1.

From the FDA Drug Label

Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs with mirtazapine tablets increases the risk of serotonin syndrome.

Intervention Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases If serotonin syndrome occurs, consider discontinuation of mirtazapine tablets and/or concomitant serotonergicdrugs Examples SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, amphetamines, St. John’s Wort, tramadol, tryptophan, buspirone

Key Interactions:

• Zoloft (sertraline) is an SSRI.
• Mirtazapine and sertraline (Zoloft) are serotonergic drugs.
• The concomitant use of serotonergic drugs, including mirtazapine and sertraline, increases the risk of serotonin syndrome.
• Reglan (metoclopramide) is not directly mentioned in the provided drug labels as a serotonergic drug, but it can have interactions with other medications.
• Monitoring is recommended for patients taking mirtazapine and other serotonergic drugs, such as sertraline, due to the increased risk of serotonin syndrome 2.
• Caution should be exercised when combining these medications, and patients should be closely monitored for signs and symptoms of serotonin syndrome 3.

From the Research

Combination Therapies

• The combination of mirtazapine with SSRIs or SNRIs for treatment-resistant depression was investigated in a study 4, which found no convincing evidence of a clinically important benefit for mirtazapine in addition to a SSRI or a SNRI antidepressant over placebo in primary care patients with TRD.
• A study comparing mirtazapine with other antidepressive agents found that mirtazapine was significantly more effective than SSRIs at two weeks and at the end of acute-phase treatment 5.
• Another study evaluated the effect of sertraline with desvenlafaxine and sertraline with mirtazapine on HAM-D score and inflammatory markers in major depressive disorder, and found that both combinations were effective and well tolerated 6.

Individual Medications

• Mirtazapine has a unique mechanism of antidepressive action and is one of the commonly used antidepressants in clinical practice 5.
• Sertraline is a selective serotonin reuptake inhibitor that has been found to be effective in the treatment of major depression 7.
• Reglan (metoclopramide) is not mentioned in the provided studies as a treatment for depression, but it is sometimes used off-label for the treatment of depression-related symptoms such as nausea and vomiting.

Efficacy and Safety

• A study found that mirtazapine was likely to have a faster onset of action than SSRIs during the acute-phase treatment of major depression 5.
• Another study found that sertraline with mirtazapine was effective and well tolerated in MDD patients with moderate to severe depression, and their therapeutic efficacy was accompanied by decreased inflammatory markers 6.
• A study comparing sertraline with other antidepressive agents found that sertraline was generally associated with a higher rate of participants experiencing diarrhoea 7.