From the Guidelines
Mirtazapine can cause hyponatremia, and patients taking this medication should be closely monitored for signs of hyponatremia, especially during the first few weeks of treatment and after dose increases. According to the most recent and highest quality study available, which is from 2018 1, the management of hyponatremia includes discontinuation or dose reduction of mirtazapine, fluid restriction, and in severe cases, administration of hypertonic saline. The mechanism behind mirtazapine-induced hyponatremia likely involves inappropriate antidiuretic hormone secretion (SIADH).
Some key points to consider when managing patients on mirtazapine include:
- Monitoring serum sodium levels regularly, especially in high-risk patients such as the elderly, females, and those with a history of hyponatremia
- Being aware of the symptoms of hyponatremia, which can include headache, confusion, nausea, seizures, and in severe cases, coma
- Considering alternative treatments for patients who develop hyponatremia while taking mirtazapine
- Using vasopressin receptor antagonists, such as tolvaptan and conivaptan, with caution and close monitoring, as they can be effective in managing hyponatremia but also have potential side effects 1
It's also important to note that the risk of hyponatremia with mirtazapine is generally considered to be lower than with other antidepressants, such as SSRIs and SNRIs. However, clinicians should still remain vigilant and monitor patients closely, particularly those at high risk of developing hyponatremia.
In terms of specific management strategies, the 2018 study 1 suggests that conivaptan and tolvaptan can be effective in managing hyponatremia, but should be used with caution and close monitoring due to potential side effects. The study also notes that satavaptan, another vasopressin receptor antagonist, can be effective in improving hyponatremia and ascites in patients with liver cirrhosis, but should be used with caution due to potential side effects and the need for close monitoring.
Overall, the key takeaways are to closely monitor patients on mirtazapine for signs of hyponatremia, to be aware of the potential risks and benefits of different management strategies, and to use vasopressin receptor antagonists with caution and close monitoring.
From the FDA Drug Label
Hyponatremia has been reported very rarely with the use of mirtazapine. Caution should be exercised in patients at risk, such as elderly patients or patients concomitantly treated with medications known to cause hyponatremia. Mirtazapine may cause hyponatremia, although it is very rare.
- Caution is advised when prescribing mirtazapine to patients at risk, including:
- Elderly patients
- Patients taking medications known to cause hyponatremia 2
From the Research
Mirtazepine and Hyponatremia
- Mirtazepine has been associated with hyponatremia, particularly in elderly patients 3, 4, 5.
- The incidence of mirtazapine-induced hyponatremia is estimated to be around 3.26% 4.
- Hyponatremia typically occurs within a mean of 6.5 days after starting mirtazapine, with doses as low as 7.5 mg daily 3.
- The mean sodium nadir is around 117.2 mEq/L, and the mean time to recovery is approximately 11 days after stopping mirtazapine 3.
- The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most probable underlying cause of mirtazapine-induced hyponatremia 4.
- Clinical manifestations of hyponatremia include confusion, somnolence, and altered speech 4.
- Mirtazapine appears to be safe for use in high-risk, elderly patients, but close monitoring of sodium levels is recommended 6.
- The risk of hyponatremia with mirtazapine is greater than what was reported in the literature, but confounding by indication cannot be ruled out 7.
- A significant linear correlation was found between the adjusted reporting odds ratios for hyponatraemia and pKi for the adrenergic receptors α1 and α2 7.