Can mirtazapine cause hyponatremia (low sodium levels)?

From the Guidelines

Yes, mirtazapine can cause hyponatremia, though it occurs less frequently compared to other antidepressants. Hyponatremia (low sodium levels in the blood) is a potential side effect of mirtazapine therapy, particularly in elderly patients, those taking diuretics, or patients with pre-existing conditions like heart failure or cirrhosis. The mechanism involves inappropriate antidiuretic hormone secretion (SIADH), where the body retains too much water, diluting sodium concentration in the blood. Symptoms of hyponatremia may include headache, confusion, nausea, muscle weakness, seizures, and in severe cases, coma. Patients starting mirtazapine should be monitored for these symptoms, especially during the initial weeks of treatment or after dose adjustments. Risk factors include older age, female gender, low body weight, and concomitant use of other medications that can affect sodium levels. Regular monitoring of sodium levels may be warranted in high-risk patients. If hyponatremia develops, treatment options include fluid restriction, sodium supplementation, or in severe cases, discontinuation of mirtazapine and switching to an alternative antidepressant with lower risk of hyponatremia. According to the study by the American College of Physicians 1, evidence evaluating adverse events, such as hyponatremia, is scarce but should be kept in mind when patients are being treated with a second-generation antidepressant.

Some key points to consider:

• Mirtazapine had a faster onset of action than fluoxetine, paroxetine, or sertraline 1
• The most commonly reported adverse events were constipation, diarrhea, dizziness, headache, insomnia, nausea, sexual adverse events, and somnolence 1
• Nausea and vomiting were the most common reasons for discontinuation in efficacy studies 1
• Regular monitoring of sodium levels may be warranted in high-risk patients, especially during the initial weeks of treatment or after dose adjustments 1

It is essential to weigh the benefits and risks of mirtazapine therapy and closely monitor patients for signs of hyponatremia, particularly those with risk factors. If hyponatremia develops, prompt treatment is necessary to prevent severe complications. As stated in the study 1, most of the second-generation antidepressants had similar adverse effects, but it is crucial to consider the individual patient's risk factors and medical history when prescribing mirtazapine.

From the FDA Drug Label

5.12 Hyponatremia Hyponatremia may occur as a result of treatment with serotonergic antidepressants, including mirtazapine tablets. Cases with serum sodium lower than 110 mmol/L have been reported.

• Hyponatremia is a potential side effect of mirtazapine, particularly in elderly patients, those taking diuretics, and those who are volume-depleted.
• The condition may be caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH).
• Patients with symptomatic hyponatremia should have mirtazapine discontinued and receive appropriate medical intervention 2. Yes, mirtazapine can cause hyponatremia.

From the Research

Mirtazapine and Hyponatremia

• Mirtazapine has been associated with hyponatremia, a condition characterized by low sodium levels in the blood 3, 4, 5, 6, 7.
• Studies have reported cases of hyponatremia in patients taking mirtazapine, with symptoms including confusion, somnolence, and altered speech 3, 4, 5, 7.
• The incidence of mirtazapine-induced hyponatremia has been reported to be around 3.26% in a systematic review of 30,851 patients 4.
• Hyponatremia associated with mirtazapine use is more common in elderly patients, particularly those over 60 years old 3, 4, 5, 6, 7.
• The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is thought to be the underlying cause of hyponatremia in many cases of mirtazapine-induced hyponatremia 4, 7.

Risk Factors and Prevention

• Elderly patients are at greater risk of developing hyponatremia while taking mirtazapine 3, 4, 5, 6, 7.
• Patients with risk factors for hyponatremia or SIADH should be monitored closely while taking mirtazapine 4, 7.
• Baseline electrolyte measurements should be taken before starting mirtazapine therapy, and these should be monitored throughout the full course of treatment 7.

Clinical Presentation and Management

• Symptoms of hyponatremia associated with mirtazapine use include confusion, somnolence, and altered speech 3, 4, 5, 7.
• Discontinuation of mirtazapine therapy is often associated with recovery of sodium levels to normal 3, 5, 7.
• Clinicians should be aware of the possibility of mirtazapine-induced hyponatremia and monitor sodium levels in high-risk patients if symptoms suggestive of hyponatremia develop 3, 4, 5, 6, 7.