Can we stop quetiapine (Seroquel) and start mirtazapine (Remeron) in an elderly patient with a history of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) and current hyponatremia?

Can Quetiapine Be Stopped and Mirtazapine Started for Hyponatremia?

No, switching from quetiapine to mirtazapine is not recommended for managing hyponatremia, as both medications carry significant risk of causing or worsening SIADH-related hyponatremia, particularly in elderly patients.

Understanding the Problem

Both quetiapine and mirtazapine are documented causes of SIADH and hyponatremia through inappropriate ADH release despite low serum osmolality, leading to water retention and dilutional hyponatremia 1, 2, 3. The FDA label for mirtazapine explicitly warns that "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" 1. Elderly patients, those taking diuretics, and volume-depleted individuals are at particularly high risk 1.

Evidence Against Switching to Mirtazapine

Mirtazapine's Hyponatremia Risk Profile

• Mirtazapine causes hyponatremia in 3.26% of patients (95% CI 3.06-3.45%), with SIADH being the most probable underlying mechanism 4
• Hyponatremia typically develops within an average of 34 days after starting mirtazapine, but can occur as early as 6-7 days 4, 5
• Mean serum sodium nadir in reported cases was 117 mEq/L (ranging 113-130 mEq/L), representing severe hyponatremia 4
• The risk exists even at low doses (as low as 7.5 mg daily) 5
• Female patients and elderly individuals are at highest risk (71.4% of cases in females) 4

Clinical Manifestations

When mirtazapine-induced hyponatremia occurs, patients present with:

• Confusion (57% of cases) 4
• Somnolence (42% of cases) 4
• Altered speech (28% of cases) 4
• Headache, difficulty concentrating, memory impairment, weakness, and unsteadiness leading to falls 1

Recommended Management Approach

Step 1: Discontinue the Offending Agent

For symptomatic hyponatremia, discontinue the causative psychotropic medication immediately 2. Both quetiapine and mirtazapine should be stopped if SIADH-related hyponatremia is confirmed 6, 2.

Step 2: Treat the Hyponatremia Based on Severity

For Severe Symptomatic Hyponatremia (Na <120 mEq/L with neurological symptoms):

• Transfer to ICU for close monitoring 6
• Administer 3% hypertonic saline targeting correction of 6 mmol/L over 6 hours or until symptoms resolve 6
• Never exceed 8 mmol/L correction in 24 hours to prevent osmotic demyelination syndrome 7, 6
• Monitor serum sodium every 2 hours initially 6

For Mild-Moderate Symptomatic or Asymptomatic SIADH:

• Implement fluid restriction to 1 L/day as first-line treatment 6, 2
• Add oral sodium chloride 100 mEq three times daily if no response to fluid restriction 7
• Monitor sodium levels every 24-48 hours initially 2

Step 3: Consider Alternative Medications with Lower SIADH Risk

Rather than switching to mirtazapine, consider antidepressants with lower hyponatremia risk:

The expert consensus from the Association of Medicine and Psychiatry recommends evaluating for and avoiding medications that cause hyponatremia, with substitution to medications less likely to cause SIADH when appropriate 2.

Medications with moderate-to-high evidence for SIADH include:

• SSRIs, SNRIs 2
• Antipsychotics (including quetiapine) 2, 3
• Carbamazepine and oxcarbazepine 2
• Mirtazapine 1, 4, 5

Step 4: Special Considerations for Elderly Patients

• Elderly patients are at greater risk of developing hyponatremia with any psychotropic medication 1
• Sedating drugs, including mirtazapine, may cause confusion and over-sedation in the elderly 1
• Pharmacokinetic studies show decreased clearance of mirtazapine in elderly patients 1
• Caution is indicated when administering mirtazapine to elderly patients, particularly those with renal impairment (75% renal excretion) 1

Critical Safety Considerations

Monitoring Requirements

If any psychotropic medication must be continued or initiated in a patient with prior hyponatremia:

• Check baseline serum sodium before starting treatment 2
• Monitor sodium levels within 2 weeks of initiation (when hyponatremia typically develops) 5
• Recheck if symptoms suggestive of hyponatremia develop (confusion, somnolence, altered speech, weakness) 4, 5
• High-risk patients (elderly, on diuretics, volume-depleted) require more frequent monitoring 1

Recovery Timeline

When mirtazapine is discontinued for hyponatremia:

• Mean time to sodium recovery is 11 days 5
• Sodium levels typically normalize to ≥132 mEq/L within 7-10 days 5
• Mental status improvement parallels sodium correction 8

Common Pitfalls to Avoid

• Do not assume mirtazapine is "safer" than quetiapine for hyponatremia risk - both carry significant SIADH risk 1, 4, 2, 3
• Do not overlook the increased risk in elderly patients - age is a major risk factor for psychotropic-induced hyponatremia 1, 4
• Do not fail to monitor sodium levels after medication changes - hyponatremia can develop within days of starting treatment 4, 5
• Do not correct chronic hyponatremia faster than 8 mmol/L in 24 hours - this causes osmotic demyelination syndrome 7, 6