Which psychiatric medications cause hyponatremia?

Psychiatric Medications That Cause Hyponatremia

Selective serotonin reuptake inhibitors (SSRIs) are the psychiatric medications most strongly associated with hyponatremia, with duloxetine and escitalopram carrying the highest risk among commonly prescribed antidepressants. 1

Antidepressants and Hyponatremia Risk

SSRIs and SNRIs

SSRIs and SNRIs are the psychiatric medications most commonly associated with hyponatremia, which typically occurs through the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The risk varies by specific medication:

• Highest risk:

  • Duloxetine (HR = 1.37 compared to sertraline) 1
  • Escitalopram (HR = 1.16 compared to sertraline) 1
  • Fluoxetine (historically most reported cases) 2

• Moderate risk:

  • Sertraline 1
  • Citalopram 1
  • Venlafaxine 3

• Lower risk:

  • Paroxetine (HR = 0.78 compared to sertraline) 1
  • Bupropion (HR = 0.83 compared to sertraline) 1
  • Mirtazapine (lower incidence than SSRIs) 3

The FDA drug label for fluoxetine specifically warns: "Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including Prozac. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)." 4

Antipsychotics

Antipsychotics can also cause hyponatremia, though less commonly than SSRIs:

• Both first-generation and second-generation antipsychotics have been associated with hyponatremia 5
• The mechanism may involve SIADH or polydipsia (excessive water intake) 5

Risk Factors for Antidepressant-Induced Hyponatremia

Several factors increase the risk of developing hyponatremia when taking psychiatric medications:

• Age: Elderly patients have significantly higher risk (odds ratio = 6.3) 3
• Sex: Female patients are at higher risk 6
• Medications: Concomitant use of diuretics dramatically increases risk (odds ratio = 11.2-13.5) 3
• Medical history: Previous episodes of hyponatremia 6
• Timing: Highest risk within first 30 days of treatment (especially first 2 weeks) 2

Clinical Presentation and Monitoring

Symptoms of hyponatremia include:

• Headache
• Difficulty concentrating
• Memory impairment
• Confusion
• Weakness
• Unsteadiness (which may lead to falls)

In severe cases:

• Hallucinations
• Syncope
• Seizure
• Coma
• Respiratory arrest
• Death 4, 7

Management of Psychiatric Medication-Induced Hyponatremia

When hyponatremia is detected in a patient on psychiatric medications:

1. For symptomatic hyponatremia: Discontinue the psychiatric medication 4, 7
2. For severe hyponatremia (serum sodium <120 mmol/L): Immediate medical intervention is required
3. For moderate hyponatremia (120-125 mmol/L): Consider fluid restriction to 1,000 mL/day 8
4. For mild hyponatremia (126-135 mmol/L): Monitor serum sodium levels and consider medication adjustment if clinically indicated 8

Prevention Strategies

To minimize the risk of hyponatremia when prescribing psychiatric medications:

1. Baseline assessment: Check serum sodium before starting treatment
2. Regular monitoring: Monitor serum sodium levels during the first month of treatment, especially in high-risk patients
3. Patient education: Inform patients about symptoms of hyponatremia that should prompt medical attention
4. Medication selection: Consider lower-risk options (bupropion, mirtazapine) in patients with risk factors for hyponatremia 1, 3

Clinical Pearls

• Hyponatremia typically develops within the first 2 weeks of treatment (median 13 days) but can occur anytime 2
• Sodium levels usually normalize within days to weeks after medication discontinuation 6
• Some patients may develop tolerance to the hyponatremic effect over time 6
• The incidence of antipsychotic-induced hyponatremia may be underreported 5
• Always consider medication-induced hyponatremia in psychiatric patients presenting with confusion, falls, or seizures