From the FDA Drug Label
Hyponatremia — 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) Cases with serum sodium lower than 110 mmol/L have been reported and appeared to be reversible when Prozac was discontinued. Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs. Also, patients taking diuretics or who are otherwise volume depleted may be at greater risk
Medications that commonly cause hyponatremia (low sodium levels) include:
- SSRIs (Selective Serotonin Reuptake Inhibitors)
- SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors) Specific examples include Prozac (fluoxetine) 1. Elderly patients and those taking diuretics may be at greater risk of developing hyponatremia with these medications.
From the Research
Thiazide diuretics and selective serotonin reuptake inhibitors (SSRIs) are the most common medications that cause hyponatremia, with thiazide diuretics impairing urinary dilution and SSRIs triggering the syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Medications Causing Hyponatremia
The medications that commonly cause hyponatremia include:
- Thiazide diuretics (such as hydrochlorothiazide and chlorthalidone) 2
- Selective serotonin reuptake inhibitors (SSRIs like fluoxetine, sertraline, and escitalopram) 3
- Certain antiepileptic drugs (particularly carbamazepine and oxcarbazepine)
- Loop diuretics (furosemide)
- Antipsychotics (especially haloperidol and olanzapine)
- Tricyclic antidepressants (amitriptyline)
- Non-steroidal anti-inflammatory drugs (NSAIDs)
- Certain cancer medications like vincristine and cyclophosphamide
Mechanism of Hyponatremia
Thiazide diuretics cause hyponatremia by impairing urinary dilution and promoting water retention while increasing sodium excretion 4. SSRIs and antiepileptics often trigger the syndrome of inappropriate antidiuretic hormone secretion (SIADH), leading to excessive water retention 3.
Patient Monitoring
Patients taking these medications should be monitored for early symptoms of hyponatremia such as headache, confusion, nausea, and fatigue, with particular attention to elderly patients and those with heart failure, liver disease, or kidney problems who are at higher risk 2. Regular serum sodium monitoring is advisable when starting these medications, especially during the first few weeks of treatment 3.
Risk Factors
Risk factors for the development of hyponatremia with SSRIs include older age, female gender, concomitant use of diuretics, low body weight, and lower baseline serum sodium concentration 3.
Treatment
Treatment of isovolemia hypotonic hyponatremia associated with SSRI use includes water restriction and mild diuresis with a loop diuretic 3. More severe cases may be treated with higher doses of loop diuretics and hypertonic saline.