From the Guidelines
Bupropion (Wellbutrin) is generally considered to have the lowest risk of hyponatremia among antidepressants, followed by mirtazapine (Remeron), which also appears to have a lower risk compared to other options. These medications work through different mechanisms than SSRIs and SNRIs, which are more commonly associated with hyponatremia. Bupropion primarily affects dopamine and norepinephrine reuptake, while mirtazapine works on different serotonin receptors and has noradrenergic effects. The lower risk of hyponatremia with these medications is likely due to their minimal impact on the antidiuretic hormone (ADH) system, which regulates water balance in the body 1.
When prescribing antidepressants to patients at higher risk for hyponatremia (elderly patients, those taking diuretics, or with history of hyponatremia), monitoring sodium levels is recommended, especially during the first few weeks of treatment. Even with these lower-risk options, clinicians should remain vigilant for symptoms of hyponatremia such as headache, confusion, seizures, and weakness.
Some key points to consider when choosing an antidepressant with a lower risk of hyponatremia include:
- Bupropion and mirtazapine have a more favorable side effect profile compared to other antidepressants, with a lower risk of hyponatremia 1
- SSRIs and SNRIs are more commonly associated with hyponatremia, and should be used with caution in patients at higher risk for this condition
- Monitoring sodium levels is crucial when prescribing antidepressants to patients at higher risk for hyponatremia, especially during the first few weeks of treatment
- Clinicians should remain vigilant for symptoms of hyponatremia, even when using lower-risk options like bupropion and mirtazapine.
From the Research
Antidepressants with Lower Risk of Hyponatremia
- Mirtazapine: Studies have consistently shown that mirtazapine has a lower risk of hyponatremia compared to other antidepressants, including SSRIs and SNRIs 2, 3, 4, 5.
- Bupropion: Bupropion has been found to have a lower risk of hyponatremia compared to SSRIs and SNRIs, making it a potential alternative for patients at risk of hyponatremia 3, 6.
- Fluvoxamine: Fluvoxamine, an SSRI, has been found to have a lower risk of hyponatremia compared to other SSRIs, although the evidence is limited 5.
- Milnacipran: Milnacipran, an SNRI, has been found to have a lower risk of hyponatremia compared to other SNRIs, although the evidence is limited 5.
- Trazodone: Trazodone has been found to have a lower risk of hyponatremia compared to SSRIs and SNRIs, although the evidence is limited 3, 4.
- Tricyclic antidepressants (TCAs): TCAs have been found to have a lower risk of hyponatremia compared to SSRIs and SNRIs, although the evidence is limited 2, 4.
Antidepressants with Higher Risk of Hyponatremia
- SSRIs: SSRIs, such as sertraline, escitalopram, and paroxetine, have been found to have a higher risk of hyponatremia compared to other antidepressants 2, 4, 6.
- SNRIs: SNRIs, such as duloxetine and venlafaxine, have been found to have a higher risk of hyponatremia compared to other antidepressants 2, 4, 6.