Can Abilify (aripiprazole) cause hyponatremia?

Can Abilify (Aripiprazole) Cause Hyponatremia?

Yes, Abilify (aripiprazole) can cause hyponatremia through syndrome of inappropriate antidiuretic hormone secretion (SIADH), though this is a rare adverse effect.

Evidence for Aripiprazole-Induced Hyponatremia

A documented case report demonstrates that aripiprazole can cause severe hyponatremia via SIADH 1. In this case, a 65-year-old patient developed severe hyponatremia (serum sodium 108 mEq/L) approximately two months after increasing aripiprazole from 10 mg to 20 mg daily 1. The diagnosis was confirmed when:

• Hyponatremia resolved within 72 hours after discontinuing aripiprazole (sodium increased from 108 to 127 mEq/L) 1
• Symptoms recurred when aripiprazole was inadvertently restarted (sodium dropped to 118 mEq/L with urine osmolality 575 mOsm/kg and urine sodium 101 mEq/L) 1
• The Naranjo adverse drug reaction probability scale yielded a score of 7, indicating probable aripiprazole-associated SIADH 1

Mechanism of Action

Aripiprazole likely causes hyponatremia through nephrogenic syndrome of inappropriate antidiuresis (NSIAD) rather than classic SIADH 2. Antipsychotic medications, including aripiprazole, may induce hyponatremia through intrarenal mechanisms that upregulate aquaporin-2 (AQP2), resulting in suppressed plasma AVP levels rather than elevated levels 2. This mechanism involves activation of V2 receptor-cAMP-PKA signaling pathways in the collecting duct 2.

Clinical Recognition

Aripiprazole is not widely recognized as a common cause of hyponatremia in major guideline reviews 3. The American Academy of Pediatrics and other guideline societies do not specifically mention brexpiprazole (Rexulti, a related compound) or aripiprazole as causes of hyponatremia in their comprehensive reviews of drug-induced hyponatremia 3.

Risk Factors and Monitoring

Patients at higher risk for developing aripiprazole-induced hyponatremia include:

• Elderly patients (the documented case involved a 65-year-old) 1
• Those with conditions predisposing to hyponatremia (cirrhosis, heart failure, SIADH) 3, 4
• Patients on higher doses or recent dose increases 1

Monitor serum sodium levels in patients with predisposing conditions when initiating or increasing aripiprazole doses 3, 4. Check sodium levels if patients develop symptoms including dizziness, headache, nausea, vomiting, confusion, or altered mental status 1.

Management Approach

If aripiprazole-induced hyponatremia is suspected:

1. Immediately discontinue aripiprazole 1
2. Implement fluid restriction to 1 L/day for euvolemic hyponatremia consistent with SIADH 5
3. Monitor serum sodium every 4-6 hours initially, then daily once stable 5
4. Ensure correction does not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 5
5. Do not restart aripiprazole once hyponatremia has occurred, as rechallenge will likely reproduce the adverse effect 1

Important Caveats

While aripiprazole can cause hyponatremia, this remains a rare adverse effect that is not commonly recognized in standard drug safety databases 3. However, the documented case with positive rechallenge provides strong evidence for causality 1. Clinicians should maintain awareness of this potential complication, particularly when managing elderly patients or those with other risk factors for hyponatremia.