Can Abilify (Aripiprazole) Cause Hyponatremia?
Yes, aripiprazole can cause hyponatremia through syndrome of inappropriate antidiuretic hormone secretion (SIADH), though this is a rare adverse effect that requires clinical vigilance, particularly in elderly patients or those with other risk factors.
Evidence for Aripiprazole-Induced Hyponatremia
A documented case report demonstrates that aripiprazole can induce severe SIADH with a Naranjo probability score of 7 (indicating "probable" causation) 1. In this case, a 65-year-old man developed severe hyponatremia (serum sodium 108 mEq/L) approximately two months after his aripiprazole dose was increased from 10 to 20 mg daily 1. The hyponatremia resolved with discontinuation of aripiprazole and fluid restriction, then recurred when the medication was inadvertently restarted 1.
Mechanism of Action
Aripiprazole-induced hyponatremia likely occurs through nephrogenic syndrome of inappropriate antidiuresis (NSIAD) rather than classic SIADH 2. Antipsychotic medications, including aripiprazole, may induce hyponatremia through intrarenal mechanisms involving aquaporin-2 (AQP2) upregulation, with suppressed plasma AVP levels due to negative feedback 2. This mechanism is compatible with NSIAD and involves activation of V2 receptor-cAMP-protein kinase A signaling pathways 2.
Clinical Presentation and Risk Factors
High-Risk Populations
- Elderly patients are at substantially increased risk 1
- Patients with pre-existing conditions predisposing to hyponatremia (cirrhosis, heart failure, SIADH) require closer monitoring 3
- Those on concurrent medications that affect sodium balance 4
Timing of Onset
Drug-induced hyponatremia from antipsychotics typically occurs shortly after treatment initiation or dose escalation 4. However, the case report demonstrates that hyponatremia can develop weeks to months after a dose increase 1.
Clinical Manifestations
The patient in the documented case presented with dizziness, headache, abdominal pain, nausea, and vomiting 1. Laboratory findings consistent with SIADH included low serum osmolality (254 mOsm/kg), elevated urine osmolality (575 mOsm/kg), and elevated urine sodium (101 mEq/L) 1.
Diagnostic Approach
When aripiprazole-induced hyponatremia is suspected:
- Confirm hyponatremia: Serum sodium <135 mEq/L, with levels <131 mmol/L warranting full workup 5
- Assess volume status: Look for euvolemia (no edema, no orthostatic hypotension, normal skin turgor, moist mucous membranes) 5
- Laboratory evaluation: Obtain serum and urine osmolality, urine sodium, and urine electrolytes 5
- SIADH criteria: Hypotonic hyponatremia with inappropriately concentrated urine (>100 mOsm/kg), urine sodium >20-40 mmol/L, and euvolemic state 5
- Rule out other causes: Check thyroid function, cortisol, and assess for other medications causing hyponatremia 5
Management Strategy
Immediate Actions
- Discontinue aripiprazole if it is the suspected causative agent 1
- Implement fluid restriction to 1 L/day as first-line treatment for euvolemic hyponatremia 5
- Monitor serum sodium every 2-4 hours initially for severe symptoms, then daily 5
Correction Rate Guidelines
- Maximum correction: 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 5
- Target correction for severe symptoms: 6 mmol/L over 6 hours or until symptoms resolve 5
- For chronic hyponatremia: More cautious correction at 4-6 mmol/L per day 5
Severe Symptomatic Hyponatremia
If the patient develops severe neurological symptoms (confusion, seizures, altered mental status):
- Administer 3% hypertonic saline with careful monitoring 5
- Target initial correction of 6 mmol/L over 6 hours 5
- Transfer to ICU for close monitoring 5
Mild to Moderate Cases
- Fluid restriction to <1 L/day 5
- If no response to fluid restriction, add oral sodium chloride 100 mEq three times daily 5
- Consider alternative pharmacological options: urea, demeclocycline, or loop diuretics for resistant cases 5
Critical Pitfalls to Avoid
- Do not ignore mild hyponatremia (130-135 mmol/L), as even mild hyponatremia increases fall risk and mortality 5
- Avoid overly rapid correction exceeding 8 mmol/L in 24 hours, which can cause osmotic demyelination syndrome 5
- Do not restart aripiprazole without addressing the hyponatremia, as recurrence is likely 1
- Monitor closely after discharge to ensure the medication is not inadvertently restarted 1
Alternative Antipsychotic Considerations
While the evidence base is limited, current guidelines do not specifically mention brexpiprazole (Rexulti) as a cause of hyponatremia 3. However, given the class effect of antipsychotics on sodium balance, caution is warranted with any antipsychotic medication in patients with risk factors for hyponatremia 2.
Monitoring Recommendations
For patients who must continue aripiprazole or are at risk: