Can Quetiapine Cause SIADH?
Yes, quetiapine can cause SIADH, though it is an uncommon adverse effect that is explicitly recognized in the FDA drug label and supported by case reports in the medical literature. 1
FDA-Recognized Association
The FDA drug label for quetiapine explicitly lists "syndrome of inappropriate antidiuretic hormone secretion (SIADH)" among post-marketing adverse reactions that were temporally related to quetiapine therapy. 1 This official recognition establishes quetiapine as a documented cause of SIADH, though the exact frequency cannot be reliably estimated due to voluntary reporting. 1
Clinical Evidence and Case Reports
Multiple case reports confirm this association in real-world clinical practice:
- A 65-year-old woman treated with quetiapine for schizophrenia developed generalized tonic-clonic seizures and was diagnosed with quetiapine-induced SIADH. 2
- A 53-year-old patient on quetiapine presented with restlessness, urinary complaints, thirst, and confusion due to hyponatremia from SIADH, which resolved with fluid restriction and dose reduction. 3
- A 45-year-old man with paranoid schizophrenia repeatedly developed SIADH-related hyponatremia with both haloperidol and quetiapine, but not with clozapine. 4
Broader Context of Antipsychotic-Induced SIADH
Quetiapine is part of a broader pattern where both typical and atypical antipsychotics can induce SIADH, though the actual incidence may be significantly underrecognized. 5 A systematic review found that antipsychotic-induced hyponatremia showed possible causality in 80% of analyzed cases and probable causality in 19% of cases. 5
Clinical Monitoring Recommendations
Monitor serum sodium levels during the first 2-4 weeks of quetiapine therapy, particularly in high-risk patients. 4 Risk factors that increase susceptibility include:
- Advanced age 4, 6
- Comorbid somatic disorders 4
- Polypharmacy, especially concurrent use of other SIADH-inducing medications (SSRIs, carbamazepine, thiazide diuretics, NSAIDs) 7, 8
- History of psychogenic polydipsia 6
- Smoking 6
Critical Diagnostic Pitfall
Early symptoms of SIADH (weakness, lethargy, headache, anorexia) are nonspecific and may mimic psychiatric symptoms themselves, leading to delayed recognition. 6 More severe manifestations include confusion, seizures, and coma. 6 Maintain high clinical suspicion when patients on quetiapine develop new neurological or cognitive symptoms.
Management Approach
When quetiapine-induced SIADH is suspected:
- Discontinue quetiapine immediately if symptomatic hyponatremia is present 7, 6
- Implement fluid restriction to 1 L/day for mild-to-moderate cases 7, 3
- For severe symptomatic hyponatremia (sodium <120 mEq/L with neurological symptoms), administer 3% hypertonic saline with target correction of 6 mmol/L over 6 hours, never exceeding 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 7
- If continued antipsychotic treatment is necessary, switch to an agent with a different pharmacological profile and monitor sodium levels closely 6
- Consider rechallenge testing or water loading test to confirm causality after acute management 6