Quetiapine Extended‐Release and Peripheral Edema: A Case Report and Literature Review

Quetiapine, an atypical antipsychotic, is widely prescribed for psychiatric disorders, particularly schizophrenia, bipolar disorder, and depressive disorders with or without psychotic symptoms. While edema is more commonly associated with olanzapine and clozapine amongst second general antipsychotics, reports involving quetiapine-particularly the extended-release (XR) formulation-are rare. We describe the case of a 52-year-old woman with severe major depressive episode with psychotic features who was initiated on escitalopram and quetiapine immediate-release (IR) 100 mg/day, later switched to quetiapine XR 100 mg/day to improve adherence and reduce sedation. Ten days after the switch, she developed symmetrical bilateral lower limb pitting edema without systemic symptoms. Comprehensive cardiac, renal, hepatic, thyroid, and immunologic evaluations were unremarkable, and venous Doppler ruled out deep vein thrombosis. The edema resolved within 10 days of discontinuing quetiapine XR and recurred upon rechallenge. The Naranjo Adverse Drug Reaction Probability Score was 9, indicating a probable to definite association. Possible mechanisms include α1-adrenergic blockade, 5-HT2 receptor antagonism, and pharmacokinetic differences in XR formulations leading to sustained peripheral receptor occupancy. Literature review reveals few comparable reports, most involving higher doses or polypharmacy. This case highlights the importance of clinician awareness of quetiapine XR-associated edema, even at low doses, and supports dechallenge-rechallenge as a useful diagnostic approach to improve patient safety and adherence.