Hyponatremia: Evolving diagnostics and emerging therapeutics in clinical practice

Table 1 Medications associated with syndrome of inappropriate antidiuretic hormone or hyponatremia

Drug class	Examples	Proposed mechanism	Clinical notes
Antidepressants	SSRIs (sertraline, fluoxetine, paroxetine), SNRIs (venlafaxine, duloxetine), tricyclics (amitriptyline), mirtazapine	Enhanced ADH release or potentiation of its renal effect	Most frequent cause in older adults, especially underweight women
Antipsychotics	Haloperidol, risperidone, olanzapine, quetiapine	Dopaminergic and serotonergic modulation of ADH	Risk increases with concomitant antidepressants
Antiepileptics/mood stabilizers	Carbamazepine, oxcarbazepine, valproate, lamotrigine	Increased ADH release and sensitivity at renal V2 receptor	Carbamazepine is a classic cause of chronic SIADH
Chemotherapeutic/oncologic agents	Cyclophosphamide, vincristine, cisplatin, ifosfamide	Direct stimulation of ADH release or renal tubular toxicity	Often transient; risk rises with concomitant nausea or stress
Analgesics	Opioids (morphine, tramadol), NSAIDs	Opioids increase ADH release; NSAIDs potentiate its action by reducing prostaglandin inhibition	Particularly relevant postoperatively
Diuretics	Thiazides (hydrochlorothiazide, indapamide)	Impaired urinary dilution, sodium loss	Responsible for up to 90% of diuretic-induced hyponatremia
Antineoplastic/immunomodulators	Interferon-α, cyclophosphamide, vincristine	Hypothalamic or renal effect on ADH	Usually dose-dependent
Other agents	Desmopressin, chlorpropamide, ecstasy (MDMA)	Direct V2 receptor agonism or ADH secretion	Seen in recreational drug users and hospitalized patients receiving DDAVP

SSRI: Selective serotonin reuptake inhibitor; SNRI: Serotonin-norepinephrine reuptake inhibitor; ADH: Antidiuretic hormone; SIADH: Syndrome of inappropriate antidiuretic hormone secretion; NSAID: Non-steroidal anti-inflammatory drug; MDMA: 3,4-methylenedioxymethamphetamine; DDAVP: 1-deamino-8-D-arginine vasopressin.