Emerging treatments
Vasopressin receptor antagonists
These increase free water clearance without affecting the handling of tubular sodium. Conivaptan, a dual vasopressin type 1A (V1A) and 2 (V2) receptor blocker, has been used to treat euvolaemic hyponatraemia in patients admitted to hospital.[41] Dual V1A/V2 receptor antagonism has also shown benefit in patients with hypervolaemic hyponatraemia.[78] A 30-day placebo-controlled trial of tolvaptan, an oral non-peptide V2 receptor antagonist, showed normalisation of hyponatraemia in 19 patients with schizophrenia and idiopathic hyponatraemia.[79] Some clinicians may use vasopressin receptor antagonists as an alternative or adjunct to clozapine in select patients.[10] Larger clinical studies are needed to confirm the effects of this class of agents in PPD.
Glucagon-like peptide 1 (GLP-1) receptor agonists
GLP-1 is a hormone with a role in appetite regulation and food intake. GLP-1 receptor agonists are well established in the treatment of diabetes and obesity, and include semaglutide, liraglutide, and dulaglutide. Emerging evidence indicates that GLP-1 may also affect thirst and drinking behaviour; this has led to the investigation of dulaglutide in PPD. In one phase 2 clinical trial, 41.2% of 34 patients were assessed as having PPD, with the remaining 20 patients being assigned a label of 'habitual polydipsia'. Treatment with dulaglutide was found to reduce fluid intake and thirst perception compared to placebo. Consistent with the known safety profile of dulaglutide, the most common adverse events were gastrointestinal in nature, and included nausea and abdominal pain. Further assessment of dulaglutide in larger clinical studies is warranted to confirm these initial findings.[80]
Demeclocycline
Demeclocycline is prescribed for nocturnal enuresis, as well as for polydipsic states. It directly inhibits antidiuretic hormone (arginine vasopressin) action at the level of the distal renal tubules, and reduces urine concentration. However, demeclocycline is associated with nephrotoxicity, and has not been found to be efficacious in double-blind placebo-controlled trials.[41][81]
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