From the Guidelines
Valproic acid has a higher risk of causing SIADH and hyponatremia compared to Invega, with reported incidence rates of 1-10%. The mechanism of valproic acid involves direct stimulation of ADH release and enhancement of renal tubular sensitivity to ADH, leading to increased water reabsorption and dilutional hyponatremia 1. In contrast, Invega, as an atypical antipsychotic, primarily causes SIADH through dopamine antagonism in the hypothalamus, which disrupts normal ADH regulation. Risk factors for both medications include older age, female gender, concomitant use of diuretics, and pre-existing renal impairment.
According to the most recent and highest quality study, monitoring sodium levels is crucial when starting either medication, particularly during the first few weeks of treatment when the risk is highest 1. Symptoms of hyponatremia include headache, confusion, seizures, and in severe cases, coma. Management typically involves dose reduction or medication discontinuation along with fluid restriction if hyponatremia develops.
Some key points to consider:
- The treatment of hypervolemic hyponatremia involves inducing a negative water balance to normalize the increased total body water, which would result in an improvement of serum sodium concentration 1.
- Vaptans, such as tolvaptan, are effective in improving serum sodium concentration in conditions associated with high vasopressin levels, such as SIADH, heart failure, or cirrhosis 1.
- Tolvaptan has been approved for the management of severe hypervolemic hyponatremia associated with cirrhosis, ascites, heart failure, and SIADH, but its use is limited in patients with liver cirrhosis or impaired liver function due to the risk of elevated alanine aminotransferase (ALT) levels 1.
In terms of management, the use of vaptans, such as tolvaptan, may be considered in patients with SIADH or hypervolemic hyponatremia, but close monitoring of serum sodium levels and liver function is necessary 1. Overall, the choice between valproic acid and Invega should be based on the individual patient's risk factors and medical history, with careful consideration of the potential risks and benefits of each medication.
From the Research
Valproic Acid and SIADH/Hyponatremia
- Valproic acid has been associated with the development of SIADH and hyponatremia in several case reports and studies 2, 3, 4.
- The mechanism by which valproic acid causes SIADH and hyponatremia is not fully understood, but it may be related to reduced sensitivity of hypothalamic osmoreceptors or direct effects on tubular cell function 4.
- The association between valproic acid and SIADH/hyponatremia has been supported by a case/non-case analysis of the WHO's Vigibase database, which found a disproportionate number of reports of hyponatremia and SIADH in patients taking valproic acid 4.
Invega and SIADH/Hyponatremia
- There is no evidence in the provided studies to suggest that Invega (paliperidone) is associated with an increased risk of SIADH or hyponatremia.
- However, it is worth noting that other antipsychotic medications have been associated with an increased risk of SIADH and hyponatremia, although the evidence for Invega specifically is limited 5, 6.
Comparison of Valproic Acid and Invega
- Based on the available evidence, valproic acid appears to be associated with a higher risk of SIADH and hyponatremia compared to Invega 2, 3, 4.
- However, more research is needed to fully understand the relative risks of these medications and to determine the optimal treatment strategies for patients at risk of SIADH and hyponatremia 5, 6.