Hyponatremia Associated with Carbamazepine and Oxcarbazepine Therapy: A Review

Abstract

Hyponatremia, an electrolyte disturbance usually without clinical significance, may sometimes lead to serious complications when overlooked or not treated appropriately. One cause of hyponatremia, the syndrome of inappropriate antidiuretic hormone (SIADH) secretion, has been associated with some drugs, including carbamazepine (CBZ). Because of its antidiuretic effects, CBZ has been used successfully to treat diabetes insipidus centralis. Possible mechanisms for the antidiuretic effects of CBZ have been proposed. Altered sensitivity to serum osmolality by the hypothalamic osmoreceptors appears likely, but an increased sensitivity of the renal tubules to circulating ADH cannot be excluded. CBZ has led to hyponatremia in patients with epilepsy, neuralgia, mental retardation, and psychiatric disorders with a frequency varying from 4.8 to 40%. Oxcarbazepine (OCBZ), which is structurally related to CBZ, has shown similar hyponatremic effects, but whether hyponatremia occurs more often than with CBZ is not yet clear. Experience with OCBZ is still limited, and there is no definite explanation for a possible difference in antidiuretic potency. Most patients with CBZ/OCBZ-induced hyponatremia are asymptomatic. In rare cases, water intoxication has been reported, necessitating treatment discontinuation.

Hyponatraemia during low-dose carbamazepine therapy

“…Carbamazepine has led to hyponatraemia in patients with epilepsy, neuralgia, mental retardation, and psychiatric disorders with a frequency varying from 4.8 to 40%. 10 It shows that this side-effect can occur at lower doses and after much shorter periods than has previously been recognized.…”

“…In rare cases, water intoxication has been reported, 10 necessitating treatment discontinuation. We therefore suggest that caution be used in prescribing carbamazepine to patients with low or borderline sodium values.…”

Heart and mind: (2) psychotropic and cardiovascular therapeutics

“…53 Carbamazepine can also produce hyponatraemia, and this effect is potentiated by other factors that cause hyponatraemia, such as diuretics and heart failure. 54 The metabolic degradation of carbamazepine may be inhibited by calcium channel blockers, thereby increasing the risk of carbamazepine toxicity. Carbamazepine and antiarrhythmics may have additive effects in slowing cardiac conduction (table 5).…”

Treatment Options in Trigeminal Neuralgia an Update

“…The FDA has recommended for screening of the HLA B*1502 allele for all people of Asian origin before initiating treatment with carbamazepine. It recommended that those Asians who tested positive for the allele should avoid exposure to carbamazepine (36).CBZ can induce the syndrome of inappropriate antidiuretic hormone (SIADH) and lead to hyponatremia (37,38). Carbamazepine should be started or stopped by changing the dose in increments over several days to reduce side effects.…”