Impact of carbamazepine on vitamin D levels: A meta-analysis

There are longstanding concerns about the impact of enzyme-inducing anti-seizure medications (ASMs) on vitamin D, an important molecule in both bone metabolism and inflammation pathways. The relationship between chronic use of carbamazepine and vitamin D levels has been studied, but no comprehensive review to inform practitioners and policymakers is currently available. We performed a meta-analysis on studies that measured 25-hydroxyvitamin D (25OHD) levels in persons taking carbamazepine to determine whether this drug significantly reduces circulating 25OHD.

From a literature search of the terms "carbamazepine" and "vitamin D", we identified 12 studies that measured 25OHD levels in persons on carbamazepine monotherapy groups and controls. Persons taking carbamazepine had significantly lower 25OHD levels than persons not taking carbamazepine. The average 25OHD levels of carbamazepine-treated patients across all studies was 21.8 ng/mL (IQR 15.4,26.0) whereas 25OHD levels of control subjects was 28.0 ng/mL (IQR 20.8,30.4). The weighted difference of means was 4.00 ng/mL of 25OHD. Neither age nor sex nor duration of carbamazepine therapy had a significant impact on this finding. The effect was similar irrespective of whether the comparator group consisted of healthy controls or epilepsy patients taking non-inducing medications.

Carbamazepine use is associated with a reduction of 25OHD levels. In combination with other literature establishing the problematic metabolic effects of carbamazepine, this meta-analysis provides additional evidence in favor of the use of alternative ASMs as first-line agents. At minimum, vitamin D supplementation should be strongly considered for patients prescribed carbamazepine.