Adverse event load in bipolar participants receiving either carbamazepine immediate-release or extended-release capsules: a blinded, randomized study

Abstract

In epilepsy, slow-release formulations of carbamazepine (CBZ) have fewer adverse events (AEs) compared with immediate-release (IR) formulations. As CBZ is used for mania, it is important to determine whether a similar pattern exists for bipolar patients. This was a 3-month, blinded, random-assignment study to an IR formulation or extended-release carbamazepine capsules (ERCC, Equetro) in type I or type II bipolar patients already on CBZ or clinically determined to benefit from it. Dosages were titrated to patients' clinical needs. Mood and AE ratings were performed at baseline and monthly for 3 months. There was no difference in mood ratings or in the total level of AEs in patients receiving IR or ERCC. However, autonomic AEs (5.0+/-1.1 vs. 2.0+/-0.7, P = 0.02) and gastrointestinal AEs (1.6+/-0.4 vs. 0.6+/-0.3, P = 0.05) were significantly less in participants receiving ERCC. CBZ level in patients receiving ERCC were higher (9.2+/-1.7 vs. IR 7.2+/-1.3 microg/ml, P = 0.005). Total AE load was directly related to CBZ level only in participants receiving the IR formulation. In conclusion, ERCC is better tolerated than IR CBZ in bipolar patients.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013

“…A small RCT in 44 patients with manic, mixed, or depressive episodes found that among patients who were on, or thought to benefit from, carbamazepine, there were no differences in mood ratings or in the total level of adverse events with immediate-release versus ER carbamazepine (63,64). However, there were significantly fewer autonomic and gastrointestinal adverse events with carbamazepine ER (64).…”

“…There is additional evidence to support the use of carbamazepine (level 2), as a small RCT in a mixed population of 44 patients with BD found that ER carbamazepine was as effective as the immediate-release form, with fewer autonomic and gastrointestinal adverse events (63,64).…”

“…Gastrointestinal symptoms: In a three-month RCT, ER carbamazepine resulted in significantly fewer autonomic and gastrointestinal adverse events compared to the immediate-release formulation (64).…”

Extended-Release Formulations of Antiepileptic Drugs: Rationale and Comparative Value

“…Serum carbamazepine levels fluctuate considerably, even with multiple daily doses (30,31) and can be associated with transient adverse effects at peak concentrations (31–33). Tolerability and even seizure control have been reported to improve with extended‐release carbamazepine, typically given twice daily (34–36), and some of these findings have been confirmed in blinded randomized trials (37,38). The value of extended‐release carbamazepine is further suggested by the results of two recent double‐blind studies that compared lamotrigine with carbamazepine among elderly patients with new‐onset epilepsy (39,40).…”