High doses of carbamazepine for refractory partial epilepsy

Abstract

Forty-eight patients with partial seizures were analysed during treatment with 1200 mg/d or more of carbamazepine (CBZ). Thirty-three were on monotherapy and fifteen on polytherapy. The other drugs were kept unchanged in the patients on polytherapy. The dose of CBZ was increased if no control was observed and the patient had no side effects. The doses used ranged between 1200 and 1900 mg/day (1200 mg/day, n=18; 1300mg/day, n=1; 1400 mg/day, n=7; 1600 mg/day, n=9; 1700 mg/day, n=4; 1800 mg/day, n=8; 1900 mg/day, n=1). Anticonvulsant plasma levels were taken to confirm patient compliance. The average plasma level was 9.6 ug/mL. The period of follow up varied from 3 to 96 months (M=25.6). Seizure's control was observed in 7 (14.48%) patients taking 1200 mg/day and in 2 (4.16%) patients taking 1400 mg/day of CBZ. Thirty-nine patients did not show any control (81.21%). Ten patients (20.81%) had signs of intoxication. When patients have no improvement with 1400 mg/day, it is difficult to obtain any control despite the use of higher doses of CBZ, which frequently expose the patient to significant side effects.

Scoping review of rational polytherapy in patients with drug‐resistant epilepsy

“…The following ASMs were specifically evaluated as an intervention by one study reporting clinical outcomes (see Table 3 ): CBZ, 13 cenobamate, 14 clobazam (CLB), 15 eslicarbazepine (ESL), 16 lacosamide (LCS), 17 levetiracetam (LEV), 18 lamotrigine (LTG), 18 perampanel (PER), 19 pregabalin (PGB). 20 Clinical outcomes of specific combinations of ASMs, including CBZ/valproic acid (VPA) compared to CBZ monotherapy 21 and VPA/LTG compared to VPA and/or LTG monotherapy, 22 were evaluated in one study each.…”

“… 23 , 24 , 25 , 26 , 27 , 29 , 31 , 32 Additionally, eight studies reported if seizure frequency was increased or exacerbated. 16 , 19 , 21 , 28 , 29 , 34 Sixteen studies addressed safety outcomes, 14 , 15 , 16 , 17 , 19 , 20 , 24 , 25 , 26 , 27 , 28 , 29 , 31 , 36 , 38 , 39 while seven studies reported plasma concentrations of the study drug 13 , 24 , 26 , 27 and/or all ASMs taken by patients. 22 , 28 , 36 …”

“…Among RCTs ( n = 10), “refractory” epilepsy was used in seven studies. 13 , 15 , 21 , 22 , 25 , 28 , 35 Additionally, five studies also used the term “adjunctive” or “adjunctive therapy” to describe the intervention. 14 , 16 , 27 , 29 , 31 Three studies also used the term “uncontrolled” or “not adequately controlled,” referring to seizures.…”

“… 23 , 24 , 26 Among non‐RCTs ( n = 23), “refractory” epilepsy was used in 15 studies. 13 , 15 , 17 , 18 , 21 , 22 , 28 , 30 , 33 , 34 , 35 , 39 , 40 , 42 , 43 Two studies specifically highlighted “medically refractory epilepsy” 38 and “treatment‐resistant epilepsy.” 14 Four studies did not specifically define DRE. 37 , 41 , 44 , 45 Humanistic and clinical outcomes were captured by three 41 , 44 , 45 and one 37 study, respectively, and compared ASM mono‐ and polytherapy.…”