Effects of oxcarbazepine and carbamazepine on the central nervous system: computerised analysis of saccadic and smooth-pursuit eye movements

Abstract

Oxcarbazepine (OXC) is a new anti‐epileptic agent structurally related to carbamazepine (CBZ). OXC seems to have a similar efficacy and a better tolerability profile than CBZ. In the present study we compared the subclinicai side‐effects on the CNS of OXC and CBZ using a computerised analysis of saccadic and smooth‐pursuit eye movements. Six healthy male volunteers (mean age 29 yrs) participated in the study, which was conducted by a double‐blind cross‐over design. Each subject was given a single dose of either CBZ 400 mg or OXC 600 mg (according to the random assignment) after which the drug effects on eye movements were evaluated. One week later, the trial was repeated using the other drug. The parametrisation of both saccadic and smooth‐pursuit eye movements was carried out by measuring a series of performance parameters [e.g. the maximum saccade peak velocity (MSPV) and the typical target velocity (TTV)]. OXC was found to induce a lesser degree of alteration on the values of both MSPV (p = 0.07) and TTV (p<0.03) than CBZ. In particular, the TTV values were virtually unaffected by OXC administration, while the effects of CBZ on both variables were particularly evident at 8 and 10 h after dosing which correspond to the time at which the plasma concentrations of CBZ and of its 10,11‐epoxide reach the peak. In conclusion, our preliminary results indicate that OXC induces negligible alterations, if any, on the eye movement parameters evaluated in our study.

Can the adverse effects of antiepileptic drugs be detected in saccadic eye movements?

“…The primary finding of this study is that AEDs can affect saccades. Previous studies also support our findings, but those studies were performed in healthy volunteers and compared the effects between AEDs [12][13][14][15][16][17][18]. This study is the first systematic approach to determine whether the AEs of AEDs can be assessed using the eye movements obtained with VEOG.…”

Retinal ganglion cell toxicity due to oxcarbazepine and valproic acid treatment in rat

“…8 It has also been found that OXC caused subtle visual alterations together with saccadic and smooth-pursuit eye movements. 18 To the best of our knowledge, there is no animal or postmortem study in the literature investigated the underlying changes or mechanisms of these visual disturbances encountered secondary to these agents used for the treatment of epilepsia. There is only one clinical study investigating the relationship between ocular symptoms and retinal anatomy by using OCT. 5 OCT is a useful clinical tool that can measure the thickness of retinal nerve fiber layer and macula.…”

“…Mean RGC number in group 1 (control) was 16.4 AE 5.3 (9-28). In group 2 (VPA), RGC number was 14.0 AE 3.1 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) and the difference between groups 1 and 2 was not found to be statistically significant (p: 0.128). On the other hand, RGC numbers in group 3 (OXC) and group 4 (combined OXC-VPA) were 12.5 AE 2.7 (8-18) and 10.0 AE 1.9 (6)(7)(8)(9)(10)(11)(12)(13)(14).…”

Pharmacological treatment effects on eye movement control

“…A reduction in smooth pursuit gain has also been reported (Bittencourt, Gresty, & Richens, 1980; Hoffmann et al, 1993) although this effect has not been consistent (Holzman et al, 1975; Noachtar et al, 1998; Pieters et al, 2003; Tedeschi et al, 1989). In a comparison of the effect on smooth pursuit performance of carbamazepine vs. a newer structurally similar agent, oxcarbazepine, in a double blind cross-over design, carbamazepine reduced tracking velocity to a greater degree than oxcarbazepine (Zaccara et al, 1992). …”