Abstracts

Both valproic acid (VPA) and zonisamide (ZNS) are widely used to treat partial and generalized seizures. VPA may cause significant weight gain, at times raising health concerns. In contrast, ZNS may cause weight loss. The overall effect of the two drugs when used in combination on weight has not been fully studied. Adult patients ([underline][gt][/underline]18y.o.) treated with VPA and ZNS concurrently were identified by the MINCEP Epilepsy Care database. Only patients who had signed consent to participate in clinical research were included in the study. Medical records were reviewed for weight, VPA and ZNS dosages and levels at each clinic visit. All patients were on VPA for [underline][gt][/underline] 6 months prior to ZNS initiation, and remained on VPA throughout the study. Weight was classified according to the following time periods: T[sub]-1[/sub] (6-12 months before ZNS initiation), T[sub]0[/sub] (at ZNS initiation), T[sub]1[/sub] (1-3 months on maximal ZNS dose[ZNS[sub]max[/sub]]), T[sub]2[/sub] (4-6 months on ZNS[sub]max[/sub]), T[sub]3[/sub] (7-9 months on ZNS[sub]max[/sub]), T[sub]4[/sub] ([gt] 9 months on ZNS[sub]max[/sub]). Where height was available, BMI was calculated by kg/cm². T[sub]-1[/sub] was used as the patient[apos]s own control to observe weight change on ZNS. Weight changes were calculated between these time points. Statistical analysis was performed with MANOVA and Student t-test. Fifty-seven subjects (25 men, 32 women) were in the study. ZNS[sub]max[/sub] ranged from 100-900 mg/dy, 1.2-14.8 mg/kg/dy (464[underline]+[/underline]184.6 mg/dy, 5.7[underline]+[/underline]2.8 mg/kg/dy) for men, and 100-700 mg/dy, 1.3-10.8 mg/kg/dy (mean 406.5[underline]+[/underline]164.5 mg/dy, 5.7[underline]+[/underline]2.4 mg/kg/dy) for women. Weight gain was observed from T[sub]-1[/sub] to T[sub]0[/sub] for both men (T[sub]-1[/sub] = 81.8[underline]+[/underline]19.9 kg, T[sub]0[/sub] = 84.2[underline]+[/underline]20.4 kg, p[lt]0.05) and women (T[sub]-1[/sub] = 71.9[underline]+[/underline]21.2 kg, T[sub]0[/sub] = 72.4[underline]+[/underline]19.4 kg, ns). Forty-one percent of men and 56% of women lost weight on ZNS. Mean weight loss on ZNS was observed when the last available time entry (T[sub]final[/sub]) was compared with T[sub]0[/sub] and T[sub]-1[/sub]. For men, weight loss was observed between T[sub]final[/sub] (82.2[underline]+[/underline]19.0 kg) and T[sub]0[/sub] (84.2[underline]+[/underline]20.4 kg) (p[lt]0.05). T[sub]final[/sub] remained high compared to T[sub]-1[/sub] (81.8[underline]+[/underline]19.9 kg). For women, weight loss was observed at T[sub]final[/sub] (69.5[underline]+[/underline]16.8 kg) compared to both T[sub]0[/sub] (72.4[underline]+[/underline]19.4 kg) and T[sub]-1[/sub] (71.9[underline]+[/underline]21.2 kg) (p[lt]0.05). The gender difference in weight pattern was also demonstrated when weight change was followed over time on ZNS[sub]max[/sub]. Women lost weight at T[sub]1[/sub] and continued losing weight at T[sub]2-3 [/sub](ns). Men showed an initial decrease at T[sub]1[/sub] (ns) and plateaued thereafter. Mean weight loss in men did not return to T[sub]-1[/sub] values. This retrospective study demonstrated weight loss in patients treated concurrently with ZNS and VPA. A gender difference in pattern of weight loss was observed. Women tended to continue losing weight at 6-9 months after being maintained on ZNS[sub]max[/sub]. Men[apos]s weight loss peaked at 1-3 months on ZNS[sub]max[/sub]. A larger series with better control of dose titration for VPA and ZNS is needed to verify these findings. (Supported by MICNEP Epilepsy Care.)