title: Safety and tolerability of the ketogenic diet in pediatric epilepsy: effects of valproate combination therapy.
abstract: OBJECTIVE
  To evaluate safety and tolerability of ketogenic diet (KGD) and valproate (VPA) cotherapy in the treatment of intractable seizures.
  
  
  METHODS
  The patient records of children who underwent KGD initiation at the Massachusetts General Hospital for Children from February 2002 to September 2004 were retrospectively assessed. Efficacy was measured by comparing reported seizure frequency at baseline and at 3-month intervals thereafter. Adverse events and reasons for terminating the diet were tabulated.
  
  
  RESULTS
  Of 71 patients who underwent KGD initiation, 24 were concomitantly using VPA at the time of initiation. The most serious adverse events were two cases of acute pancreatitis (2.8%), both of which occurred in patients not taking VPA. The most common complications in both groups were acidosis (39.4%), nausea and vomiting (23.9%), hypertriglyceridemia (21.1%), lethargy (18.3%), and behavioral changes and irritability (15.5%). No significant difference in adverse-event profiles was found between the VPA group and the non-VPA group. At 1 year, 32 patients remained on the diet, including 11 in the VPA group. Efficacy was nearly identical in these two groups.
  
  
  CONCLUSIONS
  KGD and VPA combination therapy is relatively safe and effective in refractory pediatric epilepsy. Adverse-event profiles of patients on KGD and VPA cotherapy are similar to those of patients on the KGD without VPA. In considering possible treatment options for intractable seizures, cotherapy with these two modalities should not be excluded for safety or tolerability concerns. In some patients, this combination may provide optimal seizure control.
authors.affiliation: Pediatric Epilepsy Program, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Lyczkowski
authors.forename: Heidi H
authors.initials: HH
authors.lastname: Pfeifer
authors.forename: Soumit
authors.initials: S
authors.lastname: Ghosh
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Thiele
mesh_terms: D000138:Acidosis / Q000209:etiology; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism; D004827:Epilepsy / Q000178:diet therapy* / Q000188:drug therapy*; D005260:Female; D005526:Food, Formulated / Q000009:adverse effects; D005767:Gastrointestinal Diseases / Q000209:etiology; D006801:Humans; D007223:Infant; D007657:Ketone Bodies / Q000096:biosynthesis / Q000378:metabolism; D007662:Ketosis / Q000209:etiology / Q000378:metabolism*; D008297:Male; D010195:Pancreatitis / Q000209:etiology; D012189:Retrospective Studies; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D004041:Dietary Fats; D007657:Ketone Bodies; D014635:Valproic Acid