New antiepileptic drugs: comparison of key clinical trials.
OBJECTIVE
Data accrued from clinical trials of five new antiepileptic drugs (AEDs) are compared for efficacy in reducing seizures and self-reported adverse events as a basis of selection among new AEDs. Drawbacks to use of these data also are demonstrated.


METHODS
A review of double-blind, placebo-controlled clinical trials of a new AED or placebo added to a standard AED provided data on reduction of complex partial seizures (CPSs). Success is > or =50% fewer CPSs with a new AED or placebo; Overall Improvement is the success rate with drug minus the success rate with placebo. Adverse events were tabulated from product-labeling lists of COSTART items (incidence, > or =5%). The Summary Complaint score is the total number of reports of individual events for each AED.


RESULTS
Efficacy data demonstrate differences in Overall Improvement rates among five new AEDs and placebos (p = 0.001). However, rates of response to placebo also differed significantly among trials (p = 0.01). Adverse events predominantly affect central nervous system, psychiatric, and general body systems. However, patients in the placebo control groups did not consistently report adverse effects. Summary Complaint scores differ among the five new AEDs, but variability in use of COSTART terms nullifies comparisons.


CONCLUSIONS
Comparisons of data for five new AEDs provide information for selection among treatments when a second drug is needed to improve control of CPSs. However, significant differences among the control groups and other problems make comparisons between trials problematic. The final choice should be based on the need of the individual patient for superior seizure control versus minimal adverse effects.
Cramer
J A
JA
Yale University School of Medicine, New Haven, Connecticut, USA. Joyce.Cramer@Yale.edu
Fisher
R
R
Ben-Menachem
E
E
French
J
J
Mattson
R H
RH
D000085:Acetates / Q000009:adverse effects / Q000627:therapeutic use; D000588:Amines; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D018849:Controlled Clinical Trials as Topic / Q000592:standards; D003509:Cyclohexanecarboxylic Acids; D004311:Double-Blind Method; D004827:Epilepsy / Q000188:drug therapy*; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077206:Gabapentin; D006801:Humans; D000077213:Lamotrigine; D009557:Nipecotic Acids / Q000009:adverse effects / Q000627:therapeutic use; D010919:Placebos; D012107:Research Design / Q000592:standards; D000078308:Tiagabine; D000077236:Topiramate; D016896:Treatment Outcome; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D009557:Nipecotic Acids; D010919:Placebos; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D020888:Vigabatrin; D000077213:Lamotrigine; D000078308:Tiagabine