title: Clinical features associated with placebo response in refractory focal epilepsy.
abstract: For clinical trial design and for clinical practice, it is of importance to assess factors associated with placebo response in patients with refractory epilepsy. We determined factors associated with placebo response in 359 adult patients with refractory focal epilepsy participating in three randomized placebo-controlled trials of the new antiepileptic drug lacosamide. At the end of the randomized 12-week maintenance period, 81 (23%) of the 359 patients randomized to placebo achieved at least a 50% seizure reduction (responders) compared to baseline. In contrast, 278 (77%) patients did not achieve a 50% seizure reduction (non-responders) compared to baseline. In multivariate analysis, five factors, which were present prior to the exposure to placebo, were found to be associated with placebo response. Higher age at study entry improved the chances of placebo response for each year [p=0.023, odds ratio (OR) 1.034 (95% confidence interval (95% CI): 1.005-1.063)]. In contrast, a lower chance of placebo response was seen with age at diagnosis of epilepsy of 6-20 years compared to ≤5 years [p=0.041, OR 0.475 (95% CI: 0.232-0.971)]. A history of 7 or more prior lifetime AEDs lowered the chance of achieving placebo response compared to 1-3 prior lifetime AEDs [p<0.001, OR 0.224 (95% CI: 0.101-0.493)] as did a baseline seizure frequency >10 seizures per 28 days compared to ≤5 seizures per 28 days [p=0.026, OR 0.431 (95% CI: 0.205-0.904)]. Prior epilepsy surgery lowered the likelihood of placebo response [p=0.02, OR 0.22 (95% CI: 0.062-0.785)]. We suggest that age at exposure to placebo, age at diagnosis of epilepsy, the number of prior lifetime AEDs, baseline seizure frequency and a history of epilepsy surgery appear to be associated with placebo response in adults with refractory focal epilepsy.
authors.affiliation: Epilepsy Research Group, Berlin, Germany. dbschmidt@t-online.de
authors.forename: Dieter
authors.initials: D
authors.lastname: Schmidt
authors.forename: Stefan
authors.initials: S
authors.lastname: Beyenburg
authors.forename: Joseph
authors.initials: J
authors.lastname: D'Souza
authors.forename: Knut
authors.initials: K
authors.lastname: Stavem
mesh_terms: D000081:Acetamides / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use*; D004311:Double-Blind Method; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology*; D005260:Female; D006801:Humans; D000078334:Lacosamide; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D010919:Placebos / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D010919:Placebos; D000078334:Lacosamide