scholarly journals Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures

Neurology ◽  
2020 ◽  
Vol 94 (22) ◽  
pp. e2311-e2322 ◽  
Author(s):  
Steve S. Chung ◽  
Jacqueline A. French ◽  
Jacek Kowalski ◽  
Gregory L. Krauss ◽  
Sang Kun Lee ◽  
...  
Keyword(s):  
Seizure Frequency ◽  
Maintenance Phase ◽  
Baseline Period ◽  
Adjunctive Treatment ◽  
Controlled Study ◽  
Double Blind ◽  
Focal Seizures ◽  
Free Treatment ◽  
Titration Phase ◽  
Motor Component

ObjectiveTo evaluate the efficacy and safety of adjunctive cenobamate 200 mg/d in patients with uncontrolled focal (partial-onset) seizures despite treatment with 1 to 3 antiepileptic drugs.MethodsIn this multicenter, double-blind, placebo-controlled study, adults 18 to 65 years of age with focal seizures were randomized 1:1 (cenobamate:placebo) after an 8-week baseline period. The 12-week double-blind treatment period consisted of a 6-week titration phase and a 6-week maintenance phase. The primary outcome was percent change in seizure frequency (from baseline) per 28 days during double-blind treatment.ResultsTwo hundred twenty-two patients were randomized; 113 received cenobamate and 109 received placebo; and 90.3% and 90.8% of patients, respectively, completed double-blind treatment. Median baseline seizure frequency was 6.5 in 28 days (range 0–237). Compared to placebo, cenobamate conferred a greater median percent seizure reduction (55.6% vs 21.5%; p < 0.0001) The responder rate (≥50% reduction in seizure frequency) was 50.4% for cenobamate and 22.2% for placebo (p < 0.0001). Focal seizures with motor component, impaired awareness, and focal to bilateral tonic-clonic seizures were significantly reduced with cenobamate vs placebo. During maintenance, 28.3% of cenobamate-treated and 8.8% of placebo-treated patients were seizure-free. Treatment-emergent adverse events reported in >10% in either group (cenobamate vs placebo) were somnolence (22.1% vs 11.9%), dizziness (22.1% vs 16.5%), headache (12.4% vs 12.8%), nausea (11.5% vs 4.6%), and fatigue (10.6% vs 6.4%).ConclusionAdjunctive treatment with cenobamate 200 mg/d significantly improved seizure control in adults with uncontrolled focal seizures and was well tolerated.ClinicalTrials.gov identifierNCT01397968.Classification of evidenceThis study provides Class I evidence that, for patients with uncontrolled focal seizures, adjunctive cenobamate reduces seizures.

Occipital nerve block for the short-term preventive treatment of migraine: A randomized, double-blinded, placebo-controlled study

Cephalalgia ◽  
2014 ◽  
Vol 35 (11) ◽  
pp. 959-968 ◽  
Author(s):  
Esma Dilli ◽  
Rashmi Halker ◽  
Bert Vargas ◽  
Joseph Hentz ◽  
Teresa Radam ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Nerve Block ◽  
Preventive Treatment ◽  
Placebo Treatment ◽  
Baseline Period ◽  
Controlled Study ◽  
Double Blind ◽  
Occipital Nerve ◽  
Occipital Nerve Block ◽  
Severe Migraine

Background Occipital nerve (ON) injections with corticosteroids and/or local anesthetics have been employed for the acute and preventive treatment of migraine for decades. However, to date there is no randomized, placebo-controlled evidence to support the use of occipital nerve block (ONB) for the prevention of migraine. Objective The objective of this article is to determine the efficacy of ONB with local anesthetic and corticosteroid for the preventive treatment of migraine. Participants and methods Patients between 18 and 75 years old with ICHD-II-defined episodic (> 1 attack per week) or chronic migraine (modified ICHD-II as patients with > 10 days with consumption of acute medications were permitted into the study) were randomized to receive either 2.5 ml 0.5% bupivacaine plus 0.5 ml (20 mg) methylprednisolone over the ipsilateral (unilateral headache) or bilateral (bilateral headache) ON or 2.75 ml normal saline plus 0.25 ml 1% lidocaine without epinephrine (placebo). Patients completed a one-month headache diary prior to and after the double-blind injection. The primary outcome measure was defined as a 50% or greater reduction in the frequency of days with moderate or severe migraine headache in the four-week post-injection compared to the four-week pre-injection baseline period. Results Thirty-four patients received active and 35 patients received placebo treatment. Because of missing data, the full analysis of 33 patients in the active and 30 patients in the placebo group was analyzed for efficacy. In the active and placebo groups respectively, the mean frequency of at least moderate (mean 9.8 versus 9.5) and severe (3.6 versus 4.3) migraine days and acute medication days (7.9 versus 10.0) were not substantially different at baseline. The percentage of patients with at least a 50% reduction in the frequency of moderate or severe headache days was 30% for both groups (10/30 vs nine of 30, Δ 0.00, 95% CI –0.22 to 0.23). Conclusions Greater ONB does not reduce the frequency of moderate to severe migraine days in patients with episodic or chronic migraine compared to placebo. The study was registered with ClinicalTrial.gov (NCT00915473).

Behavioral interventions as a treatment for epilepsy

Neurology ◽  
2018 ◽  
Vol 90 (11) ◽  
pp. e963-e970 ◽  
Author(s):  
Sheryl R. Haut ◽  
Richard B. Lipton ◽  
Susannah Cornes ◽  
Alok K. Dwivedi ◽  
Rachel Wasson ◽  
...  
Keyword(s):  
Seizure Frequency ◽  
Stress Reduction ◽  
Behavioral Interventions ◽  
Focal Epilepsy ◽  
Muscle Relaxation ◽  
Baseline Period ◽  
Progressive Muscle Relaxation ◽  
Focused Attention ◽  
Electronic Diary ◽  
Double Blind

ObjectiveTo evaluate the effect of a stress-reduction intervention in participants with medication-resistant epilepsy.MethodsAdults with medication-resistant focal epilepsy (n = 66) were recruited from 3 centers and randomized to 1 of 2 interventions: (1) progressive muscle relaxation (PMR) with diaphragmatic breathing, or (2) control focused-attention activity with extremity movements. Following an 8-week baseline period, participants began 12 weeks of double-blind treatment. Daily self-reported mood and stress ratings plus seizure counts were completed by participants using an electronic diary, and no medication adjustments were permitted. The primary outcome was percent reduction in seizure frequency per 28 days comparing baseline and treatment; secondary outcomes included stress reduction and stress–seizure interaction.ResultsIn the 66 participants in the intention-to-treat analysis, seizure frequency was reduced from baseline in both treatment groups (PMR: 29%, p < 0.05; focused attention: 25%, p < 0.05). PMR and focused attention did not differ in seizure reduction (p = 0.38), although PMR was associated with stress reduction relative to focused attention (p < 0.05). Daily stress was not a predictor of seizures.ConclusionsBoth PMR and the focused-attention groups showed reduced seizure frequency compared to baseline in participants with medication-resistant focal seizures, although the 2 treatments did not differ. PMR was more effective than focused attention in reducing self-reported stress.ClinicalTrials.gov identifierNCT01444183.

A Double-Blind Controlled Study of Adjunctive Treatment With Risperidone in Schizophrenic Patients Partially Responsive to Clozapine

2005 ◽  
Vol 66 (01) ◽  
pp. 63-72 ◽  
Author(s):  
A. Elif Anil Yagcioglu ◽  
Berna B. Kivircik Akdede ◽  
Tolga I. Turgut ◽  
Mevhibe Tümüklü ◽  
M. Kâzim Yazici ◽  
...  
Keyword(s):  
Adjunctive Treatment ◽  
Controlled Study ◽  
Double Blind ◽  
Schizophrenic Patients

scholarly journals Safety and Tolerability of Adjunctive Eslicarbazepine Acetate in Pediatric Patients (Aged 4-17 Years) With Focal Seizures

2019 ◽  
Vol 35 (4) ◽  
pp. 265-273 ◽  
Author(s):  
Mark Mintz ◽  
Jesus E. Pina-Garza ◽  
Steven M. Wolf ◽  
Patricia E. McGoldrick ◽  
Sergiusz Józwiak ◽  
...  
Keyword(s):  
Adverse Events ◽  
Pediatric Patients ◽  
Safety Data ◽  
Adjunctive Treatment ◽  
Eslicarbazepine Acetate ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Focal Seizures ◽  
Clear Dose Response ◽  
Cluster Seizures

Objective: To evaluate the safety and tolerability of adjunctive eslicarbazepine acetate (ESL) in pediatric patients (aged 4-17 years) with refractory focal seizures. Methods: Pooled safety data from patients aged 4-17 years in Study 208 (NCT01527513) and Study 305 (NCT00988156) were analyzed. Both were randomized, double-blind, placebo-controlled studies of ESL as adjunctive treatment in pediatric patients with refractory focal seizures receiving 1 or 2 antiepileptic drugs. Incidences of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs leading to discontinuation, and TEAEs of special interest were evaluated. Results: The safety population comprised 362 patients (placebo, n = 160; ESL, n = 202). The overall incidence of TEAEs was similar between the ESL (67.8%) and placebo groups (65.6%), with no clear dose-response relationship. The most frequently reported TEAEs with ESL were headache, somnolence, vomiting, and diplopia. Overall incidences of SAEs and TEAEs leading to discontinuation were higher with ESL versus placebo (9.9% vs 5.0% and 5.9% vs 2.5%, respectively). The majority of SAEs with ESL occurred in Study 305. Two deaths were reported, 1 with ESL (0.5%) due to cluster seizures (resulting in herniation of the cerebellar tonsils) and 1 with placebo (0.6%) due to asphyxia. TEAEs related to allergic reaction, hyponatremia, hypothyroidism, cytopenia, seizure exacerbation, cognitive dysfunction, psychiatric disorders, or suicide occurred infrequently (<9%). Conclusion: Adjunctive ESL was generally well tolerated in children aged 4-17 years with focal seizures. The safety profile of ESL in children was comparable to that observed in adults.

scholarly journals Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: Randomised double-blind placebo-controlled study

2006 ◽  
Vol 188 (1) ◽  
pp. 46-50 ◽  
Author(s):  
Sophia Frangou ◽  
Michael Lewis ◽  
Paul McCrone
Keyword(s):  
Eicosapentaenoic Acid ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Unipolar Depression ◽  
Adjunctive Treatment ◽  
Secondary Outcome ◽  
Controlled Study ◽  
Double Blind Study ◽  
Young Mania ◽  
Double Blind

BackgroundEpidemiological and clinical studies suggest that increased intake of eicosapentaenoic acid (EPA) alleviates unipolar depression.AimsTo examine the efficacy of EPA in treating depression in bipolar disorder.MethodIn a 12-week, double-blind study individuals with bipolar depression were randomly assigned to adjunctive treatment with placebo (n=26) or with 1g/day (n=24) or 2 g/day (n=25) of ethyl-EPA. Primary efficacy was assessed by the Hamilton Rating Scale for Depression (HRSD), with changes in the Young Mania Rating Scale and Clinical Global Impression Scale (CGI) as secondary outcome measures.ResultsThere was no apparent benefit of 2g over 1g ethyl-EPA daily. Significant improvement was noted with ethyl-EPA treatment compared with placebo in the HRSD (P=0.04) and the CGI (P=0.004) scores. Both doses were well tolerated.ConclusionsAdjunctive ethyl-EPA is an effective and well-tolerated intervention in bipolar depression.

scholarly journals Adopting an Orphan Drug: Rufinamide for Lennox–Gastaut Syndrome

2009 ◽  
Vol 9 (3) ◽  
pp. 72-74 ◽  
Author(s):  
Susan T. Herman
Keyword(s):  
Seizure Frequency ◽  
Therapy Group ◽  
Controlled Trial ◽  
Treatment Options ◽  
Baseline Period ◽  
Epilepsy Syndrome ◽  
Pediatric Epilepsy ◽  
Percentage Reduction ◽  
Double Blind ◽  
Median Percentage

Rufinamide for Generalized Seizures Associated with Lennox–Gastaut Syndrome. Glauser T, Kluger G, Sachdeo R, Krauss G, Perdomo C, Arroyo S. Neurology 2008;70(21):1950–1958. BACKGROUND: Lennox–Gastaut syndrome is a catastrophic pediatric epilepsy syndrome characterized by multiple types of treatment-resistant seizures and high rates of seizure-related injury. Current available treatments are inadequate, leaving patients with few treatment options and opportunities. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of the antiepileptic drug rufinamide in patients with Lennox–Gastaut syndrome. Eligible patients between 4 and 30 years of age had multiple types of seizures (including tonic–atonic and atypical absence seizures) with a minimum of 90 seizures in the month before baseline and a recent history of a slow spike-and-wave pattern on EEG. RESULTS: After a 28-day baseline period, 139 eligible patients were randomized; 138 patients received either rufinamide (n = 74) or placebo (n = 64) in addition to their other antiepileptic drugs. The median percentage reduction in total seizure frequency was greater in the rufinamide therapy group than in the placebo group (32.7% vs 11.7%, p = 0.0015). There was a difference ( p < 0.0001) in tonic–atonic (“drop attack”) seizure frequency with rufinamide (42.5% median percentage reduction) vs placebo (1.4% increase). The rufinamide group had a greater improvement in seizure severity ( p = 0.0041) and a higher 50% responder rate compared with placebo for total seizures ( p = 0.0045) and tonic–atonic seizures ( p = 0.002). The common adverse events (reported by 10% of patients receiving rufinamide) were somnolence (24.3% with rufinamide vs 12.5% with placebo) and vomiting (21.6% vs 6.3%). CONCLUSIONS: Rufinamide was an effective and well-tolerated treatment for seizures associated with Lennox–Gastaut syndrome.

A Double-Blind, Randomized, Placebo-Controlled Study of Quetiapine as Adjunctive Treatment for Adolescent Mania

2002 ◽  
Vol 41 (10) ◽  
pp. 1216-1223 ◽  
Author(s):  
MELISSA P. DELBELLO ◽  
MICHAEL L. SCHWIERS ◽  
H. LEE ROSENBERG ◽  
STEPHEN M. STRAKOWSKI
Keyword(s):  
Adjunctive Treatment ◽  
Controlled Study ◽  
Double Blind

scholarly journals Double-Blind Cross-Over Placebo Controlled Study of Flunarizine in Patients With Therapy Resistant Epilepsy

1989 ◽  
Vol 16 (2) ◽  
pp. 187-190 ◽  
Author(s):  
E. Starreveld ◽  
F. de Beukelaar ◽  
A.F. Wilson ◽  
D.R. McLean ◽  
Helen P. Findlay
Keyword(s):  
Placebo Group ◽  
Depressive Symptoms ◽  
Side Effects ◽  
Seizure Frequency ◽  
Controlled Study ◽  
Double Blind ◽  
Adverse Side Effects ◽  
Generalized Seizures ◽  
Daily Dose ◽  
The Mean

ABSTRACT:Twenty-five patients with long-standing therapy resistant epilepsy were studied in an eight-month double- blind cross-over add-on trial with a daily dose of 15 mg flunarizine. In five patients the seizure frequency decreased 50% or more. The mean seizure frequency reduction in the patients on flunarizine was 35%. Particularly the control of secondary generalized seizures improved. Flunarizine did not significantly alter the plasma levels of the regular anticonvulsant drugs. Minimal adverse side effects were reported equally in the flunarizine and the placebo group. In three patients depressive symptoms improved and two patients became free of postictal headaches. Flunarizine appears to be a safe adjuvant anticonvulsant.

Sign in / Sign up

Export Citation Format

Share Document