Карбамазепин немедленного высвобождения против карбамазепина контролируемого высвобождения в лечении эпилепсии
Referencias
References to studies included in this review
References to studies excluded from this review
Additional references
References to other published versions of this review
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Ir a:
| Methods | Single‐blind, controlled, parallel group study 3‐armed study: 1 non‐medication non‐epileptic, 1 IR CBZ, 1 CR CBZ Post‐randomisation baseline period with all patients on conventional CBZ ‐ length of time unclear Treatment period: at least 1 month | |
| Participants | Patients with a diagnosis of partial or generalised epilepsy. 11 patients were enrolled and completed both study periods. Mean age: 32.1 (16‐58) years | |
| Interventions | Both CR and IR CBZ administered as 400mg tablets twice daily. Order determined by randomisation | |
| Outcomes | Incidence of cognitive adverse events | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "assigned randomly" Comment: insufficient information provided to determine judgement for sequence generation |
| Allocation concealment (selection bias) | Unclear risk | Comment: details regarding allocation concealment were not provided |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: "single‐blind" Comment: identical tablets and dose frequency were administered |
| Blinding of outcome assessment (detection bias) | High risk | Quote: "single‐blind" |
| Incomplete outcome data (attrition bias) | Low risk | Comment: all participants were included in the analysis |
| Selective reporting (reporting bias) | Low risk | Comment: protocol unavailable, but appears all expected and pre‐specified outcomes are reported |
| Other bias | Low risk | Comment: the study appears to be free of other sources of bias |
| Methods | Double‐blind, controlled, crossover study 2 treatment arms: 1 IR CBZ, 1 CR CBZ Pre‐randomisation retrospective baseline period: 3 months Treatment period: 56 days per arm | |
| Participants | Patients diagnosed with partial or generalised epilepsy prescribed monotherapy with CBZ 200mg tablets either tds or qds as a stable regimen for at least 3 months. Participants must not have had more than 3 seizures in each of the 3 months prior to enrolment. 101 patients enrolled, 87 completed both study arms. Mean age for group 1 was 34 years, group 2 was 32 years | |
| Interventions | Monotherapy at usual daily dose with IR and CR CBZ, order determined by randomisation. Mean daily dose: 1084mg (range 400‐2000mg) | |
| Outcomes | Seizure frequency Incidence of adverse events | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "randomised" Comment: insufficient information provided to determine judgement for sequence generation |
| Allocation concealment (selection bias) | Unclear risk | Comment: details regarding allocation concealment were not provided |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: "placebo identical in appearance" |
| Blinding of outcome assessment (detection bias) | Unclear risk | Quote: "double‐blind" Comment: details of outcome assessment blinding not provided |
| Incomplete outcome data (attrition bias) | Low risk | Comment: 86 patients were included in the analysis out of 96 randomised, and study attrition has been reported. Therefore, despite no ITT analysis, there are no concerns about missing data |
| Selective reporting (reporting bias) | Low risk | Comment: protocol unavailable, but appears all expected and pre‐specified outcomes are reported |
| Other bias | Unclear risk | Comment: financial support provided by Ciba‐Geigy Corporation |
| Methods | Double‐blind, controlled, crossover study 2 treatment arms: 1 IR CBZ, 1 CR CBZ Optimal dose‐finding phase: up to 2 months (per arm) Maintenance phase (used for statistical analysis): 1 month | |
| Participants | Adult patients with epilepsy treated with CBZ monotherapy for at least 3 months with either inadequate seizure control or intermittent adverse events. 48 patients were enrolled and completed both study arms. Mean age: 34.2 (18‐64) years | |
| Interventions | Monotherapy with either CR or IR CBZ during each study arm. Optimal doses and frequencies of administration were determined over the initial 2 months of each study period. Mean daily dose: 1.125mg (400‐2400mg) | |
| Outcomes | Seizure frequency Incidence of adverse events | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "treatments were administered in randomised sequence" Comment: insufficient information provided to determine judgement for sequence generation |
| Allocation concealment (selection bias) | Unclear risk | Comment: details regarding allocation concealment were not provided |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: "the two CBZ formulations were indistinguishable in taste or physical appearance" Comment: double‐blind |
| Blinding of outcome assessment (detection bias) | Unclear risk | Comment: details of outcome assessment blinding not provided |
| Incomplete outcome data (attrition bias) | Low risk | Quote: "a total of 48 patients (...) were enrolled in the study and none of them were withdrawn from it" Comment: All 48 patients are included in the results |
| Selective reporting (reporting bias) | Low risk | Comment: protocol unavailable, but appears all expected and pre‐specified outcomes are reported |
| Other bias | Low risk | Comment: the study appears to be free of other sources of bias |
| Methods | Double‐blind, controlled, crossover study 2 treatment arms: 1 IR CBZ, 1 CR CBZ Pre‐randomisation baseline period: 30 days Treatment period: 2 weeks (per arm) | |
| Participants | Adult patients with a diagnosis of epilepsy prescribed IR CBZ at a stable and therapeutic dose for at least 30 days. 24 patients were enrolled, 23 were included in the analysis. Mean age: 36.1 (21‐54) years | |
| Interventions | CBZ dose was determined according to pre‐study dose. If a change was required the dose remained the same for 30 days prior to commencing the study. 9 patients were prescribed 800mg, 9 patients 1200mg and 6 patients 1600mg daily. IR CBZ was administered four times daily, CR CBZ twice daily with 2 placebo tablets | |
| Outcomes | Seizure frequency Incidence of adverse events | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "the order of the sequence was randomised" Comment: insufficient information provided to determine judgement for sequence generation |
| Allocation concealment (selection bias) | Unclear risk | Comment: details regarding allocation concealment were not provided |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: "All active drugs and placebos were formulated in identical capsules, which in turn were packaged in blister packs." Comment: double‐blind |
| Blinding of outcome assessment (detection bias) | Unclear risk | Comment: details of outcome assessment blinding not provided |
| Incomplete outcome data (attrition bias) | Low risk | Quote: "An additional patient was enrolled but did not complete the study for reasons related to difficulties in proper blood sampling" Comment: Only missing data for one patient, and study attrition has been reported. Therefore, no concerns about missing data |
| Selective reporting (reporting bias) | Low risk | Comment: protocol unavailable, but appears all expected and pre‐specified outcomes are reported |
| Other bias | Unclear risk | Comment: support provided by Shire Laboratories |
| Methods | Double‐blind, controlled, crossover study 2 treatment arms: 1 IR CBZ, 1 CR CBZ Pre‐randomisation baseline period: 2 months Treatment period: 10 weeks (per arm) | |
| Participants | Mentally retarded patients prescribed CBZ at a therapeutic serum level for at least 2 months and with at least 4 seizures per month despite treatment. 21 patients enrolled, 20 patients completed both arms. Mean age 24.9 (6‐38) years | |
| Interventions | Usual daily CBZ dose divided into tds for IR CBZ and bd with placebo tablet for CR CBZ. Order determined by randomisation. Mean daily dose: 780mg | |
| Outcomes | Seizure frequency | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "randomised" Comment: insufficient information provided to provide judgement for sequence generation |
| Allocation concealment (selection bias) | Unclear risk | Comment: details regarding allocation concealment were not provided |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: " the conventional CBZ, slow‐release CBZ, and placebo tablets all looked identical." Comment: double blind |
| Blinding of outcome assessment (detection bias) | Unclear risk | Comment: details of outcome assessment blinding not provided |
| Incomplete outcome data (attrition bias) | Low risk | Quote: "one of them was withdrawn because of appendicitis" Comment: Only one withdrawal, and study attrition reported |
| Selective reporting (reporting bias) | Low risk | Comment: protocol unavailable, but appears all expected and pre‐specified outcomes are reported |
| Other bias | Low risk | Comment: the study appears to be free of other bias |
| Methods | Double‐blind, controlled, crossover study 2 treatment arms: 1 IR CBZ, 1 CR CBZ Pre‐randomisation baseline period: 3 months Treatment period: 4 weeks (per arm) | |
| Participants | Adult patients with an existing diagnosis of partial or generalised epilepsy prescribed CBZ at a stable dose. 25 patients enrolled, 21 included in the final analysis Age range: 18‐53 years | |
| Interventions | IR CBZ either qds, tds or bd. CR CBZ bd. In all cases placebo tablets were included where necessary to total 4 tablets taken per day. Mean CBZ dose: 1076mg (600‐2000mg) | |
| Outcomes | Seizure frequency Incidence of cognitive adverse events | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "random order" Comment: insufficient information provided to determine judgement for sequence generation |
| Allocation concealment (selection bias) | Unclear risk | Comment: details regarding allocation concealment were not provided |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: "A double‐dummy technique was employed to control the study" Comment: patients received an identical number of tablets daily throughout both arms of the study‐ either active conventional CBZ with CBZ‐CR placebo or conventional CBZ placebo with active CBZ‐CR |
| Blinding of outcome assessment (detection bias) | Low risk | Quote: "investigator who was also unaware of the order of therapy" |
| Incomplete outcome data (attrition bias) | Low risk | Quote: "Four of the 25 patients entering the study were excluded from analysis." Comment: 21 patients were included in the analysis out of 25 randomised, and study attrition has been reported. Therefore, despite no ITT analysis, there are no concerns about missing data |
| Selective reporting (reporting bias) | Low risk | Comment: protocol unavailable, but appears all expected and pre‐specified outcomes are reported |
| Other bias | Unclear risk | Comment: financial support provided by Ciba‐Geigy Pharmaceuticals |
| Methods | Open, controlled, parallel group study 2 treatment arms: 1 IR CBZ, 1 CR CBZ No pre‐randomisation baseline period Treatment period: 20 days | |
| Participants | Adult patients with a new diagnosis of partial seizures with no previous history of antiepileptic drug treatment. 20 patients were enrolled and completed the study period. IR CBZ group mean age: 20.32 (16‐34) years. CR CBZ group mean age: 22.48 (18‐35) years | |
| Interventions | Either CR or IR CBZ treatment initiated in dose increments to a maximum of 200mg 3 times daily | |
| Outcomes | Incidence of adverse events | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "patients were randomly assigned" Comment: insufficient information provided to determine judgement for sequence generation |
| Allocation concealment (selection bias) | Unclear risk | Comment: details regarding allocation concealment were not provided |
| Blinding of participants and personnel (performance bias) | High risk | Quote: "open trial" |
| Blinding of outcome assessment (detection bias) | High risk | Quote: "open trial" |
| Incomplete outcome data (attrition bias) | Low risk | Comment: no participants were excluded from analysis |
| Selective reporting (reporting bias) | Low risk | Comment: protocol unavailable, but appears all expected and pre‐specified outcomes are reported |
| Other bias | Unclear risk | Comment: support provided by Intas Pharmaceuticals |
| Methods | Double‐blind, controlled, crossover study 2 treatment arms: 1 IR CBZ, 1 CR CBZ Pre‐randomisation baseline period: 2 months Treatment period: 3 months (per arm) | |
| Participants | Adult patients with epilepsy with few or no seizures treated with IR CBZ and experiencing moderate to severe adverse events. 21 patients were enrolled, 20 completed both study arms. Mean age: 43.35 (20‐69) years | |
| Interventions | Participants continued to take their usual dose at the same dose frequency throughout study period and in both study arms. Treatment with IR and CR CBZ as monotherapy, order determined by randomisation. Mean CBZ dose: 682mg (300‐1100mg) | |
| Outcomes | Seizure frequency Incidence of adverse events | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "patients were randomised by a computer program" |
| Allocation concealment (selection bias) | Unclear risk | Comment: details regarding allocation concealment were not provided |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: "Both tablets looked identical and were supplied in identical containers with appropriate labels." |
| Blinding of outcome assessment (detection bias) | Unclear risk | Comment: details of outcome assessment blinding not provided |
| Incomplete outcome data (attrition bias) | Low risk | Quote: "One withdrew during the trial of the first drug (C) due to ataxia and did not wish to participate further" Comment: Only 1 withdrawal, and study attrition was reported |
| Selective reporting (reporting bias) | Low risk | Comment: protocol unavailable, but appears all expected and pre‐specified outcomes are reported |
| Other bias | Low risk | Comment: the study appears to be free of other bias |
| Methods | Single‐blind, controlled, crossover study 2 treatment arms: 1 IR CBZ, 1 CR CBZ Pre‐randomisation baseline period: 3 months Treatment period: 2 weeks (per arm) | |
| Participants | Patients diagnosed with partial epilepsy and experiencing seizures prescribed a stable CBZ dose for at least 3 months. 21 patients enrolled, 18 completed both treatment arms. Mean age: 42 years | |
| Interventions | Both IR and CR CBZ were administered bd. Order determined by randomisation. Dose remained same as prior to study. Mean dose: 644mg | |
| Outcomes | Total number of seizures Total incidence of adverse events | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "randomized" Comment: insufficient information provided to determine judgement for sequence generation |
| Allocation concealment (selection bias) | Unclear risk | Comment: details regarding allocation concealment were not provided |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: given in identical containers for 2 weeks during each study period, and the observer did not know which drug was being administered." |
| Blinding of outcome assessment (detection bias) | High risk | Quote: "single‐blind" Comment: details of outcome assessment blinding not provided |
| Incomplete outcome data (attrition bias) | Low risk | Quote: "The study comprised 21 epileptic patients (...) 18 patients could be evaluated," Comment: Missing data, although study attrition reported. Therefore, no concerns about missing data |
| Selective reporting (reporting bias) | Low risk | Comment: protocol unavailable, but appears all expected and pre‐specified outcomes are reported |
| Other bias | Low risk | Comment: the study appears to be free of other bias |
| Methods | Open, controlled, crossover study 2 treatment arms: 1 IR CBZ, 1 CR CBZ Pre‐randomisation baseline period: 6 months Treatment period: 2 weeks (per arm) | |
| Participants | Adult patients with a diagnosis of epilepsy prescribed CBZ monotherapy at a stable, therapeutic dose for at least 6 months. 24 patients enrolled. 22 completed both study arms. Mean age: 36.9 (range 18‐62) years | |
| Interventions | CBZ dose remained same as prior to study. IR CBZ divided into 3 daily doses. CR CBZ divided into 2 daily doses. Mean daily dose: 615mg (300‐1100mg) | |
| Outcomes | Seizure frequency Incidence of adverse events | |
| Notes | Unclear how many participants were randomised to each group | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "randomized" Comment: insufficient information provided to determine judgement for sequence generation |
| Allocation concealment (selection bias) | Unclear risk | Comment: details regarding allocation concealment were not provided |
| Blinding of participants and personnel (performance bias) | High risk | Quote: "open" Comment: study was not blinded |
| Blinding of outcome assessment (detection bias) | High risk | Quote: "open" Comment: study was not blinded |
| Incomplete outcome data (attrition bias) | Low risk | Quote: "24 patients started the study. Four patients had to be excluded" Comment: Although there is missing data, study attrition has been reported. There is no ITT analysis |
| Selective reporting (reporting bias) | High risk | Quote: "practically no difference in side effects between the 2 treatment periods" Comment: Using the ORBIT tool we rated the study as 'A', as specific side effect outcomes were analysed, but only reported that the results are not significant. Dizziness, disturbances of vision, and any other side effects were not reported individually. It is also unclear how many participants were randomised to each group, therefore this study has been rated as high risk of bias for selective outcome reporting |
| Other bias | Low risk | Comment: the study appears to be free of other bias |
Characteristics of excluded studies [ordered by study ID]
Ir a:
| Study | Reason for exclusion |
| There was no mention of randomisation | |
| Study not published in English. Translation will be sought for an update of this review | |
| It is unclear whether a controlled‐release preparation of CBZ was used. Further information will be sought and this study will be included in an update of this review, if eligible | |
| This study concerned dose frequency of IR CBZ | |
| This study involved a comparison of two CR CBZ preparations | |
| Observational study involving one treatment cohort without comparison group | |
| This study concerned dose frequency of IR CBZ | |
| There was no mention of randomisation | |
| No relevant outcome measures were reported | |
| Study not published in English. Translation will be sought for an update of this review | |
| This study involved a comparison on two CR CBZ formulations | |
| This study compared CR CBZ to sodium valproate | |
| It is unclear whether a controlled‐release preparation of CBZ was used. Further information will be sought and this study will be included in an update of this review, if eligible |
Study flow diagram.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
