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Neuro-oncology Practice Oct 2021Comprehensive data on the efficacy and tolerability of antiepileptic drugs (AED) treatment in glioma patients with epilepsy are currently lacking. In this systematic... (Review)
Review
BACKGROUND
Comprehensive data on the efficacy and tolerability of antiepileptic drugs (AED) treatment in glioma patients with epilepsy are currently lacking. In this systematic review, we specifically assessed the efficacy of AEDs in patients with a grade II-IV glioma.
METHODS
Electronic databases PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane Library were searched up to June 2020. Three different outcomes for both mono- and polytherapy were extracted from all eligible articles: (i) seizure freedom; (ii) ≥50% reduction in seizure frequency; and (iii) treatment failure. Weighted averages (WA) were calculated for outcomes at 6 and 12 months.
RESULTS
A total of 66 studies were included. Regarding the individual outcomes on the efficacy of monotherapy, the highest seizure freedom rate at 6 months was with phenytoin (WA = 72%) while at 12-month pregabalin (WA = 75%) and levetiracetam (WA = 74%) showed highest efficacy. Concerning ≥50% seizure reduction rates, levetiracetam showed highest efficacy at 6 and 12 months (WAs of 82% and 97%, respectively). However, treatment failure rates at 12 months were highest for phenytoin (WA = 34%) and pregabalin (41%). When comparing the described polytherapy combinations with follow-up of ≥6 months, levetiracetam combined with phenytoin was most effective followed by levetiracetam combined with valproic acid.
CONCLUSION
Given the heterogeneous patient populations and the low scientific quality across the different studies, seizure rates need to be interpreted with caution. Based on the current limited evidence, with the ranking of AEDs being confined to the AEDs studied, levetiracetam, phenytoin, and pregabalin seem to be most effective as AED monotherapy in glioma patients with epilepsy, with levetiracetam showing the lowest treatment failure rate, compared to the other AEDs studied.
PubMed: 34589231
DOI: 10.1093/nop/npab030 -
The Cochrane Database of Systematic... May 2014Acupuncture is increasingly used in people with epilepsy. It remains unclear whether existing evidence is rigorous enough to support its use. This is an update of a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acupuncture is increasingly used in people with epilepsy. It remains unclear whether existing evidence is rigorous enough to support its use. This is an update of a Cochrane review first published in 2008.
OBJECTIVES
To determine the effectiveness and safety of acupuncture in people with epilepsy.
SEARCH METHODS
We searched the Cochrane Epilepsy Group Specialised Register (June 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 5), MEDLINE, EMBASE, CINAHL, AMED and other databases (from inception to June 2013). We reviewed reference lists from relevant trials. We did not impose any language restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing acupuncture with placebo or sham treatment, antiepileptic drugs or no treatment; or comparing acupuncture plus other treatments with the same other treatments, involving people of any age with any type of epilepsy.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We included 17 RCTs with 1538 participants that had a wide age range and were suffering mainly from generalized epilepsy. The duration of treatment varied from 7.5 weeks to 1 year. All included trials had a high risk of bias with short follow-up. Compared with Chinese herbs, needle acupuncture plus Chinese herbs was not effective in achieving at least 50% reduction in seizure frequency (80% in control group versus 90% in intervention group, RR 1.13, 95% CI 0.97 to 1.31, 2 trials; assumed risk 500 per 1000, corresponding risk 485 to 655 per 1000). Compared with valproate, needle acupuncture plus valproate was not effective in achieving freedom from seizures (44% in control group versus 42.7% in intervention group, RR 0.97, 95% CI 0.72 to 1.30, 2 trials; assumed risk 136 per 1000, corresponding risk 97 to 177 per 1000) or at least 50% reduction in seizure frequency (69.3% in control group versus 81.3% in intervention group, RR 1.34, 95% CI 0.52 to 3.48, 2 trials; assumed risk 556 per 1000, corresponding risk 289 to 1000 per 1000) but may have achieved better quality of life (QOL) after treatment (QOLIE-31 score (higher score indicated better QOL) mean 170.22 points in the control group versus 180.32 points in the intervention group, MD 10.10 points, 95% CI 2.51 to 17.69 points, 1 trial). Compared with phenytoin, needle acupuncture was not effective in achieving at least 50% reduction in seizure frequency (70% in control group versus 94.4% in intervention group, RR 1.43, 95% CI 0.46 to 4.44, 2 trials; assumed risk 700 per 1000, corresponding risk 322 to 1000 per 1000). Compared with valproate, needle acupuncture was not effective in achieving seizure freedom (14.1% in control group versus 25.2% in intervention group, RR 1.75, 95% CI 0.93 to 3.27, 2 trials; assumed risk 136 per 1000, corresponding risk 126 to 445 per 1000) but may be effective in achieving at least 50% reduction in seizure frequency (55.3% in control group versus 73.7% in intervention group, RR 1.32, 95% CI 1.05 to 1.66, 2 trials; assumed risk 556 per 1000, corresponding risk 583 to 923 per 1000) and better QOL after treatment (QOLIE-31 score mean 172.6 points in the control group versus 184.64 points in the intervention group, MD 12.04 points, 95% CI 4.05 to 20.03 points, 1 trial). Compared with antiepileptic drugs, catgut implantation at acupoints plus antiepileptic drugs was not effective in achieving seizure freedom (13% in control group versus 19.6% in intervention group, RR 1.51, 95% CI 0.93 to 2.43, 4 trials; assumed risk 127 per 1000, corresponding risk 118 to 309 per 1000) but may be effective in achieving at least 50% reduction in seizure frequency (63.1% in control group versus 82% in intervention group, RR 1.42, 95% CI 1.07 to 1.89, 5 trials; assumed risk 444 per 1000, corresponding risk 475 to 840 per 1000) and better QOL after treatment (QOLIE-31 score (higher score indicated worse quality of life) mean 53.21 points in the control group versus 45.67 points in the intervention group, MD -7.54 points, 95% CI -14.47 to -0.61 points, 1 trial). Compared with valproate, catgut implantation may be effective in achieving seizure freedom (8% in control group versus 19.7% in intervention group, RR 2.82, 95% CI 1.61 to 4.94, 4 trials; assumed risk 82 per 1000, corresponding risk 132 to 406 per 1000) and better QOL after treatment (QOLIE-31 score (higher score indicated better quality of life) mean 172.6 points in the control group versus 191.33 points in the intervention group, MD 18.73 points, 95% CI 11.10 to 26.36 points, 1 trial) but not at least 50% reduction in seizure frequency (65.6% in control group versus 91.7% in intervention group, RR 1.31, 95% CI 0.94 to 1.84, 4 trials; assumed risk 721 per 1000, corresponding risk 677 to 1000 per 1000). Acupuncture did not have excess adverse events compared to control treatment in the included trials.
AUTHORS' CONCLUSIONS
Available RCTs are small, heterogeneous and have high risk of bias. The current evidence does not support acupuncture for treating epilepsy.
Topics: Acupuncture Therapy; Anticonvulsants; Child; Combined Modality Therapy; Drugs, Chinese Herbal; Epilepsy, Generalized; Humans; Phenytoin; Randomized Controlled Trials as Topic; Treatment Outcome; Valproic Acid
PubMed: 24801225
DOI: 10.1002/14651858.CD005062.pub4 -
Acute Medicine & Surgery 2022Status epilepticus (SE) is a life-threatening neurological emergency. There is insufficient evidence regarding which antiepileptic therapy is most effective in patients... (Review)
Review
AIM
Status epilepticus (SE) is a life-threatening neurological emergency. There is insufficient evidence regarding which antiepileptic therapy is most effective in patients with benzodiazepine-refractory convulsive SE. Therefore, this study aimed to evaluate intravenous phenytoin (PHT) and other intravenous antiepileptic medications for SE.
METHODS
We searched PubMed, the Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi for published randomized controlled trials (RCTs) in humans up to August 2019. We compared outcomes between intravenous PHT and other intravenous medications. The important primary composite outcomes were the successful clinical cessation of seizures, mortality, and neurological outcomes at discharge. The reliability of the level of evidence for each outcome was compared using the Grading of Recommendations Assessment, Development, and Evaluation approach.
RESULTS
A total of 1,103 studies were identified from the databases, and 10 RCTs were included in the analysis. The ratio of successful clinical seizure cessation was significantly lower (risk ratio [RR] 0.89; 95% confidence interval [CI], 0.82-0.97) for patients treated with intravenous PHT than with other medications. When we compared mortality and neurological outcomes at discharge, we observed no significant differences between patients treated with PHT and those treated with other medications. The RRs were 1.07 (95% CI, 0.55-2.08) and 0.91 (95% CI, 0.72-1.15) for mortality and neurological outcomes at discharge, respectively.
CONCLUSIONS
Our findings showed that intravenous PHT was significantly inferior to other medications in terms of the cessation of seizures. No significant differences were observed in mortality or neurological outcomes between PHT and other medications.
PubMed: 35028156
DOI: 10.1002/ams2.717 -
The Canadian Journal of Hospital... 2022Status epilepticus (SE) is a neurologic emergency with potential for substantial mortality and morbidity. Parenteral benzodiazepine is the established first-line... (Review)
Review
BACKGROUND
Status epilepticus (SE) is a neurologic emergency with potential for substantial mortality and morbidity. Parenteral benzodiazepine is the established first-line treatment but fails to control SE in about one-third of patients. Levetiracetam may be used for SE that is refractory to benzodiazepine therapy.
OBJECTIVE
To examine, by means of a systematic review, the role of IV levetiracetam for the treatment of SE in adults.
DATA SOURCES
MEDLINE, Embase, CENTRAL, and CINAHL databases were searched, from inception to August 18, 2020.
STUDY SELECTION AND DATA EXTRACTION
Included in this review were prospective randomized controlled trials comparing levetiracetam with another antiepileptic drug, given with or after a benzodiazepine, in adult patients with SE. The primary outcome was cessation of SE. Quality of evidence was assessed with the Cochrane risk-of-bias tool. Characteristics of the included studies were reported using descriptive statistics.
DATA SYNTHESIS
Five studies compared IV levetiracetam with valproic acid, phenytoin (or its prodrug fosphenytoin), or both. All 5 studies found no statistically significant differences in efficacy or safety end points. There were numerically more cases of hypotension and respiratory failure with phenytoin, and more cases of psychiatric adverse effects (e.g., post-ictal psychosis) with levetiracetam.
CONCLUSIONS
Available evidence suggests that levetiracetam is as effective as valproic acid or phenytoin for the cessation of SE in adults. Other factors should therefore dictate the choice of antiepileptic drug for patients with SE, such as adverse effect profile, logistics of administration, drug cost, inclusion on hospital formularies, and drug availability.
PubMed: 34987263
DOI: 10.4212/cjhp.v75i1.3254 -
The Cochrane Database of Systematic... May 2012Antiepileptic drugs have been used in pain management since the 1960s; some have shown efficacy in treating different neuropathic pain conditions. Phenytoin is an... (Review)
Review
BACKGROUND
Antiepileptic drugs have been used in pain management since the 1960s; some have shown efficacy in treating different neuropathic pain conditions. Phenytoin is an established antiepileptic drug that has been used occasionally to treat intractable trigeminal neuralgia.
OBJECTIVES
To assess the analgesic efficacy and adverse effects of the antiepileptic drug phenytoin in neuropathic pain and fibromyalgia.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2), MEDLINE, and EMBASE to 28 February 2012, together with reference lists of retrieved papers and reviews, and ClinicalTrials.gov.
SELECTION CRITERIA
We planned to include randomised, double-blind studies of eight weeks duration or longer, comparing phenytoin with placebo or another active treatment in chronic neuropathic pain or fibromyalgia.
DATA COLLECTION AND ANALYSIS
Two review authors would independently extract data for efficacy and adverse events, and examine issues of study quality.
MAIN RESULTS
We did not identify any studies that satisfied the inclusion criteria.
AUTHORS' CONCLUSIONS
This review uncovered no evidence of sufficient quality to support the use of phenytoin in chronic neuropathic pain or fibromyalgia.
Topics: Adult; Analgesics; Anticonvulsants; Fibromyalgia; Humans; Neuralgia; Pain Management; Phenytoin
PubMed: 22592741
DOI: 10.1002/14651858.CD009485.pub2 -
Seizure Feb 2017Posttraumatic epileptic seizures (PTS) are a serious complication in patients with subdural haematoma (SDH). However, to date, several studies have shown discordances... (Review)
Review
BACKGROUND
Posttraumatic epileptic seizures (PTS) are a serious complication in patients with subdural haematoma (SDH). However, to date, several studies have shown discordances about SDH-associated seizures in terms of incidence, risk factors and prophylactic antiepileptic treatment.
OBJECTIVE
The aim of this study was to analyse the incidence, risk factors of PTS and the role of prophylactic antiepileptic treatment in patients with SDH.
DATA SOURCES
A systematic literature review examining PTS in patients with SDH was performed using PubMed gateway, Cochrane Central Register of Controlled Trials, and Excerpta Medica dataBASE between September 1961 and February 2016. Search terms included subdural haematoma, seizure, epilepsy, prophylactic antiepileptic drugs, anticonvulsive medication, and risk factors.
DATA SELECTION
Human-based clinical studies focusing on epileptic seizures in patients with SDH.
DATA EXTRACTION AND SYNTHESIS
PRISMA statements were used for assessing data quality. Two independent reviewers extracted data from included studies and disagreement was solved by consensus. Twenty-four studies were identified for inclusion into the study.
RESULTS
Overall incidence of early PTS (ePTS) and late PTS (lPTS)/2 years was 28% and 43% in acute SDH (aSDH) whereas the incidence of e- and lPTS was lower in chronic SDH (cSDH; 5.3% vs. 10%). Overall risk factors for PTS in patients with aSDH were: 24h postoperative Glasgow Coma Score (GCS) score below 9 (OR 10.5), craniotomy (OR 3.9), preoperative GCS below 8 (OR 3.1). In patients with cSDH the risk factors were alcohol abuse (OR 14.3), change of mental status (OR 7.2), previous stroke (OR 5.3) and density of haematoma in computer tomography (OR 3.8). Age, sex, haematoma size/side and midline shifts were not significant risk factors for PTS in both types of SDH. In prevention of PTS phenytoin and levetiracetam showed similar efficacy (OR 1.3), whereas levetiracetam was associated with significantly lower adverse effects (OR 0.1).
LIMITATIONS
Most of the studies were of retrospective nature with a small sample size. Due to the inclusion criteria, some studies had to be excluded and that might lead to selection bias.
CONCLUSIONS
PTS are a serious complication in patients with SDH, particularly in aSDH. The "prophylactic use" of antiepileptic drugs might be beneficial in patients with cumulative risk factors.
Topics: Adult; Anticonvulsants; Epilepsy; Hematoma, Subdural; Humans; Incidence; PubMed; Risk Factors
PubMed: 27914224
DOI: 10.1016/j.seizure.2016.11.017 -
Indian Journal of Dermatology,... 2013Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous drug reactions. No large scale epidemiological data are available for this... (Review)
Review
BACKGROUND
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous drug reactions. No large scale epidemiological data are available for this disorder in India.
AIMS
To carry out a systematic review of the published evidence of the drug-induced SJS and TEN in Indian population.
METHODS
Publications from 1995 to 2011 describing SJS and TEN in Indian population were searched in PubMed, MEDLINE, EMBASE and UK PUBMED Central electronic databases. Data were collected for the causative drugs and other clinical characteristics of SJS and TEN from the selected studies.
RESULTS
From 225 references, 10 references were included as per selection criteria. The major causative drugs were antimicrobials (37.27%), anti-epileptics (35.73%) and non-steroidal anti-inflammatory drugs (15.93%). Carbamazepine (18.25%), phenytoin (13.37%), fluoroquinolones (8.48%) and paracetamol (6.17%) were most commonly implicated drugs. Regional differences were observed for fluoroquinolones, sulfa drugs and carbamazepine. Total 62.96% of patients showed systemic complications. Most common complications were ocular (40.29%) and septicemia (17.65%). Higher mortality was observed for TEN as compared to SJS (odd ratio-7.19; 95% confidence interval (CI) 1.62-31.92; p = 0.0023). Observed mortality is higher than expected as per SCORTEN score 3. Duration of hospital stay was significantly higher in TEN (20.6 days; 95% CI 14.4-26.8) as compared to SJS (9.7 days; 95% CI 5.8-13.6; p = 0.020). Cost of management was significantly higher in TEN (Rs. 7910; 95% CI 5672-10147; p < 0.0001) as compared to SJS (Rs 2460; 95% CI 1762-3158). No statistical data were described for steroid use in the studies included.
CONCLUSION
Carbamazepine, phenytoin, fluoroquinolones and paracetamol were the major causative drugs. TEN is showing higher mortality, morbidity and economic burden than SJS.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Fluoroquinolones; Humans; India; Stevens-Johnson Syndrome
PubMed: 23619444
DOI: 10.4103/0378-6323.110749 -
The Cochrane Database of Systematic... Aug 2019More than three million persons are disabled by leprosy worldwide. The main complication of sensory nerve damage is neuropathic ulceration, particularly of the feet. In... (Review)
Review
BACKGROUND
More than three million persons are disabled by leprosy worldwide. The main complication of sensory nerve damage is neuropathic ulceration, particularly of the feet. In this review we explored interventions that can prevent and treat secondary damage to skin and limbs.
OBJECTIVES
To assess the effects of self-care, dressings and footwear in preventing and healing secondary damage to the skin in persons affected by leprosy.
SEARCH METHODS
We searched the Cochrane Skin Group Specialised Register (April 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2008), MEDLINE (from 2003 to April 2008), EMBASE (from 2005 to April 2008), CINAHL (1982-2006) and LILACS (1982- April 2008 ) as well as online registers of ongoing trials (April 2008).
SELECTION CRITERIA
Randomised controlled trials involving anyone with leprosy and damage to peripheral nerves treated with any measures designed to prevent damage with the aim of healing existing ulcers and preventing development of new ulcers.
DATA COLLECTION AND ANALYSIS
Two authors assessed trial quality and extracted data.
MAIN RESULTS
Eight trials with a total of 557 participants were included. The quality of the trials was generally poor. The interventions and outcome measures were diverse. Although three studies that compared zinc tape to more traditional dressings found some benefit, none of these showed a statistically significant effect. One trial indicated that topical ketanserin had a better effect on wound healing than clioquinol cream or zinc paste, RR was 6.00 (95% CI 1.45 to 24.75). We did not combine the results of the two studies that compared topical phenytoin to saline dressing, but both studies found statistically significant effects in favour of phenytoin for healing of ulcer (SMD -2.34; 95% CI -3.30 to -1.39; and SMD -0.79; 95% CI -1.20 to 0.39). Canvas shoes were not much better than PVC-boots, and double rocker shoes did not promote healing much more than below-knee plasters.
AUTHORS' CONCLUSIONS
One study suggested that topical ketanserin is more effective than clioquinol cream or zinc paste. Topical phenytoin (two studies) may be more effective than saline dressing regarding ulcer healing. For the other dressings the results were equivocal. Canvas shoes were a little better than PVC-boots, but not significantly, and the effect of double rocker shoes compared to below-knee plasters was no different in promoting the healing of ulcers. No side effects were documented.There is a lack of high quality research in the field of ulcer prevention and treatment in leprosy. New trials should follow the current standards for design and reporting of randomised controlled trials.
PubMed: 31425616
DOI: 10.1002/14651858.CD004833.pub4 -
The Cochrane Database of Systematic... Dec 2010Eclampsia, the occurrence of a seizure in association with pre-eclampsia, remains a rare but serious complication of pregnancy. A number of different anticonvulsants are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Eclampsia, the occurrence of a seizure in association with pre-eclampsia, remains a rare but serious complication of pregnancy. A number of different anticonvulsants are used to control eclamptic fits and to prevent further fits.
OBJECTIVES
The objective of this review was to assess the effects of magnesium sulphate compared with diazepam when used for the care of women with eclampsia. Magnesium sulphate is compared with phenytoin and with lytic cocktail in other Cochrane reviews.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2010) and CENTRAL (2010, Issue 3).
SELECTION CRITERIA
Randomised trials comparing magnesium sulphate (intravenous or intramuscular administration) with diazepam for women with a clinical diagnosis of eclampsia.
DATA COLLECTION AND ANALYSIS
Two authors assessed and extracted data independently.
MAIN RESULTS
We have included seven trials, involving 1396 women. Three trials (1030 women) were good quality. Magnesium sulphate was associated with a reduction in maternal death (seven trials;1396 women; risk ratio (RR) 0.59, 95% confidence interval (CI) 0.38 to 0.92) and recurrence of seizures (seven trials;1390 women; RR 0.43, 95% CI 0.33 to 0.55) compared to diazepam. There were no clear differences in other measures of maternal morbidity.There was no clear difference in perinatal mortality (four trials; 788 infants; RR 1.04, 95% CI 0.81 to 1.34) or neonatal mortality (four trials; 759 infants; RR 1.18, 95% CI 0.75 to 1.84). In the magnesium sulphate group, fewer liveborn babies had an Apgar score less than seven at one minute (two trials; 597 babies; RR 0.75, 95% CI 0.65 to 0.87) or at five minutes (RR 0.70, 95% CI 0.54 to 0.90), and fewer appeared to need intubation at the place of birth (two trials; 591 infants; RR 0.67, 95% CI 0.45 to 1.00). There was no difference in admission to a special care nursery (four trials; 834 infants; RR 0.91, 95% CI 0.79 to 1.05), but fewer babies in the magnesium sulphate group had a length of stay more than seven days (three trials 631 babies; RR 0.66, 95% CI 0.46 to 0.96).
AUTHORS' CONCLUSIONS
Magnesium sulphate for women with eclampsia reduces the risk ratio of maternal death and of recurrence of seizures, compared with diazepam.
Topics: Anticonvulsants; Diazepam; Eclampsia; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Magnesium Sulfate; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 21154341
DOI: 10.1002/14651858.CD000127.pub2 -
The Cochrane Database of Systematic... Apr 2016Worldwide, phenytoin and valproate are commonly used antiepileptic drugs. It is generally believed that phenytoin is more effective for partial onset seizures, and that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Worldwide, phenytoin and valproate are commonly used antiepileptic drugs. It is generally believed that phenytoin is more effective for partial onset seizures, and that valproate is more effective for generalised onset tonic-clonic seizures (with or without other generalised seizure types). This review is one in a series of Cochrane reviews investigating pair-wise monotherapy comparisons. This is the latest updated version of the review first published in 2001 and updated in 2013.
OBJECTIVES
To review the time to withdrawal, remission and first seizure of phenytoin compared to valproate when used as monotherapy in people with partial onset seizures or generalised tonic-clonic seizures (with or without other generalised seizure types).
SEARCH METHODS
We searched the Cochrane Epilepsy Group's Specialised Register (19 May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library; 2015, Issue 4), MEDLINE (1946 to 19 May 2015), SCOPUS (19 February 2013), ClinicalTrials.gov (19 May 2015), and WHO International Clinical Trials Registry Platform ICTRP (19 May 2015). We handsearched relevant journals, contacted pharmaceutical companies, original trial investigators and experts in the field.
SELECTION CRITERIA
Randomised controlled trials (RCTs) in children or adults with partial onset seizures or generalised onset tonic-clonic seizures with a comparison of valproate monotherapy versus phenytoin monotherapy.
DATA COLLECTION AND ANALYSIS
This was an individual participant data (IPD) review. Outcomes were time to: (a) withdrawal of allocated treatment (retention time); (b) achieve 12-month remission (seizure-free period); (c) achieve six-month remission (seizure-free period); and (d) first seizure (post-randomisation). We used Cox proportional hazards regression models to obtain study-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs), and the generic inverse variance method to obtain the overall pooled HR and 95% CI.
MAIN RESULTS
IPD were available for 669 individuals out of 1119 eligible individuals from five out of 11 trials, 60% of the potential data. Results apply to partial onset seizures (simple, complex and secondary generalised tonic-clonic seizures), and generalised tonic-clonic seizures, but not other generalised seizure types (absence or myoclonus seizure types). For remission outcomes: HR > 1 indicates an advantage for phenytoin; and for first seizure and withdrawal outcomes: HR > 1 indicates an advantage for valproate.The main overall results (pooled HR adjusted for seizure type) were time to: (a) withdrawal of allocated treatment 1.09 (95% CI 0.76 to 1.55); (b) achieve 12-month remission 0.98 (95% CI 0.78 to 1.23); (c) achieve six-month remission 0.95 (95% CI 0.78 to 1.15); and (d) first seizure 0.93 (95% CI 0.75 to 1.14). The results suggest no overall difference between the drugs for these outcomes. We did not find any statistical interaction between treatment and seizure type (partial versus generalised).
AUTHORS' CONCLUSIONS
We have not found evidence that a significant difference exists between phenytoin and valproate for the outcomes examined in this review. However misclassification of seizure type may have confounded the results of this review. Results do not apply to absence or myoclonus seizure types. No outright evidence was found to support or refute current treatment policies.
Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Humans; Phenytoin; Randomized Controlled Trials as Topic; Seizures; Valproic Acid
PubMed: 27123830
DOI: 10.1002/14651858.CD001769.pub3