Cognitive and mood effects of phenobarbital treatment in people with epilepsy in rural China: a prospective study
- Ding Ding1,
- Qing Zhang2,
- Dong Zhou3,
- Weihong Lin4,
- Qingsheng Wu5,
- Jixin Sun6,
- Qianhua Zhao1,
- Peimin Yu1,
- Wenzhi Wang7,
- Jianzhong Wu7,
- Gail S Bell8,
- Patrick Kwan9,10,
- Hanneke M de Boer11,
- Shichuo Li12,
- Pamela J Thompson8,
- Zhen Hong1,
- Josemir W Sander8,11
- 1Institute of Neurology, Huashan Hospital, Fudan University, WHO Collaborating Centre for Research and Training in Neurosciences, Shanghai, China
- 2Ningxia Medical University affiliated Hospital, Ningxia, China
- 3Huaxi Hospital, Sichuan Province, China
- 4No 1 Hospital, Jilin University, Jilin Province, China
- 5Centre of Disease Control, Anhui Province, China
- 6Centre of Disease Control, Hebei Province, China
- 7Beijing Neurosurgical Institute, Beijing, China
- 8Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK
- 9Chinese University of Hong Kong, Hong Kong, China
- 10Departments of Medicine and Neurology, The University of Melbourne, Royal Melbourne Hospital, Melbourne, Australia
- 11SEIN – Epilepsy Institute in the Netherlands Foundation & WHO Collaborating Centre for Research, Training and Treatment of Epilepsy, Heemstede, 2103SW, The Netherlands
- 12China Association Against Epilepsy, Beijing, China
- Correspondence to Professor Ley Sander, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK;
Contributors This work was conceptualised by JWS, ZH, WW and DD, and all authors approved the protocol. Data collection was done by QZ, DZ, WL, QW, JS, QZ and PY. Analysis was undertaken by DD, ZH, GSB and JWS. The first draft was prepared by DD, ZH, PK, PY and JWS and all authors contributed to and approved the final draft. WW, ZH, HMdB, SL and JWS organised the funding. ZH and JWS are the guarantors.
- Received 21 April 2012
- Revised 25 June 2012
- Accepted 29 June 2012
- Published Online First 31 July 2012
Background Phenobarbital is an effective treatment for epilepsy but concerns remain over its potential neurocognitive toxicity. This prospective study evaluated the effects of phenobarbital treatment on cognition and mood in people with epilepsy in rural China.
Methods We recruited 144 adults with convulsive seizures and 144 healthy controls from six sites in rural China. People with epilepsy were treated with phenobarbital monotherapy for 12 months. At baseline, and at 3, 6 and 12 months, cases and controls were evaluated with a battery of neuropsychological tests: the Mini-Mental State Examination, the Hamilton Depression Rating Scale, a digit span test, a verbal fluency test, an auditory verbal learning test and a digit cancellation test. Efficacy of phenobarbital treatment was evaluated at the end of follow-up for those with epilepsy.
Results Cognitive test scores and mood ratings were available for 136 (94%) people with epilepsy and 137 (95%) controls at the 12 month follow-up. Both groups showed slightly improved performance on a number of neuropsychological measures. The people with epilepsy showed greater performance gains (p=0.012) in verbal fluency. Nine people with epilepsy complained of memory problems during the treatment period.
Conclusion In this study, phenobarbital was not found to have a major negative impact on cognitive function of people with convulsive seizures and some cognitive gains were observed, possibly due to improved seizure control.
Funding The project was funded by the Chinese Ministry of Health and Stichting Epilepsie Instellingen Nederland. The sponsors were not directly involved in the study design, in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the paper for publication. GSB, PJT and JWS are based at University College London Hospitals/University College London, which receives a proportion of funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme. JWS is supported by the Dr Marvin Weil Epilepsy Research Fund.
Competing interests DZ serves on the editorial advisory boards of Neural Regeneration Research and Chinese Journal of Neurology; has received research support from the Chinese Ministry of Health, the Chinese Medical Association and the China Association Against Epilepsy; and has been a commissioner of the neurology branch of the Chinese Medical Association. GSB's husband works for, and has shares in, GlaxoSmithKline. PK serves on the scientific advisory board of Pfizer and receives research grants from Eisai, Johnson & Johnson, Pfizer and UCB Pharma. ZH serves on the editorial advisory boards of the Chinese Journal of Neurology; has received research support from the Chinese Ministry of health and the China Association Against Epilepsy; and has been a commissioner of the neurology branch of the Chinese Medical Association. JWS served on scientific advisory boards for GlaxoSmithKline, Eisai and UCB; has received funding for travel from UCB and Janssen; serves on the editorial boards of Lancet Neurology and Epilepsia; serves on the speaker's bureaus of UCB and GlaxosmithKline; and has received research support from UCB, Eisai, the NIH, the European Union Seventh Framework Programme, the Wellcome Trust, WHO, the National Epilepsy Funds of the Netherlands and the Epilepsy Society.
Ethics approval The study was approved by the medical ethics committee of Huashan Hospital, Fudan University, Shanghai (process No 2008-005).
Provenance and peer review Not commissioned; externally peer reviewed.