Abstract
Alcohol dependence is a complex and multi-faceted problem, with alcohol misuse costing the NHS an estimated £3.5 billion annually. Appropriate pharmacological treatment, alongside behavioural therapy, is essential to the proper management of dependent individuals. NICE recommended pharmacotherapies are still relatively under prescribed, despite their relatively low number-needed-to-treat (NNT), perhaps owing to mixed evidence across the literature. Topiramate (currently licensed for migraine prophylaxis and epilepsy) has been proposed as one drug with potential efficacy in reducing drinking behaviours. Hence, the aim of this paper is to evaluate the efficacy of topiramate in promoting and maintaining abstinence in alcohol dependence, through a review of the current literature.
Seven papers are reported after a systematic database search (PubMed, Medline, Embase, Web of Science); statistical manipulation of results has been performed to present findings in a common format. Results were consistent and showed the effectiveness of topiramate in all outcome measures evaluated: heavy drinking days (HDDs), plasma gamma-glutamyl transferase (GGT) concentration and abstinence rate. These differences over placebo reached statistical significance in all seven studies.
This paper supports the efficacy of topiramate in treating alcohol dependence. There are several recommendations for further research, including comparisons to currently licensed alcohol dependence medications (namely naltrexone) and the pharmacogenetic influence of a GRIK1 polymorphism on the efficacy of topiramate. Further research into the tolerability of topiramate is required, although evaluation of adverse events within this paper has been positive.
References
Office for National Statistics. Alcohol-specific deaths in the UK: registered in 2020. Office for National Statistics, 2021. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/causesofdeath/bulletins/alcoholrelateddeathsintheunitedkingdom/registeredin2020 (accessed 8th May 2024).
Moss HB. The impact of alcohol on society: a brief overview. Soc Work Public Health. 2013;28(3-4):175-177. Available from: https://doi.org/10.1080/19371918.2013.758987
NHS Digital. Statistics on alcohol, England, 2018 [PAS]. NHS England, 2018. Available from: https://digital.nhs.uk/data-and-information/publications/statistical/statistics-on-alcohol/2018/part-3 (accessed 8th May 2024).
National Institute for Health and Care Excellence. Alcohol-use disorders: diagnosis, assessment and management of harmful drinking (high-risk drinking) and alcohol dependence. 2011. Available from: https://www.nice.org.uk/guidance/cg115/chapter/introduction (accessed 8th May 2024).
Helbing C, Brocka M, Scherf T, Lippert MT, Angenstein F. The role of the mesolimbic dopamine system in the formation of blood-oxygen level dependent responses in the medial prefrontal/anterior cingulate cortex during high-frequency stimulation of the rat perforant pathway. J Cereb Blood Flow Metab 2016;36(12):2177-2193. Available from: https://doi.org/10.1177/0271678X15615535
Trantham-Davidson H, Neely LC, Lavin A, Seamans JK. Mechanisms underlying differential D1 versus D2 dopamine receptor regulation of inhibition in prefrontal cortex. J Neurosci 2004;24;24(47):10652-10659. Available from: https://doi.org/10.1523/JNEUROSCI.3179-04.2004
Samson HH, Hodge CW. The role of the mesoaccumbens dopamine system in ethanol reinforcement: studies using the techniques of microinjection and voltammetry. Alcohol Alcohol Suppl 1993;2:469-474.
Czachowski CL, Chappell AM, Samson HH. Effects of raclopride in the nucleus accumbens on ethanol seeking and consumption. Alcohol Clin Exp Res 2001;25(10):1431-1440. Available from: https://doi.org/10.1097/00000374-200110000-00005
Rassnick S, Pulvirenti L, Koob GF. Oral ethanol self-administration in rats is reduced by the administration of dopamine and glutamate receptor antagonists into the nucleus accumbens. Psychopharmacology (Berl) 1992;109(1-2):92-98. Available from: https://doi.org/10.1007/BF02245485
Roberto M, Madamba SG, Stouffer DG, Parsons LH, Siggins GR. Increased GABA release in the central amygdala of ethanol-dependent rats. J Neurosci 2004;10;24(45):10159-10166. Available from: https://doi.org/10.1523/JNEUROSCI.3004-04.2004
Pulvirenti L, Diana M. Drug dependence as a disorder of neuroplasticity: focus on dopamine and glutamate. Rev Neurosci 2001;12(2):141-158. Available from: https://doi.org/10.1515/revneuro.2001.12.2.141
NHS Digital. Statistics on Alcohol, England 2021. NHS England, 2022. Available from: https://digital.nhs.uk/data-and-information/publications/statistical/statistics-on-alcohol/2021/part-2 (accessed 8th May 2024)
Maisel NC, Blodgett JC, Wilbourne PL, Humphreys K, Finney JW. Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful? Addict Biol 2018;108(2):275-293. Available from: https://doi.org/10.1111/j.1360-0443.2012.04054.x
Johnson BA. Recent advances in the development of treatments for alcohol and cocaine dependence: focus on topiramate and other modulators of GABA or glutamate function. CNS Drugs 2005;19(10):873-896.
Available from: https://doi.org/10.2165/00023210-200519100-00005
Routledge PA, Hutchings AD. The immunoassay handbook (4th Ed.). 2013:945-962.
Landmark CJ, Johannessen SI. Handbook of analytical separations (vol.7). 2020:225-256.
Johnson BA, Rosenthal N, Capece JA, et al. Topiramate for treating alcohol dependence: a randomised controlled trial. JAMA 2007;298(14):1641-1651. Available from: https://doi.org/10.1001/jama.298.14.1641
Johnson BA, Ait-Dahoud N, Bowden CL, et al. Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet 2003, 17;361(9370):1677-1685. Available from: https://doi.org/10.1016/S0140-6736(03)13370-3
Paparrigopoulos T, Tzavellas E, Karaiskos D, Kourlaba G, Liappas I. Treatment of alcohol dependence with low-dose topiramate: an open label controlled study. BMC Psychiatry 2011;14;11(41). Available from: https://doi.org/10.1186/1471-244X-11-41
Kranzler HR, Covault J, Feinn R, et al. Topiramate treatment for heavy drinkers: moderation by a GRIK1 polymorphism. Am J Psychiatry 2014;171(4):445-452. Available from: https://doi.org/10.1176/appi.ajp.2013.13081014