Effects of Levetiracetam (Keppra) on Alcohol Consumption

Summary

The overall goals of this study are to (1) expand knowledge about interactions of levetiracetam with alcohol by assessing the effects of levetiracetam compared to placebo in moderate and heavy social alcohol users and (2) to test the AccuswayTM platform as a tool to measure postural control (which has been used as a marker of intoxication) and the effects of levetiracetam on postural control.

Timeline

Start

2008-11

Primary completion

2009-11

Completion

2010-11

Publications

• Background Angehagen M, Margineanu DG, Ben-Menachem E, Ronnback L, Hansson E, Klitgaard H. Levetiracetam reduces caffeine-induced Ca2+ transients and epileptiform potentials in hippocampal neurons. Neuroreport. 2003 Mar 3;14(3):471-5. doi: 10.1097/00001756-200303030-00035.
• Background Ardid D, Lamberty Y, Alloui A, Coudore-Civiale MA, Klitgaard H, Eschalier A. Antihyperalgesic effect of levetiracetam in neuropathic pain models in rats. Eur J Pharmacol. 2003 Jul 18;473(1):27-33. doi: 10.1016/s0014-2999(03)01933-2.
• Background Brockmoller J, Thomsen T, Wittstock M, Coupez R, Lochs H, Roots I. Pharmacokinetics of levetiracetam in patients with moderate to severe liver cirrhosis (Child-Pugh classes A, B, and C): characterization by dynamic liver function tests. Clin Pharmacol Ther. 2005 Jun;77(6):529-41. doi: 10.1016/j.clpt.2005.02.003.
• Background Cataldi M, Lariccia V, Secondo A, di Renzo G, Annunziato L. The antiepileptic drug levetiracetam decreases the inositol 1,4,5-trisphosphate-dependent [Ca2+]I increase induced by ATP and bradykinin in PC12 cells. J Pharmacol Exp Ther. 2005 May;313(2):720-30. doi: 10.1124/jpet.104.079327. Epub 2005 Jan 11.
• Background Dong M, Yeh F, Tepp WH, Dean C, Johnson EA, Janz R, Chapman ER. SV2 is the protein receptor for botulinum neurotoxin A. Science. 2006 Apr 28;312(5773):592-6. doi: 10.1126/science.1123654. Epub 2006 Mar 16.
• Background Grunewald R. Levetiracetam in the treatment of idiopathic generalized epilepsies. Epilepsia. 2005;46 Suppl 9:154-60. doi: 10.1111/j.1528-1167.2005.00329.x.
• Background Kim C, Jun K, Lee T, Kim SS, McEnery MW, Chin H, Kim HL, Park JM, Kim DK, Jung SJ, Kim J, Shin HS. Altered nociceptive response in mice deficient in the alpha(1B) subunit of the voltage-dependent calcium channel. Mol Cell Neurosci. 2001 Aug;18(2):235-45. doi: 10.1006/mcne.2001.1013.
• Background Krebs M, Leopold K, Richter C, Kienast T, Hinzpeter A, Heinz A, Schaefer M. Levetiracetam for the treatment of alcohol withdrawal syndrome: an open-label pilot trial. J Clin Psychopharmacol. 2006 Jun;26(3):347-9. doi: 10.1097/01.jcp.0000219926.49799.89. No abstract available.
• Background LaMotte RH, Lundberg LE, Torebjork HE. Pain, hyperalgesia and activity in nociceptive C units in humans after intradermal injection of capsaicin. J Physiol. 1992 Mar;448:749-64. doi: 10.1113/jphysiol.1992.sp019068.
• Background Lipscomb TR, Carpenter JA, Nathan PE. Static ataxia: a predictor of alcoholism? Br J Addict Alcohol Other Drugs. 1979 Sep;74(3):289-94. doi: 10.1111/j.1360-0443.1979.tb01350.x. No abstract available.
• Background Lipscomb TR, Nathan PE. Blood alcohol level discrimination. The effects of family history of alcoholism, drinking pattern, and tolerance. Arch Gen Psychiatry. 1980 May;37(5):571-6. doi: 10.1001/archpsyc.1980.01780180085010.
• Background Lukyanetz EA, Shkryl VM, Kostyuk PG. Selective blockade of N-type calcium channels by levetiracetam. Epilepsia. 2002 Jan;43(1):9-18. doi: 10.1046/j.1528-1157.2002.24501.x.
• Background Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, Fuks B. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9861-6. doi: 10.1073/pnas.0308208101. Epub 2004 Jun 21.
• Background Madeja M, Margineanu DG, Gorji A, Siep E, Boerrigter P, Klitgaard H, Speckmann EJ. Reduction of voltage-operated potassium currents by levetiracetam: a novel antiepileptic mechanism of action? Neuropharmacology. 2003 Oct;45(5):661-71. doi: 10.1016/s0028-3908(03)00248-x.
• Background Newton PM, Orr CJ, Wallace MJ, Kim C, Shin HS, Messing RO. Deletion of N-type calcium channels alters ethanol reward and reduces ethanol consumption in mice. J Neurosci. 2004 Nov 3;24(44):9862-9. doi: 10.1523/JNEUROSCI.3446-04.2004.
• Background Pisani A, Bonsi P, Martella G, De Persis C, Costa C, Pisani F, Bernardi G, Calabresi P. Intracellular calcium increase in epileptiform activity: modulation by levetiracetam and lamotrigine. Epilepsia. 2004 Jul;45(7):719-28. doi: 10.1111/j.0013-9580.2004.02204.x.
• Background Rigo JM, Hans G, Nguyen L, Rocher V, Belachew S, Malgrange B, Leprince P, Moonen G, Selak I, Matagne A, Klitgaard H. The anti-epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABA- and glycine-gated currents. Br J Pharmacol. 2002 Jul;136(5):659-72. doi: 10.1038/sj.bjp.0704766.
• Background Rowbotham MC, Manville NS, Ren J. Pilot tolerability and effectiveness study of levetiracetam for postherpetic neuralgia. Neurology. 2003 Sep 23;61(6):866-7. doi: 10.1212/01.wnl.0000079463.16377.07. No abstract available.
• Background Schuckit MA, Smith TL, Kalmijn J. Findings across subgroups regarding the level of response to alcohol as a risk factor for alcohol use disorders: a college population of women and Latinos. Alcohol Clin Exp Res. 2004 Oct;28(10):1499-508. doi: 10.1097/01.alc.0000141814.80716.32.
• Background Saegusa H, Kurihara T, Zong S, Kazuno A, Matsuda Y, Nonaka T, Han W, Toriyama H, Tanabe T. Suppression of inflammatory and neuropathic pain symptoms in mice lacking the N-type Ca2+ channel. EMBO J. 2001 May 15;20(10):2349-56. doi: 10.1093/emboj/20.10.2349.
• Results Hatakeyama S, Wakamori M, Ino M, Miyamoto N, Takahashi E, Yoshinaga T, Sawada K, Imoto K, Tanaka I, Yoshizawa T, Nishizawa Y, Mori Y, Niidome T, Shoji S. Differential nociceptive responses in mice lacking the alpha(1B) subunit of N-type Ca(2+) channels. Neuroreport. 2001 Aug 8;12(11):2423-7. doi: 10.1097/00001756-200108080-00027.
• Mitchell JM, Grossman LE, Coker AR, Messing RO. The anticonvulsant levetiracetam potentiates alcohol consumption in non-treatment seeking alcohol abusers. J Clin Psychopharmacol. 2012 Apr;32(2):269-72. doi: 10.1097/JCP.0b013e318248ba69.

Drugs

Indications