Pregabalin for Alcohol Dependence: A Critical Review of the Literature
Tóm tắt
Alcohol dependence represents a severe pathological disorder associated with a significant rate of morbidity and mortality. To date, limited pharmacological agents exist to treat this disorder, and there is a growing interest for new therapies. In this context, pregabalin represents a promising strategy. Pregabalin, like gabapentin, selectively binds to the α2δsubunit of voltage-gated calcium channels, inhibiting release of excessive levels of excitatory neurotransmitters. The main focus of this review is the clinical use of pregabalin in alcoholic patients, but the authors also reported some data about chemistry, pharmacology, and pharmacokinetics of this drug. The authors conducted a PubMed search of clinical human studies published in English from January 2000 to August 2012 using the following search terms: pregabalin alcohol dependence, pregabalin alcohol withdrawal, pregabalin alcoholism. The search revealed a total of five studies: two trials for the treatment of alcohol relapse and three articles for the management of alcohol withdrawal syndrome with pregabalin. The critical review of the literature suggests that pregabalin could be a novel and effective treatment option for the management of alcohol relapse in detoxified patients, whereas until now there have been mixed results for the treatment of alcohol withdrawal syndrome. In particular, pregabalin showed a greater beneficial effect on patients with comorbid conditions such as alcoholism and generalized anxiety disorders. The exact mechanism of action of pregabalin in the management of alcoholism is not well understood but it is thought to be due mainly to the modulation of neurotransmitters such as glutamate and norepinephrine by inhibiting activity-dependent calcium influx in nerve terminals. Pregabalin, within a dosage of 150–450 mg/day, showed beneficial effects for alcohol relapse prevention and contrasting results for the treatment of the withdrawal syndrome. Its use appears to be safe and well tolerated.
Tài liệu tham khảo
Littleton J. Neurochemical mechanisms underlying alcohol withdrawal. Alcohol Health Res World. 1998;22:13–24.
Johnson BA, Ait-Daoud N, Bowden CL, et al. Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet. 2003;361:1677–1685.
Mueller TI, Stout RL, Rudden S, et al. A doubleblind, placebo-controlled pilot study of carbamazepine for the treatment of alcohol dependence. Alcohol Clin Exp Res. 1997;21:86–92.
Martinotti G, Di Nicola M, Romanelli R, et al. High and low dosage oxcarbazepine versus naltrexone for the prevention of relapse in alcohol-dependent patients. Hum Psychopharmacol. 2007;22:149–156.
Furieri FA, Nakamura-Palacios EM. Gabapentin reduces alcohol consumption and craving: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2007;68:1691–1700.
Longo LP, Campbell T, Hubatch S. Divalproex sodium (Depakote) for alcohol withdrawal and relapse prevention. J Addict Dis. 2002;21:55–64.
Martinotti G. Pregabalin in clinical psychiatry and addiction: pros and cons. Expert Opin Investig Drugs. 2012;21:1243–1245.
Taylor CP, Angelotti T, Fauman E. Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res. 2007;73:137–150.
Feng MR, Turluck D, Burleigh J, et al. Brain microdialysis and PK/PD correlation of pregabalin in rats. Eur J Drug Metab Pharmacokinet. 2001;26:123–128.
Errante LD, Petroff OA. Acute effects of gabapentin and pregabalin on rat forebrain cellular GABA, glutamate, and glutamine concentrations. Seizure. 2003;12:300–306.
Su TZ, Feng MR, Weber ML. Mediation of highly concentrative uptake of pregabalin by L-type amino acid transport in Chinese hamster ovary and Caco-2 cells. J Pharmacol Exp Ther. 2005;313:1406–1415.
Belliotti TR, Capiris T, Ekhato IV, et al. Structureactivity relationships of pregabalin and analogues that target the alpha(2)-delta protein. J Med Chem. 2005;48:2294–2307.
Brown JP, Dissanayake VU, Briggs AR, Milic MR, Gee NS. Isolation of the [3H]gabapentin-binding protein/alpha 2 delta Ca2+ channel subunit from porcine brain: development of a radioligand binding assay for alpha 2 delta subunits using [3H] leucine. Anal Biochem. 1998;255:236–243.
Cunningham MO, Woodhall GL, Thompson SE, Dooley DJ, Jones RS. Dual effects of gabapentin and pregabalin on glutamate release at rat entorhinal synapses in vitro. Eur J Neurosci. 2004;20:1566–1576.
Bockbrader HN, Radulovic LL, Posvar EL, et al. Clinical pharmacokinetics of pregabalin in healthy volunteers. J Clin Pharmacol. 2010;50:941–950.
Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010;49:661–669.
Martinotti G, Di Nicola M, Tedeschi D, Mazza M, Janiri L, Bria P. Efficacy and safety of pregabalin in alcohol dependence. Adv Ther. 2008;25:608–618.
Martinotti G, Di Nicola M, Tedeschi D, et al. Pregabalin versus naltrexone in alcohol dependence: a randomised, double-blind, comparison trial. J Psychopharmacol. 2010;24:1367–1374.
Martinotti G, di Nicola M, Frustaci A, et al. Pregabalin, tiapride and lorazepam in alcohol withdrawal syndrome: a multi-centre, randomized, single-blind comparison trial. Addiction. 2010;105:288–299.
Di Nicola M, Martinotti G, Tedeschi D, et al. Pregabalin in outpatient detoxification of subjects with mild-to-moderate alcohol withdrawal syndrome. Hum Psychopharmacol. 2010;25:268–275.
Förg A, Hein J, Volkmar K, et al. Efficacy and safety of pregabalin in the treatment of alcohol withdrawal syndrome: a randomized placebocontrolled trial. Alcohol Alcohol. 2012;47:149–155.
French JA, Kugler AR, Robbins JL, Knapp LE, Garofalo EA. Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures. Neurology. 2003;60:1631–1637.
Siok CJ, Taylor CP, Hajós M. Anxiolytic profile of pregabalin on elicited hippocampal theta oscillation. Neuropharmacology. 2009;56:379–385.
Aupperle RL, Ravindran L, Tankersley D, et al. Pregabalin influences insula and amygdala activation during anticipation of emotional images. Neuropsychopharmacology. 2011;36:1466–1477.
Valente MM, Bortolotto V, Cuccurazzu B, et al. α2δ Ligands Act as Positive Modulators of Adult Hippocampal Neurogenesis and Prevent Depression-Like Behavior Induced by Chronic Restraint Stress. Mol Pharmacol. 2012;82:271–280.
Schwan S, Sundström A, Stjernberg E, Hallberg E, Hallberg P. A signal for an abuse liability for pregabalin—results from the Swedish spontaneous adverse drug reaction reporting system. Eur J Clin Pharmacol. 2010;66:947–953.