The Efficacy of Tiapride and Carbamazepine Combination Therapy in Reducing Alcohol Withdrawal Symptoms: A Systematic Review and Meta-Analysis

Abstract

The combination of tiapride (TIA) and carbamazepine (CBZ) as an alternative treatment option to benzodiazepines and clomethiazole has been investigated by several investigations. We performed a systematic review and meta-analysis to further explore the efficacy of this combination in order to render more definite answers whether this combination can be recommendable in the clinical practice. We systematically searched electronic databases including PubMed (MEDLINE), EMBASE, OVID, Cochrane, Google Scholar, and Scopus for human studies. Statistical homogeneity was checked by χ² test and I² using Cochran heterogeneity statistic. Our analysis showed a significant efficacy of the combination of TIA and CBZ in reducing alcohol withdrawal syndrome (AWS) (p<0.0001, z-value: 4.07). The cumulative analysis illustrated that the favorable efficacy of this combination therapy has been consistent over time. Our study shows that the combination of TIA/CBZ is an effective treatment in management of AWS in patients with alcohol abstinence. However, the safety of this combination could not be proven, so we recommend its prescription after an informed consent.

Key words

tiapride - carbamazepine - systematic review - alcoholism - withdrawal symptoms

• References

• 1 Addolorato G, Leggio L, Abenavoli L. et al. Neurobiochemical and clinical aspects of craving in alcohol addiction: A review. Addict Behav 2005; 30: 1209-1224
• 2 Littleton J. Neurochemical mechanisms underlying alcohol withdrawal. Alcohol Health ResWorld 1998; 22: 13-24
• 3 Glue P, Nutt D. Overexcitement and disinhibition. Dynamic neurotransmitter interactions in alcohol withdrawal. Br J Psychiat 1990; 157: 491-499
• 4 Swift RM. Drug therapy for alcohol dependence. N Engl J Med 1999; 340: 1482-1490
• 5 Koob GF. A role for GABA mechanisms in the motivational effects of alcohol. Biochem Pharmacol 2004; 68: 1515-1525
• 6 Stojakovic A, Walczak M, Cieślak PE. et al. Several behavioral traits relevant for alcoholism are controlled by γ2 subunit containing GABAA receptors on dopamine neurons in mice. Neuropsychopharmacology 2018; 43: 1548-1556
• 7 Laine TP, Ahonen A, Torniainen P. et al. Dopamine transporters increase in human brain after alcohol withdrawal. Mol Psychiatry 1999; 4: 189-191
• 8 De Witte P, Pinto E, Ansseau M. et al. Alcohol and withdrawal: From animal research to clinical issues. Neurosci Biobehav Rev 2003; 27: 189-197
• 9 Bonnet U, Lensing M, Specka M. et al. Comparison of two oral symptom-triggered pharmacological inpatient treatments of acute alcohol withdrawal: clomethiazole vs. clonazepam. Alcohol Alcohol 2011; 46: 68-73
• 10 Sychla H, Gründer G, Lammertz SE. Comparison of clomethiazole and diazepam in the treatment of alcohol withdrawal syndrome in clinical practice. Eur Addict Res 2017; 23: 211-218
• 11 Mayo-Smith MF. Pharmacologicalmanagement of alcohol withdrawal: A meta-analysis and evidence-based practice guideline: American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA 1997; 278: 144-151
• 12 Verthein U, Kuhn S, Gabriel K. et al. Treatment of alcohol withdrawal syndrome with oxazepam or clomethiazole – A naturalistic observational study. Psychiatr Prax 2018; 45: 95-102
• 13 Williams D, McBride AJ. The drug treatment of alcohol withdrawal symptoms: A systematic review. Alcohol Alcohol 1998; 33: 103-115
• 14 Simona G, Lanfranco P, Alberto PL. et al. Drug-drug interactions in the treatment for alcohol use disorders: A comprehensive review. Pharmacol Res 2018; 133: 65-76
• 15 Maldonado JR. Novel algorithms for the prophylaxis and management of alcohol withdrawal syndromes-beyond benzodiazepines. Crit Care Clin 2017; 33: 559-599
• 16 Ross HE. Benzodiazepine use and anxiolytic abuse and dependence in treated alcoholics. Addiction 1993; 88: 209-218
• 17 Khong E, Sim MG, Hulse G. Benzodiazepine dependence. Aust Fam Physician 2004; 33: 923-926
• 18 Kattimani S, Bharadwaj B, Arun AB. Benzodiazepine maintenance for alcohol dependence: A case series. J Family Med Prim Care 2017; 6: 431-433
• 19 Leggio L, Kenna GA, Swift RM. New developments for the pharmacological treatment of alcohol withdrawal syndrome. A focus on non-benzodiazepine GABAergic medications. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 1106-1117
• 20 Barrons R, Roberts N. The role of carbamazepine and oxcarbazepine in alcohol withdrawal syndrome. J Clin Pharm Ther 2010; 35: 153-167
• 21 Minozzi S, Amato L, Vecchi S. et al. Anticonvulsants for alcohol withdrawal. Cochrane Database Syst Rev 2010; 3: CD005064
• 22 Bonnet U, Schäfer M, Richter C. et al. Anticonvulsants in the treatment of alcoholism. Fortschr Neurol Psychiatr 2009; 77: 192-202
• 23 Prince V, Turpin KR. Treatment of alcohol withdrawal syndrome with carbamazepine, gabapentin, and nitrous oxide. Am J Health Syst Pharm 2008; 65: 1039-1047
• 24 Scatton B, Cohen C, Perrault G. et al. The preclinical pharmacologic profile of tiapride. Eur Psychiatry 2001; 16 (Suppl. 01) 29s-34s
• 25 Soyka M, Schmidt P, Franz M. et al. Treatment of alcohol withdrawal syndrome with a combination of tiapride/carbamazepine: Results of a pooled analysis in 540 patients. Eur Arch Psychiatry Clin Neurosci 2006; 256: 395-401
• 26 Soyka M, Morhart-Klute V, Horak M. A combination of carbamazepine/tiapride in outpatient alcohol detoxification. Results from an open clinical study. Eur Arch Psychiatry Clin Neurosci 2002; 252: 197-200
• 27 Soyka M, Schmidt F, Schmidt P. Efficacy and safety of outpatient alcohol detoxification with a combination of tiapride/carbamazepine: Additional evidence. Pharmacopsychiatry 2006; 39: 30-34
• 28 Russell J, Richardson N, Dar A. Use of a modified Clinical Institute Withdrawal Assessment (CIWA) for symptom-triggered management of alcohol withdrawal syndrome. Clin Med (Lond) 2015; 15 (Suppl. 03) s20
• 29 Bakhla AK, Khess CR, Verma V. et al. Factor structure of CIWA-Ar in alcohol withdrawal. J Addict 2014; 2014; 745839
• 30 Higgins JP, Thompson SG, Deeks JJ. et al. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-560
• 31 Koushki D, Latifi S, Norouzi Javidan A. et al. Efficacy of some nonconventional herbal medications (sulforaphane, tanshinone IIA, and tetramethylpyrazine) in inducing neuroprotection in comparison with interleukin-10 after spinal cord injury: A meta-analysis. J. Spinal Cord Med 2015; 38: 13-22
• 32 Kontopantelis E, Springate DA, Reeves D. A re-analysis of the Cochrane Library data: The dangers of unobserved heterogeneity in meta-analyses. PLoS One 2013; 8: e69930
• 33 Messer T, Lammers G, Müller-Siecheneder F. et al. Substance abuse in patients with bipolar disorder: A systematic review and meta-analysis. Psychiatry Res 2017; 253: 338-350
• 34 Rosenthal R. The “file drawer problem” and tolerance for null results. Psychol Bull 1979; 86: 638-641
• 35 Franz M, Dlabal H, Kunz S. et al. Treatment of alcohol withdrawal: Tiapride and carbamazepine versus clomethiazole. A pilot study. Eur Arch Psychiatry Clin Neurosci 2001; 251: 185-192
• 36 Lucht M, Kuehn KU, Armbruster J. et al. Alcohol withdrawal treatment in intoxicated vs non-intoxicated patients: A controlled open-label study with tiapride/carbamazepine, clomethiazole and diazepam. Alcohol Alcohol 2003; 38: 168-175
• 37 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
• 38 Croissant B, Loeber S, Diehl A. et al. Oxcarbazepine in combination with Tiaprid in inpatient alcohol-withdrawal–a RCT. Pharmacopsychiatry 2009; 42: 175-181
• 39 Müller CA, Schäfer M, Banas R. et al. A combination of levetiracetam and tiapride for outpatient alcohol detoxification: A case series. J Addict Med 2011; 5: 153-156
• 40 Gartenmaier A, Pelzer E, Soyka M. Treatment of alcohol withdrawal syndrome with combined carbamazepine and tiapride in a patient with probable sleep apnoe syndrome. Pharmacopsychiatry 2005; 38: 96-98
• 41 Lepola U, Kokko S, Nuutila J. et al. Tiapride and chlordiazepoxide in acute alcohol withdrawal. A controlled clinical trial. Int J Clin Pharmacol Res 1984; 4: 321-326
• 42 Agricola R, Mazzarino M, Urani R. et al. Treatment of acute alcohol withdrawal syndrome with carbamazepine: A double-blind comparison with tiapride. J Int Med Res 1982; 10: 160-165
• 43 Diehl A, Grosshans M, Herre H. et al. Carbamazepine intoxication. Complication of alcohol detoxification with combined carbamazepine and tiapride. Nervenarzt 2007; 78: 85-89
• 44 Sullivan JT, Sykora K, Schneiderman J. et al. Assessment of alcohol withdrawal: The revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict 1989; 84: 1353-1357
• 45 Eloma AS, Tucciarone JM, Hayes EM. et al. Evaluation of the appropriate use of a CIWA-Ar alcohol withdrawal protocol in the general hospital setting. Am J Drug Alcohol Abuse 2018; 44: 418-425
• 46 Pittman B, Gueorguieva R, Krupitsky E. et al. Multidimensionality of the Alcohol Withdrawal Symptom Checklist: a factor analysis of the Alcohol Withdrawal Symptom Checklist and CIWA-Ar. Alcohol Clin Exp Res 2007; 31: 612-618
• 47 Shaw GK, Waller S, Majumdar SK. et al. Tiapride in the prevention of relapse in recently detoxified alcoholics. Br J Psychiatry 1994; 165: 515-523
• 48 Bender S, Scherbaum N, Soyka M. et al. The efficacy of the dopamine D2/D3 antagonist tiapride in maintaining abstinence: A randomized, double-blind, placebo-controlled trial in 299 alcohol-dependent patients. Int J Neuropsychopharmacol 2007; 10: 653-660
• 49 Peters DH, Faulds D. Tiapride. A review of its pharmacology and therapeutic potential in the management of alcohol dependence syndrome. Drugs 1994; 47: 1010-1032
• 50 Murphy DJ, Shaw GK, Clarke L. Tiapride and chlormethiazole in alcohol withdrawal: a double-blind trial. Alcohol and Alcoholism 1983; 18: 227-237
• 51 Cazzato G, Gioseffi M, Torre P. et al. Prevention and therapy of delirium tremens with tiapride. Riv Neurol 1982; 52: 379-391
• 52 Léger JM, Herrmann C, Danot G. et al. Double-blind comparative study of lorazepam and tiapride effects on the memory capacities of subjects over 60 years of age. Sem Hop 1984; 60: 932-936
• 53 Dose M, Lange HW. The benzamide tiapride: treatment of extrapyramidal motor and other clinical syndromes. Pharmacopsychiatry 2000; 33: 19-27
• 54 Robert PH, Allain H. Clinical management of agitation in the elderly with tiapride. Eur Psychiatry 2001; 16 (Suppl. 01) 42s-47s
• 55 Yuan Y, Li LH, Huang YJ. et al. Tiapride is more effective and causes fewer adverse effects than risperidone in the treatment of senile dementia. Eur Rev Med Pharmacol Sci 2016; 20: 3119-3122
• 56 Thome J, Wiesbeck GA, Vince GH. Carbamazepine in treatment of alcohol withdrawal syndrome–an overview of current research. Fortschr Neurol Psychiatr 1994; 62: 125-133
• 57 Rybakowski J, Wankiewicz G. Mechanism of the psychotropic action of carbamazepine. Psychiatr Pol 1989; 23: 314-321
• 58 Mariani JJ, Levin FR. Pharmacotherapy for alcohol-related disorders: What clinicians should know. Harv Rev Psychiat 2004; 23: 351-366
• 59 See S. Carbamazepine effective for alcohol withdrawal. J Fam Pract 2002; 51: 778
• 60 Seifert J, Peters E, Jahn K. et al. Treatment of alcohol withdrawal: Chlormethiazole vs. carbamazepine and the effect on memory performance–a pilot study. Addict Biol 2004; 9: 43-51
• 61 Malcolm R, Myrick H, Roberts J. et al. The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial. J Gen Intern Med 2002; 17: 349-355
• 62 Eyer F, Schreckenberg M, Hecht D. et al. Carbamazepine and valproate as adjuncts in the treatment of alcohol withdrawal syndrome: A retrospective cohort study. Alcohol Alcohol 2011; 46: 177-184
• 63 Piekoszewski W, Florek E, Szpak D. et al. Carbamazepine intoxication in alcohol dependent epileptic patients. Pharmacol Rep 2010; 62: 398-404
• 64 Schik G, Wedegaertner FR, Liersch J. et al. Oxcarbazepine versus carbamazepine in the treatment of alcohol withdrawal. Addict Biol 2005; 10: 283-288
• 65 Koethe D, Juelicher A, Nolden BM. et al. Oxcarbazepine–efficacy and tolerability during treatment of alcohol withdrawal: A double-blind, randomized, placebo-controlled multicenter pilot study. Alcohol Clin Exp Res 2007; 31: 1188-1194
• 66 Croissant B, Diehl A, Klein O. et al. A pilot study of oxcarbazepine versus acamprosate in alcohol-dependent patients. Alcohol Clin Exp Res 2006; 30: 630-635
• 67 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
• 68 Kovacs N, Nagy F, Balas I. et al. Oxcarbazepine may induce psychotic symptoms in Parkinson’s disease. Epilepsy Behav 2008; 12: 492-493
• 69 Ponce G, Rodríguez-Jiménez R, Ortiz H. et al. Oxcarbazepine in the prevention of epileptic syndromes in alcohol detoxification. Rev Neurol 2005; 40: 577-580
• 70 Lu BY, Coberly R, Bogenschutz M. Use of oxcarbazepine in outpatient alcohol detoxification. Am J Addict 2005; 14: 191-192
• 71 Nozaki I, Furukawa Y, Kato-Motozaki Y. et al. Neuroleptic malignant syndrome induced by combination therapy with tetrabenazine and tiapride in a Japanese patient with Huntington’s disease at the terminal stage of recurrent breast cancer. Intern Med 2014; 53: 1201-1204
• 72 Tamion F, Petit J, Massari P. et al. Malignant Neuroleptic Syndrome during tiapride treatment. J Toxicol Clin Exp 1990; 10: 461-467
• 73 Arai M. Parkinsonism onset in a patient concurrently using tiapride and donepezil. Intern Med 2000; 39: 863
• 74 Shaw GK, Majumdar SK, Waller S. et al. Tiapride in the long-term management of alcoholics of anxious or depressive temperament. Br J Psychiatry 1987; 150: 164-168
• 75 Vandel B, Bonin B, Vandel S. et al. Interaction between tiapride and alcohol in man. Sem Hop. 1984; 60: 175-177
• 76 Chaillou E, Perré P. The weaning of alcoholic patients in a general medicine hospital department. The value of tiapride. Sem Hop 1983; 59: 1677-1678
• 77 Stecchini M, Corrias G. Treatment of alcoholic patients with tiapride. Sem Hop 1982; 58: 2724-2726