Symptoms of Protracted Alcohol Withdrawal in Patients with Alcohol Use
Disorder: A Comprehensive Systematic Review

Silvano      Gallus; Alessandra      Lugo; Elisa      Borroni; Teo      Vignoli; Lisa      Lungaro; Giacomo      Caio; Roberto      De Giorgio; Giorgio      Zoli; Fabio      Caputo

Abstract

Background: Alcohol withdrawal syndrome (AWS) is characterized by different phases (acute, early and protracted). Protracted alcohol withdrawal (PAW) presents some symptoms, which may persist for several weeks, months or even years after drinking cessation.

Methods: We conducted a systematic review of the literature in major scientific databases on selected AWS symptoms (craving, sleep disorders, and anhedonia) in patients with alcohol use disorder.

Results: Of the 102 eligible publications (70 RCTs and 32 cohort studies), 88 provided data on craving, 21 on sleep disorders, and 1 on anhedonia. Overall, 37 studies assessed craving using the Obsessive Compulsive Drinking Scale (OCDS). Pooled OCDS decreased from 24.2 at baseline to 18.8 at 1 week, 10.3 at 1 month and 9.7 at 3 months. The corresponding estimates for treated individuals were 23.9, 18.8, 8.7, and 8.8, and for non-treated subjects, they were 25.3, 13.9, 13.2, and 11.4, respectively. In 4 studies assessing sleep disorders using the Epworth Sleeping Scale (ESS), the scale remained stable in time, i.e., 7.3 at baseline, 7.3 at 1 week, 7.2 at 1 month, and 7.1 at 3 months.

Conclusion: This study confirms the presence of PAW after the resolution of the acute phase of AWS. The pharmacological approach to managing PAW may ensure a more rapid reduction of symptoms in three weeks. We highlight the importance of studying PAW and the ability of pharmacological treatment to reduce its symptoms.

This review protocol is registered in Prospero (registration number: CRD42020211265).

Summary: This systematic review summarizes literature on major symptoms of protracted alcohol withdrawal in patients with alcohol use disorder. The pharmacological approach to manage protracted alcohol withdrawal ensures a more rapid reduction of symptoms (craving in particular), achieving in three weeks similar results obtained only after almost 6 months without treatment.

Keywords: Alcohol withdrawal syndrome, anhedonia, craving, sleep disorder, protracted alcohol withdrawal, early alcohol withdrawal.

« Previous Next »

Graphical Abstract

[1]
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5, 5th ed; Arlington American Psychiatric Publishing, 2013. 
 [http://dx.doi.org/10.1176/appi.books.9780890425596]

[2]
Bayard, M.; McIntyre, J.; Hill, K.R.; Woodside, J., Jr Alcohol withdrawal syndrome. Am. Fam. Physician,  2004, 69(6), 1443-1450.
 [PMID:  15053409]

[3]
Caputo, F.; Agabio, R.; Vignoli, T.; Patussi, V.; Fanucchi, T.; Cimarosti, P.; Meneguzzi, C.; Greco, G.; Rossin, R.; Parisi, M.; Mioni, D.; Arico’, S.; Palmieri, V.O.; Zavan, V.; Allosio, P.; Balbinot, P.; Amendola, M.F.; Macciò, L.; Renzetti, D.; Scafato, E.; Testino, G. Diagnosis and treatment of acute alcohol intoxication and alcohol withdrawal syndrome: position paper of the Italian Society on Alcohol. Intern. Emerg. Med.,  2019, 14(1), 143-160.
 [http://dx.doi.org/10.1007/s11739-018-1933-8] [PMID:  30187438]

[4]
de Timary, P.; Cordovil de Sousa Uva, M.; Denoël, C.; Hebborn, L.; Derely, M.; Desseilles, M.; Luminet, O. The associations between self-consciousness, depressive state and craving to drink among alcohol dependent patients undergoing protracted withdrawal. PLoS One,  2013, 8(8), e71560.
 [http://dx.doi.org/10.1371/journal.pone.0071560] [PMID:  24013131]

[5]
Perney, P.; Lehert, P.; Mason, B.J. Sleep disturbance in alcoholism: proposal of a simple measurement, and results from a 24-week randomized controlled study of alcohol-dependent patients assessing acamprosate efficacy. Alcohol Alcohol.,  2012, 47(2), 133-139.
 [http://dx.doi.org/10.1093/alcalc/agr160] [PMID:  22218671]

[6]
Addolorato, G.; Balducci, G.; Capristo, E.; Attilia, M.L.; Taggi, F.; Gasbarrini, G.; Ceccanti, M. Gamma-hydroxybutyric acid (GHB) in the treatment of alcohol withdrawal syndrome: A randomized comparative study versus benzodiazepine. Alcohol. Clin. Exp. Res.,  1999, 23(10), 1596-1604.
 [http://dx.doi.org/10.1097/00000374-199910000-00005] [PMID:  10549990]

[7]
De Soto, C.B.; O’Donnell, W.E.; Allred, L.J.; Lopes, C.E. Symptomatology in alcoholics at various stages of abstinence. Alcohol. Clin. Exp. Res.,  1985, 9(6), 505-512.
 [http://dx.doi.org/10.1111/j.1530-0277.1985.tb05592.x] [PMID:  3911810]

[8]
Martinotti, G.; Di Nicola, M.; Reina, D.; Andreoli, S.; Focà, F.; Cunniff, A.; Tonioni, F.; Bria, P.; Janiri, L. Alcohol protracted withdrawal syndrome: the role of anhedonia. Subst. Use Misuse,  2008, 43(3-4), 271-284.
 [http://dx.doi.org/10.1080/10826080701202429] [PMID:  18365930]

[9]
Heilig, M.; Egli, M.; Crabbe, J.C.; Becker, H.C. Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked? Addict. Biol.,  2010, 15(2), 169-184.
 [http://dx.doi.org/10.1111/j.1369-1600.2009.00194.x] [PMID:  20148778]

[10]
Mirijello, A.; D’Angelo, C.; Ferrulli, A.; Vassallo, G.; Antonelli, M.; Caputo, F.; Leggio, L.; Gasbarrini, A.; Addolorato, G. Identification and management of alcohol withdrawal syndrome. Drugs,  2015, 75(4), 353-365.
 [http://dx.doi.org/10.1007/s40265-015-0358-1] [PMID:  25666543]

[11]
Keating, G.M. Sodium oxybate: a review of its use in alcohol withdrawal syndrome and in the maintenance of abstinence in alcohol dependence. Clin. Drug Investig.,  2014, 34(1), 63-80.
 [http://dx.doi.org/10.1007/s40261-013-0158-x] [PMID:  24307430]

[12]
Mason, B.J.; Quello, S.; Goodell, V.; Shadan, F.; Kyle, M.; Begovic, A. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern. Med.,  2014, 174(1), 70-77.
 [http://dx.doi.org/10.1001/jamainternmed.2013.11950] [PMID:  24190578]

[13]
Martinotti, G.; Andreoli, S.; Reina, D.; Di Nicola, M.; Ortolani, I.; Tedeschi, D.; Fanella, F.; Pozzi, G.; Iannoni, E.; D’Iddio, S.; Prof, L.J. Acetyl-l-Carnitine in the treatment of anhedonia, melancholic and negative symptoms in alcohol dependent subjects. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2011, 35(4), 953-958.
 [http://dx.doi.org/10.1016/j.pnpbp.2011.01.013] [PMID:  21256179]

[14]
Bernard, L.; Cyr, L.; Bonnet-Suard, A.; Cutarella, C.; Bréjard, V. Drawing alcohol craving process: A systematic review of its association with thought suppression, inhibition and impulsivity. Heliyon,  2021, 7(1), e05868.
 [http://dx.doi.org/10.1016/j.heliyon.2020.e05868] [PMID:  33458444]

[15]
Connor, J.P.; Jack, A.; Feeney, G.F.; Young, R.M. Validity of the obsessive compulsive drinking scale in a heavy drinking population. Alcohol. Clin. Exp. Res.,  2008, 32(6), 1067-1073.
 [http://dx.doi.org/10.1111/j.1530-0277.2008.00668.x] [PMID:  18445115]

[16]
Tiffany, S.T.; Wray, J.M. The clinical significance of drug craving. Ann. N. Y. Acad. Sci.,  2012, 1248, 1-17.
 [http://dx.doi.org/10.1111/j.1749-6632.2011.06298.x] [PMID:  22172057]

[17]
Murphy, C.M.; Stojek, M.K.; Few, L.R.; Rothbaum, A.O.; Mackillop, J. Craving as an alcohol use disorder symptom in DSM-5: an empirical examination in a treatment-seeking sample. Exp. Clin. Psychopharmacol.,  2014, 22(1), 43-49.
 [http://dx.doi.org/10.1037/a0034535] [PMID:  24490710]

[18]
Flannery, B.A.; Volpicelli, J.R.; Pettinati, H.M. Psychometric properties of the penn alcohol craving scale. Alcohol. Clin. Exp. Res.,  1999, 23(8), 1289-1295.
 [http://dx.doi.org/10.1111/j.1530-0277.1999.tb04349.x] [PMID:  10470970]

[19]
Heinz, A.; Beck, A.; Mir, J.; Grüsser, S.M.; Grace, A.A.; Wrase, J. Alcohol craving and relapse prediction: Imaging studies. In: Advances in the Neuroscience of Addiction, 2nd ed; Kuhn, C.M.; Koob, G.F., Eds.; CRC Press/Taylor & Francis: Boca Raton, 2010. 
 [http://dx.doi.org/10.1201/9781420007350-c4]

[20]
Garbusow, M.; Sebold, M.; Beck, A.; Heinz, A. Too difficult to stop: mechanisms facilitating relapse in alcohol dependence. Neuropsychobiology,  2014, 70(2), 103-110.
 [http://dx.doi.org/10.1159/000362838] [PMID:  25359490]

[21]
Tabakoff, B. Withdrawal symptoms and alcohol dependence. One man’s craving is another man’s dependence. Br. J. Addict.,  1990, 85(10), 1253-1254.
 [http://dx.doi.org/10.1111/j.1360-0443.1990.tb01600.x] [PMID:  2265284]

[22]
Roelofs, S.M. Hyperventilation, anxiety, craving for alcohol: a subacute alcohol withdrawal syndrome. Alcohol,  1985, 2(3), 501-505.
 [http://dx.doi.org/10.1016/0741-8329(85)90123-5] [PMID:  4026971]

[23]
Seo, D.; Sinha, R. The neurobiology of alcohol craving and relapse. Handb. Clin. Neurol.,  2014, 125, 355-368.
 [http://dx.doi.org/10.1016/B978-0-444-62619-6.00021-5] [PMID:  25307585]

[24]
Martinotti, G.; Di Nicola, M.; Tedeschi, D.; Callea, A.; Di Giannantonio, M.; Janiri, L. Craving Typology Questionnaire (CTQ): a scale for alcohol craving in normal controls and alcoholics. Compr. Psychiatry,  2013, 54(7), 925-932.
 [http://dx.doi.org/10.1016/j.comppsych.2013.03.023] [PMID:  23642635]

[25]
Burnette, E.M.; Grodin, E.N.; Schacht, J.P.; Ray, L.A. Clinical and neural correlates of reward and relief drinking. Alcohol. Clin. Exp. Res.,  2021, 45(1), 194-203.
 [http://dx.doi.org/10.1111/acer.14495] [PMID:  33119924]

[26]
Caputo, F.; Cibin, M.; Loche, A.; De Giorgio, R.; Zoli, G. The recognition and management of protracted alcohol withdrawal may improve and modulate the pharmacological treatment of alcohol use disorder. J. Psychopharmacol.,  2020, 34(11), 1171-1175.
 [http://dx.doi.org/10.1177/0269881120936483] [PMID:  32648800]

[27]
Roberto, M.; Varodayan, F.P. Synaptic targets: Chronic alcohol actions. Neuropharmacology,  2017, 122, 85-99.
 [http://dx.doi.org/10.1016/j.neuropharm.2017.01.013] [PMID:  28108359]

[28]
Eşel, E.; Dinç, K. Neurobiology of alcohol dependence and implications on treatment. Turk Psikiyatr. Derg.,  2017, 28(1), 51-60.

[29]
Skinner, M.D.; Aubin, H.J. Craving’s place in addiction theory: contributions of the major models. Neurosci. Biobehav. Rev.,  2010, 34(4), 606-623.
 [http://dx.doi.org/10.1016/j.neubiorev.2009.11.024] [PMID:  19961872]

[30]
Koob, G.F.; Nestler, E.J. The neurobiology of drug addiction. J. Neuropsychiatry Clin. Neurosci.,  1997, 9(3), 482-497.
 [http://dx.doi.org/10.1176/jnp.9.3.482] [PMID:  9276849]

[31]
Koob, G.F.; Volkow, N.D. Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry,  2016, 3(8), 760-773.
 [http://dx.doi.org/10.1016/S2215-0366(16)00104-8] [PMID:  27475769]

[32]
Chakravorty, S.; Chaudhary, N.S.; Brower, K.J. Alcohol Dependence and Its Relationship With Insomnia and Other Sleep Disorders. Alcohol. Clin. Exp. Res.,  2016, 40(11), 2271-2282.
 [http://dx.doi.org/10.1111/acer.13217] [PMID:  27706838]

[33]
Haario, P.; Rahkonen, O.; Laaksonen, M.; Lahelma, E.; Lallukka, T. Bidirectional associations between insomnia symptoms and unhealthy behaviours. J. Sleep Res.,  2013, 22(1), 89-95.
 [http://dx.doi.org/10.1111/j.1365-2869.2012.01043.x] [PMID:  22978579]

[34]
Brower, K.J.; Krentzman, A.; Robinson, E.A. Persistent insomnia, abstinence, and moderate drinking in alcohol-dependent individuals. Am. J. Addict.,  2011, 20(5), 435-440.
 [http://dx.doi.org/10.1111/j.1521-0391.2011.00152.x] [PMID:  21838842]

[35]
Angarita, G.A.; Emadi, N.; Hodges, S.; Morgan, P.T. Sleep abnormalities associated with alcohol, cannabis, cocaine, and opiate use: a comprehensive review. Addict. Sci. Clin. Pract.,  2016, 11(1), 9.
 [http://dx.doi.org/10.1186/s13722-016-0056-7] [PMID:  27117064]

[36]
Colrain, I.M.; Turlington, S.; Baker, F.C. Impact of alcoholism on sleep architecture and EEG power spectra in men and women. Sleep,  2009, 32(10), 1341-1352.
 [http://dx.doi.org/10.1093/sleep/32.10.1341] [PMID:  19848363]

[37]
Brower, K.J.; Aldrich, M.S.; Robinson, E.A.; Zucker, R.A.; Greden, J.F. Insomnia, self-medication, and relapse to alcoholism. Am. J. Psychiatry,  2001, 158(3), 399-404.
 [http://dx.doi.org/10.1176/appi.ajp.158.3.399] [PMID:  11229980]

[38]
Brower, K.J.; Perron, B.E. Prevalence and correlates of withdrawal-related insomnia among adults with alcohol dependence: results from a national survey. Am. J. Addict.,  2010, 19(3), 238-244.
 [http://dx.doi.org/10.1111/j.1521-0391.2010.00035.x] [PMID:  20525030]

[39]
Brower, K.J. Assessment and treatment of insomnia in adult patients with alcohol use disorders. Alcohol,  2015, 49(4), 417-427.
 [http://dx.doi.org/10.1016/j.alcohol.2014.12.003] [PMID:  25957855]

[40]
Pozzi, G.; Martinotti, G.; Reina, D.; Dario, T.; Frustaci, A.; Janiri, L.; Bria, P. The assessment of post-detoxification anhedonia: influence of clinical and psychosocial variables. Subst. Use Misuse,  2008, 43(5), 722-732.
 [http://dx.doi.org/10.1080/00952990701202954] [PMID:  18393086]

[41]
McHugh, R.K.; Weiss, R.D. Alcohol use disorder and depressive disorders. Alcohol Res.,  2019, 40(1), arcr.v40.1.01.
 [http://dx.doi.org/10.35946/arcr.v40.1.01] [PMID: 31649834]

[42]
Anker, J.J.; Kushner, M.G. Co-occurring alcohol use disorder and anxiety: Bridging psychiatric, psychological, and neurobiological perspectives. Alcohol Res.,  2019, 40(1), arcr.v40.1.03.
 [http://dx.doi.org/10.35946/arcr.v40.1.03] [PMID: 31886106]

[43]
Newton-Howes, G.; Foulds, J. Personality disorder and alcohol use disorder: An overview. Psychopathology,  2018, 51(2), 130-136.
 [http://dx.doi.org/10.1159/000486602] [PMID:  29466805]

[44]
Vitali, M.; Sorbo, F.; Mistretta, M.; Scalese, B.; Porrari, R.; Galli, D.; Coriale, G.; Rotondo, C.; Solombrino, S.; Attilia, M.L. Dual diagnosis: an intriguing and actual nosographic issue too long neglected. Riv. Psichiatr.,  2018, 53(3), 154-159.
 [PMID:  29912218]

[45]
Pribék, I.K.; Kovács, I.; Kádár, B.K.; Kovács, C.S.; Richman, M.J.; Janka, Z.; Andó, B.; Lázár, B.A. Evaluation of the course and treatment of alcohol withdrawal syndrome with the clinical institute withdrawal assessment for alcohol - Revised: A systematic review-based meta-analysis. Drug Alcohol Depend.,  2021, 220, 108536.
 [http://dx.doi.org/10.1016/j.drugalcdep.2021.108536] [PMID:  33503582]

Rights & Permissions Print Cite

Article Metrics

27

3

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/1570159X20666220706105253	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190

Current Neuropharmacology

Symptoms of Protracted Alcohol Withdrawal in Patients with Alcohol Use Disorder: A Comprehensive Systematic Review

Abstract

Graphical Abstract

Related Journals

Related Books