Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-15T12:11:14.484Z Has data issue: false hasContentIssue false
  • English
  • Français

Role of Serotonin and Serotonin-Selective Pharmacotherapy in Alcohol Dependence

Published online by Cambridge University Press:  07 November 2014

Helen M. Pettinati ,
David Oslin  and
Kelly Decker
Get access Rights & Permissions [Opens in a new window]

Abstract

The majority of studies that have examined the usefulness of pharmacotherapies selective for serotonin (5-hydroxytryptamine; 5-HT) as a treatment for alcohol dependence have been standard, double-blind clinical trials that include patients with a variety of clinical presentations. Almost all of the early studies evaluated heavy social drinkers and found only a modest advantage for 5-HT pharmacotherapies in reducing the number of drinks per day. Also, the advantage of these pharmacotherapies was observed primarily when these agents were given at higher daily dosages than suggested prescribing practices for use as an antidepressant. The few studies that evaluated treatment-seeking patients found that 5-HT pharmacotherapies were not instrumental in reducing drinking rates compared with placebo. These results led to a dampening of enthusiasm for use of these agents in treating alcohol dependence. However, more recent investigations have begun to target subgroups with potential abnormalities in 5-HT neurotransmission. The thinking is that these medications should be most useful in alcohol-dependent individuals who have more clearly delineated suggestive signs of 5-HT dysfunction, such as concomitant depression or anxiety. Although few results are available to date, there is growing evidence to suggest that alcohol-dependent subgroups are differentially responsive to 5-HT pharmacotherapies with respect to drinking-related outcomes. This may explain the modest and variable 5-HT pharmacotherapeutic effects that were reported in the earlier studies, which included large heterogeneous patient groups. Further investigations are needed to confirm these initial optimistic results.

Type
Feature Articles
Information
CNS Spectrums , Volume 5 , Issue 2: Novel Pharmacotherapies for Alcoholism , February 2000 , pp. 33 - 46
Copyright
Copyright © Cambridge University Press 2000

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Pettinati, H. Use of serotonin selective pharmacotherapy in the treatment of alcohol dependence. Alcohol Clin Exp Res. 1996;20(suppl):23A–29A.CrossRefGoogle ScholarPubMed
2.Wise, R. The neurobiology of craving: implications for the understanding and treatment of addiction. J Abnorm Psychol. 1988;97:118–132.CrossRefGoogle ScholarPubMed
3.Mereau, G, Fadda, F, Gessa, G. Ethanol stimulates the firing rate of nigral dopaminergic neurons in unanesthetized rats. Brain Res. 1984;292:63–69.CrossRefGoogle Scholar
4.Imperato, A, DiChiara, G. Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. J Pharmacol Exp Ther. 1986;239:219–228.Google ScholarPubMed
5.Koob, GF, Weiss, F. Neuropharmacology of cocaine and ethanol dependence. Recent Dev Alcohol. 1992;10:201–233.CrossRefGoogle ScholarPubMed
6.Koob, G, Roberts, A. Brain reward circuits in alcoholism. CNS Spectrums. 1999;4:23–37.CrossRefGoogle Scholar
7.Dubovsky, S, Thomas, A. Specificity: effects of serotonin and serotonergic treatments on psychobiological dysfunction. J Psychosom Res. 1995;39:429–444.CrossRefGoogle ScholarPubMed
8.Roth, BLMP. Multiple serotonin receptor subtypes: clinical and experimental aspects. Ann Clin Psychiatry. 1994;6:67–78.CrossRefGoogle ScholarPubMed
9.Teitler, M, Herrick-Davis, K. Multiple serotonin receptor subtypes: molecular cloning and functional expression. Crit Rev Neurobiol. 1994;8:175–188.Google ScholarPubMed
10.Fowler, CJ. Selective inhibitors of MAO types A and B and their clinical usefulness. Drugs Future. 1982;7:501–517.Google Scholar
11.Lejoyeux, M. Use of serotonin (5-hydroxytryptamine) reuptake inhibitors in the treatment of alcoholism. Alcohol Alcohol. 1996;1:69–75.CrossRefGoogle Scholar
12.Yoshimoto, K, McBride, WJ, Lumeng, L, Li, TK. Ethanol enhances the release of dopamine and serotonin in the nucleus accumbens of HAD and LAD lines of rats. Alcohol Clin Exp Res. 1992;16:781–785.CrossRefGoogle ScholarPubMed
13.Carmichael, F, Israel, Y. Effects of ethanol on neurotransmitter release by rat brain cortical slices. J Pharmacol Exp Ther. 1975;193:824–834.Google Scholar
14.Lovinger, D. Ethanol potentiation of 5-HT3 receptor-mediated ion current in NCB-20 neuroblastoma cells. Neurosci Lett. 1991;122:57–60.CrossRefGoogle ScholarPubMed
15.Swift, R, Davidson, D, Whelihan, W, Kuznetsov, O. Ondansetron alters human alcohol intoxication. Biol Psychiatry. 1996;40:514–521.CrossRefGoogle ScholarPubMed
16.McBride, WJ, Bodart, B, Lumeng, L, Li, TK. Association between low contents of dopamine and serotonin in8 the nucleus accumbens and high alcohol preference. Alcohol Clin Exp Res. 1995;19:1420–1422.CrossRefGoogle Scholar
17.McBride, WJ, Chernet, E, Rabold, J, et al.Serotonin-2 receptors in the CNS of alcohol -preferring and -nonpreferring rats. Pharmacol Biochem Behav. 1993;46:631–636.CrossRefGoogle ScholarPubMed
18.Pandey, S, Lumeng, L, Li, T. Serotonin-sub (2C) receptors and serotonin-sub (2C) receptor-mediated phosphoinositide hydrolysis in the brain of alcohol-preferring and alcohol-non-preferring rats. Alcohol Clin Exp Res. 1996;20:1038–1042.CrossRefGoogle Scholar
19.Roy, A, Linnoila, M. CSF studies on alcoholism and related behaviors. Prog Neuropsychopharmacol Biol Psychiatry. 1989;13:505–511.CrossRefGoogle Scholar
20.Banki, C. Factors influencing monoamine metabolites and tryptophan in patients with alcohol dependence. J Neural Transm. 1981;50:89–101.CrossRefGoogle ScholarPubMed
21.Ballenger, J, Goodwin, F, Major, L, Brown, G. Alcohol and central serotonin metabolism in man. Arch Gen Psychiatry. 1979;36:224–227.CrossRefGoogle ScholarPubMed
22.Heinz, A, Ragan, P, Jones, D, et al.Reduced central serotonin transporters in alcoholism. Am J Psychiatry. 1998;155:1544–1549.CrossRefGoogle ScholarPubMed
23.Parent, A, ed. Carpenter's Human Neuroanatomy. Baltimore, Md: Williams and Wilkens; 1996.Google Scholar
24.van Praag, H, Brown, S-L, Asnis, G. The role beyond serotonin: a muliaminergic perspective on abnormal behavior. In: Brown, SL, van Praag, HM, eds. The Role of Serotonin in Psychiatric Disorders. New York, NY: Brunner/Mazel; 1991:302–332.Google Scholar
25.Linnoila, M, Virkkunen, M, Scheinin, M, Nuutila, A, Rimon, R, Goodwin, F. Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior. Life Sci. 1983;33:2609–2614.CrossRefGoogle ScholarPubMed
26.Roy, A, Lamparski, D, Dejong, J, Moore, V, Linnoila, M. Characteristics of alcoholics who attempt suicide. Am J Psychiatry. 1990;177:761–766.Google Scholar
27.Virkkunen, M, Scheinin, M, Nuutila, A, Rimon, R, Goodwin, F, Linnoila, M. Cerbrospinal fluid monoamine metabolite levels in male arsonists. Arch Gen Psychiatry. 1987;44:241–247.CrossRefGoogle Scholar
28.Virkkunen, M, Rawlings, R, Tokola, R. CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic violent offenders, firesetters, and healthy volunteers. Arch Gen Psychiatry. 1994;51:20–27.CrossRefGoogle Scholar
29.Higley, J, Hasert, M, Suomi, S, Linnoila, M. The serotonin reuptake inhibitor sertraline reduces excessive alcohol consumption in nonhuman primates: effect of stress. Neuropsychopharmacology. 1998;18:431–443.CrossRefGoogle ScholarPubMed
30.Naranjo, C, Sellers, E, Lawrin, M. Modulation of ethanol intake by serotonin uptake inhibitors. J Clin Psychiatry. 1986;47(suppl 4):16–22.Google ScholarPubMed
31.Myers, R, Quarfordt, S. Alcohol drinking attenuated by sertraline in rats with 6-OHDA or 5, 7-DHT lesions of N. accumbens: a caloric response? Pharmacol Biochem Behav. 1991;40:923–928.CrossRefGoogle ScholarPubMed
32.Overstreet, D, Rezvani, A, Pucilowski, O, Janowsky, D. 5-HT receptors: implications for the neuropharmacology of alcohol and alcoholism. Alcohol Alcohol. 1995;2(suppl):207–212.Google Scholar
33.Yoshimoto, K, McBride, W. Regulation of nucleus accumbens dopmaine release by the dorsal raphe nucleus in the rat. Neurochem Res. 1992;17:401–407.CrossRefGoogle Scholar
34.Schreiber, R, Opitz, K, Glaser, T, DeVry, J. Ipsapirone and 8-OH-DPAT reduce ethanol preference in rats: involvement of presynaptic 5-HT1A receptors. Psychopharmacology. 1993;112:100–110.CrossRefGoogle ScholarPubMed
35.Tomkins, D, Sellers, E, Fletcher, P. Median and dorsal raphe injections of the 5-HT1A agonist, 8-OH-DPAT, and the GABA-A agonist, muscimol, increase voluntary ethanol intake in Wistar rats. Neuropharmacology. 1994;33:349–358.CrossRefGoogle Scholar
36.Zhou, FC, McKinzie, DL, Patel, TD, Lumeng, L, Li, T-K. Additive reduction of alcohol drinking by 5-HT-sub(1A) antagonist WAY 100635 and serotonin uptake blocker fluoxetine in alcohol-preferring P rats. Alcohol Clin Exp Res. 1998;22:266–269.CrossRefGoogle Scholar
37.Roberts, AJ, McArthur, RA, Hull, EE, Post, C, Koob, GF. Effects of amperozide, 8-OH-DPAT, anmd FG 5974 on operant responding for ethanol. Psychopharmacology. 1998;137:25–32.CrossRefGoogle Scholar
38.Overstreet, DH, McArthur, RA, Rezvani, AH, Post, C. Selective inhibition of alcohol intake in diverse alcohol-preferring rat strains by the 5-HT-sub(2A) antagonists amperozide and FG 5974. Alcohol Clin Exp Res. 1997;21:1448–1454.CrossRefGoogle Scholar
39.Overstreet, D, McArthur, R, Rezvani, A, Post, C. Amperozide and FG5974: 5-HT-2A receptor antagonists reduce alcohol intake in three strains of alcohol-preferring rats. Alcohol Clin Exp Res. 1996;20:15A.Google Scholar
40.Carboni, E, Acquas, E, Leone, P, DiChiara, G. 5-HT3 receptor antagonists block morphine and nicotine but not amphetamine-induced reward. Psychopharmacology. 1989;97:175–179.CrossRefGoogle Scholar
41.George, D, Benkelfat, C, Rawlings, R, et al.Behavioral and neuroendocrine responses to m-chlorophenylpiperazine in subtypes of alcoholics and in healthy comparison subjects. Am J Psychiatry. 1997;154:81–87.Google ScholarPubMed
42.Buczek, Y, Tomkins, D, Higgins, G, Sellers, E. Dissociation of serotonergic regulation of anxiety and ethanol self-administration—a study with MCPP. Behav Pharmacol. 1994;5:470–484.CrossRefGoogle ScholarPubMed
43.Maurel, S, Schreiber, R, De Vry, J. Role of 5-HT1B, 5-HT2A and 5-HT2C receptors in the generaliztion of 5-HT receptor agonists to the ethanol cue in the rat. Behav Pharmacol. 1998;9:337–343.CrossRefGoogle Scholar
44.Maurel, S, De Vry, J, De Beun, R, Schreiber, R. 5-HT2A and 5-HT2C/5-HT1B receptors are differentially involved in alcohol preference and consummatory behavior in cAA rats. Pharmacol Biochem Behav. 1999;62:89–96.CrossRefGoogle ScholarPubMed
45.Janiri, L, Hadjichristos, A, Buonanno, A, Rago, R, Mannelli, P, de Riso, S. Adjuvant trazodone in the treatment of alcoholism: an open study. Alcohol Alcohol. 1998;34:362–365.CrossRefGoogle Scholar
46.Le, AD, Tomkins, DM, Sellers, EM. Use of serotonin (5-HT) and opiate-based drugs in the pharmacotherpay of alcohol dependence: an overview of the preclinical data. Alcohol Alcohol. 1996;31(suppl 1):27–32.CrossRefGoogle Scholar
47.Naranjo, C, Poulos, C, Lanctot, K, et al.Ritanserin, a central 5-HT-sub-2 antagonist, in heavy social drinkers: desire to drink, alcohol intake and related effects. Addiction. 1995;9:893–905.CrossRefGoogle Scholar
48.Johnson, BA, Jasinski, DR, Galloway, GP, et al.Ritanserin in the treatment of alcohol dependence-A multi-center clinical trial. Psychopharmacology. 1996;128:206–215.CrossRefGoogle ScholarPubMed
49.Sellers, E, Toneatto, T, Romach, M, Somer, G, Sobell, L, Sobell, M. Clinical efficacy of the 5-HT3 antagonist ondansetron in alcohol abuse and dependence. Alcohol Clin Exp Res. 1994;18:879–885.CrossRefGoogle ScholarPubMed
50.Tollefson, G, Montague-Clouse, J, Tollefson, S. Treatment of comorbid generalized anxiety in a recently detoxified alcoholic population with a selective serotonergic drug (buspirone). J Clin Psychopharmacol. 1992;12:19–26.CrossRefGoogle Scholar
51.Kranzler, HR, Burleson, JA, Del Boca, FK, et al.Buspirone treatment of anxious alcoholics. A placebo-controlled trial. Arch Gen Psychiatry. 1994;51:720–731.CrossRefGoogle ScholarPubMed
52.Malcolm, R, Anton, R, Randall, C, Johnston, A, Brady, K, Thevos, A. A placebo-controlled trial of buspirone in anxious inpatient alcoholics. Alcohol Clin Exp Res. 1992;16:1007–1013.CrossRefGoogle ScholarPubMed
53.Malec, E, Malec, T, Gagne, MA, Dongier, M. Buspirone in the treatment of alcohol dependence: a placebo-controlled trial. Alcohol Clin Exp Res. 1996;20:307–312.CrossRefGoogle ScholarPubMed
54.Naranjo, CA, Sellers, EM, Roach, CA, Woodley, DV, Sanchez-Craig, M, Sykora, K. Zimelidine-induced variations in alcohol intake by nonde-pressed heavy drinkers. Clin Pharmacol Ther. 1984;35:374–381.CrossRefGoogle ScholarPubMed
55.Naranjo, C, Sellers, E, Sullivan, J, Woodley, D, Kadlec, K, Sykora, K. The serotonin uptake inhibitor citalopram attenuates ethanol intake. Clin Pharmacol Ther. 1987;41:266–274.CrossRefGoogle ScholarPubMed
56.Naranjo, C, Sullivan, J, Kadlec, K, Woodley-Remus, D, Kennedy, G, Sellers, E. Differential effects of viqualine on alcohol intake and other consummatory behaviors. Clin Pharmacol Ther. 1989;46:3001–3009.CrossRefGoogle ScholarPubMed
57.Naranjo, C, Kadlec, K, Sanhueza, P, Woodley-Remus, D, Sellers, E. Fluoxetine differentially alters alcohol intake and other consummatory behaviors in problem drinkers. Clin Pharmacol Ther. 1990;47:490–498.CrossRefGoogle ScholarPubMed
58.Gorelick, D, Pardes, A. Effect of fluoxetine on alcohol consumption in male alcoholics. Alcohol Clin Exp Res. 1992;16:261–265.CrossRefGoogle ScholarPubMed
59.Kabel, D, Petty, F. A double-blind study of fluoxetine in severe alcohol dependence: adjunctive therapy during and after inpatient treatment. Alcohol Clin Exp Res. 1996;20:780–784.CrossRefGoogle ScholarPubMed
60.Kranzler, HR, Burleson, JA, Korner, P, et al.Placebo-controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics. Am J Psychiatry. 1995;152:391–397.Google ScholarPubMed
61.Janiri, L, Gobbi, G, Mannelli, P, Pozzi, G. Effects of fluoxetine and antidepressant doses on short-term outcome of detoxified alcoholics. Int Clin Psychopharmacol. 1996;11:109–117.Google ScholarPubMed
62.Angelone, S, Bellini, L, Di Bella, D, Catalano, M. Effects of fluvoxamine and citalopram in maintaining abstinence in a sample of Italian detoxified alcoholics. Alcohol Alcohol. 1998;33:151–156.CrossRefGoogle Scholar
63.Babor, T, Dolinsky, Z. Alcoholic typologies: historical evolution and empirical evaluation of some common classification schemes. In: Rose, R, Barrett, J, eds. Alcoholism Origins and Outcome. New York, NY: Raven Press; 1988:245–266.Google Scholar
64.Kranzler, H, Anton, R. Implications of recent neuropharmacologic research for understanding the etiology and development of alcoholism. J Consul Clin Psychol. 1994;62:1116–1126.CrossRefGoogle Scholar
65.Hesselbrock, M, Meyer, R, Keener, J. Psychopathology in hospitalized alcoholics. Arch Gen Psychiatry. 1985;42:1050–1055.CrossRefGoogle ScholarPubMed
66.Grant, B, Harford, T. Comorbidity between DSM-IV alcohol use disorders and major depression: results of a national survey. Drug Alcohol Depend. 1995;39:197–206.CrossRefGoogle ScholarPubMed
67.Reiger, D, Farmer, M, Rae, D, et al.Comorbid of mental diorders with alcohol and other drug abuse: results from the epidemiologic catchment area (ECA) study. JAMA. 1990;264:2511–2518.CrossRefGoogle Scholar
68.Kessler, RC, Crum, RM, Warner, LA, Nelson, CB, Schulenberg, J, Anthony, JC. Lifetime co-occurrence of DSM-III-R alcohol abuse and dependence with other psychiatric disorders in the National Comorbidity Study. Arch Gen Psychiatry. 1997;54:313–321.CrossRefGoogle Scholar
69.Cornelius, JR, Salloum, I, Cornelius, MD, Perel, JM. Preliminary report: double-blind, placebo-controlled study of fluoxetine in depressed alcoholics. Psychopharmacol Bull. 1995;31:297–303.Google ScholarPubMed
70.Cornelius, JR, Salloum, IM, Ehler, JG, et al.Fluoxetine in depressed alcoholics: a double-blind, placebo-controlled trial. Arch Gen Psychiatry. 1997;54:700–705.CrossRefGoogle ScholarPubMed
71.Hamilton, M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 23:56–65.CrossRefGoogle Scholar
72.Roy, A. Placebo-controlled study of sertraline in depressed recently abstinent alcoholics. Biol Psychiatry. 1998;44:633–637.CrossRefGoogle ScholarPubMed
73.Kent, J, Coplan, J, Gorman, J. Clinical utility of the selective serotonin reuptake inhibtors in the spectrum of anxiety. Biol Psychiatry. 1998;44:812–824.CrossRefGoogle Scholar
74.Buydens-Branchey, L, Branchey, MH, Noumair, D. Age of alcoholism onset. I. relationship to psychopathology. Arch Gen Psychiatry. 1989;46:225–230.CrossRefGoogle ScholarPubMed
75.Buydens-Branchey, L, Branchey, M, Noumair, D, Lieber, C. Age of alcoholism onset. II. relationship to susceptibility to serotonin precursor availability. Arch Gen Psychiatry. 1989;46:231–236.CrossRefGoogle ScholarPubMed
76.Krystal, J, Webb, E, Cooney, N, et al.Serotonergic and noradrenergic dysregulation in alcoholism: m-CPP and yohimbine effects in recently detoxified alcoholics and healthy comparison subjects. Am J Psychiatry. 1996;153:83–92.Google ScholarPubMed
77.Benkelfat, C, Murphy, D, Hill, J, George, D, Nutt, D, Linnoila, M. Ethanol like properties of the sertonergic partial agonists, m-Chlorophenylpiperazine in chronic alcoholic patients. Arch Gen Psychiatry. 1991;48:383.CrossRefGoogle Scholar
78.Lee, M, Meltzer, H. Neuroendocrine responses to serotonergic agents in alcoholics. Biol Psychiatry. 1991;30:1017–1030.CrossRefGoogle ScholarPubMed
79.Kranzler, HR, Burleson, JA, Brown, J, Babor, TF. Fluoxetine treatment seems to reduce the beneficial effects of cognitive-behavioral therapy in type B alcoholics. Alcohol Clin Exp Res. 1996;20:1534–1541.CrossRefGoogle ScholarPubMed
80.Babor, T, Hoffmann, M, DelBoca, F, et al.Types of alcoholics, I. Evidence for an empirically derived typology based on indicators of vulnerability and severity. Arch Gen Psychiatry. 1992;49:599–608.CrossRefGoogle ScholarPubMed
81.Cloninger, CR. Neurogenetic adaptive mechanisms in alcoholism. Science. 1987;236:410–416.CrossRefGoogle ScholarPubMed
82.Kadden, RM, Cooney, NL, Getter, H, Litt, MD. Matching alcoholics to coping skills or interactional therapies: posttreatment results. J Consult Clin Psychol. 1989;57:698–704.CrossRefGoogle ScholarPubMed
83.Litt, M, Babor, T, DelBoca, F, Kadden, R, Cooney, N. Types of Alcoholics II Application of an empirically derived typology to treatment matching. Arch Gen Psychiatry. 1992;49:609–614.CrossRefGoogle ScholarPubMed
84.Irwin, M, Caldwell, C, Smith, TL, Brown, S, Schuckit, MA, Gillin, C. Major depressive disorder, alcoholism, and reduced natural killer cell cytotoxicity: role of severity of depressive symptoms and alcohol consumption. Arch Gen Psychiatry. 1990;47:713–719.CrossRefGoogle ScholarPubMed
85.Tiihonen, J, Ryynaenen, O-P, Kauhanen, J, Hakola, H. Citalopram in the treatment of alcoholism: a double-blind placebo-controlled study. Pharmacopsychiatry. 1996;29:27–29.CrossRefGoogle ScholarPubMed