Pharmacological Treatments for Gambling Disorder: A Current Review of Literature

Yıl 2025, , 94 - 105, 31.03.2025

Elif Aktan Mutlu , Gözde Yontar , Begüm Gökhan Aksoy

https://doi.org/10.51982/bagimli.1482749

Öz

This narrative review aims to examine pharmacological treatment modalities for gambling disorder (GD) by analyzing recent literature and identifying significant trends in the field. A thorough examination of relevant literature, focusing primarily on recent studies and reviews, in order to identify significant pharmacological treatment approaches and current trends. Results: The review identifies several pharmacological approaches for GD, including opioid antagonists, serotonergic agents, dopaminergic modulators, glutamatergic agents, and mood stabilizers. Recent studies suggest that opioid antagonists such as naltrexone and nalmefene show promise in reducing gambling urges and behaviors. Additionally, serotonergic agents like selective serotonin reuptake inhibitors (SSRIs) have demonstrated efficacy in alleviating the impulsivity and compulsivity associated with GD. Dopaminergic and glutamatergic agents, while showing some potential, require further investigation for their role in GD treatment. Mood stabilizers, particularly lithium, appear to be beneficial, especially in individuals with co-occurring bipolar affective disorder. Pharmacological interventions play a crucial role in the management of GD, with opioid antagonists and SSRIs emerging as promising options. However, further research is needed to elucidate the optimal pharmacotherapeutic approach and develop more targeted treatments for GD. Integration of pharmacotherapy with psychotherapeutic interventions may enhance treatment outcomes for individuals with GD.

Anahtar Kelimeler

Gambling disorder, addictive behaviors, glutamatergic agents, mood stabilizers

Kumar Oynama Bozukluğunda Farmakolojik Tedaviler: Güncel Literatürün Gözden Geçirilmesi

Öz

Bu derlemede, güncel literatür gözden geçirilerek ve bu alandaki önemli eğilimler belirlenerek kumar oynama bozukluğu (KOB) için farmakolojik tedavi yöntemlerinin araştırılması amaçlanmıştır. Öncelikle güncel ve kanıt düzeyi yüksek çalışmalara ve derlemelere odaklanılarak ilgili literatür kapsamlı bir şekilde incelenmiştir. İncelemede; KOB tedavisinde opioid antagonistleri, serotonerjik ajanlar, dopaminerjik modülatörler, glutamaterjik ajanlar ve duygudurum düzenleyicileri de içeren çeşitli farmakolojik yaklaşımlar belirlenmiştir. Son araştırmalarda, naltrekson ve nalmefen gibi opioid antagonistlerinin kumar oynama isteği ve davranışlarını azaltmada umut verici olduğu gösterilmiştir. Ek olarak, seçici serotonin geri alım inhibitörleri (SSGİ’ler) gibi serotonerjik ajanların KOB ile ilişkili impulsivite ve kompülsiviteyi hafifletmede etkin olduğu belirtilmiştir. Dopaminerjik ve glutamaterjik ajanların KOB tedavisindeki rolü net olarak gösterilememiştir. Duygudurum düzenleyicilerin, özellikle de lityumun, bipolar affektif bozukluğun eşlik ettiği bireylerde faydalı olduğu görülmüştür. KOB tedavisinde farmakolojik müdahaleler önemli bir rol oynamakta olup opioid antagonistleri ve SSGİ'ler umut verici seçenekler olarak ortaya çıkmaktadır. Bununla birlikte, optimal farmakoterapötik yaklaşımı aydınlatmak ve KOB için daha hedefe yönelik tedaviler geliştirmek için ileri çalışmalara ihtiyaç duyulmaktadır. Farmakoterapinin psikoterapötik müdahalelerle entegrasyonu KOB’a sahip bireyler için tedavi sonuçlarını iyileştirebilir.

Anahtar Kelimeler

Kumar oynama bozukluğu, davranışsal bağımlılıklar, glutamaterjik ajanlar, duygudurum düzenleyiciler

Kaynakça

• American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5®), 5th ed. Washington DC: American Psychiatric Association, 2013.
• Shah P, Quilty L, Kim J, et al. Impaired awareness of problem and pathological gambling: a review. J Gambl Stud 2020; 36(1): 39-50.
• American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-4®), 4th ed. Washington DC: American Psychiatric Association, 2000.
• Petry NM, Blanco C, Stinchfield R, Volberg R. An empirical evaluation of proposed changes for gambling diagnosis in the DSM-5. Addiction 2013; 108(3): 575-581.
• Fauth-Bühler M, Mann K, Potenza MN. Pathological gambing: a review of the neurobiological evidence relevant for its classification as an addictive disorder. Addict Biol 2017; 22(4): 885-897.
• Sauvaget A, Bulteau S, Guilleux A, et al. Both active and sham low-frequency rTMS single sessions over the right DLPFC decrease cue-induced cravings among pathological gamblers seeking treatment: a randomized, double-blind, sham-controlled crossover trial. J Behav Addict 2018; 7(1): 126-136.
• Moragas L, Granero R, Stinchfield R, et al. Comparative analysis of distinct phenotypes in gambling disorder based on gambling preferences. BMC Psychiatry 2015; 15: 86.
• Abbott MW. The changing epidemiology of gambling disorder and gambling-related harm: public health implications. Public Health 2020; 184: 41-45.
• Potenza MN, Balodis IM, Derevensky J, et al. Gambling disorder. Nat Rev Dis Primers 2019; 5(1): 51.
• Cowlishaw S, Hakes JK. Pathological and problem gambling in substance use treatment: results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Am J Addict 2015; 24(5): 467-474.
• Aragay N, Roca A, Garcia B, et al. Pathological gambling in a psychiatric sample. Compr Psychiatry 2012; 53(1): 9-14.
• Wullinger PM, Bickl AM, Loy JK, et al. Longitudinal associations between psychiatric comorbidity and the severity of gambling disorder: results from a 36-month follow-up study of clients in Bavarian outpatient addiction care. J Behav Addict 2023; 12(2): 535-546.
• Lorains FK, Cowlishaw S, Thomas SA. Prevalence of comorbid disorders in problem and pathological gambling: systematic review and meta-analysis of population surveys. Addiction 2011; 106(3): 490-498.
• Blank L, Baxter S, Woods HB, Goyder E. Interventions to reduce the public health burden of gambling-related harms: a mapping review. Lancet Public Health 2021; 6(1): e50-e63. doi:10.1016/S2468-2667(20)30230-9
• Bartley CA, Bloch MH. Meta-analysis: pharmacological treatment of pathological gambling. Expert Rev Neurother 2013; 13(8): 887-894.
• Potenza MN. The neural bases of cognitive processes in gambling disorder. Trends Cogn Sci 2014; 18(8): 429-438.
• Moccia L, Pettorruso M, De Crescenzo F, et al. Neural correlates of cognitive control in gambling disorder: a systematic review of fMRI studies. Neurosci Biobehav Rev 2017; 78: 104-116.
• Grant JE, Odlaug BL, Chamberlain SR. Neural and psychological underpinnings of gambling disorder: a review. Prog Neuropsychopharmacol Biol Psychiatry 2016; 65: 188-193.
• Levin Y, Tzelgov J. Conflict components of the stroop effect and their "control". Front Psychol 2014; 5: 463.
• Wiehler A, Peters J. Reward-based decision making in pathological gambling: the roles of risk and delay. Neurosci Res 2015; 90: 3-14.
• de Ruiter MB, Veltman DJ, Goudriaan AE, et al. Response perseveration and ventral prefrontal sensitivity to reward and punishment in male problem gamblers and smokers. Neuropsychopharmacol 2009; 34(4): 1027-1038.
• Clark L, Boileau I, Zack M. Neuroimaging of reward mechanisms in gambling disorder: an integrative review. Mol Psychiatry 2019; 24(5): 674-693.
• Linnet J, Mouridsen K, Peterson E, et al. Striatal dopamine release codes uncertainty in pathological gambling. Psychiatry Res 2012; 204(1): 55-60.
• Boileau I, Payer D, Chugani B, et al. The D2/3 dopamine receptor in pathological gambling: a positron emission tomography study with [11C]-(+)-propyl-hexahydro-naphtho-oxazin and [11C]raclopride. Addiction 2013; 108(5): 953-963.
• Clark L, Stokes PR, Wu K, et al. Striatal dopamine D₂/D₃ receptor binding in pathological gambling is correlated with mood-related impulsivity. Neuroimage 2012; 63(1): 40-46.
• Bullock SA, Potenza MN. Pathological gambling: neuropsychopharmacology and treatment. Curr Psychopharmacol 2012; 1(1).
• Marazziti D, Golia F, Picchetti M, et al. Decreased density of the platelet serotonin transporter in pathological gamblers. Neuropsychobiology 2008; 57(1-2): 38-43.
• Kalivas PW, Volkow ND. The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 2005; 162(8): 1403-1413.
• Kalivas PW, Lalumiere RT, Knackstedt L, Shen H. Glutamate transmission in addiction. Neuropharmacol 2009; 56 (Suppl 1): 169–173.
• Nordin C, Gupta RC, Sjodin I. Cerebrospinal fluid amino acids in pathological gamblers and healthy controls. Neuropsychobiology 2007; 56(2–3): 152–158.
• Grant JE, Kim SW, Potenza MN, et al. Paroxetine treatment of pathological gambling: a multi-centre randomized controlled trial. Int Clin Psychopharmacol 2003; 18(4): 243-249.
• Kalivas PW. The glutamate homeostasis hypothesis of addiction. Nat Rev Neurosci 2009; 10(8): 561-572.
• van Holst RJ, van der Meer JN, McLaren DG, et al. Interactions between affective and cognitive processing systems in problematic gamblers: a functional connectivity study. PLoS One 2012; 7(11): e49923.
• Fineberg NA, Chamberlain SR, Goudriaan AE, et al. New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity. CNS Spectr 2014; 19(1): 69-89.
• Williams AD, Grisham JR, Erskine A, Cassedy E. Deficits in emotion regulation associated with pathological gambling. Br J Clin Psychol 2012; 51(2): 223-238.
• Balodis IM, Lacadie CM, Potenza MN. A preliminary study of the neural correlates of the intensities of self-reported gambling urges and emotions in men with pathological gambling. J Gambl Stud 2012; 28(3): 493-513.
• Ward S, Smith N, Bowden-Jones H. The use of naltrexone in pathological and problem gambling: a UK case series. J Behav Addict 2018; 7(3): 827-833.
• Kraus SW, Etuk R, Potenza MN. Current pharmacotherapy for gambling disorder: a systematic review. Expert Opin Pharmacother 2020; 21(3): 287-296.
• Goslar M, Leibetseder M, Muench HM, et al. Pharmacological treatments for disordered gambling: a meta-analysis. J Gambl Stud 2019; 35(2): 415-445.
• Grant JE, Kim SW, Hartman BK. A double-blind, placebo-controlled study of the opiate antagonist naltrexone in the treatment of pathological gambling urges. J Clin Psychiatry 2008; 69(5): 783-789.
• Kim SW, Grant JE, Adson DE, Shin YC. Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling. Biol Psychiatry 2001; 49(11): 914-921.
• Grant JE, Potenza MN, Hollander E, et al. Multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling. Am J Psychiatry 2006; 163(2): 303-312.
• Grant JE, Odlaug BL, Potenza MN, et al. Nalmefene in the treatment of pathological gambling: multicentre, double-blind, placebo-controlled study [published correction appears in Br J Psychiatry. 2011 Jan; 198: 75]. Br J Psychiatry 2010; 197(4): 330-331.
• Menchon JM, Mestre-Bach G, Steward T, et al. An overview of gambling disorder: from treatment approaches to risk factors. F1000Res 2018; 7: 434.
• Piquet-Pessôa M, Fontenelle LF. Opioid antagonists in broadly defined behavioral addictions: a narrative review. Expert Opin Pharmacother 2016; 17(6): 835-844.
• Hollander E, DeCaria CM, Finkell JN, et al. A randomized double-blind fluvoxamine/placebo crossover trial in pathologic gambling. Biol Psychiatry 2000; 47(9): 813-817.
• Kim SW, Grant JE, Adson DE, et al. A double-blind placebo-controlled study of the efficacy and safety of paroxetine in the treatment of pathological gambling. J Clin Psychiatry 2002; 63(6): 501-507.
• Black DW, Shaw M, Forbush KT, Allen J. An open-label trial of escitalopram in the treatment of pathological gambling. Clin Neuropharmacol 2007; 30(4): 206-212.
• Grant JE, Potenza MN. Escitalopram treatment of pathological gambling with co-occurring anxiety: an open-label pilot study with double-blind discontinuation. Int Clin Psychopharmacol 2006; 21(4): 203-209.
• Zimmerman M, Breen RB, Posternak MA. An open-label study of citalopram in the treatment of pathological gambling. J Clin Psychiatry 2002; 63(1): 44-48.
• Grant JE, Kim SW. Medication management of pathological gambling. Minn Med 2006; 89(9): 44-48.
• Potenza MN. How central is dopamine to pathological gambling or gambling disorder? Front Behav Neurosci 2013; 7: 206.
• Weintraub D, Koester J, Potenza MN, et al. Impulse control disorders in Parkinson disease: a cross-sectional study of 3090 patients. Arch Neurol 2010; 67(5): 589-595.
• Seeman P. Parkinson's disease treatment may cause impulse-control disorder via dopamine D3 receptors. Synapse 2015; 69(4): 183-189.
• Williams BD, Lee K, Ewah SO, Neelam K. Aripiprazole and other third-generation antipsychotics as a risk factor for impulse control disorders: a systematic review and meta-analysis. J Clin Psychopharmacol 2024; 44(1): 39-48.
• Gaboriau L, Victorri-Vigneau C, Gérardin M, et al. Aripiprazole: a new risk factor for pathological gambling? A report of 8 case reports. Addict Behav 2014; 39(3): 562-565.
• Fong T, Kalechstein A, Bernhard B, et al. A double-blind, placebo controlled trial of olanzapine for the treatment of video poker pathological gamblers. Pharmacol Biochem Behav 2008; 89 (3): 298–303.
• McElroy SL, Nelson EB, Welge JA, et al. Olanzapine in the, treatment of pathological gambling: a negative randomized placebo-controlled trial. J Clin Psychiatry 2008; 69(3): 433–440.
• Zack M, Poulos CX. A D2 antagonist enhances the rewarding and priming effects of a gambling episode in pathological gamblers. Neuropsychopharmacol 2007; 32(8): 1678–1686.
• Zack, M. & Poulos, CX. Amphetamine primes motivation to gamble and gambling-related semantic networks in problem gamblers. Neuropsychopharmacol 2004; 29: 195–207.
• Black DW, Arndt S, Coryell WH, et al. Bupropion in the treatment of pathological gambling: a randomized, double-blind, placebo-controlled, flexible-dose study. J Clin Psychopharmacol 2007; 27(2): 143-150.
• Grant JE, Odlaug BL, Chamberlain SR, et al. A proof of concept study of tolcapone for pathological gambling: relationships with COMT genotype and brain activation. Eur Neuropsychopharmacol 2013; 23(11): 1587-1596.
• Pettorruso M, De Risio L, Martinotti G, et al. Targeting the glutamatergic system to treat pathological gambling: current evidence and future perspectives. Biomed Res Int 2014; 2014: 109786.
• Moran MM, McFarland K, Melendez RI, et al. Cystine/glutamate exchange regulates metabotropic glutamate receptor presynaptic inhibition of excitatory transmission and vulnerability to cocaine seeking. J Neurosci 2005; 25(27): 6389-6393.
• Baker DA, McFarland K, Lake RW, et al. N-acetyl cysteine-induced blockade of cocaine-induced reinstatement. Ann N Y Acad Sci 2003; 1003: 349-351.
• Grant JE, Kim SW, Odlaug BL. N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study. Biol Psychiatry 2007; 62(6): 652-657.
• Grant JE, Odlaug BL, Chamberlain SR, et al. A randomized, placebo-controlled trial of N-acetylcysteine plus imaginal desensitization for nicotine-dependent pathological gamblers. J Clin Psychiatry 2014; 75(1): 39-45.
• Berlin HA, Braun A, Simeon D, et al. A double-blind, placebo-controlled trial of topiramate for pathological gambling. World J Biol Psychiatry 2013; 14(2): 121–128.
• Dannon PN, Lowengrub K, Gonopolski Y, et al. Topiramate versus fluvoxamine in the treatment of pathological gambling: a randomized, blind-rater comparison study. Clin Neuropharmacol 2005; 28(1): 6-10.
• Nicolato R, Romano-Silva MA, Correa H, et al. Lithium and topiramate association in the treatment of comorbid pathological gambling and bipolar disorder. Aust N Z J Psychiatry 2007; 41(7): 628.
• Kiefer F, Mann K. Acamprosate: how, where, and for whom does it work? Mechanism of action, treatment targets, and individualized therapy. Curr Pharm Des 2010; 16(19): 2098-2102.
• Black DW, McNeilly DP, Burke WJ, et al. An open-label trial of acamprosate in the treatment of pathological gambling. Ann Clin Psychiatry 2011; 23(4): 250-256.
• Thomas A, Bonanni L, Gambi F, et al. Pathological gambling in Parkinson disease is reduced by amantadine. Ann Neurol 2010; 68(3): 400-404.
• Pettorruso M, Martinotti G, Di Nicola M, et al. Amantadine in the treatment of pathological gambling: a case report. Front Psychiatry 2012; 3: 102.
• Potenza MN. Review. The neurobiology of pathological gambling and drug addiction: an overview and new findings. Philos Trans R Soc Lond B Biol Sci 2008; 363(1507): 3181-3189.
• Quilty LC, Watson C, Robinson JJ, et al. The prevalence and course of pathological gambling in the mood disorders. J Gambl Stud 2011; 27(2): 191-201.
• Di Nicola M, De Risio L, Pettorruso M, et al. Bipolar disorder and gambling disorder comorbidity: current evidence and implications for pharmacological treatment. J Affect Disord 2014; 167: 285–298.
• Hollander E, Pallanti S, Allen A, et al. Does sustained-release lithium reduce impulsive gambling and affective instability versus placebo in pathological gamblers with bipolar spectrum disorders? Am J Psychiatry 2005; 162(1): 137–145.
• Pallanti S, Haznedar MM, Hollander E, et al. Basal Ganglia activity in pathological gambling: a fluorodeoxyglucose-positron emission tomography study. Neuropsychobiology 2010; 62(2): 132-138.
• Pallanti S, Quercioli L, Sood E, Hollander E. Lithium and valproate treatment of pathological gambling: a randomized single-blind study. J Clin Psychiatry 2002; 63(7): 559-564.
• Black DW, Shaw MC, Allen J. Extended release carbamazepine in the treatment of pathological gambling: an open-label study. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32(5): 1191-1194