Comparative pharmacogenetic study of disulfiram or cyanamide efficacy for alcohol dependence: the key role of dopamine neurotransmission gene polymorphisms
The actual direction of increasing the efficacy of alcohol dependence (AD) treatment is the search for opportunities for individualization of therapy using pharmacogenetic markers to stratify patients in order to select the most optimal therapeutic tactics. Aims. To test an associations of possible...
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Federal State Budget Scientific Institution National Medical Research Center for Psychiatry and Neurology n.a. V.M. Bekhterev Ministry of Health of the Russian Federation
2023-07-01
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| Series: | Обозрение психиатрии и медицинской психологии имени В.М. Бехтерева |
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| Online Access: | https://www.bekhterevreview.com/jour/article/view/923 |
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| author | A. O. Kibitov K. V. Rybakova V. M. Brodyansky V. A. Berntsev E. P. Skurat E. M. Krupitsky |
| author_facet | A. O. Kibitov K. V. Rybakova V. M. Brodyansky V. A. Berntsev E. P. Skurat E. M. Krupitsky |
| author_sort | A. O. Kibitov |
| collection | DOAJ |
| description | The actual direction of increasing the efficacy of alcohol dependence (AD) treatment is the search for opportunities for individualization of therapy using pharmacogenetic markers to stratify patients in order to select the most optimal therapeutic tactics. Aims. To test an associations of possible pharmacogenetic markers with indicators of the efficacy of disulfiram and cyanamide to stabilize remission in patients with AD. Materials and methods. A pharmacogenetic study was conducted on the basis of a double-blind, randomized, comparative, placebo-controlled clinical study of the efficacy and tolerability of disulfiram and cyanamide in the treatment of alcohol dependence syndrome. The main outcome: the duration of retention of patients in the treatment program (in remission), and withdrawal from the treatment program for any reason was considered a negative outcome. Secondary outcomes: time to relapse to alcohol use and time to recurrence to AD. 150 patients with AD (ICD-10 criteria) (av. age — 40.65±1.09 y.o., 19.3% females) were randomly assigned to one of three treatment groups (50 subjects in each): Disulfiram, Cyanamid and Placebo. All patients had weekly (12 weeks) visits to research clinic for brief counselling session. The genetic panel of the study consisted of 15 polymorphic loci in 9 genes: dopamine receptors 2 (DRD2) and 4 (DRD4) types, transmembrane dopamine transporter (DAT), enzymes dopamine-beta-hydroxylase (DBH) and catechol-ortho -methyl-transferase, as well as a two polymorphisms in the genes of the endogenous opioid system and the aldehyde dehydrogenase enzyme gene cluster.Results. For disulfiram, the DBH rs1108580 is associated with a longer remission (p=0.053, trend), and DRD4 VNTR 48 bp is associated with a shorter remission (p=0.006). For cyanamide, DAT VNTR 40 bp was associated with shorter remission (p=0.006) and rapid recurrence to AD (p=0.045). DAT rs27072 has an effect simultaneously in two treatment groups, while the direction of the effect is opposite. For cyanamide, the marker is slightly associated with a longer remission (p = 0.082, trend), a longer time to relapse (p = 0.063, trend) and a longer time to recurrence to AD (p = 0.083, trend). For placebo, DAT rs27072, on the contrary, is associated with a shorter time to to recurrence to AD (p = 0.066, trend). For placebo, DRD2 rs1799732 was associated with a shorter remission (p = 0.001), a shorter time to relapse (p = 0.018), and a shorter time to recurrence to AD (p = 0.001). Conclusion. Preliminary pharmacogenetic markers of the efficacy of alcohol dependence treatment have been identified in genes that control dopaminergic neurotransmission. After independent validation, the obtained genetic markers may be used for pharmacogenetic stratification of patients in order to select the optimal treatment options for alcohol dependence. |
| format | Article |
| id | doaj-art-e6f4a7ad85a6423598f13540bde1e765 |
| institution | DOAJ |
| issn | 2313-7053 2713-055X |
| language | Russian |
| publishDate | 2023-07-01 |
| publisher | Federal State Budget Scientific Institution National Medical Research Center for Psychiatry and Neurology n.a. V.M. Bekhterev Ministry of Health of the Russian Federation |
| record_format | Article |
| series | Обозрение психиатрии и медицинской психологии имени В.М. Бехтерева |
| spelling | doaj-art-e6f4a7ad85a6423598f13540bde1e7652025-08-20T03:20:23ZrusFederal State Budget Scientific Institution National Medical Research Center for Psychiatry and Neurology n.a. V.M. Bekhterev Ministry of Health of the Russian FederationОбозрение психиатрии и медицинской психологии имени В.М. Бехтерева2313-70532713-055X2023-07-0158111513010.31363/2313-7053-2024-833529Comparative pharmacogenetic study of disulfiram or cyanamide efficacy for alcohol dependence: the key role of dopamine neurotransmission gene polymorphismsA. O. Kibitov0K. V. Rybakova1V. M. Brodyansky2V. A. Berntsev3E. P. Skurat4E. M. Krupitsky5V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology; Pavlov First St. Petersburg State Medical UniversityV.M. Bekhterev National Medical Research Center for Psychiatry and NeurologyV.P. Serbsky National Medical Research Center for Psychiatry and NarcologyV.M. Bekhterev National Medical Research Center for Psychiatry and NeurologyV.M. Bekhterev National Medical Research Center for Psychiatry and NeurologyV.M. Bekhterev National Medical Research Center for Psychiatry and Neurology; Pavlov First St. Petersburg State Medical UniversityThe actual direction of increasing the efficacy of alcohol dependence (AD) treatment is the search for opportunities for individualization of therapy using pharmacogenetic markers to stratify patients in order to select the most optimal therapeutic tactics. Aims. To test an associations of possible pharmacogenetic markers with indicators of the efficacy of disulfiram and cyanamide to stabilize remission in patients with AD. Materials and methods. A pharmacogenetic study was conducted on the basis of a double-blind, randomized, comparative, placebo-controlled clinical study of the efficacy and tolerability of disulfiram and cyanamide in the treatment of alcohol dependence syndrome. The main outcome: the duration of retention of patients in the treatment program (in remission), and withdrawal from the treatment program for any reason was considered a negative outcome. Secondary outcomes: time to relapse to alcohol use and time to recurrence to AD. 150 patients with AD (ICD-10 criteria) (av. age — 40.65±1.09 y.o., 19.3% females) were randomly assigned to one of three treatment groups (50 subjects in each): Disulfiram, Cyanamid and Placebo. All patients had weekly (12 weeks) visits to research clinic for brief counselling session. The genetic panel of the study consisted of 15 polymorphic loci in 9 genes: dopamine receptors 2 (DRD2) and 4 (DRD4) types, transmembrane dopamine transporter (DAT), enzymes dopamine-beta-hydroxylase (DBH) and catechol-ortho -methyl-transferase, as well as a two polymorphisms in the genes of the endogenous opioid system and the aldehyde dehydrogenase enzyme gene cluster.Results. For disulfiram, the DBH rs1108580 is associated with a longer remission (p=0.053, trend), and DRD4 VNTR 48 bp is associated with a shorter remission (p=0.006). For cyanamide, DAT VNTR 40 bp was associated with shorter remission (p=0.006) and rapid recurrence to AD (p=0.045). DAT rs27072 has an effect simultaneously in two treatment groups, while the direction of the effect is opposite. For cyanamide, the marker is slightly associated with a longer remission (p = 0.082, trend), a longer time to relapse (p = 0.063, trend) and a longer time to recurrence to AD (p = 0.083, trend). For placebo, DAT rs27072, on the contrary, is associated with a shorter time to to recurrence to AD (p = 0.066, trend). For placebo, DRD2 rs1799732 was associated with a shorter remission (p = 0.001), a shorter time to relapse (p = 0.018), and a shorter time to recurrence to AD (p = 0.001). Conclusion. Preliminary pharmacogenetic markers of the efficacy of alcohol dependence treatment have been identified in genes that control dopaminergic neurotransmission. After independent validation, the obtained genetic markers may be used for pharmacogenetic stratification of patients in order to select the optimal treatment options for alcohol dependence.https://www.bekhterevreview.com/jour/article/view/923alcohol dependencepharmacotherapyаversive medicationsdisulfiramcyanamidegeneticspharmacogeneticsdopamine |
| spellingShingle | A. O. Kibitov K. V. Rybakova V. M. Brodyansky V. A. Berntsev E. P. Skurat E. M. Krupitsky Comparative pharmacogenetic study of disulfiram or cyanamide efficacy for alcohol dependence: the key role of dopamine neurotransmission gene polymorphisms Обозрение психиатрии и медицинской психологии имени В.М. Бехтерева alcohol dependence pharmacotherapy аversive medications disulfiram cyanamide genetics pharmacogenetics dopamine |
| title | Comparative pharmacogenetic study of disulfiram or cyanamide efficacy for alcohol dependence: the key role of dopamine neurotransmission gene polymorphisms |
| title_full | Comparative pharmacogenetic study of disulfiram or cyanamide efficacy for alcohol dependence: the key role of dopamine neurotransmission gene polymorphisms |
| title_fullStr | Comparative pharmacogenetic study of disulfiram or cyanamide efficacy for alcohol dependence: the key role of dopamine neurotransmission gene polymorphisms |
| title_full_unstemmed | Comparative pharmacogenetic study of disulfiram or cyanamide efficacy for alcohol dependence: the key role of dopamine neurotransmission gene polymorphisms |
| title_short | Comparative pharmacogenetic study of disulfiram or cyanamide efficacy for alcohol dependence: the key role of dopamine neurotransmission gene polymorphisms |
| title_sort | comparative pharmacogenetic study of disulfiram or cyanamide efficacy for alcohol dependence the key role of dopamine neurotransmission gene polymorphisms |
| topic | alcohol dependence pharmacotherapy аversive medications disulfiram cyanamide genetics pharmacogenetics dopamine |
| url | https://www.bekhterevreview.com/jour/article/view/923 |
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