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Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate.

ABSTRACT: BACKGROUND:Currently, no pharmacogenetic tests for selecting an opioid-dependence pharmacotherapy have been approved by the US Food and Drug Administration. OBJECTIVES:Determine the effects of variants in 11 genes on dropout rate and dose in patients receiving methadone or buprenorphine/naloxone (ClinicalTrials.gov Identifier: NCT00315341). METHODS:Variants in six pharmacokinetic genes (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4) and five pharmacodynamic genes (HTR2A, OPRM1, ADRA2A, COMT, SLC6A4) were genotyped in samples from a 24-week, randomized, open-label trial of methadone and buprenorphine/naloxone for the treatment of opioid dependence (n = 764; 68.7% male). Genotypes were then used to determine the metabolism phenotype for each pharmacokinetic gene. Phenotypes or genotypes for each gene were analyzed for association with dropout rate and mean dose. RESULTS:Genotype for 5-HTTLPR in the SLC6A4 gene was nominally associated with dropout rate when the methadone and buprenorphine/naloxone groups were combined. When the most significant variants associated with dropout rate were analyzed using pairwise analyses, SLC6A4 (5-HTTLPR) and COMT (Val158Met; rs4860) had nominally significant associations with dropout rate in methadone patients. None of the genes analyzed in the study was associated with mean dose of methadone or buprenorphine/naloxone. CONCLUSIONS:This study suggests that functional polymorphisms related to synaptic dopamine or serotonin levels may predict dropout rates during methadone treatment. Patients with the S/S genotype at 5-HTTLPR in SLC6A4 or the Val/Val genotype at Val158Met in COMT may require additional treatment to improve their chances of completing addiction treatment. Replication in other methadone patient populations will be necessary to ensure the validity of these findings.

SUBMITTER: Crist RC

PROVIDER: S-EPMC5940523 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate.

Crist Richard C RC Li James J Doyle Glenn A GA Gilbert Alex A Dechairo Bryan M BM Berrettini Wade H WH

The American journal of drug and alcohol abuse 20180115 4

<h4>Background</h4>Currently, no pharmacogenetic tests for selecting an opioid-dependence pharmacotherapy have been approved by the US Food and Drug Administration.<h4>Objectives</h4>Determine the effects of variants in 11 genes on dropout rate and dose in patients receiving methadone or buprenorphine/naloxone (ClinicalTrials.gov Identifier: NCT00315341).<h4>Methods</h4>Variants in six pharmacokinetic genes (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4) and five pharmacodynamic genes (HTR2A, ...[more]

PMID: 29333880

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Project description:Objectives: Opioid dependence has been a threat to public health for hundreds of years. With the increasing number of studies on acupuncture-related therapies for opioid dependence patients receiving methadone maintenance treatment (MMT), its effect of acupuncture therapy in treating MMT patients remains controversial. Therefore, we conducted a multiple-treatments meta-analysis, and incorporated both direct and indirect comparisons, in order to discover the most effective treatment for opioid dependence patients receiving MMT. Methods: Five English databases and three Chinese databases were searched from its inception to August 20, 2020, in order to compare the effects of acupuncture-related therapies and MMT, which was summarized as Western medicine (WM) in the following texts. The quality of studies was assessed according to Cochrane's risk of bias tool 5.1.0, and a pair-wise meta-analysis, cumulative meta-analysis, and the network meta-analysis was performed using the R software (Version 3.6.1) and STATA (Version 14.0). The primary outcome was the effective rate, which was calculated by the ratio of detoxifying patients to the total. The secondary outcome was the Modified Himmelsbach Opiate Withdrawal Scale (MHOWS). Results: A total of 20 trials were included, which consisted of comparisons among WM, traditional Chinese medicine (TCM), and the four types of acupuncture, namely, manual acupuncture (MA), electro-acupuncture (EA), auricular acupuncture (AA), and transcutaneous electrical acupoint stimulation (TEAS). Though none of the trials were at low risk of bias. In the pair-wise meta-analysis, no statistically significant differences were observed in terms of the effective rate. Furthermore, MA was more efficacious than WM, EA, and TEAS in MHOWS, with mean differences (MDs) of (-8.59, 95% CI: -15.96 to -1.23, P < 0.01), (-6.15, 95% CI: -9.45 to -2.85, P < 0.05), and (-10.44, 95% CI: -16.11 to -4.77, P < 0.05), respectively. In the network meta-analysis, MA was more effective than WM (RR: 1.40, 95% CI: 1.05 to 1.99) on the effective rate, and (MD: -5.74, 95% CI: -11.60 to -0.10) on MHOWS. TEAS was more effective than WM (MD: -15.34, 95% CI: -27.34 to -3.46) on MHOWS. Synthetically, MA had the highest probability to rank first in treating opioid dependence. Conclusions: The existing evidence shows that acupuncture related-therapies may effectively be used for treating patients receiving MMT, and that manual acupuncture may be the best choice for opioid dependence among all kinds of acupuncture-related therapies. Nevertheless, reducing the relapse and promoting the recovery of opioid dependence need more efforts from not only the medical industry but also government support, security system, and educational popularization. To strengthen the assurance of acupuncture-related therapies in the treatment of opioid dependence, we expected that clinical trials with high quality would be conducted, to provide more confident evidence.

Project description:Background and aimsIn a recent randomized trial, patients with opioid dependence receiving brief intervention, emergency department (ED)-initiated buprenorphine and ongoing follow-up in primary care with buprenorphine (buprenorphine) were twice as likely to be engaged in addiction treatment compared with referral to community-based treatment (referral) or brief intervention and referral (brief intervention). Our aim was to evaluate the relative cost-effectiveness of these three methods of intervening on opioid dependence in the ED.DesignMeasured health-care use was converted to dollar values. We considered a health-care system perspective and constructed cost-effectiveness acceptability curves that indicate the probability each treatment is cost-effective under different thresholds of willingness-to-pay for outcomes studied.SettingAn urban ED in the United States.ParticipantsOpioid-dependent patients aged 18 years or older.MeasurementsSelf-reported 30-day assessment data were used to construct cost-effectiveness acceptability curves for patient engagement in formal addiction treatment at 30 days and the number of days illicit opioid-free in the past week.FindingsConsidering only health-care system costs, cost-effectiveness acceptability curves indicate that at all positive willingness-to-pay values, ED-initiated buprenorphine treatment was more cost-effective than brief intervention or referral. For example, at a willingness-to-pay threshold of $1000 for 30-day treatment engagement, we are 79% certain ED-initiated buprenorphine is most cost-effective compared with other studied treatments. Similar results were found for days illicit opioid-free in the past week. Results were robust to secondary analyses that included patients with missing cost data, included crime and patient time costs in the numerator, and to changes in unit price estimates.ConclusionIn the United States, emergency department-initiated buprenorphine intervention for patients with opioid dependence provides high value compared with referral to community-based treatment or combined brief intervention and referral.

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Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate.

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Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate.

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