Pharmacogenetic guidance: individualized medicine promotes enhanced pain outcomes

Dragic, Lisa; Wegrzyn, Erica L; Schatman, Michael E; Fudin, Jeffrey

doi:10.2147/jpr.s144560

Cited by 6 publications

(3 citation statements)

References 12 publications

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“…To date, there are no data to confirm a connection between MTHFR and opioid medications. One case report of a patient with MTHFR polymorphism demonstrated a substantial reduction in pain severity following supplementation with folinic acid [ 29 ]. The study recommended that physicians initiate pharmacogenomic testing for MTHFR polymorphism, especially for those patients who are not responding to standard medications [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…One case report of a patient with MTHFR polymorphism demonstrated a substantial reduction in pain severity following supplementation with folinic acid [ 29 ]. The study recommended that physicians initiate pharmacogenomic testing for MTHFR polymorphism, especially for those patients who are not responding to standard medications [ 29 ]. In the same vein, a study evaluated the link between disulfiram treatment that is used for the treatment of cocaine addiction and MTHFR polymorphism [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

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A Study of the MTHFR Gene Prevalence in a Rural Tennessee Opioid Use Disorder Treatment Center Population

Cole

Cernasev

Webb

et al. 2022

IJERPH

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Background: Opioid Use Disorder (OUD) has been linked to dopamine and the neurological reward centers. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in the production of many neurotransmitters such as dopamine. As such, MTHFR variants that lead to decreased production of neurotransmitters may play a role in OUD. However, lacunae exist for characterizing the prevalence of the MTHFR mutations in an OUD population. The objective of this study was to determine prevalence of the MTHFR gene mutations in a rural Tennessean population with OUD. Methods: This study was a retrospective cohort of individuals with OUD that evaluated the prevalence of MTHFR variants. Patients were categorized as normal, homozygous C677T, heterozygous C677T, homozygous A1298C, or heterozygous A1298C. The primary outcome was a qualitative comparison of the prevalence of each of the MTHFR variants in our cohort to the publicly reported MTHR polymorphism prevalence. Secondary outcomes include race and ethnicity differences as well as stimulant use differences for each of the variants. Results: A total of 232 patients undergoing care for opioid use disorder were included in the study. Of those included, 30 patients had a normal MTHFR allele and 202 had a variant MTHFR allele. Overall, the prevalence of any MTHFR variant was 87.1% (95% CI 82.6–91.4%). When comparing those with a normal MTHFR allele to those with any MTHFR variant, there was no difference in age, sex, race and ethnicity, or stimulant use. Conclusion: The overall prevalence of MTHFR variants in patients with opioid use disorders is high.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Study of the MTHFR Gene Prevalence in a Rural Tennessee Opioid Use Disorder Treatment Center Population

Cole

Cernasev

Webb

et al. 2022

IJERPH

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“…Similarly, labeling “request for specific opioid” as an NMOU can be seen as prototypical medical paternalism. Many patients are intelligent and capable, and to suggest that a person experiencing chronic pain cannot facilitate evaluation of an opioid’s specific efficacy and adverse effects through patient-centered interviews ignores pharmacogenomic differences …”

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confidence: 99%

Questionable Conceptualizations of Nonmedical Use Can Contribute to Needless Distress

2021

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longest diameter should be limited to non-necrosis part in mRECIST. As a result, bias was unneglectable in comparing trials using different criteria. 5 Besides, time to progression (TTP) was set as the second end point in 4 trials (SHARP [NCT00105443], Asia-Pacific SHARP [NCT00492752], BRISK-FL [NCT00858871], and BRISK-PS [NCT00825955]). The TTP was defined as the time from randomization to radiologic disease progression. Because the numbers of patients who died without tumor progression were not available in these trials, it was difficult to evaluate the difference between TTP and PFS. It is best to disclose the criteria used in each clinical trial and which was evaluated in the original trial, TTP or PFS.Second, approximately 27.2% and 12.0% of patients with 2 previous systemic treatments were enrolled in the CELESTIAL (NCT01908426) and REACH (NCT01140347) trials, respectively, resulting in bias. In detail, the hazard ratio (HR) for death between 130 patients (28.0%) in the cabozantinib group and 62 patients (26.3%) in the placebo group with 2 previous systemic regimens was 0.90 (95% CI, 0.63-1.29), while the HR between patients with only sorafenib as the previous systemic regimen was 0.74 (95% CI, 0.59-0.92). Analysis of PFS revealed superiority of cabozantinib over placebo in both second-line and third-line cohorts. Unfortunately, the REACH trial did not supply a subgroup analysis like this. We believe that it is more reasonable to use HRs of subgroup analysis in network meta-analysis than HRs of the whole cohort, although the baseline characteristics of this subgroup were unavailable.In addition to the trials analyzed in this research, 1 trials of several immune checkpoint inhibitor-based therapies were ongoing, such as toripalimab plus lenvatinib (NCT04523493) and pembrolizumab plus lenvatinib and transcatheter arterial chemoembolization (NCT04246177). The update of this network meta-analysis 1 when these trials are completed will provide more evidence for clinical practice.

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Antidepressants

2018

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Pharmacogenetic guidance: individualized medicine promotes enhanced pain outcomes

Cited by 6 publications

References 12 publications

A Study of the MTHFR Gene Prevalence in a Rural Tennessee Opioid Use Disorder Treatment Center Population

A Study of the MTHFR Gene Prevalence in a Rural Tennessee Opioid Use Disorder Treatment Center Population

Questionable Conceptualizations of Nonmedical Use Can Contribute to Needless Distress

Antidepressants

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