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      Pharmacogenetic guidance: individualized medicine promotes enhanced pain outcomes

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          Abstract

          The use of pharmacogenomics has become more prevalent over the past several years in treating many disease states. Several cytochrome P450 enzymes play a role in the metabolism of many pain medications including opioids and antidepressants. Noncytochrome P450 enzymes such as methylenetetrahydrofolate reductase (MTHFR) and catechol- O-methyl transferase (COMT) also play a role in the explanation of opioid dosage requirements as well as in response to certain antidepressants. We present the case of a patient with reduced COMT and MTHFR expression treated with leucovorin 10 mg daily for the management of chronic pain. The use of leucovorin in this patient decreased pain scores, which were clinically significant and increased functionality. This case demonstrates the importance of pharmacogenetics testing in patients, as this can help direct providers to better therapeutic options for their patients.

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          Most cited references 13

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          L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials.

          The authors conducted two multicenter sequential parallel comparison design trials to investigate the effect of L-methylfolate augmentation in the treatment of major depressive disorder in patients who had a partial response or no response to selective serotonin reuptake inhibitors (SSRIs). In the first trial, 148 outpatients with SSRI-resistant major depressive disorder were enrolled in a 60-day study divided into two 30-day periods. Patients were randomly assigned, in a 2:3:3 ratio, to receive L-methylfolate for 60 days (7.5 mg/day for 30 days followed by 15 mg/day for 30 days), placebo for 30 days followed by L-methylfolate (7.5 mg/day) for 30 days, or placebo for 60 days. SSRI dosages were kept constant throughout the study. In the second trial, with 75 patients, the design was identical to the first, except that the l-methylfolate dosage was 15 mg/day during both 30-day periods. In the first trial, no significant difference was observed in outcomes between the treatment groups. In the second trial, adjunctive L-methylfolate at 15 mg/day showed significantly greater efficacy compared with continued SSRI therapy plus placebo on both primary outcome measures (response rate and degree of change in depression symptom score) and two secondary outcome measures of symptom severity. The number needed to treat for response was approximately six in favor of adjunctive L-methylfolate at 15 mg/day. L-Methylfolate was well tolerated, with rates of adverse events no different from those reported with placebo. Adjunctive L-methylfolate at 15 mg/day may constitute an effective, safe, and relatively well tolerated treatment strategy for patients with major depressive disorder who have a partial response or no response to SSRIs.
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            Pharmacogenetics of chronic pain management.

            The experience of chronic pain is one of the commonest reasons individuals seek medical attention, making the management of chronic pain a major issue in clinical practice. Drug metabolism and responses are affected by many factors, with genetic variations offering only a partial explanation of an individual's response. There is a paucity of evidence for the benefits of pharmacogenetic testing in the context of pain management.
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              Epidemiology of pain and relation to psychiatric disorders.

              Chronic pain is a common pain condition. Some psychiatric disorders, such as anxiety and depression, are also common in the general population. Epidemiological studies found that some psychiatric disorders are more commonly found among persons with chronic pain (e.g., headache, back pain) than those without chronic pain. Why those psychiatric disorders co-occur with chronic pain, however, is not well understood. Further, studies demonstrated that some psychiatric disorders, such as depression, increase the risk of chronic pain as well as its persistence. It is also recognized that chronic pain has a negative impact on the persistence of psychiatric disorders. The observations from clinical studies suggest that chronic pain is not a common comorbidity among individuals with other psychiatric disorders, such as dementia and schizophrenia. It is not clear if this is a consequence of any specific biological mechanism, or methodology problems in the studies. This paper provides an overview on the distribution of chronic pain and psychiatric disorders, followed by a review of studies that have demonstrated the association between psychiatric disorders and chronic pain.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2018
                22 December 2017
                : 11
                : 37-40
                Affiliations
                [1 ]Central Arkansas Veterans Healthcare System, Little Rock, AR, USA
                [2 ]Department of Pharmacy, Albany Stratton VA Medical Center, Albany, NY, USA
                [3 ]Research and Network Development, Boston Pain Care, Waltham, MA, USA
                [4 ]Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA
                [5 ]Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA
                [6 ]Scientific and Clinical Affairs, Remitigate, LLC, Delmar, NY, USA
                Author notes
                Correspondence: Jeffrey Fudin, Scientific and Clinical Affairs, Remitigate LLC, 357 Delaware Avenue, #124, Delmar, NY 12054, USA, Tel +1 518 558 5651, Email jeffrey.fudin@ 123456remitigate.com
                Article
                jpr-11-037
                10.2147/JPR.S144560
                5743122
                © 2018 Dragic et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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