Pharmacogenomics in Chronic Pain Therapy: From Disease to Treatment and Challenges for Clinical Practice

Yamamoto, Priscila Akemi; Costa, Ana Carolina Conchon; Lauretti, Gabriela Rocha; Moraes, Natália Valadares de

doi:10.2217/pgs-2019-0066

Cited by 13 publications

(14 citation statements)

References 86 publications

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“…There is no specific guideline for tramadol, but as tramadol is also a prodrug metabolized through CYP2D6, it seems reasonable to apply the same recommendations as those suggested for codeine, even though tramadol has a more complex mechanism of action [85]. For hydrocodone and oxycodone, further clinical research is still needed to be able to create specific guidelines [81,84,86].…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Phenotypic and Genotypic Variations of Drug Metabolising Enzymes and Transporters in Chronic Pain Patients Facing Adverse Drug Reactions or Non-Response to Analgesics: A Retrospective Study

Rollason

Lloret‐Linares

Lorenzini

et al. 2020

JPM

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This retrospective study evaluates the link between an adverse drug reaction (ADR) or a non-response to treatment and cytochromes P450 (CYP), P-glycoprotein (P-gp) or catechol-O-methyltransferase (COMT) activity in patients taking analgesic drugs for chronic pain. Patients referred to a pain center for an ADR or a non-response to an analgesic drug between January 2005 and November 2014 were included. The genotype and/or phenotype was obtained for assessment of the CYPs, P-gp or COMT activities. The relation between the event and the result of the genotype and/or phenotype was evaluated using a semi-quantitative scale. Our analysis included 243 individual genotypic and/or phenotypic explorations. Genotypes/phenotypes were mainly assessed because of an ADR (n = 145, 59.7%), and the majority of clinical situations were observed with prodrug opioids (n = 148, 60.9%). The probability of a link between an ADR or a non-response and the genotypic/phenotypic status of the patient was evaluated as intermediate to high in 40% and 28.2% of all cases, respectively. The drugs in which the probability of an association was the strongest were the prodrug opioids, with an intermediate to high link in 45.6% of the cases for occurrence of ADRs and 36.0% of the cases for non-response. This study shows that the genotypic and phenotypic approach is useful to understand ADRs or therapeutic resistance to a usual therapeutic dosage, and can be part of the evaluation of chronic pain patients.

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Section: Discussionmentioning

confidence: 99%

“…This has been clearly illustrated for codeine and tramadol. For hydrocodone and oxycodone, studies show a link with the PK profile of these two drugs, but clinical studies are contradictory and still fail to demonstrate a clear lack of analgesia in PM patients [81,[84][85][86].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Phenotypic and Genotypic Variations of Drug Metabolising Enzymes and Transporters in Chronic Pain Patients Facing Adverse Drug Reactions or Non-Response to Analgesics: A Retrospective Study

Rollason

Lloret‐Linares

Lorenzini

et al. 2020

JPM

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“…Data were primarily drawn from AGDS, which is a multi-aim study investigating the risk factors for depression and treatment response to antidepressants. As the AGDS employed phenotyping across an extensive range of complex traits ( 75), on balance it was not feasible to also collect detailed information from participants on dosages and (polypharmacy) combinations taken of the prescribed antidepressants (103); the duration and magnitude of benefits (e.g., for costeffectiveness analyses) (65,104,105); drug tolerability and adverse events (65,(106)(107)(108)(109)(110)(111); adjunct psychological therapies and multidisciplinary treatment/rehabilitation programs (112); other prescribed pain pharmacotherapies and questionnaires (113)(114)(115)(116)(117). Further pharmacoepidemiological studies focusing on chronic pain and a large range of psychiatric comorbidities (51, 52, 118).…”

Section: Strengths Limitations and Further Researchmentioning

confidence: 99%

Comorbid Chronic Pain and Depression: Shared Risk Factors and Differential Antidepressant Effectiveness

et al. 2021

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The bidirectional relationship between depression and chronic pain is well-recognized, but their clinical management remains challenging. Here we characterize the shared risk factors and outcomes for their comorbidity in the Australian Genetics of Depression cohort study (N = 13,839). Participants completed online questionnaires about chronic pain, psychiatric symptoms, comorbidities, treatment response and general health. Logistic regression models were used to examine the relationship between chronic pain and clinical and demographic factors. Cumulative linked logistic regressions assessed the effect of chronic pain on treatment response for 10 different antidepressants. Chronic pain was associated with an increased risk of depression (OR = 1.86 [1.37–2.54]), recent suicide attempt (OR = 1.88 [1.14–3.09]), higher use of tobacco (OR = 1.05 [1.02–1.09]) and misuse of painkillers (e.g., opioids; OR = 1.31 [1.06–1.62]). Participants with comorbid chronic pain and depression reported fewer functional benefits from antidepressant use and lower benefits from sertraline (OR = 0.75 [0.68–0.83]), escitalopram (OR = 0.75 [0.67–0.85]) and venlafaxine (OR = 0.78 [0.68–0.88]) when compared to participants without chronic pain. Furthermore, participants taking sertraline (OR = 0.45 [0.30–0.67]), escitalopram (OR = 0.45 [0.27–0.74]) and citalopram (OR = 0.32 [0.15–0.67]) specifically for chronic pain (among other indications) reported lower benefits compared to other participants taking these same medications but not for chronic pain. These findings reveal novel insights into the complex relationship between chronic pain and depression. Treatment response analyses indicate differential effectiveness between particular antidepressants and poorer functional outcomes for these comorbid conditions. Further examination is warranted in targeted interventional clinical trials, which also include neuroimaging genetics and pharmacogenomics protocols. This work will advance the delineation of disease risk indicators and novel aetiological pathways for therapeutic intervention in comorbid pain and depression as well as other psychiatric comorbidities.

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“…Nevertheless, our large-scale data-driven approach — like recent human genetic 36–52 and neuroimaging 57–59 antidepressant treatment studies — have revealed novel insights into the relationship between chronic pain and depression. Along with animal model and human pharmacogenetic studies 53– 56,118,119,123–127 , there is also independent converging evidence for the critical role of subcortical brain regions in mediating pain and mood. 128 The application of rigorous statistical genetics methodologies to large-scale neuroimaging data, for example, has already produced several major discoveries, such as advancing our understanding of causal pathways, (subcortical) brain networks and medication response markers in mood disorders.…”

Section: Discussionmentioning

confidence: 99%

Comorbid chronic pain and depression: Shared risk factors and differential antidepressant effectiveness

Roughan

Campos

García-Marín

et al. 2020

Preprint

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Background: The bidirectional relationship between depression and chronic pain is well recognized but their clinical management remains challenging. Here we characterize the shared aetiology and risk factors for their comorbidity using large population cohorts to advance understanding of pharmacological treatment outcomes. Methods: Participants completed online questionnaires about chronic pain, psychiatric symptoms, comorbidities, treatment response and general health (N=13,839). Logistic regression models were used to examine the relationship between chronic pain and clinical and demographic factors. Cumulative linked logistic regressions assessed the effect of chronic pain on treatment response for 10 different antidepressants. Findings: Chronic pain was associated with an increased risk of depression (OR=1.86 [1.37-2.54]), recent suicide attempt (OR=1.88[1.14-3.09]), higher use of alcohol, tobacco and painkiller misuse. Participants with comorbid chronic pain and depression reported fewer functional benefits from antidepressant use and lower benefits from sertraline (OR=0.75[0.68-0.83]), escitalopram (OR=0.75[0.67-0.85]) and venlafaxine (OR=0.78[0.68-0.88]) when compared to participants without chronic pain. Furthermore, participants taking sertraline (OR=0.45[0.30-0.67]), escitalopram (OR=0.45[0.27-0.74]) and citalopram (OR=0.32[0.15-0.67]) specifically for chronic pain reported lower benefits compared to other participants taking these same medications but not for chronic pain. Interpretation: The findings reveal novel insights into the complex relationship between chronic pain and depression. Treatment response analyses indicate differential effectiveness between particular antidepressants and poorer functional outcomes for these comorbid conditions. Further assessment is warranted in targeted interventional trials. This approach will advance precision psychiatry and assist in clinical management by choosing the most suitable treatment for patients, informed by specific symptoms and comorbidities.

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Pharmacogenomics in Chronic Pain Therapy: From Disease to Treatment and Challenges for Clinical Practice

Cited by 13 publications

References 86 publications

Evaluation of Phenotypic and Genotypic Variations of Drug Metabolising Enzymes and Transporters in Chronic Pain Patients Facing Adverse Drug Reactions or Non-Response to Analgesics: A Retrospective Study

Evaluation of Phenotypic and Genotypic Variations of Drug Metabolising Enzymes and Transporters in Chronic Pain Patients Facing Adverse Drug Reactions or Non-Response to Analgesics: A Retrospective Study

Comorbid Chronic Pain and Depression: Shared Risk Factors and Differential Antidepressant Effectiveness

Comorbid chronic pain and depression: Shared risk factors and differential antidepressant effectiveness

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