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Combination Drug Therapy for the Management of Chronic Neuropathic Pain.

ABSTRACT: Chronic neuropathic pain (NP) is an increasingly prevalent disease and leading cause of disability which is challenging to treat. Several distinct classes of drugs are currently used for the treatment of chronic NP, but each drug targets only narrow components of the underlying pathophysiological mechanisms, bears limited efficacy, and comes with dose-limiting side effects. Multimodal therapies have been increasingly proposed as potential therapeutic approaches to target the multiple mechanisms underlying nociceptive transmission and modulation. However, while preclinical studies with combination therapies showed promise to improve efficacy over monotherapy, clinical trial data on their efficacy in specific populations are lacking and increased risk for adverse effects should be carefully considered. Drug-drug co-crystallization has emerged as an innovative pharmacological approach which can combine two or more different active pharmaceutical ingredients in a single crystal, optimizing pharmacokinetic and physicochemical characteristics of the native molecules, thus potentially capitalizing on the synergistic efficacy between classes of drugs while simplifying adherence and minimizing the risk of side effects by reducing the doses. In this work, we review the current pharmacological options for the treatment of chronic NP, focusing on combination therapies and their ongoing developing programs and highlighting the potential of co-crystals as novel approaches to chronic NP management.

SUBMITTER: Boccella S

PROVIDER: S-EPMC10741625 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Combination Drug Therapy for the Management of Chronic Neuropathic Pain.

Boccella Serena S De Filippis Lidia L Giorgio Cristina C Brandolini Laura L Jones Meghan M Novelli Rubina R Amorizzo Ezio E Leoni Matteo Luigi Giuseppe MLG Terranova Gaetano G Maione Sabatino S Luongo Livio L Leone Manuela M Allegretti Marcello M Minnella Enrico Maria EM Aramini Andrea A

Biomolecules 20231216 12

Chronic neuropathic pain (NP) is an increasingly prevalent disease and leading cause of disability which is challenging to treat. Several distinct classes of drugs are currently used for the treatment of chronic NP, but each drug targets only narrow components of the underlying pathophysiological mechanisms, bears limited efficacy, and comes with dose-limiting side effects. Multimodal therapies have been increasingly proposed as potential therapeutic approaches to target the multiple mechanisms ...[more]

PMID: 38136672

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Project description:BackgroundNeuropathic pain is thought to arise from damage to the somatosensory nervous system. Its prevalence is increasing in line with many chronic disorders such as diabetes. All treatments have limited effectiveness. Given the evidence regarding psychological treatment for distress and disability in people with various chronic pain conditions, we were interested to investigate whether psychological treatments have any effects for those with chronic neuropathic pain.ObjectivesTo assess the effects of psychological treatments on pain experience, disability, mood, and health-care use in adults with chronic neuropathic pain.Search methodsWe searched for randomised controlled trials (RCTs) published in any language in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO, from database inception to March 2015.Selection criteriaFull publications of RCTs on psychological interventions for neuropathic pain. Trials had to have lasted at least three months, had at least 20 participants in each arm at the end of treatment, and compared a psychological intervention with any active or inactive intervention.Data collection and analysisWe used the standard methodological procedures expected by Cochrane.Main resultsTwo small studies (enrolling a total of 105 participants) met the inclusion criteria. One was a standard cognitive behavioural treatment (CBT) programme for 61 people with pain from spinal cord injury, followed up for three months, and compared with a waiting list. The other was weekly group psychotherapy for 44 people with burning mouth syndrome, compared with a daily placebo tablet. The overall risk of bias was high in both trials.The CBT study assessed participants for pain, disability, mood, and quality of life, with improvement in treatment and control groups. However, there was no more improvement in the treatment group than in the control for any outcome, either post-treatment or at follow-up. The group psychotherapy study only assessed pain, classifying participants by pain severity. There is a lack of evidence on the efficacy and safety of psychological interventions for people with neuropathic pain.Authors' conclusionsThere is insufficient evidence of the efficacy and safety of psychological interventions for chronic neuropathic pain. The two available studies show no benefit of treatment over either waiting list or placebo control groups.

Project description:ObjectiveTo develop a clinical practice guideline to support the management of chronic pain, including low back, osteoarthritic, and neuropathic pain in primary care.MethodsThe guideline was developed with an emphasis on best available evidence and shared decision-making principles. Ten health professionals (4 generalist family physicians, 1 pain management-focused family physician, 1 anesthesiologist, 1 physical therapist, 1 pharmacist, 1 nurse practitioner, and 1 psychologist), a patient representative, and a nonvoting pharmacist and guideline methodologist comprised the Guideline Committee. Member selection was based on profession, practice setting, and lack of financial conflicts of interest. The guideline process was iterative in identification of key questions, evidence review, and development of guideline recommendations. Three systematic reviews, including a total of 285 randomized controlled trials, were completed. Randomized controlled trials were included only if they reported a responder analysis (eg, how many patients achieved a 30% or greater reduction in pain). The committee directed an Evidence Team (composed of evidence experts) to address an additional 11 complementary questions. Key recommendations were derived through committee consensus. The guideline and shared decision-making tools underwent extensive review by clinicians and patients before publication.RecommendationsPhysical activity is recommended as the foundation for managing osteoarthritis and chronic low back pain; evidence of benefit is unclear for neuropathic pain. Cognitive-behavioural therapy or mindfulness-based stress reduction are also suggested as options for managing chronic pain. Treatments for which there is clear, unclear, or no benefit are outlined for each condition. Treatments for which harms likely outweigh benefits for all or most conditions studied include opioids and cannabinoids.ConclusionThis guideline for the management of chronic pain, including osteoarthritis, low back pain, and neuropathic pain, highlights best available evidence including both benefits and harms for a number of treatment interventions. A strong recommendation for exercise as the primary treatment for chronic osteoarthritic and low back pain is made based on demonstrated long-term evidence of benefit. This information is intended to assist with, not dictate, shared decision making with patients.

Project description:ObjectiveTo determine the proportion of patients with neuropathic pain who achieve a clinically meaningful improvement in their pain with the use of different pharmacologic and nonpharmacologic treatments.Data sourcesMEDLINE, EMBASE, the Cochrane Library, and a gray literature search.Study selectionRandomized controlled trials that reported a responder analysis of adults with neuropathic pain-specifically diabetic neuropathy, postherpetic neuralgia, or trigeminal neuralgia-treated with any of the following 8 treatments: exercise, acupuncture, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), topical rubefacients, opioids, anticonvulsant medications, and topical lidocaine.SynthesisA total of 67 randomized controlled trials were included. There was moderate certainty of evidence that anticonvulsant medications (risk ratio of 1.54; 95% CI 1.45 to 1.63; number needed to treat [NNT] of 7) and SNRIs (risk ratio of 1.45; 95% CI 1.33 to 1.59; NNT = 7) might provide a clinically meaningful benefit to patients with neuropathic pain. There was low certainty of evidence for a clinically meaningful benefit for rubefacients (ie, capsaicin; NNT = 7) and opioids (NNT = 8), and very low certainty of evidence for TCAs. Very low-quality evidence demonstrated that acupuncture was ineffective. All drug classes, except TCAs, had a greater likelihood of deriving a clinically meaningful benefit than having withdrawals due to adverse events (number needed to harm between 12 and 15). No trials met the inclusion criteria for exercise or lidocaine, nor were any trials identified for trigeminal neuralgia.ConclusionThere is moderate certainty of evidence that anticonvulsant medications and SNRIs provide a clinically meaningful reduction in pain in those with neuropathic pain, with lower certainty of evidence for rubefacients and opioids, and very low certainty of evidence for TCAs. Owing to low-quality evidence for many interventions, future high-quality trials that report responder analyses will be important to strengthen understanding of the relative benefits and harms of treatments in patients with neuropathic pain.

Dataset Information

Combination Drug Therapy for the Management of Chronic Neuropathic Pain.

Publications

Combination Drug Therapy for the Management of Chronic Neuropathic Pain.

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