A Clinical Overview of Off-label Use of Gabapentinoid Drugs

Goodman, Christopher W; Brett, Allan S.

doi:10.1001/jamainternmed.2019.0086

Cited by 151 publications

(158 citation statements)

References 55 publications

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“…In fact, tramadol tapentadol are situated on the second third step of the WHO analgesic scale (WHO, Bravo et al, 2017). Conversely, gabapentinoids mediate analgesia via spinal α2-ARs (Takasu et al, 2006) and they have been approved by the FDA to treat neuropathic pain (Goodman and Brett, 2019). The efficacy of gabapentinoids is comparable to that of antidepressant drugs in clinical trials, yet they differ in safety and tolerability (Morello et al, 1999;Sindrup and Jensen, 2000).…”

Section: Discussionmentioning

confidence: 99%

Monoamines as Drug Targets in Chronic Pain: Focusing on Neuropathic Pain

et al. 2019

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Monoamines are involved in regulating the endogenous pain system and indeed, peripheral and central monoaminergic dysfunction has been demonstrated in certain types of pain, particularly in neuropathic pain. Accordingly, drugs that modulate the monaminergic system and that were originally designed to treat depression are now considered to be first line treatments for certain types of neuropathic pain (e.g., serotonin and noradrenaline (and also dopamine) reuptake inhibitors). The analgesia induced by these drugs seems to be mediated by inhibiting the reuptake of these monoamines, thereby reinforcing the descending inhibitory pain pathways. Hence, it is of particular interest to study the monoaminergic mechanisms involved in the development and maintenance of chronic pain. Other analgesic drugs may also be used in combination with monoamines to facilitate descending pain inhibition (e.g., gabapentinoids and opioids) and such combinations are often also used to alleviate certain types of chronic pain. By contrast, while NSAIDs are thought to influence the monoaminergic system, they just produce consistent analgesia in inflammatory pain. Thus, in this review we will provide preclinical and clinical evidence of the role of monoamines in the modulation of chronic pain, reviewing how this system is implicated in the analgesic mechanism of action of antidepressants, gabapentinoids, atypical opioids, NSAIDs and histaminergic drugs.

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Section: Discussionmentioning

confidence: 99%

Monoamines as Drug Targets in Chronic Pain: Focusing on Neuropathic Pain

et al. 2019

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“…Gabapentinoids have been approved by the US Food and Drug Administration (FDA) for treatment of seizures, postherpetic neuralgia, and a limited number of pain conditions. Despite lack of evidence to support their efficacy in treating most pain conditions [13,14], the use of gabapentinoids more than tripled between 2002 and 2015 [15]. Marketing strategies may have substantially facilitated increased use of gabapentinoids for off-label indications of pain not approved by the FDA [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Concomitant Use of Gabapentinoids with Opioids Is Associated with Increased Mortality and Morbidity among Dialysis Patients

et al. 2020

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Background: The opioid epidemic is a public health emergency and appropriate medication prescription for pain remains challenging. Physicians have increasingly prescribed gabapentinoids for pain despite limited evidence supporting their use. We determined the prevalence of concomitant gabapentinoid and opioid prescriptions and evaluated their associations with outcomes among dialysis patients. Methods: We used the United States Renal Data System to identify patients treated with dialysis with Part A, B, and D coverage for all of 2010. Patients were grouped into 4 categories of drugs exposure status in 2010: (1) no prescriptions of either an opioid or gabapentinoid, (2) ≥1 prescription of an opioid and no prescriptions of gabapentinoids, (3) no prescriptions of an opioid and ≥1 prescription of gabapenbtinoids, (4) ≥1 prescription of both an opioid and gabapentinoid. Outcomes included 2-year all-cause death, dialysis discontinuation, and hospitalizations assessed in 2011 and 2012. Results: The study population included 153,758 dialysis patients. Concomitant prescription of an opioid and gabapentin (15%) was more common than concomitant pre-scription of an opioid and pregabalin (4%). In adjusted analyses, concomitant prescription of an opioid and gabapentin compared to no prescription of either was associated with increased risk of death (hazard ratio [HR] 1.16, 95% CI 1.12-1.19), dialysis discontinuation (HR 1.14, 95% CI 1.03-1.27), and hospitalization (HR 1.33, 95% CI 1.31-1.36). Concomitant prescription of an opioid and pregabalin compared to no prescription of either was associated with increased mortality (HR 1.22, 95% CI 1.16-1.28) and hospitalization (HR 1.37, 95% CI 1.33-1.41), but not dialysis discontinuation (HR 1.13, 95% CI 0.95-1.35). Prescription of opioids and gabepentinoids compared to only being prescribed opioids was associated with higher risk of hospitalizations, but not mortality, or dialysis discontinuation. Conclusions: Concomitant prescription of opioids and gabapentinoids among US dialysis patients is common, and both drugs have independent effects on outcomes. Future research should prospectively investigate the potential harms of such drugs and identify safer alternatives for treatment of pain in end-stage renal disease patients. cancer, whether patients had at least one pain-related hospitalization and the number of hospitalizations in 2010 [6,8].

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“…Such use is growing, possibly because clinicians are searching increasingly for alternatives to opioids. Clinicians who prescribe gabapentinoids off-label for pain should be aware of the limited evidence and should acknowledge to patients that potential benefits are uncertain for most off-label uses [41]. In a meta-analysis of eleven randomized, double-blind, placebo-controlled clinical studies the safety and tolerability profile of pregabalin was addressed.…”

Section: Pharmacological Approachmentioning

confidence: 99%

Pain and Neuropathic Pain in Rheumatic Diseases

Seifert¹,

Baerwald²

2020

Aktuelle Rheumatologie

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Pain is a challenge to rheumatologists. Not only patients with active arthritis but also patients with a good therapeutic response and even in remission complain of persistent joint pain. It has been proposed that a chronic pain stimulus may have a greater impact in a chronic inflammatory state, and the process towards a pain condition may be influenced by individual predisposition for development of chronic pain. In addition, features of peripheral pain processing may be exacerbated by inflammation, and disturbed pain processing may be a feature contributing to widespread pain. Furthermore, a neuropathic component may be part of the total pain experience of our patients. There are many different strategies of pain therapy in patients with rheumatic diseases, such as pharmacological and non- pharmacological modalities.

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A Clinical Overview of Off-label Use of Gabapentinoid Drugs

Cited by 151 publications

References 55 publications

Monoamines as Drug Targets in Chronic Pain: Focusing on Neuropathic Pain

Monoamines as Drug Targets in Chronic Pain: Focusing on Neuropathic Pain

Concomitant Use of Gabapentinoids with Opioids Is Associated with Increased Mortality and Morbidity among Dialysis Patients

Pain and Neuropathic Pain in Rheumatic Diseases

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