Lofexidine versus clonidine for mitigation of opioid withdrawal symptoms: A systematic review

Kuszmaul, Amanda K.; Palmer, Emma; Frederick, Emily K.

doi:10.1016/j.japh.2019.10.004

Cited by 24 publications

(11 citation statements)

References 19 publications

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“…Medications currently available to treat OUD are methadone, buprenorphine and naltrexone, as well as lofexidine for acute withdrawal (National Institute on Aging, 2015), all treatment options having their caveats. Lofexidine, an α 2 ‐adrenocepter agonist, was approved in May 2018 by the FDA as the first non‐opioid medication only restricted to short‐term treatment of acute opioid withdrawal and has, unlike clonidine, fewer adverse effects, specifically absence of hypotension, anergy, weakness and tiredness (Kuszmaul et al, 2020). Methadone, a full μ opioid agonist, is the gold standard for OUD, but it is tied to misuse and deadly overdoses (Rudd et al, 2010).…”

Section: Current Limitations In the Pharmacological Treatment Of Opio...mentioning

confidence: 99%

The inhibition of enkephalin catabolism by dual enkephalinase inhibitor: A novel possible therapeutic approach for opioid use disorders

Alvarez-Perez

Poras

Maldonado

2021

British J Pharmacology

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Despite the increasing impact of opioid use disorders on society, there is a disturbing lack of effective medications for their clinical management. An interesting innovative strategy to treat these disorders consists in the protection of endogenous opioid peptides to activate opioid receptors, avoiding the classical opioid-like side effects. Dual Enkephalinase Inhibitors (DENKIs) physiologically activate the endogenous opioid system by inhibiting the enzymes responsible for the breakdown of enkephalins, protecting endogenous enkephalins, increasing their half-lives and physiological actions. The activation of opioid receptors by the increased enkephalin levels, and their well-demonstrated safety, suggest that DENKIs could represent a novel analgesic therapy and a possible effective treatment for acute opioid withdrawal, as well as a promising alternative to opioid substitution therapy minimizing side effects. This new pharmacological class of compounds could bring effective and safe medications avoiding the This article is protected by copyright. All rights reserved.major limitations of exogenous opioids, representing a novel approach to overcome the problem of opioid use disorders.

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Section: Current Limitations In the Pharmacological Treatment Of Opio...mentioning

confidence: 99%

The inhibition of enkephalin catabolism by dual enkephalinase inhibitor: A novel possible therapeutic approach for opioid use disorders

Alvarez-Perez

Poras

Maldonado

2021

British J Pharmacology

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“…Unfortunately, these opioids also carry the risk of misuse and diversion to illicit use. The recent FDA approval of the α2-adrenergic agonist lofexidine to facilitate opioid withdrawal is welcome news 5 ; however, its utility is limited by hypotensive side-effects that contribute to further lowering of compliance rates 6 .…”

Section: Introductionmentioning

confidence: 99%

Neural bases for attenuation of morphine withdrawal by Heantos-4: role of l-tetrahydropalmatine

Ahn

Nesbit

Zou

et al. 2020

Sci Rep

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Severe withdrawal symptoms triggered by cessation of long-term opioid use deter many individuals from seeking treatment. Opioid substitution and α2-adrenergic agonists are the current standard of pharmacotherapy for opioid use disorder in western medicine; however, each is associated with significant complications. Heantos-4 is a non-opioid botanical formulation used to facilitate opioid detoxification in Vietnam. While ongoing clinical use continues to validate its safety and effectiveness, a mechanism of action accounting for these promising effects remains to be specified. Here, we assess the effects of Heantos-4 in a rat model of morphine-dependence and present evidence that alleviation of naloxone-precipitated somatic withdrawal signs is related to an upregulation of mesolimbic dopamine activity and a consequent reversal of a hypodopaminergic state in the nucleus accumbens, a brain region implicated in opioid withdrawal. A central dopaminergic mechanism is further supported by the identification of l-tetrahydropalmatine as a key active ingredient in Heantos-4, which crosses the blood–brain barrier and shows a therapeutic efficacy comparable to its parent formulation in attenuating withdrawal signs. The anti-hypodopaminergic effects of l-tetrahydropalmatine may be related to antagonism of the dopamine autoreceptor, thus constituting a plausible mechanism contributing to the effectiveness of Heantos-4 in facilitating opioid detoxification.

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“…Often, these medications are used for relief of specific symptoms, such as nausea, diarrhea, or body aches. For some of these off-label treatments, the evidence base is good, but it is not as strong for others [ 11 - 15 ].…”

Section: Introductionmentioning

confidence: 99%

Using Named Entity Recognition to Identify Substances Used in the Self-medication of Opioid Withdrawal: Natural Language Processing Study of Reddit Data

Preiss¹,

Baumgartner²,

Edlund³

et al. 2022

JMIR Form Res

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Background The cessation of opioid use can cause withdrawal symptoms. People often continue opioid misuse to avoid these symptoms. Many people who use opioids self-treat withdrawal symptoms with a range of substances. Little is known about the substances that people use or their effects. Objective The aim of this study is to validate a methodology for identifying the substances used to treat symptoms of opioid withdrawal by a community of people who use opioids on the social media site Reddit. Methods We developed a named entity recognition model to extract substances and effects from nearly 4 million comments from the r/opiates and r/OpiatesRecovery subreddits. To identify effects that are symptoms of opioid withdrawal and substances that are potential remedies for these symptoms, we deduplicated substances and effects by using clustering and manual review, then built a network of substance and effect co-occurrence. For each of the 16 effects identified as symptoms of opioid withdrawal in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, we identified the 10 most strongly associated substances. We classified these pairs as follows: substance is a Food and Drug Administration–approved or commonly used treatment for the symptom, substance is not often used to treat the symptom but could be potentially useful given its pharmacological profile, substance is a home or natural remedy for the symptom, substance can cause the symptom, or other or unclear. We developed the Withdrawal Remedy Explorer application to facilitate the further exploration of the data. Results Our named entity recognition model achieved F1 scores of 92.1 (substances) and 81.7 (effects) on hold-out data. We identified 458 unique substances and 235 unique effects. Of the 130 potential remedies strongly associated with withdrawal symptoms, 54 (41.5%) were Food and Drug Administration–approved or commonly used treatments for the symptom, 17 (13.1%) were not often used to treat the symptom but could be potentially useful given their pharmacological profile, 13 (10%) were natural or home remedies, 7 (5.4%) were causes of the symptom, and 39 (30%) were other or unclear. We identified both potentially promising remedies (eg, gabapentin for body aches) and potentially common but harmful remedies (eg, antihistamines for restless leg syndrome). Conclusions Many of the withdrawal remedies discussed by Reddit users are either clinically proven or potentially useful. These results suggest that this methodology is a valid way to study the self-treatment behavior of a web-based community of people who use opioids. Our Withdrawal Remedy Explorer application provides a platform for using these data for pharmacovigilance, the identification of new treatments, and the better understanding of the needs of people undergoing opioid withdrawal. Furthermore, this approach could be applied to many other disease states for which people self-manage their symptoms and discuss their experiences on the web.

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Lofexidine versus clonidine for mitigation of opioid withdrawal symptoms: A systematic review

Cited by 24 publications

References 19 publications

The inhibition of enkephalin catabolism by dual enkephalinase inhibitor: A novel possible therapeutic approach for opioid use disorders

The inhibition of enkephalin catabolism by dual enkephalinase inhibitor: A novel possible therapeutic approach for opioid use disorders

Neural bases for attenuation of morphine withdrawal by Heantos-4: role of l-tetrahydropalmatine

Using Named Entity Recognition to Identify Substances Used in the Self-medication of Opioid Withdrawal: Natural Language Processing Study of Reddit Data

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