Naloxone‐precipitated withdrawal: A method for rapid induction onto naltrexone

Resnick, Richard B.; Kestenbaum, Richard S.; Washton, Arnold M.; Poole, Doris

doi:10.1002/cpt1977214409

Cited by 84 publications

(26 citation statements)

References 2 publications

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“…Although administering a low dose of an opioid receptor antagonist (naloxone or naltrexone) shortened withdrawal by 2–4 days, withdrawal symptom severity was exacerbated. Thus began the process of introducing rapid (accelerated) withdrawal by administering naltrexone 1–2 days after the last opioid dose,31 in combination with adjunctive medications such as clonidine and benzodiazepines, to ameliorate the symptoms of withdrawal 29, 32…”

Section: Historical Perspective On Clinical Management Of Opioid Withmentioning

confidence: 99%

Antagonists in the medical management of opioid use disorders: Historical and existing treatment strategies

et al. 2018

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Background and ObjectivesOpioid use disorder (OUD) is a chronic condition with potentially severe health and social consequences. Many who develop moderate to severe OUD will repeatedly seek treatment or interact with medical care via emergency department visits or hospitalizations. Thus, there is an urgent need to develop feasible and effective approaches to help persons with OUD achieve and maintain abstinence from opioids. Treatment that includes one of the three FDA‐approved medications is an evidence‐based strategy to manage OUD. The purpose of this review is to address practices for managing persons with moderate to severe OUD with a focus on opioid withdrawal and naltrexone‐based relapse‐prevention treatment.MethodsLiterature available on PubMed was used to review the evolution of treatment strategies from the 1960s onward to manage opioid withdrawal and initiate treatment with naltrexone.ResultsEmerging practices for extended‐release naltrexone induction include the use of agonist tapers and adjuvant medications. Clinical challenges frequently encountered when initiating this therapy include managing withdrawal and ongoing opioid use during treatment. Clinical factors may inform decisions regarding patient selection and length of naltrexone treatment, such as recent opioid use and patient preferences.Conclusions and Scientific SignificanceTreatment strategies to manage opioid withdrawal have evolved, but many patients with OUD do not receive medication for the prevention of relapse. Clinical strategies for induction onto extended‐release naltrexone are now available and can be safely and effectively implemented in specialty and select primary care settings. (© 2018 The Authors. The American Journal on Addictions Published by Wiley Periodicals, Inc. on behalf of The American Academy of Addiction Psychiatry (AAAP);27:177–187)

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Section: Historical Perspective On Clinical Management Of Opioid Withmentioning

confidence: 99%

Antagonists in the medical management of opioid use disorders: Historical and existing treatment strategies

et al. 2018

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“…recep tors in certain brain regions and spinal cord [4,5], but such changes are not observed fol lowing chronic administration of K-opioid agents like U-50.488H [6], Opposite effects of p-and K-opiate agonists have been observed on the release of dopamine in the nucleus accumbens and in the dorsal caudate of freelymoving rats [3], Evidence is also presented for an interac tion between opioid antagonists like naltrex one with dopaminergic systems. Thus, nal trexone is used clinically for the treatment of opioid [7,8] and alcohol abuse [9,10], pre sumably by affecting the reward mechanisms. Naloxone and naltrexone can partially block the effect of increased dopamine levels in duced by d-amphetamine [II].…”

Section: Introductionmentioning

confidence: 99%

Chronic Blockade of Opioid Receptors Alters the Binding of [<sup>3</sup>H]GBR 12935 to Dopamine Transporter in Rat Brain Regions and Spinal Cord

Bhargava

Gudehithlu

1996

Pharmacology

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The effect of chronic administration of naltrexone, an opioid receptor antagonist, on the activity of the dopamine transporter in brain regions and spinal cord was determined. Male Sprague-Dawley rats were implanted with a pellet containing 10 mg naltrexone for 7 days. Rats serving as controls were implanted with a placebo pellet. Two groups of rats were used. In one, the pellets were left intact, and in the other they were removed 16 h prior to sacrificing. The dopamine transporter was labeled with [³H]GBR 12935. The binding of [³H]GBR 12935 in rats in which naltrexone pellets were left intact was decreased by 63 and 31% in corpus striatum and spinal cord, respectively, when compared to placebo pellet implanted controls. The decrease in binding in the striatum was due to changes in the B_max value of [³H]GBR 12935; the K_d values did not differ. In hypothalamus, ponsmedulla, hippocampus, midbrain, cortex, and amygdala of naltrexone and placebo pellet implanted rats, the binding of [³H]GBR 12935 did not differ. In naltrexone-treated rats from which pellets had been removed, the binding of [³H]GBR 12935 was decreased in hippocampus, amygdala, and spinal cord by 68, 77, and 61%, respectively, in comparison with tissues from the control rats. The results indicate that chronic blockade of opioid receptors results in downregulation of dopamine transporter in selected brain regions and spinal cord.

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“…Early studies demonstrated that this transition could be made rapidly by inducing the withdrawal under general anesthesia with high-dose antagonists. 7,8 Furthermore, data from early studies suggested that when high-dose opioid antagonists induced withdrawal, symptoms were greatest within the first few hours of treatment and declined to tolerable levels rapidly.…”

Section: Discussionmentioning

confidence: 99%

Complications of Ultrarapid Opioid Detoxification with Subcutaneous Naltrexone Pellets

et al. 2002

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Abstract. Rapid and ultrarapid opioid detoxification (ROD and UROD) centers promise quick, painless, same-day detoxification treatment for patients with opioid addiction. The goal of ROD and UROD is to provide a rapid transition from opioid dependency to oral naltrexone therapy. The patient is given general anesthesia and high-dose opioid antagonists. This induces a severe withdrawal but spares the patient the experience. In theory, the process is complete within four to five hours. The patient awakens without opioid dependency and is started on oral naltrexone. Any subsequent, persistent withdrawal symptoms are treated symptomatically. A novel, unapproved approach is to compound a pellet of naltrexone and implant it in the subcutaneous tissue. In theory, this should result in continuous therapeutic levels for this drug, and avoid issues with noncompliance. Case series: This article reports six cases of complications from the same detoxification center that performed UROD with naltrexone pellet implantation, including pulmonary edema, prolonged withdrawal, drug toxicity, withdrawal from cross-addiction to alcohol and benzodiazepines, variceal rupture, aspiration pneumonia, and death. Conclusions: The risks of this procedure are great and further studies should assess its safety and the novel use of naltrexone. Key words: opioids; heroin; addiction; detoxification; rapid detoxification; ultrarapid detoxification; naltrexone. ACADEMIC EMERGENCY MEDICINE 2002; 9:63-68 P ATIENTS with opioid addiction often struggle to achieve detoxification. Discontinuation of opioid use results in the severe discomfort of withdrawal. Many find methadone maintenance undesirable. For these patients, rapid and ultrarapid opioid detoxification (ROD and UROD) centers promise quick, painless, same-day detoxification treatment for patients with opioid addiction. This allows rapid transition from opioid dependency to oral naltrexone therapy. General anesthesia is given via endotracheal tube as well as highdose opioid antagonists. The induced withdrawal is complete within four to five hours and the patient awakens without opioid dependency. The patient is then started on oral naltrexone and any subsequent, persistent withdrawal symptoms are treated symptomatically. A novel, unapproved approach is to compound a pellet of naltrexone and

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Naloxone‐precipitated withdrawal: A method for rapid induction onto naltrexone

Cited by 84 publications

References 2 publications

Antagonists in the medical management of opioid use disorders: Historical and existing treatment strategies

Antagonists in the medical management of opioid use disorders: Historical and existing treatment strategies

Chronic Blockade of Opioid Receptors Alters the Binding of [<sup>3</sup>H]GBR 12935 to Dopamine Transporter in Rat Brain Regions and Spinal Cord

Complications of Ultrarapid Opioid Detoxification with Subcutaneous Naltrexone Pellets

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