Alleviating Symptoms of Withdrawal from an Opioid

Wakim, Judith H.

doi:10.1007/s40122-012-0004-5

Cited by 10 publications

(5 citation statements)

References 8 publications

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“…Dependence even after therapeutic exposure to opioids such as oxycodone develops even more rapidly, within 2–3 weeks as described by Wakim (2012) , Pasero and McCaffery (2010) and Dowell et al (2016) in Oxycontin label September 2018 and Roxybond label April 2017.…”

Section: Part I: Introduction Definitions and General Considerationsmentioning

confidence: 95%

Dependence, withdrawal and rebound of CNS drugs: an update and regulatory considerations for new drugs development

Lerner

Klein

2019

Brain Communications

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The purpose of this paper is to describe dependence and withdrawal phenomena related to CNS drugs discontinuation and to clarify issues related to the evaluation of clinical drug withdrawal and rebound as they relate to safety in new drug development (FDA Abuse Guidance 2017) (FDA, 2017). The paper presents current understanding and definitions of drug dependence and withdrawal which are also relevant and important features of addiction, though not the same. Addiction, called substance use disorder in DSM-5 (APA, 2013), affects an individual’s brain and behavior, represents uncontrollable drug abuse and inability to stop taking a drug regardless of the harm it causes. Characteristic withdrawal syndromes following abrupt discontinuation of CNS active drugs from numerous drug classes are described. These include drugs both scheduled and nonscheduled in the Controlled Substances Act, which categorizes drugs in five schedules based on their relative abuse potentials and dependence liabilities and for regulatory purposes (Congress, 1970). Schedules 1 and 2 contain drugs identified as those with the highest abuse potential and strictest regulations. Less recognized aspects of drug withdrawal, such as rebound and protracted withdrawal syndromes for several drug classes are also addressed. Part I presents relevant definitions and describes clinical withdrawal and dependence phenomena. Part II reviews known withdrawal syndromes for the different drug classes and describes rebound and protracted withdrawal syndromes. To our knowledge, this is the first compilation of withdrawal syndromes for CNS drugs. Part III provides details of evaluation of dependence and withdrawal in the clinical trials for CNS drugs, which includes general design recommendations, and several tools, such as withdrawal questionnaires and multiple scales that are helpful in the systematic evaluation of withdrawal. The limitations of different aspects of this method of dependence and withdrawal evaluation are also discussed.

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Section: Part I: Introduction Definitions and General Considerationsmentioning

confidence: 95%

Dependence, withdrawal and rebound of CNS drugs: an update and regulatory considerations for new drugs development

Lerner

Klein

2019

Brain Communications

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“…Two studies have reported on whether the 5-HT 3 antagonist ondansetron modifies opioid withdrawal severity in humans. The first was a case report that suggested ondansetron might reduce human opioid withdrawal syndrome severity (Wakim, 2012); however, the second was a placebo-controlled within-subject empirical evaluation that found no benefit of ondansetron relative to placebo following naloxone-precipitated withdrawal (Chu et al, 2017).…”

Section: Serotonin Systemmentioning

confidence: 99%

Non-Opioid Neurotransmitter Systems that Contribute to the Opioid Withdrawal Syndrome: A Review of Preclinical and Human Evidence

Dunn

Huhn

Bergeria

et al. 2019

The Journal of Pharmacology and Experimental Therapeutics

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Opioid misuse and abuse is a major international public health issue. Opioid use disorder (OUD) is largely maintained by a desire to suppress aversive opioid withdrawal symptoms. Opioid withdrawal in patients seeking abstinence from illicit or prescribed opioids is often managed by provision of a m-opioid agonist/partial agonist in combination with concomitant medications. Concomitant medications are administered based on their ability to treat specific symptoms rather than a mechanistic understanding of the opioid withdrawal syndrome; however, their use has not been statistically associated with improved treatment outcomes. Understanding the central and/or peripheral mechanisms that underlie individual withdrawal symptom expression in humans will help promote medication development for opioid withdrawal management. To support focused examination of mechanistically supported concomitant medications, this review summarizes evidence from preclinical (N 5 68) and human (N 5 30) studies that administered drugs acting on the dopamine, serotonin, cannabinoid, orexin/hypocretin, and glutamate systems and reported outcomes related to opioid withdrawal. These studies provide evidence that each of these systems contribute to opioid withdrawal severity. The Food and Drug Administration has approved medications acting on these respective systems for other indications and research in this area could support the repurposing of these medications to enhance opioid withdrawal treatment. These data support a focused examination of mechanistically informed concomitant medications to help reduce opioid withdrawal severity and enhance the continuum of care available for persons with OUD.

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“…Single IV administration of 8 mg in eight healthy male volunteers significantly reduced naloxone‐induced withdrawal symptoms in seven of them . A case report indicated that oral 8 mg administered twice a day eliminated oxycodone‐induced withdrawal symptoms in a 44‐year‐old female . A preliminary controlled clinical trial in adults suggested that oral administration of 4 mg of ondansetron twice a day is promising for treating cocaine dependence …”

Section: Discussionmentioning

confidence: 99%

“…The dosing regimen described in the package insert for treatment of postoperative nausea and vomiting in 1‐month‐old patients is a single IV 0.1 mg/kg. Assuming an adult dose for dependence treatment of 8 mg twice a day, the equivalent exposure in neonates, based on our model, will be achieved by combined administration of IV 8 mg to the mothers before labor and external administration of doses ranging between 0.07 and 0.1 mg/kg in newborns. This dose is higher than the labeled dosing for older patients closest in age to the neonates.…”

Section: Discussionmentioning

confidence: 99%

Ondansetron Pharmacokinetics in Pregnant Women and Neonates: Towards a New Treatment for Neonatal Abstinence Syndrome

Elkomy

Sultan

Carvalho

et al. 2014

Clin Pharma and Therapeutics

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Ondansetron is the drug of choice to prevent nausea in women undergoing cesarean surgery and can be used to prevent neonatal abstinence syndrome (NAS). Pharmacokinetics of ondansetron has not been characterized in pregnant women or in newborns. A nonlinear mixed-effects modeling approach was used to analyze plasma samples obtained from 20 non-pregnant and 40 pregnant women following single administration of 4 or 8 mg ondansetron, from umbilical cord blood at delivery, and from neonates after birth. The analysis indicates that: ondansetron disposition is not affected by pregnancy (p>0.05), but influenced by dose (p<0.05), and is characterized by rapid transplacental transfer and longer elimination half-life in neonates compared to their mother. A dosing regimen for prevention of NAS was designed based on the model. The regimen involves IV administration of 4 mg to the mothers shortly before cord clamping, or oral administration of 0.07 mg/kg (or equivalently 0.04 mg/kg IV) to neonates.

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Alleviating Symptoms of Withdrawal from an Opioid

Cited by 10 publications

References 8 publications

Dependence, withdrawal and rebound of CNS drugs: an update and regulatory considerations for new drugs development

Dependence, withdrawal and rebound of CNS drugs: an update and regulatory considerations for new drugs development

Non-Opioid Neurotransmitter Systems that Contribute to the Opioid Withdrawal Syndrome: A Review of Preclinical and Human Evidence

Ondansetron Pharmacokinetics in Pregnant Women and Neonates: Towards a New Treatment for Neonatal Abstinence Syndrome

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