Use of promethazine, gabapentin and clonidine in combination with opioids or opioid agonist therapies among individuals attending a syringe service program

Applewhite, Dinah; Regan, Susan; Koenigs, Kathleen J.; Mackin, Sarah; Schmidt, Clare; Wakeman, Sarah E.

doi:10.1016/j.drugpo.2020.102752

Cited by 9 publications

(8 citation statements)

References 24 publications

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“…Concomitant use of gabapentin with high‐dose opioids (≥50 morphine mg equivalents) significantly increased the risk of inpatient hospitalization (odds ratio [OR], 4.08; 95% confidence interval [CI], 2.58‐6.45) in a large study of a US commercial insurance database, 28 whereas 2 Canadian general population studies identified an increased risk of opioid‐related overdose mortality with concomitant gabapentin (OR, 1.49; 95%CI, 1.18‐1.88) or pregabalin (OR, 1.68; 95%CI, 1.19‐2.36), and these risks were found to be dose dependent 29,32 . Similarly, receipt of gabapentinoids has been found to significantly increase opioid‐related overdose mortality in several substance use disorder cohorts as well 30,31,67 . Although harm resulting from poly‐intoxication involving gabapentinoids is increasingly being reported, 68–70 the major contributing substance and the role of gabapentinoids in these overdoses is often unknown.…”

Section: Adverse Events and Management Of Respiratory Depression Overdose And Withdrawalmentioning

confidence: 99%

Gabapentinoid Pharmacology in the Context of Emerging Misuse Liability

Evoy

Peckham

Covvey

et al. 2021

The Journal of Clinical Pharma

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This article will review the epidemiology and pharmacology of gabapentinoids (gabapentin and pregabalin) relevant to their emerging misuse potential and provide guidance for clinical and regulatory management. Gabapentinoids are γ‐aminobutyric acid analogues that produce their therapeutic effects by inhibiting voltage‐gated calcium channels and decreasing neurotransmitter release. Recently gabapentinoid prescribing and use have increased tremendously. Although traditionally thought to possess a favorable safety profile, gabapentinoid misuse has also risen significantly. Gabapentinoid misuse generally occurs in combination with other substances, most notably opioids, and may be for purposes of eliciting euphoric effects, enhancing the effects of other substances, or self‐treating conditions such as withdrawal, pain, anxiety, or insomnia. Given its faster onset, increased bioavailability and potency, and nonsaturable absorption, pregabalin's pharmacokinetics theoretically enhance its misuse liability versus gabapentin. However, gabapentin can produce similar euphoric effects, and epidemiologic studies have identified higher rates of gabapentin misuse in the United States, likely because of greater availability and less regulated prescribing. Although adverse events of gabapentinoid‐only ingestion are relatively benign, a growing body of evidence indicates that gabapentinoids significantly increase opioid‐related morbidity and mortality when used concomitantly. In addition, significant withdrawal effects may occur on abrupt discontinuation. As a result of these trends, several US states have begun to further regulate gabapentinoid prescribing, reclassifying it as a controlled substance or mandating reporting to local prescription drug‐monitoring programs. Although increased regulation of gabapentin prescribing may be warranted, harm reduction efforts and increased patient and provider education are necessary to mitigate this concerning gabapentinoid misuse trend.

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Section: Adverse Events and Management Of Respiratory Depression Overdose And Withdrawalmentioning

confidence: 99%

Gabapentinoid Pharmacology in the Context of Emerging Misuse Liability

Evoy

Peckham

Covvey

et al. 2021

The Journal of Clinical Pharma

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“…27 Since 2017, there has been a substantial increase in research examining gabapentinoid-related harms that are broader than misuse. International studies have been undertaken both at a population-level 10,11,22,[28][29][30][31][32] and in high-risk cohorts including people who use drugs, 33,34 people with bipolar disorder, 35 people with opioid use disorder, 14,36,37 and in people who experience non-fatal 17,38 and fatal 18,[39][40][41] overdoses; however, we could not identify any studies specifically conducted in a primary care context.…”

Section: How Can Prescribers Identify Patients At Risk Of Harm?mentioning

confidence: 99%

Managing the misuse potential and risk of psychological harm from gabapentinoids in primary care in New Zealand

Aindow

Crossin

Toop

et al. 2021

J. Prim. Health Care

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Gabapentinoid prescribing is increasing in New Zealand. International evidence suggests that this prescribing trend is followed by increasing harms, including misuse, dependence, overdose, and psychological harms including suicidal thoughts or behaviours. However, there is limited guidance for prescribers on how to manage these potential harms. Here, we summarise the current international literature and identify three main risk factors that can be used for screening purposes when considering prescribing a gabapentinoid, to identify patients that may be at greater risk of harm. Based on current knowledge of harms, we provide guidance to prescribers on monitoring patients taking gabapentinoids. Finally, we summarise the evidence regarding tapering, and highlight key knowledge gaps including other interventions, referral, and data from primary care populations.

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“…One found attenuation of opioid withdrawal symptoms as the most common reason, endorsed by 67% of respondents, but found abuse indicators such as synergism with other substances (52%), recreation (47%) and curiosity (41%) reported in similar magnitude [9]. Another found that gabapentin made the respondent feel intoxicated in 76% of cases, while also helping to relieve pain (76%), withdrawal (70%), anxiety (63%), sleep problems (69%) and low mood (58%) [10]. While we agree relief of withdrawal symptoms is a common reason for use, more than half of respondents endorse other abuse or misuse indicators as key reasons for use [9,10].…”

mentioning

confidence: 99%

“…Another found that gabapentin made the respondent feel intoxicated in 76% of cases, while also helping to relieve pain (76%), withdrawal (70%), anxiety (63%), sleep problems (69%) and low mood (58%) [10]. While we agree relief of withdrawal symptoms is a common reason for use, more than half of respondents endorse other abuse or misuse indicators as key reasons for use [9,10]. The authors also discount or fail to include pertinent epidemiologic data.…”

mentioning

confidence: 99%

“…When used appropriately under the guidance of healthcare professionals, these represent relatively safe medication options for most patients. However, there is significant evidence that these medications are being misused outside of medical recommendations [5,6,9,10], often in excess of FDA recommended doses [12], and obtained from non-regulated sources [5]. As pharmacist clinicians, it is our professional responsibility to understand and educate healthcare professionals and the public alike on the delicate balance of safety/efficacy of pharmacologic treatments.…”

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confidence: 99%

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Letter to the Editor: Comment on “Gabapentinoid Benefit and Risk Stratification: Mechanisms Over Myth”

2021

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This letter was written in response to ''Gabapentinoid Benefit and Risk Stratification: Mechanisms Over Myth'' as a large body of evidence exists supporting the potential for gabapentinoid abuse that was overlooked in the named article. This letter was written to bridge the knowledge gap not addressed by the authors related to the significant, original research evidence that supports gabapentinoid abuse. DIGITAL FEATURES This article is published with digital features, including a summary slide, to facilitate understanding of the article. To view digital features for this article go to https://doi.org/10.6084/ m9.figshare.12994247. To the Editor, We recently read with concern the article entitled ''Gabapentinoid benefit and risk stratification: mechanisms over myth,'' published by McAnally and colleagues [1]. While we agree that gabapentinoids have important therapeutic roles and represent a relatively low-risk option for many patients, we believe this paper fails to accurately characterize the significant body of evidence identifying misuse/abuse associated with these medications. In particular,

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Use of promethazine, gabapentin and clonidine in combination with opioids or opioid agonist therapies among individuals attending a syringe service program

Cited by 9 publications

References 24 publications

Gabapentinoid Pharmacology in the Context of Emerging Misuse Liability

Gabapentinoid Pharmacology in the Context of Emerging Misuse Liability

Managing the misuse potential and risk of psychological harm from gabapentinoids in primary care in New Zealand

Letter to the Editor: Comment on “Gabapentinoid Benefit and Risk Stratification: Mechanisms Over Myth”

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