The Effect of Scheduling and Withdrawal of Carisoprodol on Prevalence of Intoxications with the Drug

Høiseth, Gudrun; Karinen, Ritva; Sørlid, Hanne Kristin; Bramness, JÃ ̧rgen G.

doi:10.1111/j.1742-7843.2009.00459.x

Cited by 18 publications

(11 citation statements)

References 27 publications

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“…Re‐scheduling of carisoprodol (a muscle relaxant with a misuse potential) to Schedule IV reduced carisoprodol utilization in the United States and poisoning calls in California . Similar trends were seen with re‐scheduling and later withdrawal of carisoprodol in Norway . Codeine is still available OTC in many countries, and re‐scheduling should be considered to target misuse.…”

Section: Discussionmentioning

confidence: 78%

Codeine use and harms in Australia: evaluating the effects of re‐scheduling

et al. 2019

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Background and aims Globally, codeine is the most‐used opioid. In December 2016, Australia announced that low‐strength codeine (≤ 15 mg) would be re‐scheduled and no longer available for purchase over‐the‐counter; this was implemented in February 2018. We aimed to evaluate the effect of this scheduling change on codeine misuse and use and misuse of other opioids. Design and setting Interrupted time–series analysis of monthly opioid exposure calls to New South Wales Poisons Information Centre (NSWPIC, captures 50% of Australia's poisoning calls), January 2015– January 2019 and monthly national codeine sales, March 2015–March 2019. We incorporated a washout period (January 2017 – January 2018) between the announcement and implementation, when prescriber/consumer behaviour may have been influenced. Participants Intentional opioid overdoses resulting in a call to NSWPIC. Measurements We used linear segmented regression to identify abrupt changes in level and slope of fitted lines. Codeine poisonings and sales were stratified into high strength (> 15 mg per dose unit) and low strength (≤ 15 mg). Only low‐strength formulations were re‐scheduled. Findings We observed an abrupt −50.8 percentage [95% confidence interval (CI) = −79.0 to −22.6%] level change in monthly codeine‐related poisonings and no change in slope in the 12 months after February 2018. There was no increase in calls to the NSWPIC for high‐strength products, level change: –37.2% (95% CI = −82.3 to 8%) or non‐codeine opioids, level change: –4.4% (95% CI = −33.3 to 24.4%). Overall, the re‐scheduling resulted in a level change in opioid calls of −35.8% calls/month (95% CI = −51.2 to −20.4%). Low‐strength codeine sales decreased by 87.3% (95% CI = −88.5 to −85.9%), with no increase in high‐strength codeine sales in the 14 months following re‐scheduling, −4.0% (95% CI = −19.6 to 14.6%). Conclusions Codeine re‐scheduling in Australia appears to have reduced codeine misuse and sales.

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Section: Discussionmentioning

confidence: 78%

Codeine use and harms in Australia: evaluating the effects of re‐scheduling

et al. 2019

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“…This is a situation unlike the one for carisoprodol, where the correlation between sales numbers and findings in drugged drivers was very high; this indicates that most drug use came from legal sources. This drug was removed from the Norwegian market due to its potential for misuse and toxic effects [18,19]. Moreover, an Australian study found that alprazolam findings in drug-related deaths were more related to prescribed alprazolam than clonazepam in our study [20].…”

Section: Discussionmentioning

confidence: 88%

Has Previous Abuse of Flunitrazepam Been Replaced by Clonazepam?

et al. 2015

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Background and Aims: For many years, flunitrazepam was the benzodiazepine of choice among users of illegal drugs. The aim of this study was to investigate to which extent clonazepam use has increased in this population, and whether this was related to increased prescription or because of illegal availability. Methods: We used data from three sources to study the changes in the use of clonazepam: (1) Presence and concentrations of clonazepam and flunitrazepam in blood samples collected from Norwegian drugged drivers; (2) Sales numbers (legal market) for clonazepam, extracted from the Norwegian prescription database (NorPD), and (3) Specific seizures (illegal market) for clonazepam in Norway. Results: In 2004, 13.0% of the analysed blood samples from drugged drivers contained clonazepam, whereas this proportion had increased to 27.7% in 2013. In the same period, the frequency of flunitrazepam in drugged drivers decreased from 16.6% in 2004 to 3.2% in 2013. The number of clonazepam prescriptions decreased, while the number of seized tablets containing clonazepam increased considerably from 2004 to 2013. Conclusions: For the last 10 years, a significant increase in the illegal use of clonazepam has been seen, now replacing flunitrazepam as the most used illegal benzodiazepine in Norway.

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“…In the year 2000, the Drug Abuse Warning Network (Substance Abuse and Mental Health Services Administration, 2001) ranked carisoprodol as the 20 th most abused drug, and its nonmedical use more than doubled between 2004 and 2008 (Substance Abuse and Mental Health Services Administration, 2011). The abuse potential of carisoprodol in humans has been outlined in several reviews over the past decade (Bailey and Briggs, 2002; Hoiseth et al, 2009; Reeves and Burke, 2010). …”

Section: Introductionmentioning

confidence: 99%

“…For carisoprodol, there is substantial evidence of abuse in humans (Bailey and Briggs, 2002; Hoiseth et al, 2009; Reeves and Burke, 2010); as well as confirmation that it is self-administered in monkeys (France et al, 1999). The discriminative stimulus effects of carisoprodol are similar to known GABAergic drugs of abuse (Gonzalez et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Carisoprodol tolerance and precipitated withdrawal

Gatch¹,

Nguyen²,

Carbonaro³

et al. 2012

Drug and Alcohol Dependence

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Aims Carisoprodol is a muscle relaxant that acts at the GABAA receptor. Concerns about the abuse liability of carisoprodol are increasing, but evidence that carisoprodol produces tolerance and a significant withdrawal syndrome has yet to be established. The purpose of the current study was to determine if repeated administration of carisoprodol produces tolerance and withdrawal signs in a mouse model. Methods Carisoprodol (0, 100, 200, 300, or 500 mg/kg bid, i.p.) was administered to Swiss-Webster mice for 4 days and loss-of-righting reflex was measured 20 to 30 minutes following each administration. On the fourth day, bemegride (20 mg/kg), flumazenil (20 mg/kg), or vehicle was administered following carisoprodol and withdrawal signs were measured. Separate groups of mice receiving the same treatment regimen and dose range were tested for spontaneous withdrawal at 6, 12 and 24 hr after the last dose of carisoprodol. Results The righting reflex was dose-dependently impaired following the first administration of carisoprodol. A 75 to 100% decrease in the magnitude of the impairment occurred over the four days of exposure, indicating the development of tolerance to the carisoprodol-elicited loss-of-righting reflex. Withdrawal signs were not observed within 24 hours following spontaneous withdrawal; however, bemegride and flumazenil each precipitated withdrawal within 15 to 30 min of administration. Conclusions Carisoprodol treatment resulted in tolerance and antagonist-precipitated withdrawal, suggesting it may have an addiction potential similar to that of other long-acting benzodiazepine or barbiturate compounds.

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The Effect of Scheduling and Withdrawal of Carisoprodol on Prevalence of Intoxications with the Drug

Cited by 18 publications

References 27 publications

Codeine use and harms in Australia: evaluating the effects of re‐scheduling

Codeine use and harms in Australia: evaluating the effects of re‐scheduling

Has Previous Abuse of Flunitrazepam Been Replaced by Clonazepam?

Carisoprodol tolerance and precipitated withdrawal

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