Alprazolam upschedule cuts overall use, adverse events

pharmacists sitting at a computer

Since alprazolam was rescheduled to S8, there has been a notable reduction in overall use and adverse events, a study published today has found.

Interrupted Time Series Analysis of the Effect of Rescheduling Alprazolam in Australia: Taking Control of Prescription Drug Use, published in JAMA Internal Medicine, showed that the February 2014 rescheduling decision has led to a drop in prescriptions for the drug by 22%.

It has also cut the number of alprazolam-related calls to the Poisons Information Centre by 50% in the first 12 months.

Alprazolam (Xanax) has been implicated in several high-profile overdoses, including that of actor Heath Ledger, who died in 2008.

The study used data from a 10% random sample of PBS data, including authorities to prescribe and pharmacy claims for dispensed medicines, over the period February 2010 to July 2015.

The authors calculated the monthly number of alprazolam prescriptions per 100,000 population; dispensings of PBS-listed benzodiazepines (alprazolam, diazepam, oxazepam, nitrazepam and temazepam); and switching from alprazolam to a new benzodiazepine, antidepressant or antipsychotic.

The rescheduling decision has been particularly useful in reducing long-term use of the drug, the study shows.

“In Australia, selectively rescheduling alprazolam led to a reduction in overall use and adverse events and increased switching to less toxic benzodiazepines,” the authors wrote.

“More important, the greatest decrease in use was in individuals using alprazolam inappropriately in the long term.

“Rescheduling opioids to address misuse in the United States has similarly resulted in decreased use.

“Our findings suggest that when one medicine within a class is more toxic and/or more commonly abused, selective rescheduling should be considered to address its misuse.”

Study co-author Dr Rose Cairns, a pharmacist and Senior Poisons Specialist: Research at Poisons Information, told the AJP that these were positive findings.

“Since alprazolam is more toxic than other benzodiazepines with no additional therapeutic benefit, a decline in use (including a switch to less problematic benzodiazepines) is positive,” Dr Cairns says.

“We also saw a decrease in intentional poisonings with alprazolam, with no concurrent increase in poisonings with other benzodiazepines, which is a good outcome.”

She says that pharmacists can play a strong role in reducing the inappropriate use of alprazolam, including giving patients recently started on the drug information about its S8 status and the importance of short-term use.

“The decision to up-schedule alprazolam was quite widely publicised at the time and information for patients was released by state governments,” she says. “Patients newly prescribed alprazolam may ask why there are additional rules compared to Schedule 4 medications.

“Pharmacists can play a role in explaining that alprazolam is potent and fast acting, and that it is more controlled to prevent harms from misuse.

“They can also use the opportunity to discuss the appropriate, short-term, use of the medication.

“It may be useful to explain that beneficial effects (like being able to get to sleep) wear off over time and with ongoing use they are at increased risk of becoming dependent.

“If a pharmacist identifies potentially problematic use, they can refer the patient to their GP for a re-evaluation of their condition, for consideration of other options (including non-pharmacological), and for specialist referral, where appropriate.”

Pharmacists are uniquely placed to identify inappropriate use of medications including benzodiazepines, Dr Cairns told the AJP.

“They can identify how often scripts are being filled which can indicate escalating use/misuse.

“Pharmacists are well-placed to identify whether the patient is getting scripts from multiple prescribers (doctor shopping), and can also be on the lookout for forged/altered prescriptions.”

She says a prescription monitoring program to help identify doctor shopping and misuse could be very useful.

The study did not examine private prescriptions for alprazolam, which make up about a third of scripts for the drug.

The authors said that more research is needed to determine how the rescheduling affected the private benzodiazepine market.

“Currently there is no easy way to access data on private prescribing/dispensing,” Dr Cairns told the AJP.

“Ideally we would be able to access this to provide a more comprehensive picture of alprazolam use.

“We would like to know whether patterns of alprazolam use are the same in the private market and PBS market (e.g. is there the same trend following re-scheduling, what is the prevalence of long-term use?)”

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