Alprazolam changes ‘too blunt an instrument’


pharmacist double checking prescription

Moves to limit inappropriate use and prescribing of alprazolam have not had the intended effect, according to a new study

The study, published in JAMA Network Open, sought to investigate whether changes to the public subside of the anti-anxiety drug were associated with changes in prescribing, dispensing and/or poisonings.

It found that while there had been a reduction in subsidised alprazolam use after the policy shift, prescribing contrary to best practice recommendations remains common – and the researchers warn of a “likely” shift to the private market.

The researchers, led by UNSW Medicine’s Centre for Big Data Research in Health, conducted an interrupted time series analysis and cross-sectional study, using data such as PBS dispensing databases and calls to a poisons information service.

The research followed the February 2017 decision by the Federal Government to implement three changes to how alprazolam was subsidised: the delisting of the 2mg tablet strength from public subsidy (intended to discourage its prescribing, as it was the most commonly misused item); the reduction of pack sizes from 50 tablet to 10; and the elimination of refills, meaning new prescription and approval from authorities was needed for continued use.

“In recent years alprazolam has come under scrutiny worldwide due to the drug’s addictive nature and the high risk of fatal overdose when it is mixed with opioids,” says study lead and biostatistician Dr Andrea Schaffer.

“The reclassification of alprazolam to a controlled drug in 2014 resulted in a marked reduction in harms – particularly poisoning – but the same clear-cut change has not occurred following the policy changes in 2017,” Dr Schaffer says.

“While there was a 51% decrease in subsidised use of alprazolam after the policy change, prescription approvals went up by 18% and people were still receiving large amounts of alprazolam which is not consistent with best practice guidelines.

“Data from the poisons information centre hotline also shows that there has been little change in poisonings, and suggests people were still obtaining 2mg strength tablets, whether as non-subsidised prescriptions or perhaps on the black market.”

The researchers also found that dispensing of more than 50 tablets increased overall, including among patients receiving new scripts for the drug.

“From 2015 to 2018, there were 71 481 alprazolam dispensings to 6772 people,” the researchers wrote.

“After the intervention, overall dispensing decreased by 51.2% (95% CI, 50.5%-51.9%) and prescribing approvals increased by 17.5% (95% CI, 13.0%-22.2%).

“Overall, the proportion of dispensing of packs of 51 to 100 tablets increased from 5,776 of 24,282 dispensings (23.8%) to 4,888 of 10,676 dispensings (45.8%) (risk difference [RD], 22.0% [95% CI, 19.4%-24.6%]) and dispensing of packs of more than 100 tablets increased from 1029 of 24 282 dispensings (4.2%) to 1774 of 10 676 dispensings (16.6%) (RD, 12.4% [95% CI, 10.6%-14.2%]).

“Among people receiving their first alprazolam prescription, initiation with packs of 10 tablets or fewer increased from 16 of 1,127 people (1.4%) before the intervention to 139 of 589 people (23.6%) after the intervention (RD, 22.2% [95% CI, 18.7%-25.7%]).

“Alprazolam treatment initiation with packs of more than 50 tablets also increased from 63 of 1,127 people (5.6%) before the intervention to 144 of 589 people (24.4%) after the intervention (RD, 18.9% [95% CI, 15.1%-22.6%]).

“During one year before the intervention, patients received a median (interquartile range [IQR]) total of 250 (50-600) tablets and median (IQR) total combined tablet strength of 188 (50-550) mg.

“During one year after the intervention, people were dispensed less alprazolam, with a median (IQR) total of 200 (50-500) tablets and median (IQR) total combined tablet strength of 120 (30-360) mg. There was little change in poisoning calls involving alprazolam.”

The removal of the 2mg tablet strength from public subsidy and reduced pack size did not have the desired effect of reducing misuse, they said.

“It’s likely that many users were able to absorb the out-of-pocket cost, approximately $10 per pack of 50 tablets of 2mg, and continue acquiring alprazolam through private, non-subsidised means,” Dr Schaffer said.

A previous study in Canada found a similar shift in the market after high-strength opioids were removed from public subsidy, with one in three people accessing the same drugs via private insurance or paying out of pocket.

“Even among people initiating treatment, there was an increase in people initiating with more than 50 tablets, which is concerning as these larger packet sizes come with a greater risk of transition to long-term use and dependence,” Dr Schaffer said.

Dr Schaffer says the 2017 changes to public subsidy of Xanax have proved too blunt an instrument for affecting prescribing and misuse of the drug. The change targets all people using the drug, even people who are using the medicine appropriately or those at low or no risk of harm. 

“The evidence shows the policy changes made in 2017 are not the best way to improve use of this medicine and further changes are needed to better address misuse and reduce the risk of long-term dependence,” she said.

“Once you’re on benzodiazepines, and alprazolam in particular, it’s very hard to go off of them so I think we need a more multi-faceted approach to curb inappropriate use in the community. 

“It’s also important to note that many people are prescribed Xanax for legitimate reasons, for treatment of real pain and disorder, and its addictive properties then lead to problematic use.”

The researchers said future work may include access to data for private market prescriptions.

Read the study here.

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