Mereani was 23 years old and living in the inner city of Melbourne when the insomnia that orbited her life became unbearable. Desperate for a solution, she spoke to her GP, who wrote her a prescription.
“He prescribed me Seroquel to help me sleep,” Mereani, now 28, told VICE. “[But] it didn’t work.”
Seroquel, one of the brand names for the antipsychotic quetiapine, is a medication intended to treat schizophrenia and bipolar.
Because a known side effect of the drug is sedation, though, lower doses are occasionally prescribed “off label” – that is, to treat a condition for which the medication has not been approved.
In Mereani’s case, the intention was to use quetiapine as an off-label treatment for her insomnia. She had previously been diagnosed with bipolar and had been taking Lexapro – an antidepressant known to induce insomnia – when she first spoke to her doctor about the drug.
“The first time I took it, it put me to sleep – but I woke up feeling really groggy and I couldn’t really get myself out of bed,” she recalled. “Then, later, I would take it and it wouldn't make me go to sleep. I would eat a few more and I would just stay awake in this haze. Just kind of groggy and angry.”
Despite Mereani telling her doctor that the new medication wasn’t having the desired effect, her prescription swelled from 25 milligrams to 100 milligrams over the course of five months. The doctor, she said, was reluctant to offer benzodiazepines.
“He didn’t want to give me a benzo because they were too addictive,” she explained. “And he really pushed forward that they were too addictive.”
In the last decade, the harm potential of prescription medications –specifically opioids and benzodiazepines – has become illuminated across the world. Films, books, and mainstream media have mirrored the sweeping narrative of how their over-accessibility directly influenced an overdose crisis. Some countries have responded by bolstering their drug policies in order to reduce access.
In Australia, this has been enforced with restrictions to benzodiazepines such as alprazolam – or Xanax – and the opioid oxycodone, as well as the ongoing introduction of state-based prescription monitoring systems.
But while attention has shifted towards reducing certain prescriptions, others – such as those for antipsychotics and anti-epileptics – have increased.
According to the Australian Institute of Health and Welfare’s Mental Health-Related Prescriptions 2019–20 data, the number of people receiving at least one prescription of an antipsychotic increased from 332,366 in 2009-10, to 411,125 in 2019-20.
A spokesperson for the Department of Health told VICE that, between July 2020 and June 2021, there were a total of 2,431,130 subsidised prescriptions of anti-epileptics and 3,778,499 subsidised prescriptions of antipsychotics.
“My sense is that it's a pretty old story of medicating distress,” says Dr. Jonathan Brett, a staff specialist in clinical pharmacology, toxicology and addiction medicine at Sydney’s St. Vincent's Hospital, who first reported on quetiapine misuse in 2015.
“I think this is just an age-old story of a person who goes to a doctor, is having a difficult time with one thing or another, probably doesn't have a mood disorder that fits into one of the DSM-5 [Diagnostic and Statistical Manual of Disorder, 5th Edition] criteria, but certainly is unhappy and not sleeping, or anxious.”
For Dr. Brett, the uptick in prescriptions of an antipsychotic like quetiapine is representative of the “medicalisation of distress” – a phrase he uses to describe the reliance on medication to treat chronic or emotional pain. Since at least the 1940s, this phenomenon has seen one medication replace another following restrictions over emerging harms.
First-hand accounts from both patients and medical professionals, provided to VICE on background, indicate that antipsychotics and anti-epileptics have found space in the void created by crackdowns on benzodiazepines and prescription opioids. Australians across varying demographics are being prescribed them off-label, or using them non-medically, to treat anxiety, sleeplessness, or chronic pain.
A spokesperson for the Department of Health confirmed that in the last financial year there were over 3.25 million subsidised prescriptions of the anti-epileptic pregabalin, also known as Lyrica, as well as more than 916,000 prescriptions of quetiapine.
Speaking on background, one doctor based in Victoria’s metropolitan hospital system said that the appeal in prescribing off-label alternatives has to do with the negative connotations that orbit benzodiazepines and opioids, as well as the hurdles to providing them in quantity.
A 10mg prescription of oxycodone – a substance considered a “controlled drug” by the TGA – can be prescribed with 20 doses and no repeats, according to public Pharmaceutical Benefits Scheme information, while a prescription for 25mg of pregabalin – considered a “prescribed restricted substance” – comes with 56 doses and room for five repeats. That’s a lot more bang for your buck.
In a statement to VICE, the Pharmacological Society of Australia claimed that prescribing off-label can be considered “clinically appropriate”. Another, from the Australian Medical Association President (AMA), Dr. Omar Khorshid, noted that off-label prescribing is relatively common, but there are “clinical, safety, ethical, medico-legal, and financial issues related to off-label use”.
In the statement, Dr. Khorshid said the AMA supports guiding principles developed by the Council of Australian Therapeutic Advisory Groups. These principles, focusing on the use of off-label medicines, include that the patient must be involved in decision making, that outcomes should be monitored, and that off-label use of medicine “should only be considered when other options are unavailable, exhausted, not tolerable, or unsuited’.
However, Dr. Brett points out that there is minimal evidence supporting the effectiveness and safety of antipsychotics and anti-epileptics in treating anxiety, insomnia or chronic pain. In fact, in 2010, the producer of Seroquel, AstraZeneca, paid USD$520 million to settle US federal investigations that alleged the pharmaceutical company had illegally marketed the medication as an approved treatment for anxiety, depression and sleeplessness.
“We just don't know [the safety or efficacy] because large enough trials haven't been done,” Dr. Brett says. “And now it's generic, there's really no incentive to do those trials.”
While lacking awareness about the safety and efficacy of these substances, the recent increase in access appears to be associated with additional emerging harms.
According to the Penington Institute’s Australia's Annual Overdose Report 2021, antipsychotics and antiepileptics respectively accounted for 197 and 154 of 2019’s 1,644 unintentional drug-related deaths. Six years earlier, neither class of medication was connected to a drug-related death whatsoever.
One study from 2018 reported that both quetiapine misuse and overdoses increased sixfold between 2006 and 2016 in Victoria, while a second concluded that ambulance callouts for pregabalin misuse increased tenfold between 2012 and 2017.
Dr. Reuben Weissman, an emergency department doctor based in Queensland, told VICE that there’s definitely been a significant increase in prescriptions in general over the past few years – “but the big issue that we see from our point of view is that we get more and more occurrences of overdoses related to both [quetiapine and pregabalin].”
“So a lot of it is pregabalin being prescribed for any kind of pain,” he explained. “[Even though] there's no real good evidence that pregabalin works in general.”
Not only is there the immediate concern about how an abundance of under-researched medicines could induce harm, there are also fears around how they might interact with other substances.
“When we talk about one medicine in isolation, maybe the safety profile of pregabalin is better than opioids,” says Dr Suzanne Nielsen, an Associate Professor and Deputy Director of the Monash Addiction Research Centre.
“You could argue that, but we're not necessarily choosing.What we're often doing is adding on top of it. Then we're not talking about whether this medicine is safer than the other one; often they're all being taken at once.”
While it’s not clear that this increase of antipsychotic and anti-epileptic prescriptions will mirror the harms linked with prescription opioids, it does reveal something: That there are serious questions over the implications in preventing access to medications deemed “harmful”.
It’s a point that Dr. Nielsen marks as worrying, particularly in the context of how long-term therapeutic treatments aren’t universally accessible.
“Even though we know that, for example, opioids are probably not the best long term solution, in the short term people get good effects,” Dr. Nielsen says.
“In the long term, they generally get tolerance and side effects, and the benefits are not outweighed by the harms. But when you don't have good alternatives to offer people, or those alternatives require a lot of time or access to pain services that aren't available to everyone – I think we find ourselves in a really tricky position.”
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