If pregabalin is unsuitable for some - or many If pregabalin is unsuitable for some - or many? - people for whom it has been prescribed as an alternative to opioids etc. – what happens next? Melanie Walker Chief Executive Officer Australian Injecting and Illicit Drug Users League (AIVL)

So what do we know about Lyrica (pregabalin)? According to www.lyrica.com: IMPORTANT SAFETY INFORMATION LYRICA and LYRICA CR are not for everyone. LYRICA and LYRICA CR may cause suicidal thoughts or actions in a very small number of people, about 1 in 500. Patients, family members, or caregivers should call the doctor right away if they notice suicidal thoughts or actions, thoughts of self-harm, or any unusual changes in mood or behavior. These changes may include new or worsening depression, anxiety, restlessness, trouble sleeping, panic attacks, anger, irritability, agitation, aggression, dangerous impulses or violence, or extreme increases in activity or talking. If you have suicidal thoughts or actions, do not stop LYRICA or LYRICA CR without first talking to your doctor.

…and how many scripts are being dispensed? The information contained in this spreadsheet was taken from: Australian Government, Department of Human Services. Medicare Australia Statistics. Pharmaceutical Benefits Schedule Item Report. Accessed at http://medicarestatistics.humanservices.gov.au/statistics/pbs_item.jsp on 26 March 2019. PBS Item information http://www.pbs.gov.au/pbs/search?term=Lyrica 2335X PREGABALIN pregabalin 75 mg capsule, 56 (PI, CMI) 2348N pregabalin 25 mg capsule, 56 (PI, CMI) 2363J pregabalin 300 mg capsule, 56 (PI, CMI) 2355Y pregabalin 150 mg capsule, 56 (PI, CMI)

…and how many scripts are being dispensed? Summary of services and benefit for PBS items 2335X, 2348N, 2355Y, 2363J   NSW VIC QLD SA WA TAS ACT NT Total $Benefit Services 2012/2013 1,785,733 41,783 1,189,395 28,311 1,485,140 35,039 526,124 11,769 728,128 17,051 300,238 7,185 85,300 2,064 12,741 306 6,112,800 143,508 2013/2014 22,792,654 510,825 16,118,716 365,373 17,052,122 371,697 6,194,290 131,746 8,250,047 186,651 3,150,809 70,652 991,355 23,236 240,155 5,368 74,790,148 1,665,548 2014/2015 36,890,348 816,772 27,184,945 608,135 26,873,025 573,598 9,370,981 196,900 12,298,749 276,847 4,716,773 104,064 1,591,456 37,723 354,091 7,800 119,280,369 2,621,839 2015/2016 44,742,804 1,013,925 32,822,399 758,081 33,065,306 719,868 11,522,668 249,453 14,592,827 336,235 5,470,749 123,432 1,880,761 46,485 461,662 10,592 144,559,176 3,258,071 2016/2017 48,727,476 1,108,824 36,657,524 854,603 36,772,205 798,549 12,703,186 276,782 16,439,239 380,341 5,844,087 131,280 2,069,109 51,445 511,291 11,913 159,724,119 3,613,737 2017/2018 42,270,598 1,175,913 30,985,513 890,821 30,580,151 811,471 10,773,426 286,625 13,708,501 387,681 4,669,556 126,799 1,684,258 52,815 453,791 13,179 135,125,794 3,745,304 197,209,614 4,668,042 144,958,493 3,505,324 145,827,949 3,310,222 51,090,676 1,153,275 66,017,491 1,584,806 24,152,212 563,412 8,302,239 213,768 2,033,732 49,158 639,592,406 15,048,007 Difference 40,484,865 1,134,130 29,796,118 862,510 29,095,011 776,432 10,247,302 274,856 12,980,373 370,630 4,369,318 119,614 1,598,958 50,751 441,050 12,873 129,012,994 3,601,796 % increase 2267% 2714% 2505% 3047% 1959% 2216% 1948% 2335% 1783% 2174% 1455% 1665% 1875% 2459% 3462% 4207% 2111% 2510%

What do we know from ambulance attendances? The rate of pregabalin-related ambulance attendances has increased tenfold since 2012, associated with an increase in the national prescription rate. Patients frequently misused pregabalin with other sedatives, particularly benzodiazepines, and almost 40% of misuse-related events requiring paramedic attendance were suicide attempts. Of the 1201 attendances, 593 (49.3%) were for people who had a history of depression, self-harm, suicidal ideation, suicide attempt, or misuse of alcohol or other drugs that may have contraindicated prescribing pregabalin. Of the five pre-existing conditions that contributed to such histories, the most frequent were a history of depression (485 patients, 40.4%) or a suicide attempt (195, 16.2%). Crossin, R. et al., MJA, Feb 2019

Is anyone else worried? At the National Drug and Alcohol Research Centre (NDARC) Symposium in October 2018, Dr Amy Peacock’s presentation on ‘Emerging trends in drug use, harms, and markets: Findings from Drug Trends 2018’ highlighted ‘Increased non prescribed use of other drugs (e.g., pregabalin)’ as being ‘of concern’. Of the sample of people who inject drugs, 16.4% had been prescribed pregabalin and a further 26.6% reported non-prescribed use.

Is anyone else worried? Meanwhile, a 2019 Cochrane Review on ‘Pregabalin for neuropathic pain in adults’ found that: Moderate-quality evidence shows that oral pregabalin at doses of 300 mg or 600 mg daily has an important effect on pain in some people with moderate or severe neuropathic pain after shingles, or due to diabetes. Low-quality evidence suggests that oral pregabalin is effective after trauma due to stroke or spinal cord injury. Pregabalin appears not to be effective in neuropathic pain associated with HIV. Very limited evidence is available for neuropathic back pain, neuropathic cancer pain, and some other forms of neuropathic pain.

Is anyone else worried? An investigation by The Age and The Sydney Morning Herald can reveal: In Victoria, there were 164 overdose deaths linked to the drug between 2013 and 2017, according to coronial data There have been 88 pregabalin-associated deaths in NSW since 2005, increasing at almost 60 per cent a year Health authorities have records of six suicides of patients taking the drug 86,000 Australians who have been prescribed the drug appear to be abusing it, according to one study. Yet many doctors consider it a ‘safe’ medicine to replace opiates. Pregabalin’s officially listed side effects include depression, blurred vision, confusion, and suicidal thoughts. Yet it is often given to people who have depression or a history of self-harm. Pregabalin’s use exploded after it was approved as a treatment for nerve pain. But later studies now have some experts fearing it may not work at all for as many as half the conditions it is being prescribed for. The Age, ‘This popular drug is linked to addiction and suicide. Why do doctors keep prescribing it?’, 18 Dec 2018.

Why is AIVL worried? What is Melanie on about and who has she been talking to? Service providers Researchers People who use drugs and their families and friends

For further consideration/discussion • Key messages for service users (e.g. Should service delivery agencies be highlighting the link with depression, suicide and overdose and advising people to talk to their doctor if they have concerns?) • Key messages for clinicians (e.g. What should prescribers be saying to/doing for people for whom pregabalin use may be problematic/have become a concern? What are the implications for withdrawal and pain management?) • Consequential actions for consideration o Who will deliver these key messages to service users and clinicians? o Are there systemic capacity issues in terms of withdrawal services and the broader AOD treatment system that will present barriers for service users and clinicians? o What are the resourcing implications for different stakeholder groups? • Do we need further targeted research to inform the development of responses by different stakeholder groups?