Trends in transdermal fentanyl utilisation and fatal fentanyl overdose across Australia (2003-2015).

INTRODUCTION: Fentanyl-related overdose is an ongoing concern among countries with high prescription opioid utilisation. This study examines trends in transdermal fentanyl utilisation and fatal fentanyl overdose across Australia between 2003 and 2015, overall, and by age/sex. METHODS: This was a retrospective nationwide study of prescription dispensings and coronial records. Transdermal fentanyl utilisation was examined using Pharmaceutical Benefits Scheme dispensing records. Details of fatal fentanyl overdoses were extracted from the National Coronial Information System. RESULTS: Transdermal fentanyl utilisation increased 5.1-fold between 2003 and 2015, from 0.28 to 1.39 mg/1000 population/day and was consistently higher among females and adults aged ≥85 years. The utilisation of higher strength patches (75 and 100 mcg/h) was more common among males aged 25-44 years. A total of 291 fatal fentanyl overdoses were recorded, increasing from no recorded deaths in 2003 to 2.23 deaths/1 000 000 population in 2015. Rates were higher among males (increasing from 0 to 3.72 deaths/1 000 000 population) and for adults aged 25-44 years (increasing from 0 to 5.34 deaths/1 000 000 population). The number of deaths/kg fentanyl dispensed was highest among males aged <25 years (45.45, 95% confidence interval 21.80-83.59). Most deaths (70.1%) involved the intravenous administration of fentanyl from transdermal patches. DISCUSSION AND CONCLUSIONS: Rates of transdermal fentanyl utilisation and fatal fentanyl overdose across Australia increased between 2003 and 2015. Although transdermal fentanyl utilisation was consistently greater among females and older adults, rates of fatal fentanyl overdose were highest among younger males. Interventions to reduce extramedical use among this high-risk population group are necessary to minimise fentanyl-related harms.

The changing face of Australian data reforms: impact on pharmacoepidemiology research.

OBJECTIVE: A wealth of data is generated through Australia's universal health care arrangements. However, use of these data has been hampered by different federal and state legislation, privacy concerns and challenges in linking data across jurisdictions. A series of data reforms have been touted to increase population health research capacity in Australia, including pharmacoepidemiology research. Here we catalogued research leveraging Australia's Pharmaceutical Benefits Scheme (PBS) data (2014-2018) and discussed these outputs in the context of previously implemented and new data reforms. METHODS: We conducted a systematic review of population-based studies using PBS dispensing claims. Independent reviewers screened abstracts of 4,996 articles and 310 full-text manuscripts. We characterised publications according to study population, analytical approach, data sources used, aims and medicines focus. RESULTS: We identified 180 studies; 133 used individual-level data, 70 linked PBS dispensing claims with other health data (66 across jurisdictions). Studies using individual-level data focussed on Australians receiving government benefits (87 studies) rather than all PBS-eligible persons. 63 studies examined clinician or patient practices and 33 examined exposure-outcome relationships (27 evaluated medicines safety, 6 evaluated effectiveness). Medicines acting on the nervous and cardiovascular system account for the greatest volume of PBS medicines dispensed and were the most commonly studied (67 and 40 studies, respectively). Antineoplastic and immunomodulating agents account for approximately one third of PBS expenditure but represented only 10% of studies in this review. CONCLUSIONS: The studies in this review represent more than a third of all population-based pharmacoepidemiology research published in the last three decades in Australia. Recent data reforms have contributed to this escalating output. However, studies are concentrated among specific subpopulations and medicines classes, and there remains a limited understanding of population benefits and harms derived from medicines use. The current draft Data Availability and Transparency legislation should further bolster efforts in population health research.

A comparison of educational events for physicians and nurses in Australia sponsored by opioid manufacturers.

BACKGROUND: Educational activities for physicians sponsored by opioid manufacturers are implicated in the over- and mis-prescribing of opioids. However, the implications of promotion to nurses are poorly understood. Nurses play a key role in assessing pain, addressing the determinants of pain, and administering opioid medications. We sought to understand the nature and content of pain-related educational events sponsored by opioid manufacturers and to compare events targeting physicians and nurses. METHODS: We conducted a cross sectional, descriptive analysis of pharmaceutical company reports detailing 116,845 sponsored educational events attended by health professionals from 2011 to 2015 in Australia. We included events that were sponsored by manufacturers of prescription opioid analgesics and were pain related. We compared event characteristics across three attendee groups: (a) physicians only; (b) at least one nurse in attendance; and (c) nurses only. We coded the unstructured data using iteratively generated keywords for variables related to location, format, and content focus. RESULTS: We identified 3,411 pain-related events sponsored by 3 companies: bioCSL/CSL (n = 15), Janssen (n = 134); and Mundipharma (n = 3,262). Pain-related events were most often multidisciplinary, including at least one nurse (1,964/3,411; 58%); 38% (1,281/3,411) included physicians only, and 5% (166/3,411) nurses only. The majority of events were held in clinical settings (61%) and 43% took the form of a journal club. Chronic pain was the most common event topic (26%) followed by cancer pain and palliative care (18%), and then generic or unspecified references to pain (15%); nearly a third (32%) of event descriptions contained insufficient information to determine the content focus. Nurse-only events were less frequently held in clinical settings (32%; p < .001) and more frequently were product launches (17%; p < .001) and a significantly larger proportion focused on cancer or palliative care (33%; p < .001), generic pain topics (27%; p < .001), and geriatrics (25%; p < .001) than physician-only or multidisciplinary events. DISCUSSION: Opioid promotion via sponsored educational events extends beyond physicians to multidisciplinary teams and specifically, nurses. Despite lack of evidence that opioids improve outcomes for long-term chronic non-cancer pain, hundreds of sponsored educational events focused on chronic pain. Regulators should consider the validity of distinguishing between pharmaceutical companies' "promotional" and "non-promotional" activities.

"There are ways drug companies will get into DTC decisions": How Australian drug and therapeutics committees address pharmaceutical industry influence.

AIMS: One tool for protecting quality use of medicines in hospitals is a drug and therapeutics committee (DTC) that oversees medicines availability. Pharmaceutical industry marketing to prescribers is associated with less appropriate prescribing and increased costs. There is little data on decision-making practices of DTCs so it is unknown whether or how they might be vulnerable to pharmaceutical industry influence. This project explores DTC decision-making with a focus on how pharmaceutical industry influence on access and use of medicines is identified and managed. METHODS: We used a qualitative methodology with individual interviews of 29 participants who were current or recent members of public hospital DTCs across New South Wales, Australia. Participants included medical, pharmacy and nursing staff and 1 citizen. Committees were linked to specific hospitals or regions, and some were affiliated with paediatric, neonatal, rural or mental health services. RESULTS: Drug committee processes for oversight of medicines in public hospitals are vulnerable to pharmaceutical industry influence at several points. Applications for formulary additions are sometimes initiated and completed by company representatives. Conflict of interest disclosures among applicants and committee members may be incomplete. In some institutions, medicines are available from pharmaceutical companies without committee review, including through free samples and industry-supported medicines access programmes. Participants noticed the presence and impact of pharmaceutical company marketing activities to local clinicians, resulting in increased prescriber demand for products. CONCLUSION: Improved DTC practices and review of hospital policies concerning pharmaceutical marketing activities might preserve the independence of evidence-based decision-making for safe, cost-effective prescribing.

Policies affecting the supply and access of opioid analgesics: a scoping review protocol.

OBJECTIVE: This scoping review aims to describe and map the range of evaluated policies that affect the supply and access of opioids for analgesic therapy. INTRODUCTION: There has been increasing concern regarding the rise in opioid analgesic misuse and related harms, including overdose deaths. In response, policies have been developed and implemented to reduce the burden of opioid-related problems, including strategies that aim to affect the supply and/or access of opioid analgesics. However, little is known about the range and nature of these policies, including whether they have been evaluated for effectiveness and how. INCLUSION CRITERIA: Studies to be included must evaluate the effectiveness of policies directly designed to affect the supply and/or access of opioids for analgesic therapy, and measure clinical and health services outcomes quantitatively. Studies that assessed interventions or factors impacting the use of these policies, measured only utilization of the policy itself, and/or measured outcomes regarding attitudes and behaviors towards these policies will be excluded. Literature on policies for the treatment and management of opioid abuse, overdose, or addiction will be excluded. METHODS: Multiple databases will be searched including MEDLINE, Embase, PsycINFO, Scopus, and Web of Science using keywords, indexed terms, and phrases for the following concepts: opioid, policy, evaluation, and clinical context. Each included study will be rated using a modified version of the JBI Levels of Evidence framework. Details on included policies and their assessment will be extracted, and results presented in diagrams and tables.

Pharmaceutical industry payments to leaders of professional medical associations in Australia: Focus on cardiovascular disease and diabetes.

BACKGROUND AND OBJECTIVES: Pharmaceutical industry interactions with professional medical associations have come under scrutiny, yet industry ties among the leadership of these associations are often overlooked. The aim of this study was to investigate pharmaceutical industry payments to leaders of Australian diabetes or cardiovascular associations, and general associations serving doctors who manage these conditions. METHOD: Payments were identified using publicly available industry transparency reports (October 2015 to April 2018). RESULTS: Overall, 48/197 (24.4%) leaders received payments, predominantly for speaker (51.4%) and advisory board (25.3%) engagements. The proportion of paid leaders was higher for diabetes- and cardiovascular-specific associations (72.7% and 41.2%, respectively) than for general associations (7.6%). DISCUSSION: These findings raise concerns about industry influence on clinical practice and policy.

Pharmaceutical industry funding of events for healthcare professionals on non-vitamin K oral anticoagulants in Australia: an observational study.

OBJECTIVES: To describe the nature, frequency and content of non-vitamin K oral anticoagulant (NOAC)-related events for healthcare professionals sponsored by the manufacturers of the NOACs in Australia. A secondary objective is to compare these data to the rate of dispensing of the NOACs in Australia. DESIGN AND SETTING: This cross-sectional study examined consolidated data from publicly available Australian pharmaceutical industry transparency reports from October 2011 to September 2015 on NOAC-related educational events. Data from April 2011 to June 2016 on NOAC dispensing, subsidised under Australia's Pharmaceutical Benefits Scheme (PBS), were obtained from the Department of Health and the Department of Human Services. MAIN OUTCOME MEASURES: Characteristics of NOAC-related educational events including costs (in Australian dollars, $A), numbers of events, information on healthcare professional attendees and content of events; and NOAC dispensing rates. RESULTS: During the study period, there were 2797 NOAC-related events, costing manufacturers a total of $A10 578 745. Total expenditure for meals and beverages at all events was $A4 238 962. Events were predominantly attended by general practitioners (42%, 1174/2797), cardiologists (35%, 977/2797) and haematologists (23%, 635/2797). About 48% (1347/2797) of events were held in non-clinical settings, mainly restaurants, bars and cafes. Around 55% (1551/2797) of events consisted of either conferences, meetings or seminars. The analysis of the content presented at two events detected promotion of NOACs for unapproved indications, an emphasis on a favourable benefit/harm profile, and that all speakers had close ties with the manufacturers of the NOACs. Following PBS listings relevant to each NOAC, the numbers of events related to that NOAC and the prescribing of that NOAC increased. CONCLUSIONS: Our findings suggest that the substantial investment in NOAC-related events made by four pharmaceutical companies had a promotional purpose. Healthcare professionals should seek independent information on newly subsidised medicines from, for example, government agencies or drug bulletins.

Trends in self-poisoning and psychotropic drug use in people aged 5-19 years: a population-based retrospective cohort study in Australia.

OBJECTIVES: To characterise trends in self-poisoning and psychotropic medicine use in young Australians. DESIGN: Population-based retrospective cohort study. SETTING: Calls taken by the New South Wales and Victorian Poisons Information Centres (2006-2016, accounting for 70% of Australian poisoning calls); medicine dispensings in the 10% sample of Australian Pharmaceutical Benefits Scheme data (July 2012 to June 2016). PARTICIPANTS: People aged 5-19 years. MAIN OUTCOME MEASURES: Yearly trends in intentional poisoning exposure calls, substances taken in intentional poisonings, a prevalence of psychotropic use (dispensing of antidepressants, antipsychotics, benzodiazepines and medicines for attention deficit hyperactivity disorder (ADHD)). RESULTS: There were 33 501 intentional poisonings in people aged 5-19 years, with an increase of 8.39% per year (95% CI 6.08% to 10.74%, p<0.0001), with a 98% increase overall, 2006-2016. This effect was driven by increased poisonings in those born after 1997, suggesting a birth cohort effect. Females outnumbered males 3:1. Substances most commonly taken in self-poisonings were paracetamol, ibuprofen, fluoxetine, ethanol, quetiapine, paracetamol/opioid combinations, sertraline and escitalopram. Psychotropic dispensing also increased, with selective serotonin reuptake inhibitors (SSRIs) increasing 40% and 35% July 2012 to June 2016 in those aged 5-14 and 15-19, respectively. Fluoxetine was the most dispensed SSRI. Antipsychotics increased by 13% and 10%, while ADHD medication dispensing increased by 16% and 10%, in those aged 5-14 and 15-19, respectively. Conversely, dispensing of benzodiazepines to these age groups decreased by 4% and 5%, respectively. CONCLUSIONS: Our results signal a generation that is increasingly engaging in self-harm and is increasingly prescribed psychotropic medications. These findings indicate growing mental distress in this cohort. Since people who self-harm are at increased risk of suicide later in life, these results may foretell future increases in suicide rates in Australia.

Changes in the type and amount of spending disclosed by Australian pharmaceutical companies: an observational study.

OBJECTIVES: To describe and quantify disclosed payments from the pharmaceutical industry to the healthcare sector, and to examine the impact of the 2015 changes to Australia's self-regulated system of transparency. DESIGN: Observational database study. SETTING: Australia. PARTICIPANTS: Publicly available reports submitted by members of Australian pharmaceutical industry trade organisations, Medicines Australia and the Generic and Biosimilar Medicines Association (GBMA) (October 2011-December 2017). EXPOSURE: Changes to transparency reporting requirements with the updates of pharmaceutical industry Codes of Conduct in 2015. MAIN OUTCOME MEASURES: Elements of healthcare sector spending that members of industry organisations are required to publicly disclose; cumulative amount of disclosed spending (monthly average) in the year prior to and following the revision. RESULTS: There was a 34.1% reduction in disclosed spending from Medicines Australia member companies in the year after the 2015 changes to the Code of Conduct were introduced ($A89 658 566 in the preceding year, October 2014-September 2015; $A59 052 551 in the following year). The new Code allowed for reduced reporting of spending on food and beverages at events and for sponsored healthcare professionals. However, there was enhanced transparency around identification of individual health professionals receiving payments. GBMA member reporting totalled $A2 580 402 in the year prior to the revision, then ceased. CONCLUSIONS: This study shows the limitations of a self-regulatory system around industry disclosure of spending. We advocate for robust regulatory systems, such as legislation, to promote mandatory long-lasting public transparency.

Increases in controlled-release oxycodone utilisation following the subsidy of oxycodone with naloxone formulations: An Australian population-based study.

PURPOSE: Despite increasing use of oxycodone/naloxone controlled-release (CR) in Australia, little is known about how it has affected the overall oxycodone CR market since its subsidy in 2011. METHODS: We used Pharmaceutical Benefits Scheme dispensing claims (2006-2016) and interrupted time series analysis to examine changes in the quarterly rates of dispensing of oral oxycodone CR formulations (oxycodone/naloxone CR and single-ingredient oxycodone CR) and new oxycodone CR treatment episodes. We also performed a retrospective cohort study in a sample of people initiating a new oxycodone CR treatment episode in 2009, 2012/2013, and 2016 to compare opioid utilisation patterns over time. RESULTS: The subsidy of oxycodone/naloxone CR was associated with a 1.6-fold increase in the growth rate of oxycodone CR dispensing, resulting from rapid uptake of low strength (≤5 mg) oxycodone/naloxone CR. In our cohort of initiators, the number of new oxycodone CR treatment episodes increased 2.1-fold between 2009 and 2016; in 2016, 91.4% of new treatment episodes involved oxycodone/naloxone CR. Comparing 2016 with 2009, we observed an increase in people initiating with a tablet strength less than or equal to 5-mg (risk difference [RD] = 21.1%, 95% CI, 19.9%-22.4%) in people initiating with no other opioid dispensing 90 days prior to initiation (RD = 5.2%, 3.8%-6.6%) and with no further opioid dispensing 90 days after initiation (RD = 8.8%, 7.4%-10.2%). CONCLUSIONS: After its subsidy, the uptake of low-dose oxycodone/naloxone CR was greater than expected if it were substituting the single-ingredient oxycodone CR, resulting in an expansion of the oxycodone CR market.

Knowledge and attitudes of Australian general practitioners towards medicinal cannabis: a cross-sectional survey.

OBJECTIVES: To examine the knowledge and attitudes of Australian general practitioners (GP) towards medicinal cannabis, including patient demand, GP perceptions of therapeutic effects and potential harms, perceived knowledge and willingness to prescribe. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional survey completed by 640 GPs (response rate=37%) attending multiple-topic educational seminars in five major Australian cities between August and November 2017. MAIN OUTCOME MEASURES: Number of patients enquiring about medicinal cannabis, perceived knowledge of GPs, conditions where GPs perceived it to be beneficial, willingness to prescribe, preferred models of access, perceived adverse effects and safety relative to other prescription drugs. RESULTS: The majority of GPs (61.5%) reported one or more patient enquiries about medicinal cannabis in the last three months. Most felt that their own knowledge was inadequate and only 28.8% felt comfortable discussing medicinal cannabis with patients. Over half (56.5%) supported availability on prescription, with the preferred access model involving trained GPs prescribing independently of specialists. Support for use of medicinal cannabis was condition-specific, with strong support for use in cancer pain, palliative care and epilepsy, and much lower support for use in depression and anxiety. CONCLUSIONS: The majority of GPs are supportive or neutral with regards to medicinal cannabis use. Our results highlight the need for improved training of GPs around medicinal cannabis, and the discrepancy between GP-preferred models of access and the current specialist-led models.

Trends in opioid utilisation in Australia, 2006-2015: Insights from multiple metrics.

PURPOSE: Population-based observational studies have documented global increases in opioid analgesic use. Many studies have used a single population-adjusted metric (number of dispensings, defined daily doses [DDDs], or oral morphine equivalents [OMEs]). We combine these volume-based metrics with a measure of the number of persons dispensed opioids to gain insights into Australian trends in prescribed opioid use. METHODS: We obtained records of prescribed opioid dispensings (2006-2015) subsidised under Australia's Pharmaceutical Benefits Scheme. We used dispensing claims to quantify annual changes in use according to 3 volume-based metrics: DDD/1000 pop/day, OME/1000 pop/day, and dispensings/1000 pop. We estimated the number of persons dispensed at least one opioid in a given year (persons)/1000 pop using data from a 10% random sample of Pharmaceutical Benefits Scheme-eligible Australians. RESULTS: Total opioid use increased according to all metrics, especially OME/1000 pop/day (51% increase) and dispensings/1000 pop (44%). Weaker opioid use remained stable or declined; strong opioid use increased. The rate of persons accessing weaker opioids only decreased 31%, and there was a 238% increase in persons dispensed only strong opioids. Strong opioid use also increased according to dispensings/1000 pop (140%), OME/1000 pop/day (80%), and DDD/1000 pop/day (71% increase). CONCLUSIONS: Our results suggest that the increases in total opioid use between 2006 and 2015 were predominantly driven by a growing number of people treated with strong opioids at lower medicine strengths/doses. This method can be used with or without person-level data to provide insights into factors driving changes in medicine use over time.

Prescription Opioid Access Patterns and Factors Associated with Increasing Number of Prescribers, Pharmacies, and Dispensings: An Observational Study Using Pharmaceutical Claims.

Objective: To examine associations between patient factors and increasing opioid access measured by three metrics: number of unique prescribers, pharmacies, and dispensings in 12 months. Methods: We used pharmaceutical claims for a random 10% sample of Australians age 18 years or older initiating or reinitiating strong opioid treatment (≥90 days of no strong opioid dispensing) between July 2010 and December 2012. We report the distribution of opioid access by metric. We used three separate zero-truncated negative binomial regressions to explore associations. We censored individuals 365 days after index date or at death, whichever occurred first. Results: Approximately 69,088 persons initiated or reinitiated strong opioid treatment; they were predominantly female (59.7%) with a median age of 71 years (interquartile range [IQR] = 58-81). Over one year, persons visited a median of two prescribers (IQR = 1-3), visited one dispensing pharmacy (IQR = 1-2), and had four opioid dispensings (IQR = 2-10). Three percent of people were in the top decile of opioid access distribution for all three metrics (four or more prescribers, three or more dispensing pharmacies, and 20 or more dispensings). Increasing opioid access was strongly associated with male sex, history of pain treatment (3 to 12 months prior to index date), malignancy treatment, or treatment for three or more other medical conditions. Conclusions: Delineating legitimate from extramedical opioid use based on pharmaceutical claims is imprecise. We demonstrated that "high" levels of access, defined in previous research, may reflect routine care for complex patients. Pharmaceutical claims have utility in examining population norms of prescription drug use and access patterns, and flagging persons at the extreme end of access, for at least one measure, who may warrant further investigation.

To what extent do data from pharmaceutical claims under-estimate opioid analgesic utilisation in Australia?

PURPOSE: Although pharmaceutical claims are an essential data source for pharmacoepidemiological studies, these data potentially under-estimate opioid utilisation. Therefore, this study aimed to quantify the extent to which pharmaceutical claims from Australia's national medicines subsidy programs (Pharmaceutical Benefits Scheme [PBS] and Repatriation Schedule of Pharmaceutical Benefits [RPBS]) under-estimate prescription-only and total national opioid utilisation across time and for different opioids. A secondary aim was to examine the impact of the 2012 policy change to record all PBS/RPBS dispensed medicines, irrespective of government subsidy, on the degree of under-estimation. METHODS: Aggregated data on Australian opioid utilisation were obtained for the 2010 to 2014 calendar years, including all single ingredient and combination opioid analgesic preparations available on prescription or over-the-counter (OTC). Total opioid utilisation (oral morphine equivalent kilogrammes) was quantified using sales data from IMS Health and compared with pharmaceutical claims data from the PBS/RPBS. RESULTS: PBS/RPBS claims data did not account for 12.4% of prescription-only opioid utilisation in 2014 and 19.1% in 2010, and 18.4% to 25.4% of total opioid use when accounting for OTC preparations. Between 2010 and 2014, 5.6% to 5.3% of buprenorphine, 8.1% to 6.3% fentanyl, 17.7% to 10.7% oxycodone, 18.4% to 11.0% tramadol, 38.4% to 21.0% hydromorphone, and 28.6% to 21.0% of prescription-only codeine utilisation were not accounted for in PBS/RPBS claims. CONCLUSIONS: Despite increased capture of less expensive (under co-payment) opioid items since 2012, PBS/RPBS claims still under-estimate opioid use in Australia, with varying degrees across opioids. The estimates generated in this study allow us to better understand the degree of under-estimation and account for these in research using Australia's national pharmaceutical claims data.

Psychotropic medication use in Australia, 2007 to 2015: Changes in annual incidence, prevalence and treatment exposure.

OBJECTIVE: To examine changes in annual patterns of psychotropic medication use in Australia from 2007 to 2015. METHODS: We used a 10% sample of individual-level nationwide dispensing claims for concessional beneficiaries dispensed psychotropic medications (stratified by class, subclass) to investigate annual trends and changes in the incidence and prevalence of use, median annual duration of exposure, proportion of people with single psychotropic dispensing and median defined daily doses per person dispensed each medicine per year. RESULTS: Over the study period, there was a 26.1% decrease in the incidence and a 2.6% increase in the prevalence of all psychotropic medicine use. We observed a decrease in the annual incidence and prevalence of antidepressants (11.6% and 16.8%, respectively) but increases in the median annual duration of exposure (7.4%). Amitriptyline had the highest proportion of single dispensings of all antidepressants throughout the study period (26.5% in 2015) and defined daily doses per person dispensed each medicine per year increased by 20% for antidepressants overall. Benzodiazepine use decreased across all measures over the study period apart from long-term use (exposure for >240 days of the year), which in 2015 was 23.6% of those dispensed a benzodiazepine. We observed a relative increase in the incidence and prevalence of antipsychotic use (14.2% and 26.8%, respectively), and haloperidol had the highest proportion of single dispensings of any antipsychotic throughout the study period (47.5% in 2015). We observed a relative increase in the incidence and prevalence of attention-deficit hyperactivity disorder medication use of 114.0% and 101.8%, respectively, over the study period. CONCLUSION: Increasing doses and treatment durations of antidepressants warrants further investigation due to concerns about overuse. Single dispensings of amitriptyline and haloperidol may indicate off-label use and long-term use of benzodiazepines remains problematic. Despite increases in attention-deficit hyperactivity disorder medication use, prevalence of use is still much lower than the estimated prevalence of attention-deficit hyperactivity disorder in the adult population.

Psychotropic polypharmacy in Australia, 2006 to 2015: a descriptive cohort study.

AIMS: To describe psychotropic polypharmacy in Australia between 2006 and 2015. METHODS: We used pharmaceutical claims from a national 10% sample of people with complete dispensing histories to estimate the annual prevalence of the combined use (overlap of >60 days exposure) of ≥2 psychotropics overall and within the same class or subclass (class and subclass polypharmacy). We also estimated the proportion of polypharmacy episodes involving one, two, three and four or more unique prescribers. RESULTS: The prevalence of class polypharmacy between 2006 and 2015 in people dispensed specific psychotropic classes was 5.9-7.3% for antipsychotics, 2.1-3.7% for antidepressants and 4.3-2.9% for benzodiazepines. The prevalence of antipsychotic polypharmacy was higher than expected given the prevalence of antipsychotic exposure and combinations of sedating agents were notably common. Overall, 26.7% of polypharmacy episodes involved multiple prescribers but having multiple prescribers occurred more frequently for class and subclass polypharmacy and people with four or more concomitant psychotropics. DISCUSSION: Psychotropic polypharmacy is common, despite limited evidence of risks and benefits. Increases in polypharmacy with multiple prescribers may be due to poor communication with patients and between health care professionals.

Twenty-five years of prescription opioid use in Australia: a whole-of-population analysis using pharmaceutical claims.

AIM: The aim of this paper is to investigate 25-year trends in community use of prescribed opioid analgesics in Australia, and to map these trends against major changes to opioid registration and subsidy. METHODS: We obtained dispensing data from 1990 to 2014 from two sources: dispensing claims processed under Australia's national drug subsidy programme, the Pharmaceutical Benefits Scheme, including under co-payment records from 2012; and estimates of non-subsidized medicine use from a survey of Australian pharmacies (until 2011). Utilization was expressed in defined daily doses (DDD)/1000 population/day. RESULTS: Opioid dispensing increased almost four-fold between 1990 and 2014, from 4.6 to 17.4 DDD/1000 pop/day. In 1990, weak, short-acting or orally administered opioids accounted for over 90% of utilization. Use of long-acting opioids increased over 17-fold between 1990 and 2000, due primarily to the subsidy of long-acting morphine and increased use of methadone for pain management. Between 2000 and 2011, oxycodone, fentanyl, buprenorphine, tramadol and hydromorphone use increased markedly. Use of strong opioids, long-acting and transdermal preparations also increased, largely following the subsidy of various opioids for noncancer pain. In 2011, the most dispensed opioids were codeine (41.1% of total opioid use), oxycodone (19.7%) and tramadol (16.1%); long-acting formulations comprised approximately half, and strong opioids 40%, of opioid dispensing. CONCLUSIONS: Opioid utilization in Australia is increasing, although these figures remain below levels reported in the US and Canada. The increased use of opioids was largely driven by the subsidy of long-acting formulations and opioids for the treatment of noncancer pain.

Contrasting regional Fos expression in adolescent and young adult rats following acute administration of the antidepressant paroxetine.

Adolescents and adults may respond differently to antidepressants, with poorer efficacy and greater probability of adverse effects in adolescents. The mechanisms underlying this differential response are largely unknown, but likely relate to an interaction between the neural effects of antidepressants and brain development. We used Fos immunohistochemistry to examine regional differences in adolescent (postnatal day (PND) 28) and young adult (PND 56) male, Wistar rats given a single injection of the selective serotonin reuptake inhibitor paroxetine (10mg/kg). Paroxetine induced widespread Fos expression in both adolescent and young adult rats. Commonly affected areas include the bed nucleus of the stria terminalis (dorsolateral), medial preoptic area, paraventricular hypothalamic and thalamic nuclei and central nucleus of the amygdala. Fos expression was generally lower in adolescents with significantly greater Fos expression observed in young adults in the prelimbic cortex, supraoptic nucleus, basolateral amygdala, lateral parabrachial and Kölliker-Fuse nuclei. However, a small subset of regions showed greater adolescent Fos expression including the nucleus accumbens shell, lateral habenula and dorsal raphe. Paroxetine increased plasma corticosterone concentrations in young adults, but not adolescents. Plasma paroxetine levels were not significantly different between the age groups. These results indicate a different c-Fos signature of acute paroxetine in adolescent rats, with greater activation in key mesolimbic and serotonergic regions, but a more subdued cortical, brainstem and hypothalamic response. This suggests that the atypical response of adolescents to paroxetine may be related to a blunted neuroendocrine response, combined with insufficient top-down regulation of limbic regions involved in reward and impulsivity.