Opioids: the real concern is they are not being used for pain in Italy

Earlier this year, at the presentation of the OsMed/AIFA report on drug consumption in Italy, health Minister Lorenzin expressed "grave concern at the increased consumption of opiates." Are Minister's concerns justified? Were we not the country with one of the lowest morphine consumption rates in the world? What has changed? Where did this "grave concern" come from?

Consumption in Italy

Opioids are essential drugs for the treatment of pain, acute and chronic, moderate to severe, originating from cancers as well as from other causes, like, for example, post-operative pain. The prevalence of cancer pain varies from 52% to 77% in older studies to values between 24% and 60% in more recent studies of medically treated patients, and between 62% and 86 % for patients with advanced cancers. The prevalence of chronic non-cancer pain in Italy, which is one of the indications for using opioid analgesics on the basis of pain and patient type, is estimated to be around 26%.¹ It is within this context that data on consumption in Italy have to be read and interpreted, bearing in mind the alert from the United States - which was probably the source of Minister's concern - about potential abuse of opioids prescribed as pain medications.

As can be seen in Table, opioid consumption in Italy was not particularly high in 2013, when it amounted to 5.2 defined daily doses/1,000 inhabitants per day. The opioid whose use has most increased is codeine in combination with acetaminophen (a typical drug on the second step of the WHO ladder for cancer pain treatment) followed by tramadol, whilst amongst the strong opioid medications the most increased consumption is of fentanyl (in particular as transdermal patch formulations).
The time pattern for opioid consumption in Italy shows a particular increase (as a higher percentage, but not in absolute terms) in the first few years of the last decade. The increase was due to the change in prescribing legislation (2001) and, since 2005, the release onto the market of new pharmaceutical formulations and active substances, which were on the market for some time in other countries but not in Italy (for example oxycodone and hydromorphone). Codeine, in combination with acetaminophen, was the active ingredient with the largest recorded increase, followed by fentanyl and tramadol use. Morphine is under-used at a community level, and the increase observed between 2010 and 2011 can be attributed to public consumption levels, which were not counted in previous years; this also applies to other opioids, such as buprenorphine, which is typically used in the context of public health units for drug addict detoxification. Over the last three years however, overall records have stabilised, with consumption increases only for the codeine plus acetaminophen combination.

Comparison with other countries

On the international stage, Italy has long been known as one of the countries with the lowest consumption of opioids. In 2005 for example the percentage of Italian drug charges for opioids out of the total pharmaceutical expenditure was 0.6% - higher only than that of Greece and Portugal, but much lower than other European countries, like Germany (3.8%) and the United Kingdom (3.9%).² Morphine consumption in particular has always been very low in comparison to other countries: for example, in Italy in 2006 it was less than 5 mg per capita, well below the European average (12.6 mg per head) and the global average (6.0 mg per capita) too, so much so that some Italian epidemiologists referred to a "morphinephobia".³ This situation, which remained almost constant over subsequent years until 2010, placed Italy amongst the countries of the world with a low (inadequate) consumption of opioid analgesics - at least 5 times lower than the consumption needed to treat chronic pain from cancer and HIV/AIDS, or due to acute injuries.⁴ Even European IMS data, although in the context of a general increase in opioid consumption in Europe (+9% in 2009), saw Italy as one of the countries paying less attention to the pain problem in general, and with the lowest use of opioids in particular. In 2013, Italy ranked last of the top five EU countries for opioid consumption level in terms of standard units (SU), with a consumption of 397 million SUs vs 5.5 billion SUs in the UK, 2.4 billion SUs in France, 1.16 billion SUs in Germany and 761 million SUs in Spain. In contrast, Italy is the European country with the highest use of NSAIDs, as a percentage of total analgesics used.⁵
In 2006, an analysis of drugs used to treat pain in the Veneto region revealed that the use of opioids was much lower than the consumption of NSAIDs, not only at a community level (1.5 compared to 18.0 defined daily doses/1,000 inhabitants per day), as might be expected, but in hospitals too (13.0 compared to 51.⁶ defined daily doses/100 days of hospitalization). On the other hand, the reluctance of Italian hospital doctors to prescribe opioids was also confirmed by a recent survey⁶ which showed the prevalence of elderly patients discharged from hospital with an opioid prescription was only slightly higher than that of patients on admission, with a slight increase in the last of the three periods considered: 5.8% compared to 3.8% in 2008, 5.3% compared to 3.6% in 2010 and 6.6% compared to 4.1% in 2012. The study authors also pointed out that the majority of prescriptions involved codeine and tramadol, and that 58% of patients with severe pain were discharged without any prescribed analgesics.

The right balance

The data analysis above does not show a tendency in Italy towards excessive therapeutic use of opioids, with the consequent risks of abuse and addiction. On the contrary, it appears that in Italy, despite legislative changes, there has not yet been an adequate response to the real needs of patients with pain. The old cultural barriers that restrict access to opioid drugs still remain. The fear of abuse, dependency and addiction are amongst the main reasons why some countries, including Italy, restrict access to opioid analgesics. The United States and Canada have some of the highest levels of misuse, abuse and dependency. Recent US research showed that opioid prescription saw an increase in the period 2002-2010, then settled back down between 2011 and 2013, and that the mortality associated with this class of drugs showed an almost parallel performance.⁷ Weisberg et al. recently compared two systems for prescribing opioid analgesics: those in the US and the UK.⁸ The comparison between these two countries highlights important features of the prescribing systems, culture and health that can be permissive or protect against the development of a public health crisis. In the UK over recent years, there has been a similar trend in the increased consumption of opioids to that in America, although at lower levels, but without an increase in recorded misuse or deaths. According to the authors, the British system has implemented a series of measures (such as guidelines, roundtables, training, monitoring, research) aimed at the balanced prescription of opioids.
The situation in the UK is a clear example (given also the similarities of the national health system in Italy and in Great Britain, which are quite different from the American one) of how the correct and proper prescription of opioid analgesics might be managed in Italy too, without incurring the phenomena of abuse, dependency or addiction. It is however important to strike a good balance between using appropriate prescribin, without limiting access to these drugs, or facilitating the abuse of drugs that we know to be indispensable in the treatment of pain and during the dying phase. It is therefore vital to create a shared culture among the professionals involved in managing cancer patients and pain in general. The hope is that a range of initiatives will help to raise operator's attention thresholds towards using opioid drugs, particularly for treating severe pain, a field that still faces severe retardation in our country. This increase in prescribing should, obviously, follow the recommendations published in the literature to prevent the epidemic of prescribing abuses highlighted in other countries, particularly in the United States.⁹