What is an opioid?
Opioids can either be sourced synthetically or derived
naturally from opium; the latter are referred to as opiates. Examples of
opiates include:
Heroin (diacetylmorphine) is an ester of morphine and being
more natural than the semi-synthetics is still considered an opiate. Synthetic
opioids include:
- Tramadol
- Methadone
- Pethidine
- Oxycodone
- Fentanyl
Why are opioids prescribed?
Opioids are mainly prescribed for pain relief, for example,
patients may have cancer and need end-of-life care. It is critical that they
are as pain-free as possible. Other patients requiring opioids may have painful
musculoskeletal disorders, some have acute post-operative, or post infarction
pain. Another group require opioid-substitution therapy for drug dependence and
addiction, and some may use opioids during the detoxification process.
Who is using opioids?
Interestingly, just seven countries, including the UK and
the USA, use 77% of the world’s available morphine, depriving poorer countries
of a ready supply.
While an essential element of pain-relief in some
circumstances, it cannot be forgotten that these are dangerous drugs and
over-prescribing may be contributing to a public health problem with enormous
implications for clinical practice.
Last year alone in the UK:
50 million
prescriptions for opioids were written
This is a 35%
increase over 10 years
Overdoses have
increased by 87% to 12,000
Deaths have
increased by 41%, to 2,000 each year
There are three
times more deaths in the North East of the UK than in London, partly reflecting
a greater usage of opioids amongst the socially disadvantaged
Opioid use and fatalities
Of the 115,000 prescriptions written every day, five result
in a death.
Overall, the most widely prescribed opioid is tramadol,
although for people presenting with musculoskeletal pain, 47% receive codeine,
or one of its analogues, co-codamol or co-dydramol.
Tramadol filled the void left by coproxamol, when it was
withdrawn around 2005. It is more likely to be prescribed by GPs than
non-steroidal anti-inflammatory drugs (NSAIDs), due to the fact that the latter
may cause complications especially in the older population. Tramadol may be
perceived, in therapeutic terms, as lying somewhere between a weak and a strong
opioid (an unhelpful distinction because this depends on dose), providing a
false sense of security to prescribers hoping to avoid the stigma and risk of
prescribing a ‘strong opioid’. Tramadol-related deaths amongst the opioid group
increased from 9% in 2001 to 40% in 2011.
In 2017, the British Medical Journal (BMJ) published an
interesting paper that focused on the opioid prescribing habits of 25 GP
surgeries in London and the Midlands (Ashaye, et al., 2018). Researchers found
that, of the 703 participants with musculoskeletal pain:
59% were
prescribed opioids
One quarter of
participating patients were prescribed outside of National Institute for Health
and Care Excellence (NICE) guidelines
Fewer than three
prescriptions were given to individuals each year
There is no real definition for ‘over-prescribing’. Patients
want pain relief, and social media platforms are awash with indignant sufferers
attesting to their dependent but not ‘addicted’ status, because they have been
relatively pain-free for so many years. Over 1.5 million people with
musculoskeletal problems receive opioids, and according to guidelines, 45% are
over-prescribed, at a loss to the NHS of £100 million per year. This does not
include the cost of managing the side effects of opioid addiction or reliance,
or of treating people who have overdosed.
Fatalities from recreational opioid misuse are now
overshadowed by medically prescribed opioid-related deaths. In the US, this
accounts for 60% of opioid-related deaths. However, the opioid problem in the
US is not remotely comparable with the situation in the UK. As yet, we do not
have marketing that directly promotes opioids to individuals, and our GPs do
not receive huge financial incentives for prescribing particular drugs.
Nevertheless, the prescription of opioids has increased by 60% in the last 10
years.
According to the Office of National Statistics (ONS):
There were 4,359
deaths from drug poisoning in 2018
This is up 16%
from the previous year and is the highest annual increase since records began
in 1993
Deaths amongst men
increased from 89.6 per million in 2017 to 105.4 per million in 2018 - two
thirds of these were linked to the misuse of drugs
Opioids, such as
heroin and morphine, continue to be the most frequently mentioned substances on
death certificates
Mixing opioids with other drugs
Incidentally, deaths involving cocaine doubled between 2015
and 2018. It is often impossible to tell the primary substance, as alcohol is
frequently involved, and many people taking opioids are also using cocaine and
other drugs, especially benzodiazepines. Since 2006, over half of all
drug-poisoning deaths have involved opioids.
Any appearance of a decline in drug-related mortality is
linked to a fall in cannabis usage. The addition of poly-substance misuse, club
drug culture, chemsex, and new psychoactive and illicit substances (formerly
known as ‘legal highs’), have only served to muddy the waters. With
opioid-related deaths, toxicity is often not clearly related to dose as chronic
use leads to tolerance. However, even if alcohol is present, the primary cause
of death linked to an opioid is usually clear.
With the addition of cocaine, everything changes. Death may
be due to serotonin syndrome or to hyperpyrexia. These cannot be diagnosed at
post-mortem examination. Unless there is a cocaine-induced myocarditis, or an
associate fulminant hepatic failure, the cause of death relies on eliminating
other possible causes.
Just how strong is fentanyl?
Despite dire warnings from the US, and a blip here in 2017,
deaths from fentanyl have remained relatively stable – 74 in both 2017 and
2018. It is likely that the analogue, carfentanil, contributed to most of these
deaths. Police investigations uprooted a number of ‘dark web’ vendors who were
subsequently arrested. Since then, there has been a dramatic decline in the
number of deaths.
Fentanyl may be 80 times more potent than morphine.
Carfentanil may be many thousand times more potent still,
and even 2mg can be fatal.
Respiratory depression and death can occur in under two
minutes, as opposed to 20 or 30 minutes for heroin, giving time for the user to
be treated. The prescription of ‘take-home’ naloxone must be considered here.
Multi-faceted treatment
The 2017 Drugs Strategy aimed to reduce the demand, restrict
the supply and improve recovery by enhancing the quality of treatment and
outcomes. The strategy asked for global action and new initiatives to respond
to the emergence of new psychoactive and illicit substances.
The Care Quality Commission (CQC), recognising that
opioid-related death was the third most common cause of preventable death for
15 – 49 year olds, asked that treatment be safe, effective, caring, responsive,
and well-led. Treatment was found to be well-evidenced and to provide value for
money. Every £1 spent on structured drug therapy saved the local society £2.50.
Unfortunately, the government’s attempts to reduce the
supply of legal opioids has driven users back to street heroin, itself much
cheaper and widely available. In one year, treatment presentations for opioid
drug misuse has climbed from 120,000, to 250,000. Of these, 140,000 were linked
to opioids and almost half (2/5) were for primary heroin use.
Treatment needs to be structured with:
- Goal-setting and planning
- Feedback and
monitoring
- Social support
- Contingency
management
Cognitive
behavioural therapy (CBT) and motivational interviewing are encouraged, along
with evidence-based psycho-social interventions
In December 2018, Jeffrey Singer of the Cato Institute dared
to reintroduce the policy of ‘harm reduction’. His paper, Shifting the war on
drugs, to the war on drug-related deaths (policy analysis 10858), quoted my own
papers published with Nicky Metrebian, as far back as 1998, and 2001,
suggesting that it was feasible to prescribe opioids safely to some users and
thereby to reap health and social gains. Others take this even further; states
in the US where cannabis is legalised have a 25% lower rate of opioid painkiller
overdose deaths. It may be asked: ‘is it time to look at cannabinoids as a
reasonable substitute for opioid pain relief?’
Adverse effects of using opioids for pain management
Overall, there is a lack of evidence supporting the efficacy
of opioid prescribing in the management of non-malignant pain. Treatment with
opioids can lead to a plethora of adverse effects, including depression,
anxiety, headache, hyperalgesia, inadvertent overdose, diversion, coma, and
even death.
Remember:
Prescribing daily oral
morphine equivalents of between 50 and 99mg increases the risk of overdose by
3.7 times
Prescribing over
100mg of morphine equivalent increases the risk of overdosing ten-fold
References: