The opioid crisis: evaluating the safety and efficacy of opioid analgesia in the management of acute post-operative dental pain

Opioid consumption

The US, Canada, Oceania, Central and Western Europe account for 15% of the world's population but 95.7% of total opioid consumption.²¹ Australia and the US report high levels of opioid use in the dental setting.^22,23 In Australia in 2012, of all dental analgesic prescriptions, 87.3% were for paracetamol plus codeine.^24,25 The prescription of opioid analgesics in the US increased by 400% from 1998 to 2008 with 58.5 opioid prescriptions per 100 people in 2017, having fallen from a peak of 72.4 in 2006.²⁶ The recent decrease in prescription rates may be influenced by revised guidelines recommending use of NSAIDs as first-line management of acute dental pain.^10,27 Overall, US dental opioid prescriptions per 100 patients between 2010 and 2015 rose from 13.06 to 14.47, and within the cohort of 11–18 year olds, it rose from 9.97 to 16.59.²⁶ From 2007 to 2012 there was a 5.7% decrease in US opioid prescribing rates, yet a high dependence on opioid analgesia remains.^28,29 Centrally acting opioids are ‘almost always’ prescribed following third molar extractions by 85.1% of US oral and maxillofacial surgeons.³⁰ Dentists contributed 31% of total opioid prescriptions in the 10–19 age group in 2009.³¹ Practices of opioid prescriptions are often against established guidelines for using NSAIDs as first-line management of acute dental pain. ^10,27

Not every country is heavily dependent on opioid analgesics in dental pain management. In contrast to the US and Australia, low dental opioid prescribing rates are cited in England and Germany.^22,23 A disparity exists between the US and UK when prescribing analgesia for dental pain. In the US, 22.6% of dental analgesic prescriptions are for opioid analgesics, while in England, the rate is 0.6%.²³ This can possibly be explained by UK dentists having a restricted prescribing profile. Dihydrocodeine is the only opioid listed in the dental practitioners formulary for treating NHS patients, but opioid-containing formulations are available over the counter or through private prescriptions, which may skew results.²³ In Ireland and the US, there are no such restrictions on prescribing medications for management of dental pain.^23,32

Opioid analgesics used in post-operative dental pain

In this section, we evaluate the analgesics available (hydrocodone is not available in UK), the pharmacology of the drugs and their effectiveness in the management of acute post-operative dental pain. Some pain trials were conducted in the US and used paracetamol at doses of 600–650 mg, commonly available in the US, but not in the UK.

Discussion

Analgesics should be used as an adjunct to treatment intervention.² Paracetamol and NSAIDs are widely recommended as first-line management for acute dental pain except when contraindicated (Tables 1 and 2).^24,50,69,70

The US, UK and Ireland advocate a policy of NSAID use as the first-line treatment of acute post-operative dental pain.^71,72 Adoption of these guidelines varies from country to country, with the number of opioid prescriptions per dentist per 1000 of population standing at 35.4 in the US versus 0.5 in the UK.²³

For pain classed as mild, prescription of 6 hourly ibuprofen 400 mg should provide safe and effective analgesia.^12,50,69 For moderate/severe pain, 6 hourly ibuprofen 400 mg plus paracetamol 1000 mg should provide effective analgesia, more effective than opioid-containing alternatives.^50,51,69 Although this dose of ibuprofen is lower than the maximum dose of 6 hourly 800 mg, the ceiling dose of ibuprofen and paracetamol pain relief is reached at 400 mg and 1000 mg, respectively.⁵ Although, the anti-inflammatory effect of ibuprofen does improve up to the maximum dose of 6 hourly 800 mg.⁵

In the US, in contrast to the UK, supplemental use of opioids is recommended in severe pain with ibuprofen 400–600 mg, paracetamol 650 mg and 10 mg hydrocodone being recommended.^16,18 If NSAIDs are contraindicated, paracetamol 650 mg plus hydrocodone 10 mg is recommended for pain management every 6 hours.¹⁶

Due to the high incidence of adverse effects resulting from opioid prescriptions, pharmacologists have voiced a need to revise dental opioid prescribing practices in the US.^24,73 In 2016, the Centres for Disease Control and Prevention recommended limiting the duration and dose of opioid-containing medications, stating that opioid use for 3 days is often sufficient, and use for greater than 7 days is rarely needed in the management of acute pain.^74,75 In the US, opioids are arguably prescribed at higher strengths, in greater quantities and for longer periods of time than is necessary, with some drugs being transferred to friends, family or remaining unused allowing for potential misuse/abuse of opioid analgesics.^{76,77,78,79,80} It should be borne in mind that the mechanism of dental pain is often inflammatory, so it is generally reasonable in the first instance to use NSAIDs, unless contraindicated.

Ibuprofen plus paracetamol is reported to be at least as good as, if not more effective, than opioid-containing analgesics for the management of acute oral pain, while producing significantly fewer adverse effects (Figure 1).^20,50,51 Ibuprofen 200 mg plus paracetamol 500 mg, and ibuprofen 400 mg plus paracetamol 400 mg have been shown to have statistically significantly fewer adverse effects versus placebo controls with an NNH of 0.7 and 0.6, respectively.⁵⁰ Double-blind randomized control trials have concluded that paracetamol plus ibuprofen provide a synergistic effect.^81,82 These trials had low selection and performance bias due to random allocation and double-blinding, but were funded by companies that manufacture ibuprofen.^81,82 A Cochrane review stated that the quality of these studies was high but sample sizes were limited.⁸³ The NNT of ibuprofen 400 mg plus paracetamol 1000 mg was 1.5, the best efficacy of any drug used alone or in combination.⁸³

Both the decision to prescribe and choice of analgesic for acute dental pain management must be made judiciously. Dental opioid use varies from country to country.^22,23,24,28 Geographic variation in the availability of non-prescription opioid containing products can skew national results. This has been observed in the UK, where dihydrocodeine is the only drug available for dentists to prescribe while treating NHS patients. Other opioid analgesics are available privately on prescription and co-codamol (paracetamol 500 mg plus codeine 8 mg) is available over the counter, which would be prescription only in other countries.²³ Non-opioid analgesics should not be the only opioid-sparing strategy. The use of long-acting local anaesthesia, for example bupivicaine and pre-operative peripheral-acting analgesics can reduce the severity of post-operative pain.^84,85,86 In 2019, a US single-centre study reported that after a protocol of first-line NSAID analgesia was introduced, strong opioid prescriptions decreased from 58.7% to 19% suggesting that the ADA guideline for first-line non-opioid analgesia for post-operative dental pain is effective in reducing opioid consumption.^70,71,87

Evaluation of the literature

When evaluating the efficacy of opioid and non-opioid analgesics DB/RCT have focused on dental pain models. The use DB/RCTs as the study model of choice decreased the risk of selection bias and performance bias and produced more robust results.

Pain is subjective and its perception differs from person to person. Typically up to 18% of those in the placebo cohort experience effective analgesia, making the evaluation of clinically effective pain reduction difficult.⁸⁸

Many studies were funded by industry, which increased the risk of funding/industry bias. Barden et al attempted to evaluate whethre industry bias affected pain trials by examining the conflict of interest within studies and found that clinical trials in acute pain were safe from industry bias.⁸⁹ This improved the validity of results so long as the comparison studies met quality, validity and size standards and compared similar dose duration and outcome.⁸⁹

Sample sizes varied from study to study as did the age of participants. Study populations are very important to the quality of results. Many of the included studies had small sample sizes. Moore et al reported that in order to measure NNT to ±0.5, a sample of 400 people was needed.⁹⁰ Powering the smaller population study sizes for statistical analysis was not considered to be effective because the magnitude of clinical effect would still be uncertain.⁹⁰ Within a sample size of 40, the NNT of a drug can vary from 1 to 9 by random chance alone when the actual value is 3, a discrepancy that can be decreased if future study populations increase.⁹⁰

Older people are not excluded from studies but third molar extractions are usually carried out in young people, who are often healthy individuals with no comorbidities.

Future prospective DB/RCTs, not funded by industry, with larger and more diverse study populations covering different pain models are needed to definitively identify the most efficacious analgesic. It should be borne in mind that the mechanism of dental pain is often inflammatory, so it is generally reasonable in the first instance to use NSAIDs unless contraindicated.

Conclusion

This narrative literature review, of the effectiveness of opioid and non-opioid analgesics used for the management of acute post-operative dental pain found a geographical disparity in opioid prescribing practices and use. Opioid analgesics should be used with caution owing to their adverse effects, and should be limited to cases where non-opioid analgesics have been insufficient to achieve analgesia or where they are contraindicated. The non-opioid analgesics of choice for the management of acute post-operative dental pain are a combination of paracetamol and ibuprofen, which were evaluated to have as good, if not better, analgesic properties compared to opioid alternatives, and with fewer adverse effects.