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19th May 2023
Patients with rheumatic and musculoskeletal conditions are particularly vulnerable to long-term opioid use, new research has found.
A study of GP research database between 2006 and 2021 found one in three of those with rheumatoid arthritis or fibromyalgia had received long-term prescriptions for the potentially addictive drugs to manage their pain.
Overall, the team analysed more than 840,000 patient records and looked at different patterns of opioid use depending on frequency and number of prescriptions.
There were 1,081,216 new episodes of opioid use among all patients with just under 17% transitioning to ‘standard’ long-term use, defined as three or more prescriptions within a 90-day period, or more than 90 days supply in the first year.
Another 11% were categorised as having ‘stringent’ opioid prescribing with 10 or more prescriptions over more than 90 days, or 120 plus days of supply in the first year.
The research also found that 22% moved onto ‘broad’ opioid prescriptions which was classed as more than three opioid prescriptions at monthly intervals in the first year.
Reporting the findings in the Annals of Rheumatic Diseases, the team said the highest proportion of long-term users were patients with fibromyalgia—27.5%, 21%, and 34% for standard, stringent and broad prescribing categories.
This was followed by those with rheumatoid arthritis (26%, 18.5%, and 32% respectively) and those with axial spondyloarthritis at 24%, 17%, and 30%.
The results also showed an increasing proportion of patients with systemic lupus erythematosus and fibromyalgia who moved from one opioid prescription to long-term prescribing between 2006 and 2019.
But the converse pattern was true in rheumatoid arthritis with a decreasing trend over the time period, although the researchers noted the overall proportion remained high at 24.5% in 2020.
A 2019 review by Public Health England, found one in four adults were prescribed medications associated with dependence, including opioids, benzodiazepines and antidepressants.
NICE has since issued guidance on safe prescribing and withdrawal management for addictive drugs.
Dr Joyce Huang, study author and research associate in the Division of Musculoskeletal and Dermatological sciences at the University of Manchester, said: ‘Our study does not intend to stigmatise patients who use opioids.
‘We want to highlight the high frequency of long-term opioid use needs to be optimised and prevent people living with [rheumatic and musculoskeletal disorders] from opioid-related harm.’
Study lead Dr Meghna Jani, senior lecturer at the Centre for Epidemiology Versus Arthritis, said the results show that a ‘considerable proportion of patients’ with these conditions starting opioids for the first time, transition to long-term use that is much higher than people who are starting an opioid for non-cancer pain in general which is around one in seven people.
‘Because long-term opioid therapy is associated with poor health outcomes, these findings warrant vigilance when prescribing these drugs.
‘Long term use is particularly pronounced in fibromyalgia patients, who suffer chronic widespread pain for which there are no disease modifying treatment options. This is also more common than we initially thought, in rheumatoid arthritis and axial spondyloarthritis.’
A version of this story was originally published by our sister publication Pulse.
18th May 2023
IV paracetamol provides similar analgesic relief to other treatments used for acute pain in emergency care, but might not be the best first-line drug, a new study has found.
Use of intravenous (IV) paracetamol for patients presenting at an emergency department (ED) with acute pain, irrespective of the aetiology, provides a similar level of analgesia after 30 minutes as both IV NSAIDs or opiates. However, NSAIDs require less rescue analgesia than paracetamol, suggesting that in the absence of contra-indications, the former would be a better first-line choice. This is according to the findings of a meta-analysis by Qatarian researchers.
Pain is a common presenting complaint within an ED. For instance, a review of 1,665 visits to ED found that in 61.2% of cases, pain was documented somewhere on the chart. IV paracetamol is a commonly used analgesic, with some, albeit limited evidence of efficacy according to a review of 14 studies. Nevertheless, many of the studies included in the review had several methodological flaws, hence lowering the certainty of the findings.
Given these flaws, the researchers undertook the current study to update the earlier review, particularly as over 20 studies had been published since the original review in 2016. The team examined the comparative analgesia provided by IV paracetamol, NSAIDs (intravenous or intramuscular) or IV opioids all used alone, in adults attending an ED with acute pain due to various causes.
The primary outcome was the mean difference (MD) in pain reduction for each group (i.e. IV paracetamol, NSAIDs or opiates), 30 minutes (T30) post-dose. Secondary outcomes were the MD in pain reduction after 60 (T60), 90 (T90) and 120 (T120) minutes. The team also considered the need for rescue medication at the different time points for the three treatment interventions.
The review identified 27 trials with 5,427 patients and of which, 25 trials had data for use in the meta-analysis.
There was no significant difference in the mean pain reduction at T30 between IV paracetamol and opiates (MD = −0.13, 95% CI −1.49 to 1.22). Similarly, the difference between paracetamol and NSAIDs was also non-significant (MD = −0.27, 95% CI −1.0 to 1.54). However, while there were no important analgesic differences between the treatments, the researchers did identify significant heterogeneity across trials for all comparisons (p < 0.001 in all cases).
Despite the similar analgesic effects, the need for rescue analgesia at T30 was higher in the paracetamol compared to NSAID group (risk ratio, RR = 1.50, 95% CI 1.23 – 1.83) but not for paracetamol and opiates (RR = 1.07, 95% CI 0.67 – 1.70). Furthermore, adverse effects were 50% lower with paracetamol in comparison to opiates (RR = 0.50, 95% CI 0.40 – 0.62) but not different compared to NSAIDs (RR = 1.30, 95% CI 0.78 – 2.15).
At T60, T90 and T120, there was no difference between paracetamol and opiates though paracetamol was inferior to NSAIDs at T60.
These findings led the authors to conclude that while reductions in pain from IV paracetamol after 30 minutes were similar to the other two drug classes, since NSAID use was associated with a lower need for rescue analgesia, these drugs should be considered as a first-line treatment option unless there are contra-indications.
5th January 2023
A placebo response makes a significant contribution to the reduction in pain scores seen in cannabinoid clinical trials according to the findings of a systematic review and meta-analysis by Swedish researchers.
Pain is one of the most common symptoms experienced by patients in different health care settings, often leading to loss of function for the affected individual as well as a decline in their quality of life. Although there are wide range of medicines which act as pain-killers, in recent years, there has been increasing interest in the medical properties of cannabinoids. However, the evidence supporting the value of cannabinoids in pain management is limited. In fact, a 2021 systematic review concluded on how the available evidence neither supports nor refutes claims of efficacy and safety for cannabinoids, cannabis, or cannabis-based medicines in the management of pain. These findings suggest that there may be an important placebo response in such trials and which arise from patients’ positive expectancies. Furthermore, it is believed that different systems and mechanisms trigger placebo effects that highly impact pain processing, clinical outcomes and create a sense of well-being.
But how large is the placebo response in clinical trials examining the role of cannabinoids in the management of pain? This was the key question addressed in the current study where researchers set out to evaluate the size of placebo responses in double-blind randomised clinical trials in which cannabinoids, cannabis, and cannabis-based medicine were compared with placebo in the treatment of clinical pain. The researchers measured the change in pain intensity from before to after treatment, measured as bias-corrected standardised mean difference (Hedges g), which provides an assessment of the effect size. A small effect is represented by a value of 0.2, whereas a medium effect is 0.5 and a large effect 0.8.
Placebo response in cannabinoid trials
The researchers identified a total of 20 eligible trials with 1459 individuals (mean age = 51 years, 56% female). Studies included patients with neuropathic pain and multiple sclerosis.
The effect size of the active drug (cannabinoids) on pain intensity was large (mean Hedges g = 0.95, p <0 .001). However, pain intensity was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean Hedges g = 0.64, p < 0.001).
In a further analysis, the researchers looked at the media attention paid to these findings and found that this attention was independent of how biased the study was, the extent of the placebo response or how low the treatment effect was.
The authors concluded that placebos contribute significantly to the pain reduction seen in cannabinoid clinical trials. In addition, the positive media attention and wide dissemination possibly leads to high expectations and hence may shape the placebo response in future trials.
Gedin F et al. Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis. JAMA Netw Open. 2022