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11th May 2023
There is insufficient evidence to justify the use of most antidepressants that are currently prescribed for chronic pain, Cochrane reviewers have concluded.
A team from Newcastle and Southampton universities analysed 175 trials of almost 30,000 patients and found only duloxetine was associated with reliable evidence of pain relief at least in the short-term for fibromyalgia, musculoskeletal, and neuropathic pain conditions.
There was no evidence of benefit for amitriptyline, which the researchers said was the most commonly prescribed antidepressant for pain management worldwide.
Other drugs for which there was a lack of evidence in chronic pain were fluoxetine, citalopram, paroxetine, and sertraline, the review found.
And data on long-term safety of antidepressants in this context was particularly poor, the researchers noted, saying they were ‘uncertain’ about unwanted effects and this needs to be studied further.
But the team stressed that ‘adopting a person-centred approach is critical’ concluding: ‘Pain is a very individual experience and certain medications may work for people even while the research evidence is inconclusive or unavailable.
‘Future studies should last longer and focus on unwanted effects of antidepressants.’
A guideline last year from NICE on medicines associated with withdrawal or dependence recommended regular reviews for patients on antidepressants and drugs for chronic pain.
Co-author Dr Gavin Stewart a statistician at Newcastle University, said: ‘Our study is one of the biggest of its kind and demonstrates the need for large-scale studies in this field.
‘Data is often complex and nuanced but the evidence underpinning the use of these treatments is not conclusive for most of the antidepressants we studied and, therefore, current treatment options are hard to justify.’
Study lead Professor Tamar Pincus, who researches the psychological aspects of chronic pain at the University of Southampton, said: ‘Chronic pain is a problem for millions who are prescribed antidepressants without sufficient scientific proof they help, nor an understanding of the long-term impact on health.
‘Our review found no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for their safety for chronic pain at any point.
‘Though we did find that duloxetine provided short-term pain relief for patients we studied, we remain concerned about its possible long-term harm due to the gaps in current evidence.’
But she stressed the findings did not mean people should stop taking prescribed medication without consulting their GP.
Dr Cathy Stannard, clinical lead on the NICE Guideline for Chronic Pain said: ‘This well conducted review adds to the substantial evidence we now have that shows that the use of medicines to treat long term pain is disappointing.’
She added that the conclusion that the best evidence is for duloxetine is unsurprising because trials for this newer drug were more rigorously done.
‘The study rightly highlights the significant adverse effect that chronic pain has on the quality of life for the people living with it. It’s equally important to emphasise the many social and psychological influences on the pain experience.
‘There is good evidence that for people with pain, compassionate and consistent relationships with clinicians remain the foundations of successful care.’
A version of this story was originally published by our sister publication Pulse.
8th February 2023
An overview of systematic reviews by researchers from Australia and the UK which examined the use of an antidepressant for the management of a range of chronic pain conditions, has concluded that the evidence of efficacy for all classes of drugs was moderate to low.
The presence of chronic pain is a common condition with one US survey finding that 50.2 million adults reported experiencing pain on most days or every day. Although both opioids and non-steroidal anti-inflammatory agents can be used to treat chronic pain, guidance from NICE in the UK, advises that the pharmacological management of such pain should involve the use of an antidepressant and which should be either amitriptyline, citalopram, duloxetine, fluoxetine, paroxetine or sertraline. But exactly how effective are antidepressant drugs for the management of chronic pain was the subject of the recent review by the Australian and UK researchers. The team undertook an overview of all available systematic reviews describing the use of an antidepressant (compared to placebo) for the management of any chronic painful condition in adults. The researchers set their primary outcome as pain and which could be measured with any instrument. The pain outcomes were then converted to a 0 to 100 scale and for which 0 represented no pain and 100, worst pain.
Antidepressant use and pain outcomes
A total of 26 studies with over 25,000 participants were included in the final analysis and which covered 22 distinct pain conditions and 42 antidepressants (8 different classes) versus placebo comparisons.
Overall, none of the reviews provided high certainty evidence on the efficacy of an antidepressant for pain in the management of any of the conditions examined. There were 11 comparisons of 9 different conditions where antidepressants were effective, largely serotonin-norepinephrine (noradrenaline) re-uptake inhibitors. This latter class was effective (mainly duloxetine) for back pain, postoperative pain, neuropathic pain and fibromyalgia. In the other cases, the antidepressants were deemed to be either ineffective or the evidence was inconclusive.
Interestingly, the researchers found that 74% of tricyclic antidepressant prescriptions were for a pain condition yet of 14 pain problems examined, this class of drugs were only effective for three conditions (irritable bowel syndrome, neuropathic pain and chronic tension-type headache). However, the certainty of the evidence was low in each case.
The authors concluded that overall, the efficacy of antidepressants was found in only 11 of the 42 comparisons and suggested that a more nuanced approach was needed when using these drugs for a painful condition.
Citation
Ferreira GE et al. Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews. BMJ 2023
8th September 2022
Patients prescribed medicinal cannabis products for the management of chronic pain are at a higher risk of a new-onset arrhythmia according to the findings of a retrospective study by researchers from Gentofte University Hospital, Denmark.
Cannabis is a generic term used to denote the several psychoactive preparations of the plant Cannabis sativa and according to the World Health Organisation, around 147 million people, 2.5% of the world population, consume cannabis every year.
There are recognised medical benefits from using cannabis and in 2018, the Danish government began a medical cannabis pilot program and by 2021, it was estimated that medical cannabis was used by approximately 1,500 patients on a quarterly basis.
Nevertheless, cannabis use is associated with adverse cardiovascular effects, including tachycardia and an elevation of blood pressure, effects that were first noticed in the early 1970’s.
Moreover, in a 2020 systematic review, the authors concluded that use of cannabis was associated with an increased risk of new-onset cardiac dysrhythmia, which, though rate, may be life-threatening.
In the current study, which was presented at the 2022 European Cardiology Society Congress, the Danish researchers sought to get a better understanding of the cardiovascular side effects of medical cannabis and in particular, arrhythmias in those using cannabis for pain relief.
There are currently only three cannabis products available for prescription in Denmark, dronabinol, cannabinoid, and cannabidiol, which can be inhaled, eaten, or sprayed in the mouth.
The researchers looked at patients prescribed these three drugs for chronic pain, between 2018 and 2021 and propensity-matched them, based on age, sex and pain diagnosis, on a 1:5 basis, with chronic pain patients not prescribed cannabis.
Both cannabis users and controls were followed for 180 days and their risks of new-onset cardiovascular conditions were compared.
New-onset arrhythmia and cannabis use
A total of 1.6 million patients with a median age of 60 (63% women) were included in the analysis. Cannabis use was reported for cancer (17.8%), arthritis (17.1%), back pain (14.9%), neurological diseases (9.8%), headaches (4.4%), complicated fractures (3%) and other diagnoses (mainly unspecified pain), 33.1%.
The absolute risk of new-onset arrhythmia was 0.86% among medical cannabis users compared with 0.49% in non-users (relative risk = 1.74). The risks of new-onset acute coronary syndrome and heart failure was no different between cannabis users and control and were similar for each chronic pain condition and each type of medical cannabis.
Lead author for the study, Dr Nouhravesh said: ‘The absolute risk difference was modest and it should be noted that a higher proportion of those in the cannabis group were taking other pain medications, namely non-steroidal anti-inflammatory drugs, opioids and anti-epileptics, and we cannot rule out that this might explain the greater likelihood of arrhythmias.’
She added: ‘This study indicates that there may be a previously unreported risk of arrhythmias following medical cannabis use. Even though the absolute risk difference is small, both patients and physicians should have as much information as possible when weighing up the pros and cons of any treatment.’
Citation
Cardiovascular risk following cannabinoid treatment for patients with chronic pain
21st September 2021
In a 2006 European survey of over 46,000 respondents in 15 countries, 19% reported experiencing pain which lasted for at least 6 months. Moreover, a more recent 2019 study in developing countries found a similar incidence (18%) among the general population. However, the impact of chronic pain, i.e., which persists past the normal healing time and lasts or recurs for more than 3 to 6 months, has a much wider impact upon affected individuals, reducing physical functioning, daily activities and mental health. Although opioid drugs have been used for the management of chronic pain, evidence suggests that compared with placebo, there are only small beneficial effects. Consequently, there has been increased interest in the use of alternative pain management strategies, one of which is the use of medical cannabis. In fact, its use as a therapeutic alternative has been recommended in some guidance for chronic pain, especially in cases where other treatments have been ineffective. However, the overall effectiveness of medical cannabis in chronic pain remains unclear with some organisations such as NICE in the UK, advising against the use of cannabis-based medicinal products to manage chronic pain in adults unless as part of a clinical trial.
With uncertainty over the effectiveness of medical cannabis in chronic pain, Canadian researchers led by a team from the Department of Anesthesia, McMaster University, Ontario, Canada, performed a systematic review and meta-analysis to determine the benefits and harms of medical cannabis in patients with chronic pain, including cancer pain. They included randomised controlled trials that enrolled at least 20 patients with chronic pain (defined as lasting longer than 3 months) and who were assigned to any form of medical cannabis and which was compared to placebo with a follow-up period of at least one month. As well as the impact on pain, the team also captured data on physical, emotional and social functioning and sleep quality. They assessment the benefits in terms of change scores from baseline as opposed to end of study results and determined whether use of cannabis achieved the minimally important difference (MID). This represents the smallest amount of improvement in a treatment outcome that patients recognise as important. For example, using a 10 cm visual analogue scale for pain, the MID is approximately 1 cm. The researchers modelled the risk difference (RD) of achieving at least the MID.
Findings
A total of 32 trials with 5174 adults in which 29 compared medical cannabis with placebo were included in the analysis. In terms of pain relief, there was moderate certainty evidence from 27 trials that medical cannabis compared to placebo, resulted in a small increase in the proportion of patients experiencing pain relief at or above the MID. This difference was modelled as 10 % (95% CI 5% to 15%). Data from 10 trials suggested a 7% increase in the proportion of patient experiencing at least a 30% reduction in pain with medical cannabis compared to placebo. Similarly, there was a 4% modelled difference in physical functioning and a 6% modelled risk difference for an improvement in sleep quality. However, there was no apparent improvement in emotional or social functioning. With respect to adverse effects, it appeared that medical cannabis gave rise to a 2% risk of transient cognitive impairment, impaired attention (3%) and nausea (5%).
The authors concluded that there was moderate to high certainty evidence of a small to very small increase in the proportion if people with chronic pain who experience an important improvement in their pain. Their results have been summarised in an accompanying rapid recommendation.
Citation
Wang L et al. Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: a systematic review and meta-analysis of randomised clinical trials. BMJ 2021
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