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Take a look at a selection of our recent media coverage:

Cochrane reviewers find insufficient evidence to justify most antidepressant prescribing in chronic pain

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.’

‘No reliable evidence’

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.

Adverse effect on quality of life

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.

Faecal transplantation increases remission in ulcerative colitis

2nd May 2023

A Cochrane review found that faecal transplantation improves clinical and possibly endoscopic remission in ulcerative colitis

Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) that presents with inflammation of the colonic mucosa. Estimates suggest that in 2017 there were 6·8 million global cases of IBS. To date, conventional IBD medical therapies currently only target the inflammatory component of the condition. However, evidence suggests microorganisms within the intestine have pro-inflammatory or anti-inflammatory activities which may modulate IBD. The concept of ‘dysbiosis‘, i.e., an alteration of the commensal microbial organisms relative to those in healthy individuals, may play a role in IBD. Faecal transplantation (FT) may play a role to correct dysbiosis in UC. In fact, there is evidence that the strategy is effective for Clostridium difficile infection.

Whether faecal transplantation is effective for ulcerative colitis was the subject of a recent Cochrane review. The researchers looked for randomised controlled trials that studied adults and children with UC or Crohn’s disease (CD). Eligible studies made use of FT, which is the delivery of healthy donor stool containing gut microbiota to a recipient’s gastrointestinal tract to treat UC or CD. The review examined both clinical and endoscopic disease remission.

Faecal transplantation and ulcerative colitis

A total of 12 studies with 550 participants were included. Studies lasted for 6 to 12 weeks.

Findings suggest that faecal transplantation may increase rates of induction of clinical remission in UC compared to control (risk ratio, RR = 1.79, 95% CI 1.13 – 2.84). Similarly, FT may increase rates of induction of endoscopic remission in UC (RR = 1.45, 95% CI 0.64 – 3.29). However, since the confidence intervals are wide, there is low certainty evidence for this effect. Two additional studies gave very uncertain evidence that FT could maintain clinical remission.

Taken together, it appears that FT may increase the proportion of people with active UC who achieve clinical and endoscopic remission. But there was less evidence that FT was effective for maintenance of remission in people with the condition.

Updated review finds vitamin D has no impact on asthma control

16th February 2023

Asthma control is not improved with the use of vitamin D supplementation according to the findings of an updated Cochrane systemic review

Supplementing with vitamin D has no effect on asthma control or the risk of disease exacerbations according to the findings of an updated Cochrane systemic review.

Asthma is a chronic inflammatory respiratory disease and which globally, in 2019, was estimated to affect 262 million people in 2019, leading to 455,000 deaths. The potential role of vitamin D in asthma control is unclear though one study observed that among those deficient in the vitamin, the odds of having an exacerbation were 25% greater compared to those with levels in the normal range. Moreover, other work in children with severe, therapy-resistant asthma, found that lower vitamin D levels were linked to increased airway smooth muscle mass together with worse asthma control and lung function.

In 2016, a Cochrane review examined the possible value of vitamin D for the management of asthma and concluded that the vitamin is likely to reduce the risk of severe asthma exacerbations and healthcare. However, the authors could not determine if these benefits were confined to those who had suboptimal vitamin D levels. The current review provided an updated meta-analysis based on subsequently published trials and included patients with mild to moderate asthma.

Asthma control and vitamin D use

A total of 20 studies, 15 of which included 1,155 children and 5 with 1,070 adults were included in the updated analysis. The researchers performed several subgroup analyses based on initial vitamin D status as well as the dosage and regime of the vitamin used.

Overall, use of vitamin D did not reduce or increase the proportion of patients who experienced one or more disease exacerbations requiring treatment with systemic corticosteroids (Odds ratio, OR = 1.04, 95% CI 0.81 – 1.34). In addition, vitamin D had no effect on the rate of asthma exacerbations and subgroup analysis failed to reveal any effect based on vitamin D status, dose, dosage frequency or patient age.

Secondary outcomes examined included exacerbations leading to hospitalisation and measures of asthma control but again, vitamin D had no impact on any of the assessed outcomes.

The authors concluded that in contrast to their 2016 review, the current analysis failed to identify any benefits from vitamin D supplementation on asthma exacerbations or asthma control.

Williamson A et al. Vitamin D for the management of asthma. Cochrane Database of Systematic reviews, 2023

Cochrane systematic review answers only some questions on topical steroids use in eczema

4th April 2022

Use of topical steroids in atopic eczema was examined in Cochrane review but only answered some relevant clinical usage questions

A Cochrane review on the use of topical steroids, has offered some, but not all, of the answers to help clinicians and patients to use these drugs optimally in the treatment of adults and children with atopic eczema, despite the fact that these agents have been used in practice for many decades.

Atopic eczema (atopic dermatitis) is defined as a chronic, itchy, inflammatory skin condition that affects people of all ages, although it presents most frequently in childhood.

According to NICE guidance, which, although focusing on children, is applicable to adults, emollients should form the mainstay of atopic eczema management and should always be used, even when the condition has cleared. Where the disease flares, NICE advocates a stepped approach to management involving the use of emollients and topical steroids.

The first use of topical steroids, in the form of cortisone acetate ointment (referred to as compound F) was reported in 1952 and topical steroids are categorised in terms of their potency which ranges from mild, moderate, potent and very potent with more potent agents inducing a greater degree of skin blanching (i.e., vasoconstriction).

They are also available in different strengths and formulations, e.g., creams, ointments and foams, with designed to be used only once daily.

Nevertheless, despite the widespread availability of the drugs, there is surprising lack of clarity on how to best use topical steroids in clinical practice. The purpose of the current Cochrane review was therefore to try and answer several relevant questions to support clinicians and patients.

In trying to answer these questions, the review included only randomised controlled trials in adults and children with eczema and which compared at least two strategies of topical corticosteroid use.

Optimal use of topical steroids

A total of 104 trials with 8443 participants were included in the analysis although 55 trials had a high risk of bias in at least one domain, mostly due to lack of blinding or missing outcome data.

The use of moderate compared to mild potency topical steroids resulted in more participants achieving treatment success, which was defined as cleared or marked improvement in eczema, based on an investigator global assessment scale (odds ratio, OR = 2.07, 95% CI 1.41 – 3.04).

In trials assessing adults and children with moderate or severe eczema, the use of potent topical steroids once compared to twice daily, did not reduce the number of patients achieving treatment success (OR = 0.97, 95% CI 0.68 – 1.38).

One strategy advocated by the NHS is weekend treatment, where a person whose eczema is under control, uses the topical corticosteroid every weekend on the trouble sites to prevent a disease relapse. flare. The review found supportive evidence for this approach and concluded that this resulted in a large decrease in likelihood of a relapse from 58% to 25% (risk ratio, RR = 0.43, 95% CI 0.32 – 0.57).

Another area explored included whether to use a cream or ointment formulation but there was no evidence to support use of either formulation. Advice from the NHS is that if a topical corticosteroid is prescribed, patients should wait about 15–30 mins after applying an emollient before using topical steroids. However, the review found no evidence to support this recommendation.

Although the Cochrane review provided some answers to support clinicians in their use of topical steroids, as the authors noted, there was a lack of evidence on adverse effects since studies were small and did not always use the most reliable methods. Therefore, the review offers some, but not all, of the answers to support the optimal use of topical steroids.

Lax SJ et al. Strategies for using topical corticosteroids in children and adults with eczema. Cochrane Database Sys Rev; March 2022