Most antidepressants used for chronic pain are being prescribed with “insufficient” evidence of their effectiveness, scientists have warned. A major investigation into medications used to manage long-term pain found that harms of many of the commonly recommended drugs have not been well studied.
In a Cochrane review, scientists examined 176 trials consisting of nearly 30 000 patients involved in assessments which prescribed antidepressants for chronic pain.
Among the drugs studied were amitriptyline, fluoxetine, citalopram, paroxetine, sertraline, and duloxetine – with only the latter showing reliable evidence for pain relief. One third of people globally are living with chronic pain, World Health Organization data shows, with many prescribed antidepressants for relieving symptoms.
Lead author Professor Tamar Pincus from the University of Southampton said: “This is a global public health concern. 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.”
The two-year Cochrane study was the largest ever assessment of antidepressants recommended by leading bodies including the UK’s National Institute for Health and Care Excellence (NICE) and the Food and Drug Administration (FDA) in the USA.
Statistician Gavin Stewart, review co-author from Newcastle University, said: “We are calling on governing health bodies NICE and the FDA to update their guidelines to reflect the new scientific evidence, and on funders to stop supporting small and flawed trials. Evidence synthesis is often complex and nuanced but the evidence underpinning the use of these treatments is not equivalent, so current treatment modalities are hard to justify.”
The review revealed that duloxetine was consistently the highest-rated medication and was equally as effective for fibromyalgia, musculoskeletal, and neuropathic pain conditions.
Other results showed:
Standard doses of duloxetine are as successful for reducing pain as higher quantities,
Milnacipran was also effective at reducing pain, but scientists are not as confident as duloxetine due to fewer studies with fewer people.
Prof Tamar Pincus added: “We simply cannot tell about other antidepressants because sufficiently good studies are not available – but it does not mean that people should stop taking prescribed medication without consulting their GP.”
Scientists responsible for the review, funded by the NIHR’s Health Technology Assessment programme, were from the universities of Southampton, Newcastle, Bristol, UCL, Bath, and Keele, alongside Oxford University Hospital.
The team assessed the trials using a statistical method that enables researchers to combine data from relevant studies to estimate the effects of different drugs, which have not been compared directly in individual trials.
University of Southampton researcher Dr Hollie Birkinshaw said: “Though previous investigations show that some antidepressants might relieve pain, there has never been a comprehensive study examining all medications across all chronic conditions – until now.
“The only reliable evidence is for duloxetine. Adopting a person-centred approach is critical to treatment, and when patients and clinicians decide together to try antidepressants they should start from the drug for which there is good evidence.”
Ccancer-associated fibroplasts surrounding a prostate tumour. Credit: Moscat and Diaz Meco lab.
Transgender women keep their prostates after gender-affirming surgery, and as a result are still at risk for prostate cancer, though to what extent remained unclear. A first-of-its-kind study estimates the risk at about 14 cases per 10 000, a little less than half the risk for cisgender males.
The UC San Francisco-led study drew on 22 years of data from the Veterans Affairs Health System. Despite the small sample size due to the size of the transgender population, it is still the largest of its kind.
“What we know about prostate cancer to date is almost exclusively based on cisgender men,” said the study’s lead author, Farnoosh Nik-Ahd, MD, a urology resident at UCSF. “This is an important first step in reshaping how clinicians think about prostate cancer in transgender women.”
Transgender people often face discrimination and disparities, and there has been a growing acknowledgment of the complexities involved in their health care.
The study found 155 confirmed transgender women with prostate cancer and stratified them according to whether they had used oestrogen: 116 had never used oestrogen, 17 had once used oestrogen but stopped before they were diagnosed with prostate cancer and 22 were actively on oestrogen.
The median age of diagnosis was 61 years, and 88% of the patients were white. Just 8% were Black, suggesting possible disparities affecting this group. Black cisgender men are at higher risk of being diagnosed with and dying from prostate cancer.
Though reduced compared to cisgender males, risk remains
The authors found that prostate cancer occurs in transgender women more frequently than published accounts suggest, with about 14 prostate cancer cases annually per 10 000 transgender women. Still, that rate was lower than what could be expected based on cisgender males, with 33 cases annually per 10 000.
While the numbers were small in the new study, the data suggests that transgender women who take estrogen may have delayed diagnoses. The authors also said that lower rates of prostate cancer may have been due to less PSA screening, misinterpretation of PSA levels in patients on gender-affirming hormone therapies, stigma, lack of awareness of prostate cancer risk and the effects of estrogen.
“We still have a lot of work to do to determine optimal prostate cancer screening for transgender women on oestrogen and related treatments,” said co-senior author Matthew R. Cooperberg, MD, MPH, of the UCSF Department of Urology. “This study should be a reminder to clinicians and patients alike that, regardless of gender, people with prostates are at risk for prostate cancer.”
Photo by Anna Shvets: https://www.pexels.com/photo/person-holding-white-printer-paper-4226124/
A recent phase III clinical trial showed that the drug combination of cemiplimab plus platinum chemotherapy can prolong survival in patients with advanced lung cancer when compared with placebo plus platinum chemotherapy. Now, an analysis published in CANCER indicates that cemiplimab plus platinum chemotherapy also improves quality of life (QoL) compared to chemotherapy alone.
In the multinational phase III EMPOWER-Lung 3 trial, the addition of cemiplimab to platinum-based chemotherapy was associated with improved survival in patients with advanced stage non–small cell lung cancer compared to chemotherapy alone. Because QoL is also an important parameter for treatment benefit, investigators examined how cemiplimab plus platinum affected symptoms in comparison to chemotherapy alone for patients enrolled into this trial using the EORTC QLQ-C30 and QLQ-LC13 questionnaires.
Patients who received cemiplimab plus chemotherapy experienced significant improvements in pain, dyspnoea, constipation, nausea, and vomiting compared to those who received placebo plus chemotherapy. Patients enrolled in the cemiplimab arm also had a significant delay in the clinically meaningful deterioration of symptoms including cough, haemoptysis, and dysphagia.
“The findings support the concept that the superior efficacy and favourable safety profile of cemiplimab plus chemotherapy translate to better patient-reported outcomes compared with chemotherapy alone in patients with advanced non–small cell lung cancer,” said corresponding author Tamta Makharadze, MD, of LTD High Technology Hospital Med Center in Batumi, Georgia.
The cooler months bring with them a surge in cases of influenza or ‘flu’. Flu infection causes up to 650 000 deaths globally each year, and the highest numbers occur in sub-Saharan Africa.1
Seasonal flu is characterised by a sudden onset of fever, cough (usually dry), headache, muscle and joint pain, severe malaise, sore throat and a runny nose. The cough can be severe and can last two or more weeks.2
South Africa’s seasonal flu usually has its highest number of recorded cases between May and September each year, with over 11 000 flu-related deaths occurring in the country annually.1 It is therefore important that healthcare professionals (HCPs) and high-risk population groups such as those living with chronic illnesses do not delay getting their flu shot this winter season.
Who is at risk of contracting severe flu, and of experiencing complications?
According to the National Institute for Communicable Diseases (NICD), the people most at risk for severe/complicated influenza include:1
Pregnant women and women up to 2 weeks postpartum
Young children (particularly those under 2 years of age)
Persons over the age of 65 years
Individuals who are morbidly obese (body mass index ≥40)
immunosuppression (e.g. those on immunosuppressive medication, or who have cancer)
heart disease (e.g. congestive cardiac failure), except for hypertension
metabolic disorders (e.g. diabetes mellitus)
kidney or liver disease
neurological and neurodevelopmental conditions
abnormal production or structure of haemoglobin (e.g. sickle cell disease)
Those under 18 years receiving chronic aspirin therapy
HCPs are particularly vulnerable for contracting flu: a systematic review comparing the incidence of flu in healthy adults and HCPs found a significantly higher incidence in HCPs, since they are exposed to the virus via their patients.3 The World Health Organization (WHO) adds that “Because healthcare workers are dedicated individuals, they often come to work when they are sick, increasing the risk of transmission,” and therefore recommends that all HCPs are vaccinated against seasonal flu every autumn.3
The NICD indicates that it is particularly important to protect HCPs and ensure that they are able to continue to work and to reduce any additional burden on the health system.1
Most people recover from fever and other symptoms within a week of contracting the flu, without requiring medical attention. However, among high-risk groups, and those with serious medical conditions, flu can cause severe illness or death.2
Complicated influenza includes cases requiring hospital admission and/or with symptoms and signs of lower respiratory tract infection (hypoxaemia, dyspnoea, tachypnoea, lower chest wall indrawing and inability to feed), central nervous system involvement and/or a significant exacerbation of an underlying medical condition.1
When is the best time to get vaccinated?
Dr Lourens Terblanche, Medical Head: South Africa, Sanofi Vaccines, says: “People should ideally get vaccinated against flu before the flu season begins for the most effective coverage, although vaccination at any time during the flu season can still help protect against flu infections.”
“Influenza viruses evolve constantly, so twice a year the WHO makes recommendations to update vaccine compositions. HCPs and patients who are known to be at high risk for developing severe or complicated illness as a result of contracting the flu, should prioritise immunisation against flu every year, as recommended by the NICD,” says Dr Terblanche. “The vaccine is however available to any individual from the age of 6 months to help prevent influenza infection.”
How vaccination could protect beyond flu
Flu can impact many systems in the body, so flu vaccination can provide protection where these systems would have been affected. For example, complications of flu include a 10x higher risk of having a heart attack,4 an 8x higher risk of stroke,4 and an 8x greater risk of pneumonia in children under the age of 14,5 while persons with diabetes experience a 75% increase in glycaemic events.6
According to the US Centers for Disease Control (CDC), during the 2019-2020 season, flu vaccination averted 7.5 million cases of flu, 3.7 million medical visits, 105 000 flu-associated hospitalisations, and 6 300 deaths.7
A 2021 study by the CDC also showed that among adults hospitalised with flu, vaccinated patients had a 26% lower risk of having to go into the ICU and a 31% lower risk of death from flu, compared with those who were unvaccinated.7
“Flu vaccination is also essential considering the possible co-circulation of both the flu and SARS-Cov-2 or other respiratory pathogens. However, it is important to remember that the flu vaccine will not prevent COVID-19 and vice versa; therefore, it is important to ensure that HCPs and their patients are vaccinated against both. Simultaneous infection with flu and COVID-19 canresult in severe disease,8” says Dr Terblanche.
Current guidance from the Department of Health regarding administering flu and COVID-19 vaccinations at the same time is that this may be done, if they are given in different arms.9
The WHO reports that there are still a number of myths about the flu vaccine10 – myths to which HCPs are not immune – including that ‘Flu is not serious, so I don’t need the vaccine’. The WHO responds as follows: “As many as 650 000 people a year can die of the flu. This only represents respiratory deaths, so the likely impact is even higher. Even healthy people can get the flu, but especially people whose immune systems are vulnerable. Most people will recover within a few weeks, but some can develop complications including sinus and ear infections, pneumonia, heart or brain inflammation.”
“It is good to be aware of the myths surrounding flu vaccination in order to encourage high-risk individuals to have their flu vaccine timeously,” says Dr Terblanche.
The quadrivalent Vaxigrip Tetra vaccine produced by Sanofi Pasteur complies with the WHO’s Southern Hemisphere recommendations for the 2023 season11 and protects against the following strains:
∙ an A/Sydney/5/2021 (H1N1)pdm09-like virus;
∙ an A/Darwin/9/2021 (H3N2)-like virus;
∙ a B/Austria/1359417/2021 (B/Victoria lineage)-like virus; and
∙ a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.
4. Warren-Gash C, et al. Laboratory-confirmed respiratory infections as triggers for acute myocardial infarction and stroke: a self-controlled case series analysis of national linked datasets from Scotland. Eur Respir J. 2018; DOI: 10.1183/13993003.01794-2017
5. Kubale J, et al. Individual-level Association of Influenza Infection With Subsequent Pneumonia: A Case-control and Prospective Cohort Study. Clin Inf Dis. 2021; 73(11): e4288–e4295.
6. Samson SI, et al. Quantifying the Impact of Influenza Among Persons With Type 2 Diabetes Mellitus: A New Approach to Determine Medical and Physical Activity Impact. J Diabetes Sci Technol. 2019; 15(1):44-52.
8. Stowe J, et al. Interactions between SARS-CoV-2 and influenza, and the impact of coinfection on disease severity: a test-negative design. International Journal of Epidemiology 2021;1-10. doi: 10.1093/ije/dyab081.
In a move bringing it closer in line with other organisations’ breast cancer screening guidelines, The United States Preventative Task Force (USPSTF) has released a draft statement recommending mammography every other year (biennially) from ages 40 to 74.
These recommendations are not applicable to women with a genetic marker or syndrome linked to increased breast cancer risk, a history of high-dose chest radiotherapy at a young age, or previous breast cancer or a high-risk breast lesion on previous biopsies.
According to the USPSTF, “new and more inclusive science about breast cancer in people younger than 50 has enabled us to expand our prior recommendation and encourage all women to get screened in their 40s. We have long known that screening for breast cancer saves lives, and the science now supports all women getting screened, every other year, starting at age 40.”
South African cancer screening guidelines typically closely follow American ones, according to an article by Lipschitz in the South African Journal of Radiology. Many countries had not recommended screening at the ages of 40–50 due to fears of overdiagnosis.
The UPSTF made particular attention the fact that black women are 40% more likely to die of breast cancer than white women, and have a high rate of aggressive cancers at young ages.
The recommendations are not without criticism. Biennial screenings are not seen as worth it by Desountis et al., as it leaving two years between tests leaves too much time for a tumour to grow.
Debra Monticciolo, MD, of Massachusetts General Hospital in Boston, and a member of the Society of Breast Imaging’s board of directors, told MedPage Today that she was “disappointed” with the decision to recommend biennial scans.
“Even if you look at their own data,” Monticciolo said, “annual screening results in more deaths averted, no matter what type of screening program you put in those models.”
Regarding the ongoing debated about continued screening in women ages 75 and older, and supplemental screening for those with dense breasts, the UPSTF found there was not enough evidence for a recommendation.
Most antidepressants used for chronic pain are being prescribed with “insufficient” evidence of their effectiveness, scientists have warned. A major investigation into medications used to manage long-term pain found that harms of many of the commonly recommended drugs have not been well studied.
