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Drugs prescribed off-label may do more harm than good

Researchers warn prescribing medicines for a use which it has not been licensed could make things worse, even though the prescriber was trying to help.

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A new study from King’s College London shows that off-label prescriptions of a common antidepressant doesn’t help breathlessness in patients with respiratory disease – and may cause side effects.

Researchers warn prescribing medicines for a use which it has not been licensed could make things worse, even though the prescriber was trying to help.

The findings, presented at the ERS Congress in Vienna and published today in The Lancet Respiratory Medicine, show the desperate need for options to treat the symptoms of severe breathlessness, as there are no drugs licensed for this in the UK or most countries.

The severe breathlessness caused by chronic respiratory diseases greatly impacts patient’s quality of life. As well as creating substantial clinical challenges and health care costs. Most patients with diseases like this have few options to help with their symptoms.

Ahead of the trial, researchers surveyed doctors in respiratory and palliative medicine and found doctors were often using off-label prescribing – where a clinician prescribes a medicine for use in a different way than that stated in its licence. Various off-label prescriptions were being used, including common anti-anxiety and anti-depressant drugs like benzodiazepines and SSRIs.

Mirtazapine, a common antidepressant, was one of the types of drugs being prescribed. Case series and early studies showed it had potential. However, in this international trial, the first large-scale study to be done, researchers found that mirtazapine does not improve breathlessness in patients with respiratory disease compared with placebo. They also found that patients receiving mirtazapine had slightly more side effects and needed more care from hospitals and family members.

Chronic respiratory diseases affect 454.6 million people worldwide, with numbers predicted to increase with an aging population. Over 217 million people globally have Chronic Obstructive Pulmonary Disease (COPD) or Interstitial Lung Disease (ILD), both of which can cause severe breathlessness as they progress.

Off-label use can be as safe as on-label use if based on good evidence. It is often used when symptoms can’t be controlled with licenced medicines, particularly in serious illnesses. This is common in severe breathlessness care, making proper evaluation of medicines vital. Off-label prescribing doesn’t mean a doctor is making a mistake; it often happens when there are no other options to manage symptoms like breathlessness.

First author Professor Irene Higginson, King’s College London said: “Breathlessness is a widespread issue in palliative care as a symptom of respiratory diseases, heart disease and some cancers. When severe, it’s distressing for patients, as well as their caregivers, family and friends.  It diminishes people’s quality of life and often leads to considerable health and social care use, including driving emergency hospital admissions.

“Despite being a widespread issue we still don’t have effective treatments available. As such, many doctors turn to off-label prescribing, trying to help their patients.

“Our earlier survey found that 19% of respiratory and 11% of palliative physicians frequently recommend antidepressants for severe breathlessness in COPD, so these medicines are already being used off-label. This new trial concludes that mirtazapine is not recommended for the treatment of breathlessness, that the use of unlicensed medicines should be approached with caution and that it’s crucial to subject medicines in palliative care to rigorous trials.

“We need further research into potential therapies for severe breathlessness. In the meantime, we recommend clinicians use early identification and non-pharmacological approaches, such as those offered from breathlessness support services, to treat the symptom.”

The paper is published in The Lancet Respiratory Medicine.

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Surgery in kids with mild sleep-disordered breathing tied to fewer doctor visits, meds

Surgery, called adenotonsillectomy, was tied to a 32% reduction in medical visits and a 48% reduction in prescription use among children with a mild form of the condition.

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Surgical removal of enlarged tonsils and adenoids in children with mild sleep-disordered breathing (SDB) appears to significantly reduce the frequency of medical office visits and prescription medicine use in this group, according to a clinical study supported by the National Institutes of Health (NIH).

The findings, published in JAMA Pediatrics, show that the surgery, called adenotonsillectomy, was tied to a 32% reduction in medical visits and a 48% reduction in prescription use among children with a mild form of the condition.

SDB refers to breathing disturbances during sleep that can range from loud snoring to occasional breathing pauses. About 6 to 17% of children in the United States have it, and for those with moderate to severe cases, adenotonsillectomy is a standard treatment commonly used. It can help reduce breathing problems, minimize behavioral issues, and also lower the risk of high blood pressure, full-blown sleep apnea, and other problems that may occur if the condition is left untreated. A recent NIH-supported clinical trial showed that for children with mild SDB, the surgery helped lower blood pressure and improve sleep and quality of life.  

In the new study, researchers sought to determine whether adenotonsillectomy in comparison to watchful waiting (non-intervention) with supportive care is associated with fewer health care encounters and prescriptions. To find out, the researchers analyzed data from a randomized clinical trial that involved 459 children and adolescents with mild SDB who were recruited between 2016 and 2021 and followed for one year. The participants were ages 3 to 12 and were studied at seven academic sleep centers in the U.S.

During the trial, half the participants received an adenotonsillectomy, and the other half received supportive care without surgery, which included standardized education on healthy sleep and lifestyle and referral for untreated allergies or asthma. An analysis after the 12-month study period found 32% fewer health care encounters and 48% fewer prescriptions used among participants who underwent adenotonsillectomy, compared to those who did not undergo the surgery. For every 100 children, this equates to 125 fewer health care encounters and 253 fewer prescriptions — including for pain, skin, and respiratory medications — administered during the first year following surgery.

The reduced health care encounters included fewer office visits and outpatient procedures, particularly for sleep- and respiratory-related problems, but the mechanisms linking SDB treatment to health care outcomes are not clear.

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Maternal depression can lead to children’s emotional overeating, study shows

“In our sample, almost 12% of mothers met the criteria for postpartum depression, and we found that maternal postpartum depression at six weeks negatively influenced children’s executive function with inhibition and emotional control at 24 months and overeating at 48 months.”

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Up to 25% of new mothers suffer from postpartum depression, which can significantly impact their parenting behavior and the wellbeing of their children. A new study from the University of Illinois Urbana-Champaign looks at long-term effects of early maternal depression on children, underscoring the need to provide adequate support for mothers who might be struggling.

“We wanted to explore how mother’s early postpartum depression might influence children’s executive function and emotional overeating, focusing on the psychological mechanisms driving the effects,” said lead author Samantha Iwinski, postdoctoral research associate in the Department of Human Development and Family Studies at Illinois.

“Emotional overeating is about using food to cope with stress or emotions rather than using it to satisfy hunger. Instead of thinking about food as a source of nourishment or enjoyment, it becomes a coping strategy for negative emotions. If children aren’t able to talk about their emotions or show how they really feel, they may react to a stressful situation by grabbing something to eat,” Iwinski said.

The study included families participating in the Midwest STRONG Kids2 project, which investigates how individual biology interacts with the family environment to promote healthy eating habits in young children. Mothers filled out questionnaires to assess postpartum depression at six weeks, children’s emotional functioning at 24 months, and children’s eating behavior at 48 months.

The researchers analyzed the data using the biopsychosocial pathways model, which outlines how interactions between biological, psychological, and social factors affect health outcomes, including appetite self-regulation. They focused on postpartum depression as a critical social factor predicting children’s emotional overeating, mediated through emotional and cognitive psychological processes.

“In our sample, almost 12% of mothers met the criteria for postpartum depression, and we found that maternal postpartum depression at six weeks negatively influenced children’s executive function with inhibition and emotional control at 24 months and overeating at 48 months,” Iwinski said.

“Inhibition involves being able to control one’s attention, behaviors, and thoughts. This can include doing what may be appropriate in a given situation, which may involve overriding internal predispositions For example, if a child is doing their homework and the TV is playing, they can direct their attention and focus on their homework rather than the TV. Emotional control is about being able to regulate oneself when certain situations are happening; for example, crying might help in response to distress.”

In addition to the indirect effects on eating behavior through executive functioning, there was also a direct correlation between maternal depression and children’s overeating. 

Mothers who suffer from postpartum depression may be less responsive to their children’s cognitive and emotional needs, which can affect healthy development and capacity for self-regulation. Women with postpartum depression symptoms may also engage in appetite fluctuation, modeling this behavior for their children. 

The researchers say their findings underscore the need for early intervention and support for women who suffer from depression. 

“By supporting the mother’s mental health, we’re really supporting the families, because of the long-term effects on children. It’s important to have early identification of what might be happening in order to help families teach their children healthy strategies for coping with emotions, such as play, mindfulness, or even just talking about our feelings,” Iwinski stated.

“Teachers and other supportive adults can also participate in supporting children and families. For example, they can be looking at eating patterns, noticing how children might be reacting in certain situations, and if food might be a coping mechanism for them. They can then use that information to talk about other ways to deal with emotions and bring the family more into the conversation.”

The paper, “Maternal postpartum depression and children’s emotional overeating: The mediating role of executive function,” is published in Eating Behaviors. Authors include Samantha Iwinski, Sehyun Ju, Qiujie Gong, and Kelly Bost.

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Poor sleep health linked to increased Type 2 diabetes risk in high-risk women with history of gestational diabetes

By prioritising better sleep, women with a history of GDM can take proactive steps toward reducing their long-term risk of developing T2D and improving overall metabolic health.

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Underscoring the critical role of sleep in diabetes prevention, investigators from the Global Centre for Asian Women’s Health (GloW) and the Department of Obstetrics and Gynaecology, based at the NUS Yong Loo Lin School of Medicine (NUS Medicine), in collaboration with Harvard T.H. Chan School of Public Health, Brigham and Women’s Hospital and Harvard Medical School, has identified a significant link between sleep health and the risk of developing Type 2 diabetes (T2D) among women with a history of gestational diabetes (GDM).

GDM is one of the most common pregnancy complications, affecting up to 30% of pregnancies globally. Women with a history of GDM are nearly 10 times more likely to develop T2D later in life compared to those without GDM. More strikingly, in Singapore, more than 40 per cent of women may develop T2D within 5 years following pregnancies complicated by GDM.  While lifestyle factors such as diet and exercise are well-known preventive measures, this study sheds light on the often-overlooked role of sleep health in mitigating diabetes risk.

By prioritising better sleep, women with a history of GDM can take proactive steps toward reducing their long-term risk of developing T2D and improving overall metabolic health. Led by Professor Zhang Cuilin, Director of GloW, and Dr Yin Xin, Research Fellow at GloW, their team analysed data of nearly 3,000 women with a history of GDM over 17 years from the Nurses’ Health Study II and found that those who slept six hours or fewer per night had a 32 per cent higher risk of developing T2D compared to those who met the recommended seven to eight hours of sleep.

Additionally, regular snoring—defined as snoring most nights per week or every night—was associated with a 61% increased risk of T2D. Women who experienced both short sleep duration and regular snoring faced more than double the risk compared to those with healthy sleep patterns. Beyond increasing diabetes risk, regular snoring was also associated with unfavourable glucose metabolism biomarkers, including elevated levels of HbA1c, insulin, and C-peptide, all of which signal potential metabolic dysfunction.

“Our research highlights that improving sleep habits—such as increasing sleep duration and addressing snoring—can be a powerful, actionable step in preventing Type 2 diabetes among women with a high-risk of diabetes,” said Prof Zhang. She further emphasised, “Given the rising prevalence of GDM and diabetes, particularly in Asia, it is crucial to expand prevention strategies to include the improvement of sleep health, especially for women with a history of GDM. Dr Yin also pointed out that, “Women with GDM may have had sub-optimal glucose metabolism even before pregnancy.”

Having opened new avenues for diabetes prevention, the study’s researchers are now looking to develop tailored interventions for Asian women that include improving sleep quality, diet, and other lifestyles, and to better understand underlying molecular mechanisms.

The study titled ‘Sleep Characteristics and Long-Term Risk of Type 2 Diabetes Among Women With Gestational Diabetes’ was published in JAMA Network Open.

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