Psychiatric drugs may cause adverse cardiac event in young people

Estelle Naumburg is Senior Lecturer in Child and Adolescent Medicine and Consultant at the Department of Clinical Sciences at Umeå University. She lives in Jämtland and works as a pediatric cardiologist in Östersund.

The origin in her research is often raised from the daily clinical practice with young patients and their relatives.

"I often get questions about cardiac drug safety for children and adolescents, especially in association with different diseases, but I seldom have researched based answers and have identified a knowledge gap. Meeting with patients and relatives have always been a source of inspiration for me," says Estelle Naumburg.

antidepressants and ADHD medications may have cardiac adverse events

As a pediatric cardiologist she got the idea to through epidemiological methods assess a possible association between the increased prescription rate of psychotropic drugs to children and young adults, and the increased number of children and young adults to seek health care for cardiac related symptoms.

"I was asked questions like 'can this patient be prescribed ADHD medication?' but had no research based answers. Most of the knowledge is based on expert options, and few clinical trials are performed in children, and documented safety issues are lacking. It is well known that antidepressants and ADHD medications have cardiac side effects in adults. Further, although ADHD drugs are tested on children and young, this has not been performed in combination with other drugs or in children with different conditions.

"Off-label drug use is common in pediatrics as most drugs are not tested in children in clinical trials, so I think it is definitely a reason to take a closer look at the issue. Some of these side effects are serious – arrythmias, unexpected fainting and sudden death.

Interested in polypharmacy

The P-TACO study is led by Estelle Naumburg and a pharmacovigilance study based on register data provided by several national registers. By the study´s large sample size and power to detect even smaller risk estimates, the study will contribute substantially to a better risk-benefit assessment. It makes it possible to study many different variables; such as individual or a combination of drugs, different lengths of treatments, different ages and genders or underlying diseases of the patients and more.

"We are particularly interested in polypharmacy, i.e. when a patient is taking combinations of several drugs, and assess an increased risk of cardiac side effects. We also want to see if children with congenital heart defects have an increased risk associated with psychotropic drug medications and polypharmacy" says Estelle Naumburg.

The risk of cardiac adverse events in children and young people with psychotropic drug treatment will be compared to a group of people of the same age but without this medication.

Estelle Naumburg leads the P-TACO study and has specialists in several different disciplines in the research group. A reference group of patients and parents is also linked with the project.

This project has just started and the funds, including support from the Swedish Heart-Lung Foundation and FORTE, will last for 4 years, but Estelle Naumburg believes that this study will continue longer .

"I think the result will be very valuable to doctors who give advise on medicines to young patients with psychiatric symptoms, and especially to us pediatric cardiologists who are asked questions on drug cardiac safety. The aim is that this national-wide population-based study will contribute substantially to a better risk-benefit assessment, and in the long term, lead to better personalized psychopharmacological drug treatment.

Blood pressure in arteries of the lung and right side of the heart

Estelle Naumburg has also studied the risk of pulmonary hypertension in infants born premature. Pulmonary hypertension is a type of increased high blood pressure that affects the arteries in the lungs and the right side of the heart. The right chamber of the heart pumps blood through the lungs to be oxygenated.

the premature born baby has not a fully developed lung to breath, and several problems related to this

"Premature babies have an increased risk of developing pulmonary hypertension, PAH, which can be seen even up to adulthood. They also have an increased risk of atrial septal defect, ASD, which is a birth defect of the heart where there is a hole in the wall (septum) that divides the upper chambers (atria). We have in several studies assessed the risk of PAH and ASD, in children born premature. Now we must evaluate if these children would benefit from some treatment, for example through drugs or surgery, and the timing of this. "The origin behind these conditions is that the premature baby is not fully developed, neither the lungs nor the heart. The to improve pulmonary vascular growth  in these children we do not know.

This study has been going on for years and Estelle Naumburg now hopes it can lead to a national follow-up program for premature babies including heart function, pulmonary circulation and lung function.

"It's amazing that we manage to save even very young premature born babies in Sweden today. But, we need to understand and improve treatment for conditions that may have the origin in an early birth," says Estelle Naumburg. 

A boost to our academic environment

She grew up in Stockholm but ended up in the early 2000s in Östersund, where she still works, after studying medicine in Uppsala and a doctoral dissertation. After the regionalization of medical school at Umeå University to four campus, she became a senior lecturer in pediatrics and has since then experienced that the research activity have improved at the pediatric department in Östersund.

"When the regionalized medical school started, few doctors at the pediatric department in Östersund had a PhD degree. Now, after 9 years of medical school at the clinic, we have two more PhDs and four Doctoral students. In total, we are just under 25 doctors, specialists and residents. Our academic environment has really been given a boost – and that's good for both patients and clinic. I hope that our nurses and other staff will start to do research. She herself enjoys working clinically alongside with her research and teaching at the medical school.

An open and equal climate

"I like the holistic perspective and think that as a teacher in at the medical program and for young doctors to be, you should have to be linked to the health care and clinical work. 

Umeå University is also a fantastic university, she says.  

"I really like it here in Östersund and at Umeå University. It is spirited, has a fairly open and equal climate. We have excellent research in all sorts of areas and often collaborate across borders.