Researcher from SUND develops new concept for treating refractory depression – University of Copenhagen

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01 November 2016

Researcher from SUND develops new concept for treating refractory depression

Depression

Professor Steen Dissing was teaching medical students how neurons are signaling. He got an idea on how to apply the measured electric signals and put them into practical use. It has now resulted in a new treatment concept for refractory depressions which is offered to patients at 6 psychiatric centers in Denmark.

Danish patients suffering from refractory depressions can now look forward to being offered a new type of treatment. Refractory depression is a term used to describe cases of major depressive disorders that do not respond adequately to at least two antidepressants as well as other types of treatment. The treatment concept is developed by Danish researchers from the University of Copenhagen as well as by psychiatrists in Danish hospitals. Behind the clinical trials is professor dr. med. Per Bech and he states that the new concept is a paradigm shift for psychiatric treatments.  

"Paradigm shift for psychiatric treatments

Professor dr. med. Per Bech 

The treatment concept is approved in the EU and the EFTA countries Iceland, Norway and Lichtenstein. Treatments of patients have now started at leading psychiatry centers in Glostrup, Aalborg, Aarhus, Odense, Rigshospitalet and Hillerød. Professor and chief physician at the Institute for Clinical Medicine and Psychiatric Center Glostrup, Poul Videbech, looks forward to testing the new treatment concept on patients with major depressive disorders.   

“It is a potentially important discovery because there are a lot of people who have a chronic depression and have tried a number of treatments without positive effects. It is probably between 30 and 40.000 Danes and it is thus important to try out a new treatment concept” says Poul Videbech.

Poul Videbech also emphasizes that the new concept is an example of an interesting collaboration between the basic research area and the clinical sector and together they can solve the problems and challenges for a group of patients that have an unmet and significant medical need for a new type of treatment.  

From laboratory data to a medical device.

"If you as a researcher come upon a good idea with a great potential and you also feel it is very different, in terms of how people think in this research field, one has to find good and open minded collaborators. And one has to be very persistent and accept challenges. And if one believes in it the idea, it can survive and succeed

Professor Steen Dissing

Basic research behind the discovery of the electric pulses and their application is conducted by professor dr. scient. Steen Dissing and his research group at the Institute for Cellular and Molecular Medicine in collaborations with Danish hospitals. Here the clinical research has been conducted by a team of clinicians headed by professor and chief clinician, dr. med. Per Bech, Psychiatric Research Unit, Hillerød in collaboration with Erik Roj Larsen who is chief physician and associate professor, PhD, at the Department for Depression and Anxiety Q at Aarhus University Hospital, Risskov.

”I came upon the idea when I was teaching medical students on how to measure electric potentials outside neurons when they are signaling. All cells in the body communicate with neighbours and I hypothesized that the very small electric potentials could be sensed by neighbouring cells (small capillaries etc). I tested the idea in the laboratory be applying pulsed electromagnetic fields and found that endothelial cells do respond to such electric potentials. I then hypothesized that such interactions might also occur in the brain between the many cell types. It has been an interesting and challenging route from the first observation to a finished product. If you as a researcher come upon a good idea with a great potential and you also feel it is very different, in terms of how people think in this research field, one has to find good and open minded collaborators. And one has to be very persistent and accept challenges. And if one believes in it the idea, it can survive and succeed” says Steen Dissing

This is how it works

Pulsating electromagnetic fields induces pulsating electric potential changes in brain tissue by placing coils on the head as shown in the picture. The pulses are designed in such a way that they mimic existing electric potential changes measured outside nerves as the action potential propagates. (see picture)

Steen Dissings research group have shown that such small pulsating potential changes activate a cytoplasmatic protein kinase Src, which is associated to a number of receptors and control their down-stream signaling. In the laboratory it was shown that endothelial cells, which constitute part of the blood brain barrier, upregulate mRNA for a number of important signaling proteins such as BDNF (brain derived neurotrophic factor), IL-8, FGFR1 and other proteins and secretion of IL-8 from endothelial cells was measured following cell activation with the pulses. In a mouse cornea model it was shown that these electric pulses enhance VEGF-induced angiogenesis.   

In the first double blinded, placebo controlled study with 50 patients diagnosed with refractory depression, there was a significant beneficial effect of treatment using the device 30 min/day for 5 weeks Martiny et al., 2010. In the next study with  65 patients with refractory depression more than  60% were in remission after being treated  30 min/day for 8 weeks using the device in a home treatment setting. Straasø et al., 2014. A smart card was inserted into the pulse generator that could be read by the clinician in order to  follow patient compliance. In both studies none of the patients reported side effects. A few patients reported a brief period of nausea at the  beginning of treatment.

In a follow up trial conducted 2 years after the Straasø et al. (2014) study,  amongst the 73% who were in a clear remission 52% were still in remission. The remaining 13 patients were in a follow up trial treated for 8 weeks as home treatment and reported positive effects.

Treatment with the Re5-NTS device is recommended to be 30 min/day over 8 weeks. Steen Dissing states that “we hope  the device can substitute for ECT treatment for a number of patients”.    

The Norwegian company Navamedic ASA is marketing the device in Denmark and is planning on entering the Swedish market in the beginning of 2017. The treatment concept is patented in EU as well as USA. The US patent was issued 2 years ago and covers treatment of refractory depressions.

About refractory depressions.

  • It is estimated that in the Danish population that there is a prevalence of people suffering from depressions of about 3-4%. About 20% of the patients suffering from depression become resistant to medical treatment. Refractory depression is a term used to describe cases of major depressive disorders that do not respond adequately to at least two antidepressants as well as other types of treatment. 
  • The cost for the Danish society of depressions is about 10 billion DKR mostly due to sickness benefits, pensions, loss of earnings, medical treatments, nursing and more. 
  • The research group at SUND wishes to continue the basic research with the device in order to further develop the understanding of ”its mode of action”  as well as expanding the investigations into more clinical trials. Hopefully, these initiatives can further develop the technology and promote the use of the device into other countries. 

Read more

1) Rahbek UL, Tritsaris K., Dissing S. Interactions of Low-Frequency, Pulsed Electromagnetic Fields with Living Tissue: Biochemical Responses and Clinical Results. Oral Biosciences & Medicine, 2005, 29-40. 2005. 

2)  Martiny K.,   Lunde M.,  Bech P. Transcranial Low Voltage Pulsed Electromagnetic Fields in Patients with Treatment-Resistant Depression. Biological Psychiatry, 2010; 68; 163-168, 2010.

3) Straasø B, Lauritzen L, Lunde M, Vinberg M, Lindberg L, Larsen ER, Dissing S,  Bech P. Dose-remission of pulsating electromagnetic fields as augmentation in therapy-resistant depression: a randomized, double-blind controlled study. Acta Neuropsychiatry 26(5): 272-9. 2014

4) Bech P, Lindberg L, Straasø B, Larsen ER. A 2-year follow-up study of patients participating in our transcranial pulsating electromagnetic fields augmentation in treatment-resistant depression. Acta Neuropsychiatry 27(2): 119-25.  2015.

Patents:

Dissing et al., A method and an apparatus for stimulating/modulating biochemical processes using pulsed electromagnetic fields. US 6, 561,968 B1, WO 01/15774 A2

S. Dissing and M. Undèn. Apparatus and method for Pulsed Electrical Field Treatment. US 2012/0101327 A1

Contact:
Professor Steen Dissing, e-mail: sdissing@sund.ku.dk; Phone: +45 35 32 75 70