Introduction
Depression is a common mental disorder that affects over 280 million people worldwide. Although depression can usually be controlled using therapy and medications, there is a considerable minority who suffer from a more severe form called major depressive disorder (MDD), many of whom are less responsive to available treatments.1,2
This was the case for Sarah, a 36 year-old from Northern California, whose story has been widely reported and may come to be seen as a milestone in psychiatric treatment. Over a 5-year period, Sarah had spent months in hospital beds, taken around 20 different medications and tried various electroconvulsive therapies (ECTs), which involved her being anaesthetised and supplied with muscle relaxants and electrical pulses, usually to the front cortex of the brain, via external electrodes. Clinical trials have shown that ECT works in some patients, but it has a bad reputation in the popular imagination, perhaps because it is associated with enforced treatment, like in the 1975 psychological drama, One Flew Over the Cuckoo’s Nest.3
In Sarah’s case, ECT proved ineffective: “I was at the end of the line”, she has since recalled. “I was severely depressed. I could not see myself continuing if this was all I’d be able to do, if I could never move beyond this. It was not a life worth living.”4
A few months later, Sarah’s depressive symptoms had rapidly improved and her score on the standard depression scale had dropped from 33 to 10, which is considered remission.2 Since the treatment, Sarah has said that her suicidal thoughts disappeared and she is now “seeing things that are beautiful in the world”, whereas before all she “could see was what was ugly”.5 So what brought about this drastic change in Sarah’s mental wellbeing?
Deep Brain Stimulation (DBS) Therapy
A group of researchers from the University of California, San Francisco (UCSF) were able to implant a small ‘matchbox’ sized device in Sarah’s brain, which is able to recognise when her depressive thoughts are about to arise. Then, acting almost like a pacemaker for the brain, the device interrupts and relieves the depressive symptoms by sending short, electrical signals to the regions of the brain that are affected.2,3,4
This technique is known as deep brain stimulation (DBS) and is by no means a novel discovery. For over 30 years, DBS has been used to treat various neurological and psychiatric disorders such as Parkinson’s disease, obsessive compulsive disorder and epilepsy, and although it is not a cure, it is widely accepted to relieve symptoms and allow a reduction in medication.6,7,8
In the early 2000s, researchers began experimenting whether DBS could be used as a treatment for MDD. Some clinical trials suggested strong benefits, but others showed that DBS was no more effective than placebo, so the approach never passed regulatory approval.9,10 The limited success in some trials is likely because the DBS was applied using an open-loop approach. This can be thought of as a general ‘one-size-fits-all’ approach where fixed electrical stimulations are delivered to the same area of the brain and for the same length of time. However, large-scale neuroimaging studies have revealed that one person’s depression looks very different from another person’s and different areas of the brain are affected.11 This means a more targeted approach is likely required for MDD.
The Personalised Journey
To create a device that was personalised for Sarah, researchers at UCSF first conducted a 10-day assessment of her brain. Different areas of her brain were connected to temporary electrodes and subjected to electrical signals of varying strength. Depending on the location and strength of the signal, Sarah felt a range of sensations: some joyous moments, where she would spontaneously laugh out loud, whereas other experiences were so awful they reminded her of nails scratching along a black board. This 10-day exploration allowed researchers to map a specific pattern of electrical activity in Sarah’s brain that was associated with the onset of depressive feelings.2,5
The team then tested the activity and the effects of stimulating different areas of Sarah’s brain. For example, they discovered that stimulating the right ventral capsule/ventral striatum – a region that is thought to play a key role in reward processing and motivation12 – resulted in a consistent and sustained improvement of symptoms. They were also able to detect that a particular activity state in the amygdala was associated with higher symptom severity, which suggests this could be a valuable biomarker for symptoms in MDD.2
Equipped with this information, the team implanted their customised DBS device in the two predetermined locations in the right hemisphere of her brain. Unlike the earlier open-loop studies, Sarah’s device followed a ‘closed-loop’ approach meaning it was programmed to deliver a short, 6s pulse at 1mA whenever symptoms arose – a stimulation strong enough to alleviate her depressive symptoms whilst also ensuring she did not feel any physical sensations. In order to prevent any disturbances to Sarah’s everyday lifestyle the team capped the device to 30 minutes of stimulation per day and programmed it to switch off at 6pm as stimulations after that often kept her awake.2,3
“The device has kept my depression at bay,” Sarah has since said, “allowing me to return to my best self and rebuild a life worth living.”5
Conclusion
There were limitations to the investigation into this treatment for Sarah. Due to the nature of the therapy it was difficult – and in some instances not possible – to ensure that Sarah and the doctors were blinded to when the treatment was being administered. Also, while the approach worked for Sarah, this may not be the case for everyone – or even most people – suffering from MDD. There is more research still to be done.2
For the long term, it is difficult to assess the implications of Sarah’s treatment. For example, researchers are unsure for how long the device will function and whether it may permanently alter the brain’s circuitry altogether so that therapy is no longer needed.4
Closed-loop DBS therapy for MDD is in its early stages of development, and it’s important to appreciate that Sarah still takes psychiatric medications and her depression has by no means disappeared. However, it is a huge improvement that she has said allows her to keep her negative, emotional thoughts at a distance.4 If closed-loop DBS could help even a proportion of the people suffering from MDD that would be a great success. For example, there is some uncertainty over the efficacy of Cognitive Behavioural Therapy (CBT) – a standard treatment for people suffering with depression – in treating MDD13 and some patients, such as Sarah, do not find it an effective treatment. However, once Sarah’s device was implanted, she said she noticed CBT beginning to make a difference to her life.3
In terms of developing this treatment for more patients with MDD, there remain significant obstacles. It is important to remember that the popular, negative perception of ECT persists and, while this DBS technology has been developed for the clinical benefit of patients, the ability to manipulate a person’s emotions could be considered a rather Orwellian idea. Furthermore, Closed-loop DBS therapy is expensive and there are risks associated with the brain surgery required to implant the device. For these reasons, it’s going to be years before individualised brain stimulation approaches are considered for approval by regulatory agencies. Regardless, it is certainly an approach with potentially far reaching possibilities for treating depression and other psychiatric illnesses.
How Can TVF Help?
Communicating the science surrounding psychiatric disorders in a clear and impartial way is critical to promote the overall health and wellbeing of our community. The negative public attitudes surrounding psychiatric disorders, as well as other disease and therapy areas are improving but there is still work to be done. At TVF, we aim to improve public knowledge and understanding of disease and therapy areas by developing clear disease awareness campaigns, multimedia strategies and top tier publications. Get in touch today if you’re interested in any of our services!
By Martin Todd
