Treating severe depression with on-demand brain stimulation

Physicians have successfully treated a patient with severe depression by tapping into the specific brain circuit involved in depressive brain patterns and resetting them using the equivalent of a pacemaker for the brain.

University of California – San Francisco

The research, which will be published in Nature Medicine on October 4, 2021, marks a major milestone in the decades-long quest to apply neuroscience discoveries to the treatment of mental health issues. Andrew Krystal, PhD, professor of psychiatry and part of the UCSF Weill Institute for Neurosciences, said the research paves the way to a new paradigm that is urgently required in psychiatry. To treat our patient’s treatment-resistant depression, we used precision medicine to identify and modulate the brain circuit responsible for her particular set of symptoms. Because most devices only provide continuous electrical stimulation to a single region of the brain, previous studies have shown little effectiveness treating depression using conventional deep brain stimulation (DBS). The fact that sadness affects various parts of the brain in different individuals is a significant problem for the profession.

Because of the identification of a neural biomarker — a particular pattern in brain activity that signals the beginning of symptoms — and the team’s ability to tailor a novel DBS device to only react when it detects that pattern, this proof-of-principle experiment was a success. A separate part of the brain circuit is then stimulated by the device, providing a treatment that is specific to the patient’s brain as well as the neural circuit that is causing her disease. In contrast to conventional therapy methods, which may take four to eight weeks to relieve the patient’s depressive symptoms, Krystal claims that her personalized technique had effect almost immediately and has lasted for 15 months after she had the implanted device. This outcome may be life-changing for individuals with long-standing depression who have failed to respond to previous treatments.

The patient, who requested to be identified only by her first name, Sarah, stated, “I was at the end of the line.” “I was in a deep state of depression. In the event that this is all I’m capable of, I don’t see the point in continuing. It was a pointless existence.” It was President Obama’s BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies) that paved the way for this UCSF study in 2014. Dr. Edward Chang of the University of California, San Francisco (UCSF) and colleagues used that initiative to study sadness and anxiety in patients with epilepsy receiving surgical treatment, who are also prone to mental health issues including bipolar disorder. They found electrical brain activity patterns that were associated with mood states and revealed novel brain areas that might be activated to alleviate depression. The Weill Institute’s Chang, Krystal, and first author Katherine Scangos, MD, PhD, utilized findings from prior research to create a method based on two hitherto unexplored stages in psychiatric research: mapping a patient’s depression circuit and defining her brain biomarker.

Chang, the Joan and Sanford Weill Chair of Neurological Surgery and a co-senior author on the article, stated, “This new study brings almost all of the important results from our prior research together into one comprehensive therapy targeted at relieving depression. Chang implanted a responsive neurostimulation device that he has successfully used to treat epilepsy in June 2020 as part of the team’s evaluation of the novel method under an FDA experimental device exemption. We were able to provide this patient with depression a tailored therapy, and it made a big difference in how she felt, according to Scangos.” “Prior to this, no one in psychiatry has been able to perform this sort of customized treatment.” A lead from the gadget was placed in Chang’s brain location where the researchers discovered a biomarker, and a lead from Sarah’s depression circuit was placed in the area where stimulation best alleviated her mood problems. To see whether the biomarker was being produced, one of the leads monitored activity continuously while the other was given a brief (1mA) burst of electricity for 6 seconds.

Researchers were able to recreate the proper brain circuit and biomarker using an implanted device during a later phase of the study, proving the therapy’s efficacy, according to Scangos. “This accomplishment represents a huge step forward in our understanding of how the brain malfunctions in mental disease.” It was “so sudden” in the first months that she didn’t know whether the reduction of melancholy would continue. “But it’s been around for a while. And now that I’m a patient at UCSF, I see how the gadget complements my treatment and self-care skills.” A new perspective has emerged on the emotional and illogical ideas that she used to be preoccupied with. These ideas sometimes pop into her head, she said, but “the cycle has stopped.”After enrolling two additional patients in the study, Scangos says there is still more work to do. He wants to recruit a total of nine more patients. “We must examine how patients’ circuits differ and carry out this research again. A person’s biomarker or brain circuit must be monitored throughout time while therapy is continued.” It’s too early to tell whether this technique will work, but the researchers stress that this is just the first patient in the study. There is still a long way to go before the FDA approves this therapy, but the research does hint to new avenues for treating severe depression. Identifying the brain circuits that underlie depression, according to Krystal, can help drive the development of non-invasive therapies that regulate those circuits in the future. A novel approach to treating depression’s most severe instances may be found in Scangos’ theory that treating symptoms as they occur may be a viable option for those suffering from the condition.

Reference : Scangos, K.W., Khambhati, A.N., Daly, P.M. et al. Closed-loop neuromodulation in an individual with treatment-resistant depressionNat Med, 2021 DOI: 10.1038/s41591-021-01480-w

Categories: Clinical