New innovations in mood disorders herald 'the edge of the future'

TORONTO — The latest innovations in mood disorder treatment will focus on addressing these conditions at every level by harnessing emerging pharmacological treatments, new devices, patient resources and therapeutic apps, according to a presentation at the American Psychiatric Association Annual Meeting.

“We have a lot of new opportunities, new treatments, and cutting edge, evidence-based apps,” said Andrew A. Nierenberg, MD, director of the Bipolar Clinic and Research Program and associate director of the Depression Clinical and Research Program at Massachusetts General Hospital.

Predictive analytics

One significant development on the horizon is predictive analytics, Nierenberg said. Through this futuristic-sounding concept, sophisticated techniques could be used to predict a mood episode in a patient before it occurs.

“When people come to us in distress, they aren’t at the very edge or beginning of a mood episode, they are deep into it; they have distress that provokes them to seek help,” he said. “Once they are well past the middle of it, that is when we tend to intervene. But there is now an enormous amount of data that we can harness in very sophisticated ways from smartphones by using a combination of GPS accelerometers, texts, and something called voice physics.”

Voice physics, he explained, is a means of assessing a patient’s psychiatric state not through what they are saying, but through an analysis of their vocal patterns.

“It’s actually the mathematics of the oscillating nature of the biological signal of the voice,” Nierenberg said. “There are very sophisticated analytics that can be used for that, and companies that have been formed to do this.”

He discussed an important book on this topic, Social Physics by Alex Pentland, PhD, Toshiba Professor at Massachusetts Institute of Technology, which discusses the mathematics of human interaction. A company founded by Pentland, Cogito Health, recently received an NIMH grant to evaluate these concepts in approximately 1,000 patients.

“This study will track very objective changes that have nothing to do with anything the patient reports, before someone actually gets into a mood episode,” Nierenberg said.

This could be particularly valuable, given that the current method of analyzing patients with mood disorders relies upon patient self-observation, recall and self-report.

“These are all problems of people with mood disorders,” Nierenberg said. “So, when we ask a patient how they’ve been over the past week, we’re really getting a window into the past 3 to 6 hours. What these predictive analyses allow is real-time data on what’s happening with patients, and that’s exciting.”

Big data

As is the case with many medical specialties and subspecialties, psychiatry and mood disorder treatment will become increasingly focused on harnessing big data. Nierenberg said there are many programs currently being developed with that goal in mind. Patient communities, patient/practitioner collaborative networks and patient support websites and apps are only a few of the resources now underway. He discussed patient communities such as Patients Like Me and emotional health networks such as Big White Wall, which connect patient communities. Additionally, there is the Patient Centered Outcomes Research Institute, which is part of the Affordable Care Act, and its associated patient resource, the Patient Centered Outcomes Research Network.

“This is quite remarkable — I think it is a game-changer,” Nierenberg said. “It is a patient-powered research network, and it allows patients to choose how they want to be monitored through self-report.”

Nierenberg said the goal of the network, which is now live, is to transform the lives of people with mood disorders by a collaboration, to be able to conduct prospective comparative effectiveness research and to serve as an infrastructure for researchers and clinicians.
“We want to be able to collect clinically useful data, not only from patient-reported outcomes, but also by integrating electronic health networks,” he said.

The network, which aims to bring together at least 50,000 patients, has support from the National Alliance on Mental Illness, the International Bipolar Foundation and other organizations.

Nierenberg cited some other emerging therapeutic apps and websites, including Pacifica, MoodGym, and Now Matters Now, a web site offering help to patients experiencing suicidal thoughts.

“It’s really an extraordinary web site, and helps people deal acutely when they are having suicidal thoughts,” Nierenberg said of Now Matters Now. “Most people who have suicidal thoughts don’t have them when they’re in your office. These are just a few of the really cutting-edge apps and web sites that we are going to see only grow over time.”

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Emerging treatments

While Nierenberg briefly cited the latest antidepressants approved by the FDA, such as Fetzima (levomilnacipran, Forest Labs Inc.), Viibryd (vilazodone, Forest Labs Inc.) and Brintellix (vortioxetine, Takeda Pharmaceuticals),he also noted one area in which very little progress has been made.

“There have been no specific treatments for bipolar disorder that have been released since lithium,” he said. “Every other medication was originally developed for another reason and repurposed.”

Nierenberg discussed the increasing use of glutamatergic drugs such as ketamine and riluzole for mood disorders, despite these drugs being potentially, “not ready for prime time.”

“What’s fascinating, sociologically, is the rise of ketamine in the absence of actual data that it can work in the real world or over time,” Nierenberg said. “There are ketamine clinics that are springing up all over the place, and we need to be careful about that.”

At the cutting edge of mood disorder treatments are novel therapies such as transcranial magnetic stimulation. This treatment uses near infrared light, which passes through the skull. This therapy, which is being investigated for traumatic brain injury, is now also being investigated for mood disorders, Nierenberg said.

“Its mechanism is to stabilize mitochondria by stimulating them,” he said. “When the photon passes through the skull, it stimulates cytochrome C oxidase through the mitochondria, and that increases energy production and also protects neurons.”

Low-frequency magnetic stimulation is another innovation that is being investigated.

“This technology was discovered when a tech noticed that people coming out of an fMRI machine said they felt a little bit better,” he said.

This approach utilizes peroxisome proliferator-activated receptors (PPARs), which act as a switch that essentially regulates DNA in a neuroprotective manner.

“PPARs basically sit on the nucleus and turn the DNA on or off,” he said. “And there is an associated protein, called PGC-1 alpha, which activates PPARs.”

PPAR agonists called thiazolidinediones are currently used to treat the metabolic syndrome. The thiazolidinedione Actos (pioglitazone, Takeda) is being investigated for use in major depressive disorder and bipolar disorder, he said.

“There is the first proof-of-concept for pioglitazone for bipolar depression” Nierenberg said. “This is one of the technologies which are really amazing and on the cutting edge.” – by Jennifer Byrne

Reference:

Nierenberg AA. Advances in research in mood disorders: new opportunities, new treatments. Presented at: American Psychiatric Association Annual Meeting; May 16-20, 2015; Toronto.

Disclosure: Nierenberg reports consultancy with the following: Abbott Laboratories, AstraZeneca, Basilea, Brain Cells Inc., Bristol-Myers Squibb, Cephalon, Clintara, Corcept, Eli Lilly and Co., Forest, Genaissance, Genentech, GlaxoSmithKline, Innapharma, Janssen Pharmaceutica, Jazz Pharmaceuticals, Lundbeck, Medavante, Merck, Naurex, Novartis, PamLabs, PGx Health, Pfizer, Roche, Sepracor, Schering-Plough, Shire, Somerset, Sunovion, Takeda, and Targacept and Teva. He is a stockholder in Appliance Computing, Brain Cells Inc. and Medavante. He reports grant support from AFSP, AHRQ, BBRF, Bristol-Myers Squibb, Cederroth, Cyberonics, Forest Pharmaceuticals, GlaxoSmithKline Janssen Pharmaceutica, Lichtwer Pharma, Eli Lilly, NARSAD, NIMH, PCORI, Pfizer, Shire, Stanley Foundation, Takeda, and Wyeth-Ayerst. He reports receiving honoraria from the MGH Psychiatry Academy in the past 3 years, and prior to 3 years ago from Bristol Myers Squibb, Cyberonics, Forest Pharmaceuticals, GlaxoSmithKline, Eli Lilly, Shire, and Wyeth-Ayerst.