It’s an exciting time in the field of mental health, with new treatments emerging and promising research underway, UT Southwestern psychiatrists told those gathered at the recent 2019 Carolyn P. Horchow Women’s Health Symposium.

Dr. Andrew Czysz

Just this March, the Food and Drug Administration approved a new drug for treatment-resistant depression that relies on a completely new approach and is capable of creating results within days – even hours in some patients – said Dr. Andrew Czysz, a fourth-year psychiatry resident and one of the Symposium presenters. The drug, esketamine, is administered as a nasal spray in conjunction with an oral antidepressant.

The drug is generating excitement for its quick impact and all-new approach. Unlike many existing antidepressants that work on the neurotransmitters serotonin, norepinephrine, or dopamine to treat chemical imbalances in the brain, esketamine affects a different brain chemical called glutamate, Dr. Czysz said. It’s a completely new mechanism.

Dr. Mary “Molly” Camp

Depression is highly treatable and is becoming more so with such new treatment options, added Dr. Mary “Molly” Camp, Assistant Professor of Psychiatry, who co-presented with Dr. Czysz. In a landmark study done at UT Southwestern and elsewhere and reported in the American Journal of Psychiatry in 2006, 67 percent of the adult outpatients treated during the study for major depression achieved remission. In the study, patients moved through up to four progressively more intense treatment options as they tried to attain remission. In the first stage, patients received only a single antidepressant, and about a third of the patients responded at this stage. But if that did not work, the initial medication might be changed and either a second antidepressant or cognitive therapy was added to the treatment mix.

Sometimes, Dr. Camp said, success takes time and a succession of medications. But more than 30 kinds of antidepressants are now on the market, and other treatment options include psychotherapy, transcranial magnetic stimulation (which uses magnets to create electrical currents in the brain), and electroconvulsive therapy, she said.

Psychotherapy doesn’t mean just hours spent talking to a psychiatrist; it is intended to be transformative, Dr. Camp said. Functional MRI images show it actually changes brain activity.

Electroconvulsive therapy, formerly known as electroshock therapy, is “extremely safe” and one of, if not the most, effective treatments for treatment-resistant depression, she added.

Another treatment still in the research stage is magnetic seizure therapy. In this treatment, a patient undergoes controlled seizures similar to those in electroconvulsive therapy, but perhaps with fewer side effects, Dr. Czysz said. There’s something we don’t quite understand that’s very therapeutic about a controlled seizure in people with mood disorders. Some people liken it to rebooting the brain.

In addition to such medical interventions, those suffering from depression can use exercise to improve their mood, Dr. Camp said.

Inflammation could be one reason stress affects the brain, Dr. Czysz said. Chronic stress can lead to inflammation and changes in immune function, in turn associated with major psychiatric disorders, he said. “Exercise really is one of the best anti-inflammatories out there,” he noted.

Studies are underway to tailor treatment for depression based on a patient’s level of an inflammation biomarker, C-reactive protein, Dr. Czysz added. Early results using the information to choose the right antidepressant have been promising.

Part of what makes people more susceptible to depression is genetic; those born with a short variation of the serotonin transporter gene can be at increased risk, he said. But, Dr. Czysz told attendees, this effect is only seen in those who have also experienced maltreatment.

If you had no maltreatment, this particular gene that you had didn’t matter, he said. According to the research, It was only the individuals who had experienced maltreatment and had the short version of the gene that had this dramatically increased risk of developing depression.

Given that early life events can have a profound impact on mental illness later in life, UT  Southwestern is involved in two longitudinal depression studies that researchers hope to continue for 10 years. One examines biologic factors that impact whether someone with depression gets better or worse; the other involves studying what factors lead to depression or resilience in adolescents.

In responding to a question about the growing movement to legalize marijuana, Dr. Czysz pointed out that marijuana use has been associated with schizophrenia, especially in users under the age of 25.

Dr. Camp was also cautious about CBD oil, a nonintoxicating marijuana derivative often used as a sleep aid. The over-the-counter and mail-order medication is not regulated, she told the audience, adding: You don’t really know what’s in there. Some users have sometimes found the intoxicant THC in it, she said.