Finding a break in the clouds
New therapies, including a modernized approach to electroconvulsive therapy, offer hope for treatment-resistant depression
By Claire Kowalick
For some people struggling with their mental health, available treatments can be ineffective, effective for only a short time or cause insufferable side effects. About 30% of people with depression are treatment resistant, meaning they have tried two or more medications or therapies and are still experiencing significant symptoms.
Melissa Martinez, MD, professor of psychiatry and behavioral sciences at the Joe R. and Teresa Lozano Long School of Medicine, specializes in treatment-resistant major depressive disorders, bipolar disorder and schizoaffective disorders. She also sees patients at UT Health San Antonio’s Behavioral Health and Wellness Center.
“By the time they get to me, I am going to add something with a completely different mechanism of action and treat the condition from a different angle. The hope is that the new treatment added will work synergistically with other treatments, like different branches of the military fighting together, to attack the illness and win the battle against suffering.”
Now within her treatment arsenal are three interventional methods that are safe, fast-acting and highly effective for people diagnosed with treatment-resistant depression. Along with conventional talk therapy and medications, two new interventional psychiatry methods are available at the center, as well as one long-standing treatment with a history of success that is being revisited with a modern approach.
Intranasal esketamine
Ketamine, a compound of the anesthetic and recreational drug phencyclidine, was originally used as an anesthetic that produced less delirium than phencyclidine. An intranasal spray containing esketamine, sold under the brand name SPRAVATO and used for the treatment of depression, was approved by the Food and Drug Administration in 2019.
The drug works by blocking the N-methyl-D-aspartate (NMDA) receptor, which is different from how most antidepressants work, as they usually block the reuptake of serotonin and norepinephrine. The drug decreases symptoms of depression in 60% to 70% of individuals and provides complete remission for up to half of people.
Another plus is that it does all this much faster than other treatments. Regularly available antidepressant medications can take eight to 12 weeks to begin working, whereas esketamine users can begin to see relief in as little as 24 hours after their first treatment.
For treatment, patients come to the clinic where they self-administer a dose of nasal spray under the watch of a health provider. They remain under observation for a couple of hours and then must be driven home.
Martinez said that as soon as she saw this treatment was FDA-approved in March 2019, she sent a message to her department chair about making it available at the center. UT Health San Antonio became one of the first locations in the community to offer intranasal esketamine.
“You can see people who have not responded to other treatments respond to this very quickly. They feel a ‘break in the clouds,’” Martinez said.
The treatment is also approved for people with suicidal thoughts, and Martinez said she has patients experiencing relief on this front. She notes that success for mental health treatment can vary greatly from person to person. For one person, progress might mean experiencing suicidal thoughts only a couple times a week instead of daily. For another person, success means getting out of bed and going to work or taking care of their family.
Because esketamine treatment is new, the center continues to monitor how long each person needs treatment and at what dose. Some patients come in, complete the protocol and discharge from the program, said Martinez. For others, a maintenance protocol is needed where the person returns every four to six weeks.
“We continue to use esketamine with caution, as we are still trying to figure out where it lies in the treatment algorithm and how it is best used,” Martinez said.
For patients receiving maintenance esketamine, Martinez works with them to try to decrease treatment frequency by suggesting other approaches such as exercise, a change in medications or more intense therapy to avoid the possibility of esketamine dependency.
Transcranial magnetic stimulation
During repetitive transcranial magnetic stimulation (TMS), an individual lies on a table while a TMS device is strategically placed near their head. TMS is believed to work for depression by stimulating the lateral prefrontal cortex, which is thought to be underactive in people with depression. Martinez describes the sensation for most people as a tapping that is perhaps annoying, but not painful. Treatment takes about 20-30 minutes daily for about a month. The treatment does not affect a person’s ability to drive, so a patient can leave directly afterward.
“People come every day, but it is only for 30 minutes. They could come over their lunch break or before work. The key is the repetition — that they come every day to get that area of the brain firing,” Martinez said.
TMS is a drug-free treatment, so it will not interfere with medications a person is taking. After a full protocol, about 60% of people see some positive response from TMS, and 30% to 40% have full remission of their depression.
Electroconvulsive therapy (ECT)
The image of patients strapped to a table, fitted with electrodes on their temples and delivered painful, high-voltage shocks is what many people imagine when they think about electroconvulsive therapy (ECT). This image, however, is a thing of the distant past, as modernized, evidence-based approaches to ECT are implemented with highly efficacious results.
“It has been around for 100 years, and it has a historically negative association with it. However, things have changed over the years, and new techniques minimize cognitive side effects,” Martinez said.
ECT involves the introduction of a controlled electric current to the individual’s brain. According to Martinez, one of the reasons ECT has been around for so long is that it is highly effective, with 80% of people reporting some response and up to 50% of people going into full remission from their depressive condition.
The updated program of treatment used at UT Health San Antonio uses ultra-brief bursts of electric charge and a unilateral stimulation approach rather than the historical bilateral approach to minimize side effects like confusion and short-term memory loss. The procedure itself takes about 30 minutes, including preparation before the procedure and waking up afterward.
“[Patients] do not feel like they are checking into a psychiatric hospital. They do not feel stigmatized. They check in with all the other patients and they are in and out within a few hours,” Martinez said.
Treatments are spaced apart two times a week for approximately six weeks to minimize side effects.
Patients recommended for ECT have depression that has failed to respond to multiple antidepressants, usually four or more kinds. Of the three treatments, Martinez said ECT has the highest response and remission rate and is extremely safe.
Choosing the right treatment for a person suffering with major depression comes down to a decision between that person and their health care provider, said Martinez. Of these three treatments, Martinez said her patients are more likely to choose intranasal esketamine or transcranial magnetic stimulation due to lingering fears surrounding ECT. But as education improves about the modernized approach, more people are considering ECT among these innovative approaches to mental health treatment.
