To date, The Jordan Elizabeth Harris Foundation has contributed $400,000 to vital research on depression and suicide. In 2014 we contributed $50,000 to a UT Southwestern study which, in part, explored the use of the drug Ketamine as a fast-acting antidepressant. So we were thrilled to learn in 2019 that the FDA approved an exciting new drug related to Ketamine, called Esketamine, for use in patients with treatment-resistant depression disorder.
We asked experienced Fort Worth psychiatrist and friend of The JEH Foundation Diana Ghelber, M.D. if she would help us understand how these drugs work and their specific use. Dr. Ghelber spoke on the subject as a featured guest at our Annual Luncheon back in 2017. Here she shares her fascinating background working in Israel with Holocaust survivors & trauma victims and tells us about her modern methods for fighting severe depression in her patients.
Dyar Bentz What’s your earliest memory of being interested in psychology or psychiatry?
Diana Ghelber, M.D. I am from Romania originally, and as a child I lived through the communist times. The communist party had banned many foreign and scientific books, and one day, when I was in middle school, my father came home and pulled from his bag a psychology book by Sigmund Freud which was most definitely illegal to possess then. I know that was an important moment for me which set me on a path of thinking about the brain and psychology and psychiatry.
It’s amazing he even got his hands on it! You had to buy many basic goods and necessities off the black market, and somehow he found this banned book as well. He thought it would interest me and my brother, and my brother is also a psychiatrist today, so definitely this was a formative event for both of us.
DB Wow! So, moving through time a bit, what was your early career path like?
DG After I finished medical school in Romania we emigrated to Israel. In Israel I did my first psychiatry training and became a certified psychiatrist. There I conducted a few studies for eating disorders and was involved in clinical work with the Ministry of Defense for families who lost loved ones to war or terrorist attacks. So I got quite a lot of experience in the area of PTSD and major depressive disorder. I also treated Holocaust survivors, as well as 2nd generation Holocaust survivors.
“First, no matter what, my job is to listen to people and validate their emotions.”
DG Truly traumatic. We are talking about patients who have lost children or spouses or parents in wars or terrorist attacks. What's interesting, looking retrospectively, the coping mechanism for each individual is entirely unique. There are people who lost one or more loved ones tragically, and they commemorate that person’s history by assisting other wounded or grieving people amidst or after a tragic event so they're not solely focused on their own loss and trauma. That reaction is not uncommon.
DB How do you even begin to treat someone who’s gone through that?
DG First, no matter what, my job is to listen to people and validate their emotions. I'm trying to help them find meaning in their life in order to be able to function again after. Often, parents who lose a child are so despondent in their loss that they forget about their remaining children, for example. If I needed to prescribe them medication then I would, but the main objective was to focus on their lifestyle and slowly getting them re-integrated into society amidst the struggle of accepting their loss.
DB What kind of special training is required to learn how to talk with trauma victims to this degree?
DG I didn't receive any specific training for these cases at the time. I think with my parents being Holocaust survivors, both my mother and my father, and living in a country with an extremely turbulent history, you inevitably become an autodidact, somehow you educate yourself.
DB And eventually you ended up here.
DG I arrived in the US in 2003, and in 2006 I started my 2nd round of residency in psychiatry, which I finished in 2010.
I focus on treatment-resistant depressive patients from all over the state.
Treatment-resistant depressive: patients for whom at least two different anti-depression medications failed to adequately treat the depression.
DG What is unique in my practice is that a majority of my patients I'm treating have been on multiple medications already without any success, sometimes 20 or 30 different medications over a long period. So when patients are essentially "at the end of their rope" so to say, with no success after many different medications, they come to see me.
It’s evident they likely won't respond well to most medications, so first we're attempting to identify what is blocking these medications from having the desired effect, be it a deficiency of some kind or a physical disorder. But on the other hand, because these patients are so severe, we have to also work on alternative strategies to combat their intense suicidal ideations immediately.
The two predominant treatments I’m working with currently are Transcranial Magnetic Stimulation therapy and Esketamine.
Dr. Ghelber’s friendly assistant demonstrating the standard positioning of the TMS equipment, towards the right side of the brain.
TRANSCRANIAL MAGNETIC STIMULATION
DG I decided to open my private practice just when Transcranial Magnetic Stimulation (TMS) was approved as a treatment option for major depressive disorder.
TMS is treating depression and is having some success with treatment-resistant depression even. With TMS, the positive change can be so rapid that sometimes we'll have patients who come in the morning in complete suicidal despair, and after a few sessions in a period of just a few hours, they leave the clinic unable to understand how they were ever considering suicide as an option in the first place.
DB How does it work? What’s the gist of it?
DG Basically, a targeted area of the brain is stimulated with an electromagnetic field. Imagine the brain as a strong battery, an electric circuit. When you have a magnet and an electric circuit, pulses from the magnet induce electric current in the circuit. So we're talking about millions of neuronal connections, a whole neuronal network, being stimulated.
DG With this treatment, neurons are sprouting and reconnecting in areas of the brain that have been literally exhausted by the depression, and so the simple explanation is that stimulating these areas revitalizes these 'exhausted' areas of neurons, and the end result is that people can think more clearly. They aren't as bogged down by foggy, pessimistic thinking. The idea of suicide as a means of coping now feels foreign to them, even though just a few hours ago they were unshaken in their determination that there was no other way out.
“Neuroplasticity” is the key word here. By stimulating these neurons, they reconnect and rewire, like when you reboot a computer.
Neuroplasticity: the ability of the brain to form and reorganize synaptic connections
DG Typically TMS is used over a period of four to eight weeks, with general improvement throughout, but it can also be used in a series of successive treatments over a few hours in cases of extreme suicidal risk, when you are afraid the patient may attempt to take their life before they even make it home from the clinic that day.
DB What does this TMS actually look like when being used?
DG (After a full physical and psychiatric evaluation to determine they are suitable candidates) Patients wear a helmet with a uniquely shaped magnet. Before we start the treatment we map out their cortex, taking measurements and figuring out the appropriate area to be stimulated. Once that’s honed in, the stimulation session can begin. A typical session is about 20 minutes.
There are generally no dramatic side effects. They are completely able to drive safely and return to their normal day and job after the treatment.
KETAMINE/ESKETAMINE
“Ketamine and Esketamine are similar but they’re not the same. Simply stated, they have the same molecular makeup but Esketamine is more potent than Ketamine. Both can be used to treat resistant depression...” -Psychology Today
DG I would say, in 2012 or 2013, I had a few patients who were very depressive and suicidal, and they tried many different medications to treat it with no success, and right around then there was a trial for the use of ketamine to treat major depressive disorder, so I opened a clinic in Fort Worth in order to carry out these trials here as well (the first to do so in the DFW area). We began performing trials of ketamine on major cases of treatment resistant depressive disorder, high suicide risk individuals.
DB What sets ketamine/esketamine apart from other antidepressants?
DG For some time now we have had a lot of antidepressants with a variety of mechanisms of action. What is common among all these traditional antidepressants is that they take about four to six weeks to take effect. And about thirty to forty percent who are treated with these antidepressants get no effect from them or suffer side effects too great to warrant their continued use.
We also have people who are extremely suicidal NOW and can't wait 4-6 weeks for the medication to kick in, so traditionally the only option was to send them to a psychiatric hospital.
So it's for these cases that Ketamine or Esketamine can come into practice. The biggest benefit of these compounds is that they are fast-acting. Within just a few hours of administering the compound, the patient can think much more clearly and logically, and make smarter, safer decisions. Some describe this as a thick cloud moving out from their brain.
The suicidal ideas no longer make sense, they seem like a foreign notion. It's not a sense of euphoria, it's a sense of relief.
Dr. Ghelber and some members of her team.
DB How would you address the common stigmas associated with Ketamine? It seems to be most commonly known as a “horse tranquilizer” or a party drug.
DG When I hear Ketamine talked about in these ways it really makes me laugh! This horse tranquilizer notion implies a hyper-strong sedative quality; I think most people would be surprised to learn that ketamine is an incredibly safe anesthetic used commonly in pediatric anesthesia. It was also incredibly common in the Vietnam War, where it was regularly carried by soldiers in the field, to be administered as a fast-acting safe anesthetic.
Yes, it can be a party drug. There are very many greatly beneficial drugs which can be transformed and abused for recreation, some of which do have a risk for addiction.
Ultimately, despite what many think today, ketamine is very safe when used in the right hands by the right people at the right dosage.
DB So the same drug can be used for two different effects? Do the anesthetic properties carry over when used as an antidepressant, and vice versa?
DG The mechanism of action of ketamine when fighting depression is different than when used for anesthesia. In anesthesia you give a high dose very rapidly to achieve the desired level of sedation. Whereas when used to treat depression, a patient receives a relatively much lower dose, administered over a slow, constant drip infusion. It takes about forty minutes or so. The pharmacological effect is altered due to this different form of administration and dosage.
And used at this appropriate, minimal dosage there is little to no risk at all of addiction or dependency formation.
“Most people would be surprised to learn that ketamine is an incredibly safe anesthetic used commonly in pediatric anesthesia.”
DB Well that’s all I have! Thank you so much for your work, for your time, and for so clearly elucidating these exciting new methods of treatment.
Earlier you mentioned encountering victims of trauma in Israel turning to helping others as a means of coping with their pain, that made me think of the Harris family and the work they do through this Foundation.
DG Yes, exactly. It really amazes me, the degree to which the Harris family bears the pain of their loss over the years for the good of society. It would be entirely justified for them to instead attempt to shut out the pain of that loss and leave it behind. I find their dedication and work very admirable.
Images, interview, and writing by Dyar Bentz
