Editor’s Note: One of my favorite shows right now is CBS Sunday Morning with Jane Pauley. They do such a great job at presenting interesting topics in a meaningful way. When I saw the spot about the promising treatments for depression, I thought of dad (eshrink) and knew it would be a great topic for eshrink’s blog. This post is a wealth of information on depression and Eshrink FINALLY weighs in on the TV program that prompted me to have him write it (that’s a little sarcasm that you’ll get when you read his blog) That’s just how we roll 🙂 Here is link to the spot that aired. SAINT: Hope for new treatment of depression – CBS

CHASING DEPRESSION
My slave driving editor who sometimes masquerades as a loving daughter has directed me to write a critique of a Jane Pauley TV show that featured information about a newly discovered treatment for depression. Maggie’s interest comes naturally since she had worked in my office as a receptionist when she was in high school, and her interest was undoubtedly enhanced by the presence of depression in our own family. There is no doubt that what we call Clinical Depression is a very common disabling and often fatal disease. Unfortunately, the word depression is also used for less serious mood deviations which often leads to a lot of misunderstanding. It is estimated that over 1 million people worldwide commit suicide each year and no ethnic group or race is immune from its paralyzing grip. Nearly all these victims are suffering from depression.

In 2017 there were 9.6 million people receiving treatment for depression, never mind the millions who were not treated. According to data from the 2017 National Survey on Drug Use and Health, 17.3 million adults in the United States—equaling 7.1% of all adults in the country—had experienced a major depressive episode in the past year.

There is said to be an alarming increase in suicide rates in the United States over the past decade however; such stats must be viewed with caution for in the past, coroners, who in order to spare family members the stigma of mental illness, would often rule suicides as accidental or from natural causes. Unfortunately, the stigma persists although there has been considerable progress towards classifying depression, the major cause of suicide, as a medical illness.

DEPRESSION of the AGES

It seems as if depression has always been endemic in human populations. There are multiple Biblical references offering solace to the despondent, and fables from even older times suggestive of unwarranted sadness. Perhaps the high level of consciousness afforded us by our massively complex brains has in some way contributed to our vulnerability. Throughout history, there have been endless speculation and theories put forth as to the cause of depression including: moral failure, demon possession, witchcraft, sinfulness, masturbation, or sexual deviancy to name a few. Most of these theories blame the victim, which further contributes to the self-loathing that typically accompanies the disease. To this day there are those well-meaning souls who unwittingly aggravate the depression of the one they are trying to help. In my practice, I had some patients with a strong spiritual orientation who become depressed,  sought help from their pastor who diagnosed the problem as lack of faith, and suggested they pray harder.

The COMPLEXITY of DEPRESSION

In medicine, as with most things, transparency minimizes speculation. There is little doubt in my mind that an understanding of the causes of mental illnesses would go a long way towards eliminating the stigma associated with psychiatric illnesses. There is also the maxim in medicine that prevention is preferable to treatment of a disease. It is my belief that since it comes in many different shapes and sizes, depression is not a single entity, but more likely a cluster of illnesses producing similar symptoms, much as we see the symptom of fever in many different types of infections. Depression also takes different forms as for example, some patients suffer from severe insomnia while others find escape from the horrible feelings of hopelessness by sleeping for days.

Although depression often occurs spontaneously, it can also be precipitated by extreme stress or loss. For example, grief presents with symptoms indistinguishable from depression. Seasonal affective disorder with its recurrent depressive episodes appears to be related to disturbance of circadian rhythms, and one could make a case for it having resulted from the migration of humans to temperate zones a few hundred thousand years ago. As a matter of fact, depression frequently accompanies a variety of mental health syndromes, not the least of which is bipolar illness in which a manic episode is frequently followed by extreme depression. There is even a separate category of bipolar illness where those afflicted only cycle to depression and don’t experience manic episodes.

A Little Shrink History

It has been my good fortune to have been involved in the shrink business during a time in which there has been more discoveries leading toward an unraveling of the mysteries of the mind than have happened since the beginning of time. For centuries a cure for what was called “the black dog” by the Roman poet Horace and later repeated by Churchill occupied the greatest minds to no avail. Hippocrates was the first to identify the brain as the major control center of the body. The pseudo-science of phrenology became popular in the 19th century, which was the idea that one could diagnose problems, estimate intelligence and diagnose personality types by measuring the size of the bumps on their skull. Although it was soon discredited, its proponent, Franz Gall, is credited for advancing the idea that there is localization of brain function. He identified 27 different areas of the skull which he said controlled different functions.

In the early 1900’s along comes a Viennese neurologist who would influence thinking about the entire field of psychiatry and psychology for a half century. Freud’s focus on sexuality, in a Victorian society in which even uttering the word sex itself was considered in bad taste, gained him much world-wide attention. He developed a form of treatment both lengthy and intensive which he called psychoanalysis. Even now that many of his theories have been discredited, many terms which he introduced have become part of our every-day lexicon.

The Pharma Era

Fast forward a half century and I was in medical school witnessing miraculous advances in medicine almost daily. Following Fleming’s accidental discovery of penicillin there had been a rush to develop antibiotics that might be effective in treating organisms refractory to penicillin. Among those was isoniazid which had proven to be effective in the treatment of tuberculosis. In those days total bed rest was required as essentially the only treatment for TB consequently; patients who were confined to continuously stay in bed for months at a time often became depressed. However, following the use of isoniazid, moods of patients in TB wards often brightened, they became more verbal, less angry, and even happy. This led to investigation of similar compounds and the first group of antidepressant compounds called Monamine oxidase inhibitors (MAOs) were developed. These drugs were effective for some, but not for all patients. They also required great care in their administration as they interacted with many other drugs and there were severe dietary restrictions.

Depression and Pharma

1956 was my junior year in medical school and it was a banner year for the pharmaceutical industry. It marked the development of broad-spectrum antibiotics, i.e., those effective against penicillin resistant organisms. Thorazine, the first drug to ever prove effective in the treatment of schizophrenia was introduced. Within a year more than 70% of patients in psychiatric hospitals in the US were discharged, and there would be no more barbaric lobotomies performed. A group of antidepressants called Tricyclics whose side effects were less onerous than with MAOs came on the market at the same time. The response to these antidepressants, even though understanding of their mode of action was largely theoretical, led to the development of what came to be called the catecholamine hypothesis of depression. It theorized that the symptoms of depression were due to defects in the transmission of chemicals called neurotransmitters which were necessary to transmit electrical impulses between nerve fibers.

No Silver Bullet

Despite all these treatment, relief from depression was still elusive for many patients. Electroencephalography had been around for nearly 20 years, and it had become more sophisticated and especially valuable in the treatment of seizure disorders. Before Freud, there was a guy named Bleuler who wrote a widely quoted book on schizophrenia. As a matter of fact, he is credited with coining the term. He noted that he had never seen schizophrenia and epilepsy coexist therefore concluded that seizures must protect against schizophrenia. With that in mind several people set out to induce seizures as a treatment for schizophrenia by giving drugs known to cause grand mal seizures. The problem was that response to the drugs was unpredictable and the mortality rate was too high even in a non-litigious time. They also noted that although seizures did not have any effect on schizophrenia except for those in a catatonic state, it did seem to be remarkably effective for those who were depressed.

In the 1930s Italians Cerletti and Bini found they could induce seizures by passing an electric current through the brain. This method allowed for better control, and proved to be remarkably effective in cases of severe depression. Electroconvulsive Therapy or ECT as it is called, was widely used throughout the world and I saw firsthand how effective it could be to treating depression that was resistant to drug therapy. It got a bad rap due to the type of complications that could accompany it, such as broken bones, and the movie ONE FLEW OVER THE CUCKOO’S NEST. Additionally, ECT was sometimes used in cases where it was not indicated, yet were we in the shoes of those guys would we not be willing to try it if it were our only tool? Recent developments of anesthetics and muscle relaxants have made it much safer and better tolerated, but it is still mostly reserved for antidepressant resistant cases, yet there are some cases of depression that don’t even respond to ECT, which has been designated the last line of defense.

My Experience with the NEXT SILVER BULLET to TREAT DEPRESSION

After years of research, primarily investigating the neurotransmitters, norepinephrine and dopamine, researchers had become interested in another neurotransmitter, serotonin, which eventually led to the breakthrough development of Prozac in 1987. I vividly recall the first person for whom I prescribed Prozac. He was a very depressed young man in his mid-20s who had been an outstanding athlete and valedictorian of his high school. Unfortunately, he had become severely depressed, and developed a disabling social phobia. He rarely left the home where he lived with his parents, except to keep his appointments, and requested to be allowed to come in via the back door of my office in order to avoid occupants of the waiting room. I had been seeing him for some time, but my efforts were to no avail. On this particular day, a drug rep had left a sample of this new drug called Prozac which had just been approved for general use, and I thought “What the hell, I ‘ll give it a shot!” Two weeks later, David (not his real name) bounced into the waiting room and with a broad smile announced to the receptionist that he had arrived. Indeed, he had. He was proud to inform me that he had just come from a theatre where he had enjoyed the first movie he had seen in several years. My first thought was, “Could I have misdiagnosed this problem, and this guy is actually bipolar?” but he continued to improve and said: “I have finally got my life back”. The last time I saw him he was a sophomore studying engineering at Ohio State University.

Needless to say, David sold me on Prozac. It proved to have a remarkably good side effect profile other than for occasional sexual dysfunction which most people thought was a small price to pay for relief from the horrors of clinical depression. There would follow, as always is the case, a number of other “me too” drugs all of which came under the heading of SSRI’s (selective serotonin reuptake inhibitors), and after prolonged usage would sometimes lose their effectiveness a phenomenon called Prozac poop out, but in my opinion they have remained heads above other treatments. Unfortunately, the SSRIs as with other antidepressants are only effective about 70% of the time, and psychiatrists are often forced to make use of the trial and error method of finding an effective medication.

Seeing is Believing

Other than the unraveling of the human genome, nothing has impressed me more that the development of scans. They always remind me of the STAR TREK physician Bones who could diagnose and simultaneously treat any problem by putting people in his scanner. I am in awe of those engineering types who figure out all this stuff. The Curie’s invention of the x-ray was monumental, but the enhancement of that technology with computers to produce a cross section view was over the top. It was called Computerized Axial Tomography (CAT or CT scan) and provided a much more detailed look at the brain. In addition to hundreds of other medical uses, it was a valuable tool for brain research and a straight forward way to eliminate brain tumors and other brain diseases which often mimic psychiatric syndromes, a problem that had bedeviled psychiatrists forever. It was not long (the late 70s) when along came the PET scan with which one could actually visualize brain function. Even more fascinating and incredulous to me was the MRI which use a powerful magnet to actually turn protons on end to produce an image from the energy given off when they return to their normal position. They produced amazingly detailed pictures especially useful to orthopedists.

MAGNETISM

There has long been interest dating back 200 years or so on the effects of magnetism on the human body. In 1989, after studies suggested that magnetic energy could be effective in the treatment of depression, the FDA approved TMS (trans-magnetic stimulation) as a treatment. It was a very benign procedure that involved placing a 2-pronged electrical coil which produced a weak magnetic field on the patient’s head. The procedure was simple, painless and without side effects, and could easily be performed in a doctor’s office. Analysis of effectiveness of treatments for depression are difficult due to the placebo effect, but double-blind studies (clinical trials in which some administrations are real, others shams, and neither the patient or the physician is aware of which treatment is real) demonstrated effectiveness in some patients, but not all. In general, responses were not seen as very robust, and it was used mostly as an adjunctive therapy along with antidepressants.

This paper is in no way meant to provide comprehensive review of past and presently available treatments of depression, but believe me they are numerous and sometimes bizarre. In the November 13, 2021 issue of PSYCHIATRIC NEWS, Charles Nemeroff MD, PH.D in his review of treatments for depression, notes there are currently 26 medications approved by the FDA for the treatment of depression and another 12 in the pipeline. There is one study published in the May 2020 American Journal of Psychiatry regarding the use of psychedelics like LSD and psilocybin in the treatment of depression. Who’d a thunk it? In addition to the many types of psychotherapy, there also are always a plethora of non-medical procedures touted to be effective. Lest I get carried away and in deference to my editor who is by now tearing out fists full of that beautiful red hair as she screams “When in the hell is he going to talk about the spot on the TV show?” I will proceed to offer my humble thoughts.

SAINT

After watching the Jane Pauley show about the Stanford Accelerated Intelligent Neuromodulation Therapy or SAINT (thank God for acronyms), I found the original publication that described their novel treatment of depression to be in the August 2020 issue of The American Journal of Psychiatry which I had discarded long ago. Since I am a lifetime member of the American Psychiatric association, I continue to be automatically subscribed, but I must confess that since my retirement eight years ago, I tend to scan rather than peruse journals in much detail. Frankly, because the rapid changes in the field with its increasingly complex technologies have left me often wondering what they are talking about. Nevertheless, the Stanford U website reported an astonishing 87% recovery rate in the treatment with this new procedure named SAINT. Even more impressive, was the fact that these patients had all failed on other conventional treatments. Dr. Nemeroff mentioned in his review that the effectiveness of SAINT had recently been confirmed by a double-blind study which lent even more credibility to the reports of its effectiveness.

SAINT: What it is

The procedure involved is a much more complex, powerful and targeted version of the TMS mentioned previously. The researchers (Dr. Cole et al) were able to direct a burst of very powerful magnetic energy to the dorso-lateral prefrontal cortex (you must look that up in an anatomy book if you plan to do this at home) of the brain for 5 minutes per hour for 10 hours daily times 5. They are convinced that their success is dependent on their ability to target that particular area of the brain which has long been suspected of playing a prominent role in mood regulation. The patients and their families who were interviewed on TV were absolutely euphoric in their endorsement of the treatments. They used the phrase “game changer” and one was convinced this procedure would change the world, and I guess it has changed her world. I agree that this treatment holds promise, but think changing the world may be a bit over the top.

CAUTION: With Experience Comes Pragmatic Skepticism

Members of my illustrious family have accused me of being pessimistic by nature, while I insist that I am simply a realist, and much too naïve to be a bona fide pessimist. In spite of this alleged cynicism, Maggie has asked me to share my opinion of this SAINT thing, and I do find it promising however; all those years practicing medicine have taught me that although all people are the same, they are also all different, or as Grandma used to say: “One size doesn’t fit everybody.” Time after time I have found the initial exhilaration associated with ground breaking discoveries in medicine are later tempered by experience. I do feel this may well be a large step towards conquering this dreadful disease.

Nothing that I have written here should be construed to mean that I believe pills or procedures alone are the answer to the problems of mankind. At best I feel that medications or other somatic treatments enhance the therapeutic benefit of human intervention. Pills are important, but so is the hand that dispenses them. I have been heartened by a trend towards more balance in the nature versus nurture debate which has persisted for generations, for in recent years neurochemistry has dominated the psychiatric literature. Those of you who have read some of my other blogs probably know that I have strong feelings about that subject. Again, one size doesn’t fit everybody, but the more tools (based on scientific research) that psychiatrists have to treat the black dog of depression, the better off the world will be. The brain is a wondrously complex organ and the acceleration of knowledge is promising indeed.