Speech given November 22, 2014 at FirstHealth Hospice and Palliative Care Campus, Campus Walk for Suicide Awareness

Edward N. Squire, Jr MD, MPH

Board Member, National Alliance on Mental Illness of Moore County

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Good Afternoon!  It is nice to be here.  I need to thank Tera Duthie [Grief Counselor and Group Leader for the Coping and Adjusting to Suicide Loss Group (CASL), and organizer of today’s Campus Walk for Suicide Awareness]; who invited NAMI-Moore County’s representation. (I happen to know one of Tera’s CASL-Group members; she has described her as being wonderfully supportive, interactive, creative, and instructive; with respect to the last, she uses her experience to advantage; as  there have been several suicides within her own family.)

This is not the first time I have been to the FirstHealth Hospice and Palliative Care Center. In  2012, the Center gave my  mother wonderful care while extending support to other members of my family.

Before beginning, I would like to tell you a story.  It really has nothing to do with what I am going to say; other than, it took place this past week just outside the Chapel where we are now.  I am calling this story the “Cold Tree Frog on the Sidewalk.”

The Cold Tree Frog on the Sidewalk

As Tera and I were walking to the Chapel, she noticed what turned out to be an Eastern Gray Tree Frog (Hyla versicolor). It took a  surprising, one-foot hop when touched.  Closer inspection revealed the characteristic, bright  orange patches on the groin and upper legs.  I grew quickly curious as to where this frog-species would normally spend the winter, and what it was doing out  in the cold weather.  (The temperature was about 40 degrees.)

I later learned; that tree frogs can tolerate periods of subfreezing temperatures as well as being partially frozen. Two mechanisms allow them to do this. The first is that they form glycerol, a material chemically related to anti-freeze; it keeps their blood from freezing. The second is that they pump extra glucose into their cells and thereby prevent their cells from freezing.  Thus in sub-freezing weather, tree frog-bodies can withstand being partially frozen as well as a freezing thawing cycle.  They spend the winter buried beneath logs, roots, or dead vegetation.  I found this information so fascinating, that  I wanted to share it with you.

Today, I want to tell you two other stories.  The first has to do with the suicide of my nephew, William Mark Squire, whose picture appears below.  The other story has to do with an intravenous, anesthetic drug known as ketamine, which is increasingly being used as an antidepressant.

It’s ironic, but exactly 4 years ago today, I received the call from my brother Mark telling me that his son Will, who had a serious mental illness, had taken his own life the previous evening on September 21, 2010.

“ . .  Will, who had a serious mental illness, had taken his own life the previous evening  . .”

In remembering Will afterwards, one incident stands out in my mind.  I was traveling to visit with his family in Colorado Springs, but found myself arriving late.

In fact, it was very late, close to 4:00 AM in the morning, but who should be awake to greet me?  Will, who was excited to see his Uncle Ed; I found this an action an endearing one. Furthermore, I could  identify with Will’s plight because I have a serious mental illness myself also. For me, Will’s illness was a source of continuing sadness.

Nationally, about 1% of the population (2.2 million people) lose a loved one to suicide each year, and with each suicide, about 6 to 8 friends and / or relatives are affected.

WILL SQUIRE’S SUICIDE AND THE FOUNDING OF “WILL’S HOPE”

Reflections on a Nephews’ Suicide

“Nationally, about 1% of the population (2.2 million people) lose a loved one to suicide each year, and with each suicide, about 6 to 8 friends and / or relatives are affected.”

(Will’s Hope is the name of the non-profit, organization that my brother Mark, and sister-in-law, Sarah formed in the aftermath of Will’s death.)

Mark and Sarah’s Psychological Journey –> Destination Will’s Hope

Mark and Sarah had to traverse two, major emotional milestones.  First, they had the immediate challenge of managing their shock and sorrow; second, they had to deal with guilt, an emotion that refused to go away, even as they sought to establish Will’s Hope, but Mark and Sarah were driven by Will’s vision, which they adopted and expanded.

“Mark and Sarah were driven by Will’s vision, which they adopted and expanded.”

Will had the ability to recognize and understand the plight of others who were similarly disabled by mental illness.  He felt that they likely experienced the same suffering, the same lack of understanding, the same prejudice, and the same discrimination as he did.  He found his own feelings painful,  and he could not help but be cognizant about the feelings of others also.

“Will’s compassion was evident throughout his youth . . . ”

Will’s  compassion was evident throughout his youth and took on many forms.  He would become an advocate who directed his parents’ attention to others in need.  He would ask his Mom while she was driving, to make a U-turn to help someone who appeared to be in need on the opposite side of the road.  In addition, he would  urge them to provide money for others he saw as needy. He was the McDonalds employee who went out of his way to wait cheerfully on customers whom he saw as disabled.  It was as if he was tacitly saying, “I understand you, you’re like me.”

Following Will’s death, and after three years of work by Mark and Sarah, the IRS officially approved Will’s Hope as a non-profit, tax exempt, 501 c organization.

By way of further background, Mark and Sarah had often observed how much more at ease Will was during family activities outdoors.  He seemed more at peace with himself in natural settings than in almost any other place.  Knowing how much Will would have wanted to share these benefits with others; Mark and Sarah set out to create a program that would provide a similar “self-enabling and self-discovery” experience in a natural setting.

They wanted activities that would create a sense of accomplishment for mentally disabled participants, young men or women,  ranging in age from 16 to 30.  They wanted participant- activities to instill self-confidence and  a more positive outlook on life. Most if not all, had had  little or no previous experience in a national park setting; in addition they would be performing activities unlike anything they had ever performed previously.

Yellowstone National Park

Mark and Sarah therefore channeled their altruism and their interest in nature into setting up a program in Yellowstone National Park.  Using their knowledge of Yellowstone and contacts there, they planned a diverse program that was rich in outdoor experiences.

“Mark and Sarah planned a diverse program that was rich in outdoor experiences.”

On any one day, participants might view: large mammals, such as grizzly bear and moose; see birds of prey, such as a Bald  Eagle or Osprey; see geological formations, thermal features such as geysers; learn about Native American culture by building a tepee / lodge and meeting with  a Native American crow-family. They also learned how to cast with a fly rod, catch trout, and clean them. They didn’t need to learn how to eat them.  As they hiked and explored Yellowstone, they found many curious objects, such as a bison skull.

What Yellowstone provided these  participants with,  was a supportive atmosphere and unparalleled opportunities to derive insight from their unique experience. Indeed, they had round-the-clock exposure to one of the most beautiful and interesting places on the face of the earth.

With support and empathy from Mark, Sarah, the Yellowstone Association, Native Americans, and others, these young adults (There were six last year.) were awake and together for close to 16 hours per day and for nine to ten days.. These figures translate into close to 140 total hours of Program-activity. (A support group meeting for 90 minutes on a weekly basis would have to meet for close to two years–or about 90 weeks–to achieve the same number of contact hours.)

Will’s Hope is an experience, calculated to change participants’ outlook on life. Small wonder then, as was the case with Will, that these young men (Could be women also.) experienced relief from the stress at home and in their communities, and  the chronic distress that went with it. Moreover, relief of stress and distress with absorbing Program-activity, could be expected to improve their mental health, and with that improvement, allow them realize that  their lives could actually be more fulfilling. Mark and Sarah have referred to this process as “empowerment by hope!”

“Mark and Sarah have referred to this process as empowerment by hope!”

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I would now like to move onto the second part of this presentation, which is the story of an old drug, being used in a new way. The drug is the intravenous anesthetic known as ketamine and its new additional use is for depression.

DEPRESSION AND HOPE FOR A BETTER DRUG

Ketamine first came onto the market in 1962 as an intravenous anesthetic; one that works in 30 seconds and has a half-life of 10 to 15 minutes.  It began to be used for depression about 10 years ago.  I first learned about its use for depression, when I read reports about its use in emergency departments among acutely suicidal patients.  I could not forget what I learned.  Ketamine worked fast, and its effects were dramatic!

“I could not forget what I learned.  Ketamine worked fast, and its effects were dramatic!”

However, as is the case with any medication, ketamine, when prescribed for depression, has  risks and benefits,  pros and cons,  advantages and disadvantages.  The issue with ketamine is two-fold; it not only represents a cause for caution, it also represent a cause for hope.

Ketamine: a Cause for Caution

Why is there a cause for caution?  First, it is not licensed for bipolar or major depression.  It is being used “off-label” and experimentally, though legally because physicians have the prerogative of using medications for unlicensed indications, even if the FDA has not licensed their being marketed an unapproved indication; such is the case with ketamine’s use as an antidepressant.

Like any other drug, ketamine has risks and side effects–of greatest concern are those that affect the central nervous system.  These side effects include disturbing out-of-body experiences, hallucinations, confusion, and agitation.

To obtain ketamine, you cannot simply see a psychiatrist to obtain a prescription, but if you go to the Internet under “Ketamine Advocacy Network,” you will find at least 17 providers and clinics around the country.

Below is the information about one of these clinics; this one is run by an anesthesiologist, Dr. Mark Murphy whose group includes a clinical psychologist.  (In actuality, more clinics are run by psychiatrists than anesthesiologists.) At Dr. Murphy’s Clinic, the cost for a single, intravenous infusion of ketamine is about $500.

Depression Recovery Centers
Doctor: Dr. Mark Murphy, MD
Address: 14362 N Frank Lloyd Wright Blvd, Scottsdale, AZ 85260
Specialty: Anesthesiology
Treatment type: IV infusion
Phone: 480-788-5536

Some psychiatrists have reservations about the use of ketamine for either bipolar or major depression.  Their objections include the fact that depression is too complex for any, one-drug therapy;  (It need not be used alone.) that ketamine is not a “miracle drug” and that it isn’t “ready for prime time.”  Moreover in the treatment of depression, psychotherapy may be critical to optimize the benefits of psychopharmacology.

At least one psychiatrist, concerned with patient-safety, advises interested patients to volunteer for a clinical ketamine-trial, rather than going to a ketamine clinic.  Other psychiatrists may say that given the long record of accomplishment with ECT (electroconvulsive therapy); they would recommend that ECT be tried prior to the use of ketamine.

Ketamine:  a Causes for Hope

My Limitations in Evaluating this Medication

I am not an anesthesiologist or a psychiatrist; I have no personal experience with ketamine.

My knowledge comes entirely from the medical literature and the Internet.  However, I do have experience in reading medical publications for scientific merit and clinical relevance.

In my view, on April 14, 2014, the journal Therapeutic Advances in Psychopharmacology published the most informative article to date related to ketamine’s use for bipolar or unipolar depression. Therapeutic Advances in Psychopharmacology is a peer-reviewed journal; manuscripts submitted for publication must pass the scrutiny of an editorial staff and two expert reviewers before a manuscript is accepted for publication.

“In my view, on April 14, 2014, the journal Therapeutic Advances in Psychopharmacology published the most informative article to date, related to ketamine’s use for bipolar and unipolar depression.”

I will refer to this study as the Caddy-study, because Dr. Caroline Caddy was the first of its four authors.  The Caddy-study assembled data on 629 patients  who had been included in 26 other highly reliable reports of patients treated with ketamine.

The response rate among these 629 patients was about 75%; three out of four, treated with ketamine, benefited from this treatment, but there is much more to this study than this single statistic.  All of these patients had been depressed for decades, and the duration of the current episodes of their illnesses ranged from 15 to 260 months.

Proof of Outcome

The Caddy-study reviewed how its component studies proved that ketamine had an antidepressant effect.  The outcome measures, included for example, the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale,  the Beck Depression Inventory; all were accepted methods for detecting changes i.e. improvement or worsening of depression.

Response Rate

“ . . .  nearly three out of four treatment-resistant patients responded.

Among theses 26 studies, 16 included only treatment resistant patients; thus nearly three out of four treatment-resistant patients responded.  Moreover, these patients did not similarly obtain improvement, about one-half also obtained complete, symptomatic-remissions, many after having been sick for decades.  Add to that, the fact that even among patients without improvement in other depressive, symptoms; most, nonetheless had relief from their suicidal ideation.

“ . . .about one-half also obtained complete symptomatic-remissions. . .”

“ . . . among patients without improvement in other depressive, symptoms, most, nonetheless had relief from their suicidal ideation.”

Lower and Safer Dosage

A word about side effects—the anesthetic dose of ketamine is 2 to 8 times larger than the dosage used for depression; thereby making its latter use safer with there being fewer and milder side effects.  Typical ketamine-side effects, at the dose for depression (0.5 mg / kg) included drowsiness, a dream-like state, mental detachment, and mental fuzziness.

A few patients hallucinated. These symptoms would be treated first  by slowing the infusion rate, and if needed, by using intravenous Valium (diazepam).  An ultra-short acting barbiturate would be used for the few patients who did not respond to the first two measures.

Onset of Action—within Four Hours

As previously thought, ketamine’s onset of action is within 1 hour for some patients, within 2 hours for others, and virtually all by four hours.  There has been no dispute that the onset of action occurs this rapidly.

I would like to move on from “Causes for Caution” and “Causes for Hope” in order to  speculate about ketamine’s future as an antidepressant.

What the Future May Hold for Ketamine as an Antidepressant

I would like to look to the future next, and to try to predict what may happen in the next 5 years, and the next 15 years.  Please bear in mind that these predictions are strictly my opinion and may easily be wrong.  Furthermore, physicians more knowledgeable than I may well regard these predictions as premature, presumptuous, naïve, even foolish. However, Thomas Insel MD, Director of the National Institute of Mental Health has himself said, “Recent data suggest that ketamine, given intravenously, might be the most important breakthrough in antidepressant treatment in decades.”

Projected Events within the Next Five Years

  • The existing practice of giving off-label, intravenous ketamine will cost less:
  • There will be economies of scale as clinic-sizes increase and clinic chains develop.
  • Competition will increase: between clinics and between clinics directed by psychiatrists and by anesthesiologists.
  • Ketamine will be administered more often by the intramuscular route.
  • The existing practice of giving off-label ketamine by intravenous infusion will prove effective for two out of 3 patients who respond initially, but one out of three of these  patients will become resistant and relapse.
  • The nasal formulation Esketamine currently being tested by Janssen Pharmaceutica and on a fast track through the FDA, will be licensed and insurance companies will begin to cover this treatment.  Besides fast tracking it, the FDA has also designated it as “breakthrough therapy,” a rare classification for a psychotropic medication. With the licensure of Esketamine, clinics giving ketamine intravenously will begin to close.

Projected Events within the Next Fifteen Years

  • Ketamine, or ketamine-like drugs, will become the drug of choice for suicidal depression.
  • Oral formulations (One is now being used in the United Kingdom.) will be licensed by the FDA. Clinics that have administered intravenous ketamine will, by now, have closed.
  • Clinical trials for Naurex’s GLYX-13 and NRX-1074 plus Cerecor’s CERC-301 will have been completed with FDA decisions on licensure pending
  • Ketamine will prove to be as effective as ECT (electroconvulsive treatment), and without impairment of patients’ memories, but the combination of ECT and ketamine will prove disappointing as no additional benefit develops over either one used alone.

That completes my list of predictions; I would like to move on to conclude this presentation by focusing upon four examples of hope.  Two are related to the stories about Will and Will’s Hope, a third is related to my own hopes, and a fourth relates to the hopes that you have brought here with you today.

CONCLUSIONS

The Hope That Will Had

In his lifetime, Will’s disabilities prevented him from fulfilling any aspirations that he might have had for social, academic, or occupational success.  Nonetheless, Will demonstrated great compassion for others as he reached out to those with mental disabilities.  In so doing, he hoped to relieve their suffering and leave them feeling better about themselves.

Will’s actions inspired Mark and Sarah.  After Will’s death, they chose to reclaim the hope that Will had had for himself.  They believed that given the resources, Will would have done far more for others.  Mark and Sarah thus took it upon themselves to see that Will’s vision was extended.  They did so by creating an organization known as Will’s Hope, which represented a melding of Will’s desires and their own ambition to do more for those with disabilities like his. This commitment gave life to Will’s Hope.  Will would be extremely proud of what his parents have accomplished through the non-profit company that bears his name.

“Will would be extremely proud of what his parents have accomplished through the non-profit company that bears his name.”

The Hope that “Will’s Hope” Has

“Will’s Hope” is an embodiment of the hopes that Will had.  It aims to extend to other disabled young adults,  the experiences with nature that were of such comfort to Will; experiences that gave him an abiding peace; a sense of accomplishment and a respite from the ubiquitous stresses and struggles elsewhere in his life.

Will’s Hope thus aims to create a warm and supportive environment in the beauty and majesty of Yellowstone Park.  It aims to serve disabled young persons, men, or women, and to inspire them, to develop a similar sense of purpose, peace, accomplishment, and self-confidence–in short, to empower them with hope!

In this regard, the goal is  to raise their expectations for  having fulfilling lives as they return to their respective homes and communities.  That is the Hope that Will’s Hope has!

My Own Hopes for the Future

I have four sets of hopes:  The first is that Mark and Sarah’s grief will continue to heal and that  remaining anniversary reactions will subside.  Second, I hope that Will’s Hope will have as much impact upon the lives of its participants as Mark and Sarah could ever hope.  Accordingly I hope that the young adults who participate, will find their experience the most memorable, the most meaningful, and the most influential experience of their lives; even as they continue to struggle with their respective disabilities.

Second, I would like to see all of my ketamine-related predictions come true earlier than projected so that old codgers like me will see some of this progress.  I would love to hear that the FDA has approved Esketamine; thus making a highly effective, intranasal formulation of ketamine widely available and one that is covered by health insurance. Fourth, with the advent of Esketamine’s use, I would like to see cases such as Will’s truly drop dramatically and see the annual suicide-incidence of 30,000 deaths plummet precipitously.

“I would like to see an explosion of new knowledge about the neurobiology of depression.”

Fourth and last, I would like to see an explosion of new knowledge about the neurobiology of depression.  I think it is almost inevitable that knowledge of how ketamine works will lead to a more fundamental understanding of the nature of depression.  I would like to see that knowledge quickly translated into better treatment measures, but I would also like to see this knowledge hold some promise for preventative actions; much as new vaccines hold promise for prevention of infectious diseases.

Your Hopes

You have come here with your own hopes, and I would like to believe that some of them are to be realized today in a significant way.  I would like to think that you found some meaning in this presentation.  It has been my privilege and pleasure speaking with you.  I thank you for your attendance and your attention. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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