Improving Suicide Risk Assessment

Flower Owl Butterfly 2I read an interesting short online article on suicide risk assessment in which an expert, Dr. Morton Silverman, MD, points out that we should change our focus from predicting suicide to preventing it [1]. This is from a presentation by Dr. Silverman at the 2015 U.S. Psychiatric and Mental Health Congress:

“We need to reconceptualize risk factors into enduring risk factors and dynamic risk factors. We need to reconceptualize risk status from a prediction model to a prevention model, and our argument is [that] we are not interested in predicting something, we are interested most in preventing someone from engaging in self-harm. I believe it is our duty and responsibility, not only to prevent it, but to come up with a treatment plan or approach that is in the patient’s best interest and will result in their not engaging in suicidal behavior,” Morton M. Silverman, MD, assistant clinical professor of psychiatry, University of Colorado School of Medicine, Denver, said during a presentation. 

Well said. I’m always looking for ways to improve my practice. Dr. Silverman clearly makes these points:

  1. We shouldn’t just ask the one screening question “Are you suicidal?” and drop the inquiry if the patient says “No.”
  2. We should inquire about suicidality with a timeline, asking not just about suicide ideation now but in the recent past as well.
  3. We are at risk for failing to look for the behavioral cues indicating someone might not be answering questions about suicidality honestly.
  4. We may assign less importance to so-called “passive” suicide ideation, believing that the risk for eventual suicide is lower than active suicide ideation–it isn’t.

Dr. Silverman went on to say, “We have to recognize that people die by suicide, even when they don’t express suicidal ideation. What are really missing in our field are good studies that look at the 30-day span of lifetime before someone kills themselves; [we need] to identify those risk factors that play an important part in making them vulnerable and leading them to engage in actual suicidal behaviors.”

That reminded me of of what I often notice is on the list of my most frequently viewed blog posts, the one about the Columbia Suicide Severity Rating Scale. I had a look at the link, Learn to Save a Life: Training in the C-SSRS (you might want to open this in a new window rather than a new tab if you’re using Google Chrome). The video at this link pretty much outlines the approach Dr. Silverman says is needed. It takes about 30 minutes to get through it and I think it’s worth your time. As a psychiatric consultant, I get requests to assess suicide risk nearly every day and even I learned something useful from this site. It would be worthwhile for anyone to view; and try the post test. It may surprise some to learn that a few non-psychiatric physicians don’t know what a suicide attempt is.

This is critically important and the emergency room (ED) is only one place where the skill of suicide risk assessment is vital. Our ED physicians are getting experience in doing these and other types of psychiatric assessments, even asking magistrates for emergency legal hold orders when necessary in order to ensure patients’ safety. While the Columbia Suicide Severity Rating Scale could be a useful tool for them (in fact, it can be used by non-medical personnel), the forms look like they could take too much time. However, as I’ve said in a previous blog post, you can use the C-SSRS as a cheat sheet as a reminder of the important questions to ask. ED physicians (and psychiatrists as well) can have trouble remembering to document their suicide risk assessments, according to a recent survey [2]. One of the authors of the study, Dr. Taras Reshetukha, MD, says:

“The only tools we have are actual skills in clinical assessment, the gold standard in assessing patient risk of suicidal behavior. The whole idea behind suicide risk assessment is not to predict suicide from happening [sic] but rather to appreciate the basis of suicidality done through eliciting important risk factors that would allow us to implement well informed intervention for a particular patient.”

So what does Dr. Reshetukha mean by “actual skills in clinical assessment” as the gold standard of suicide risk assessment? For now, in part, it means conducting a structured, evidence-based empathic inquiry guided by experience (as opposed to an interrogation using only a checkbox list) in paying attention in the moment to behavioral cues as well as verbal communication from the patient. I say “for now” because we probably don’t yet have enough reliable research evidence in blood tests and iPad apps to predict suicide risk–although I acknowledge the progress.

Should we be screening every patient in primary care? Probably not, based on the most current research. The Academy of Psychosomatic Medicine annotated abstract about this is below [3]:

“Screening for Suicide Risk in Adolescents, Adults, and Older Adults in Primary Care: U.S. Preventive Services Task Force Recommendation Statement

LeFevre ML: Ann Intern Med 2014; 160:719–726

The Finding: Although the United States Preventive Services Task Force recommended that primary care clinicians should remain attentive to screening patients in high-risk groups (such as immediately following dismissal from an emergency department visit for a suicidal act or following a psychiatric hospitalization), there was insufficient evidence of benefit to support routine screening for suicide risk in primary care. The American Academy of Family Physicians and the Canadian Task Force on Preventive Health Care reached similar conclusions. The United States Preventive Services Task Force continues to support screening for depression in primary care, provided such screening is coupled with adequate resources to ensure accurate diagnosis, treatment, and follow-up. However, the United States Preventive Services Task Force concluded that there was no clear evidence that screening for suicide risk in asymptomatic primary care patients yielded improved health outcomes.

Strengths and Weaknesses: Given that suicide was the 10th leading cause of death in the United States in 2010, this update of the 2004 United States Preventive Services Task Force recommendations is timely. Unfortunately, available studies for review were sparse, the accuracy of the screening instruments used varied widely, and no 2 studies used the same instrument.

Relevance: Recent emphases on patient safety and the recognition of the potential adverse effects of depression in select groups of medical and surgical patients have increased the attention given to suicide screening in and out of the hospital. Awareness of the paucity of evidence for benefit from routine screening for suicide risk in primary care patients may enable consultation psychiatrists to inform these efforts, such that the energy and work invested are directed toward high-risk individuals where intervention may favorably influence outcome.”

This is hardly the last word on suicide risk assessment. Here are a couple of other posts you might find interesting:

CPCP on suicide risk assessment  by Dr. Andrew Segraves

Look for ways to improve suicide risk assessment


  1. Hower, C. (2015) Expert calls for change in suicide assessment, formulation models. Healio Psychiatric Annals. Accessed on line September 15, 2015.
  2. Oldt, A. (2015) Important suicide risk factors may be missed in ED. Healio Psychiatric Annals. Accessed on line September 15, 2015.
  3. Freudenreich, O., et al. (2015). “Updates in Psychosomatic Medicine: 2014.” Psychosomatics 56(5): 445-459. BACKGROUND: The amount of literature published annually related to psychosomatic medicine is vast; this poses a challenge for practitioners to keep up-to-date in all but a small area of expertise. OBJECTIVES: To introduce how a group process using volunteer experts can be harnessed to provide clinicians with a manageable selection of important publications in psychosomatic medicine, organized by specialty area, for 2014. METHODS: We used quarterly annotated abstracts selected by experts from the Academy of Psychosomatic Medicine and the European Association of Psychosomatic Medicine in 15 subspecialties to create a list of important articles. RESULTS: In 2014, subspecialty experts selected 88 articles of interest for practitioners of psychosomatic medicine. For this review, 14 articles were chosen. CONCLUSIONS: A group process can be used to whittle down the vast literature in psychosomatic medicine and compile a list of important articles for individual practitioners. Such an approach is consistent with the idea of physicians as lifelong learners and educators.

Make Way for the Learners

never-stop-learning_designAll resident psychiatrists undergo periodic assessments of their patient interviewing and diagnostic skills called Clinical Skills Evaluations (CSEs) which allows experienced faculty to directly observe them conduct psychiatric evaluations of patients unknown to either the teacher or the learner. It’s a vital part of training the next generation of doctors, in whom I have great confidence.

Teachers listen to the residents elicit rapport and ask the patients key questions, but not just that. Following the interview, the trainee must present a summary of the information gleaned from the patient, along with a diagnostic formulation and treatment recommendations. The whole thing takes about an hour and the vast majority of trainees do a great job.

This form of evaluation started in response to the elimination of the live patient interview (as of 2012) as part of the live patient exam (Step 2) as part of the American Board of Psychiatry and Neurology (ABPN) certification examination because Step 2 was considered a poor as well as a very expensive test of a freshly minted psychiatrist’s interview skills.

As a colleague put it, “In the era of competencies—we need to prove our residents know how to do this.” And we need to prove this to the ABPN and the Accreditation Council for Graduate Medical Education (ACGME).

This includes suicide risk assessments, which so far do not include listening for the trainees recommending blood tests for suicide biomarkers. Neither have I listened for recommendations for ketamine to be used in the management of severe suicidality and depression.

Following my CSE session with one of the senior residents (a star performer), I thought about this after reading new articles about both interventions, one in an open access article in Molecular Psychiatry, which touted a combination of genomic blood tests and clinical risk assessments, the latter comprised of a couple of apps. The other was a sort of tongue-in-cheek article about ketamine, a paper written by Caroline Winter, who somehow managed to animate it with psychedelic special effects.

Caveats are in order. The biomarker study is hampered by small sample sizes and probably would overestimate acute suicidality, despite the authors’ admission that the risk factors discussed are relevant for prediction over a year’s time.

And one of the lead authors (A.B. Niculescu) is “listed as inventor on a patent application being filed by Indiana University.” Yet the “authors declare no conflict of interest.” I’m not sure what that means; maybe nothing.

Obvious criticisms and cautions regarding the Niculescu, et al paper help bring us back down to earth.

And I got a big kick out of Caroline Winter’s humorous treatment of the ketamine issue, which I think carries a healthy undercurrent of common sense though I’m all for looking under every rock for methods to prevent suffering and suicide.

By the way, the Urban Dictionary definition for “common sense” is “What I think you should know.”

I don’t think I’ll be requiring residents to be recommending the interventions in this sort of literature just yet on their CSEs.

But if they speculate about them during their presentations—I’ll probably give them credit for open-mindedness and creativity that often enough mark major paradigm-shifting innovations which can move humanity forward.

National Suicide Prevention Week: Suicide Risk Assessment

Since September is Suicide Prevention Month and next week will be National Suicide Prevention Week, I thought it would be timely to post a presentation about suicide risk assessment. Nearly every day in my role as a psychiatric consultant I’m asked to assess someone’s suicide risk, usually after the patient has been admitted following a suicide attempt. There are a lot of guidelines about conducting suicide risk assessments and this one barely touches the surface. I think the most important lesson I’ve learned after doing this for many years is to pay close attention to the person’s life story. In it, I usually find a lot more than risk factors and protective factors. If we’re lucky, we find a reason to hope.

Suicide touches almost all of us in the places we often keep secret. It can take a long time for the meaning of that story to surface, nearly a lifetime for some.

As always with this presentation shortcode thingy, you have to use the arrow keys to navigate each and every line on the slides. If you want to see the slideshow in full screen, click the 4 arrrow icon in the lower right hand corner. Hit ESC to exit full screen.

The link to a great article about suicide risk assessment doesn’t work in the WordPress Presentation Shortcode slide where it first appears (but works on the last slide with the references), so anyway, it’s here at[tt_news]=175062

This slideshow could not be started. Try refreshing the page or viewing it in another browser.

Can We Walk The Talk About Preventing Suicide?

I may have to rethink my resolve not to practice what I call the Walking Dead Meditation. I know I’ve made fun of it and, of course, the real name is the Walking Meditation. I learned about it in my Mindfulness-Based Stress Reduction (MBSR) class. It could be a great way to deepen my mindfulness practice given the often high stress level of my work.

In fact, I rediscovered what Jon Kabat-Zinn wrote about Walking Meditation in his book on mindfulness, “Full Catastrophe Living,” because I’m rereading my copy of it,  which I bought about 10 years ago and didn’t get much out of at the time [1]. In the book he describes it and admits that it looks pretty weird, suggesting that you practice it in private so people don’t get the wrong idea and suggest you seek psychiatric help.

Actually what I learned in class is that you can eventually learn to practice mindful walking without looking weird, although Kabat-Zinn also mentions a technique called Crazy Walk, which involves walking in random directions, even backwards, bumping into others, almost cartoon-like.

However, the general idea is that Walking Meditation is just another way to pay attention, although it’s not very much like simply going for a walk.

The reason this issue is arising is that, in my role as a general hospital psychiatric consultant, I do a great deal of walking all over our academic medical center, and it seems I’ve been walking to the intensive care units (ICUs) a lot more frequently over the last several years, sadly to assess suicide risk of patients who’ve ingested medications and other drugs in apparent suicide attempts.

It’s very painful. But the patients I see are alive to tell about their experience, giving me an opportunity to help them. My walks to the ICU can be accompanied by all sorts of speculations, questions, doubts, memories, and anxieties. A little mindfulness couldn’t hurt.

And pursuant to that, I just recently saw the news about reports suggesting a significant uptick in the occurrence rates of drug-related suicide attempts in the past few years, which tends to validate my clinical impression.

A related news report was relayed to me by colleagues, along with some other perspectives on suicide that led to important reflections. Can a blood test help predict suicide? I don’t know, but we’d all love to have something like it because of the suffering it causes to those who eventually commit suicide, and the devastating effect suicide has on all those who are left behind when someones takes his or her own life. If a blood test could predict suicidality with 80% accuracy, I would certainly welcome it [2].

However, there’s a fair amount of criticism of the test across the web, even suggesting that it’s not very good science. My colleagues here have conducted critically important research in this area. Between 1975-1991, they published 17 papers in major peer-reviewed journals. The results swing in different directions, sending hopes skyward one year and plummeting back to earth the next [3,4].

It made me wonder whether there is any way to predict suicide, as was concluded many years ago [5].

It also makes me wonder whether what’s being done with mindfulness research which could point the way out of the laboratory maze. In fact, there is some work indicating it might make sense to focus at least some energy on teaching people to care for themselves and influence the tendency to suicidality by teaching them to pay more non-judgemental attention to their bodies, thoughts, and emotions. It has risks, among them the possibility it could promote rumination, although there could also be considerable benefits as well [6,7].

Maybe we should be mindful of all of the resources we can bring to bear on the challenge of suicidality.


1. Kabat-Zinn, J. and University of Massachusetts Medical Center/Worcester. Stress Reduction Clinic. (1991). Full catastrophe living : using the wisdom of your body and mind to face stress, pain, and illness. New York, N.Y., Pub. by Dell Publishing, a division of Bantam Doubleday Dell Pub. Group.

2. Guintivano, J., et al. (2014). “Identification and Replication of a Combined Epigenetic and Genetic Biomarker Predicting Suicide and Suicidal Behaviors.” Am J Psychiatry.
Objective: Reliable identification of individuals at high risk for suicide is a priority for suicide prevention. This study was conducted to identify genes exhibiting epigenetic variation associated with suicide and suicidal behaviors. Method: Genome-wide DNA methylation profiling was employed separately on neuronal and glial nuclei in a discovery set of postmortem brains from the National Institute of Child Health and Human Development to identify associations with suicide. Pyrosequencing-based validation was conducted in prefrontal cortical tissue in cohorts from the Stanley Medical Research Institute and Harvard Brain Bank at McLean Hospital and peripheral blood from three living groups. Functional associations with gene expression, stress and anxiety, and salivary cortisol were assessed. Results: The DNA methylation scan identified an additive epigenetic and genetic association with suicide at rs7208505 within the 3′ untranslated region of the SKA2 gene independently in the three brain cohorts. This finding was replicated with suicidal ideation in blood from three live cohorts. SKA2 gene expression was significantly lower in suicide decedents and was associated with genetic and epigenetic variation of rs7208505, possibly mediated by interaction with an intronic microRNA, miR-301a. Analysis of salivary cortisol measurements suggested that SKA2 epigenetic and genetic variation may modulate cortisol suppression, consistent with its implicated role in glucocorticoid receptor transactivation. SKA2 significantly interacted with anxiety and stress to explain about 80% of suicidal behavior and progression from suicidal ideation to suicide attempt. Conclusions: These findings implicate SKA2 as a novel genetic and epigenetic target involved in the etiology of suicide and suicidal behaviors.

3. Coryell, W. and M. Schlesser (2001). “The dexamethasone suppression test and suicide prediction.” Am J Psychiatry 158(5): 748-753.
OBJECTIVE: Despite the substantial risks of eventual suicide associated with major depressive disorder, clinicians lack robust predictors with which to quantify these risks. This study compared the validity of demographic and historical risk factors with that of the dexamethasone suppression test (DST), a clinically practical measure of hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. METHOD: Seventy-eight inpatients with Research Diagnostic Criteria major depressive disorder or schizoaffective disorder, depressed type, entered a long-term follow-up study between 1978 and 1981, and, in addition, underwent a 1-mg DST. The number of suicides in this group during a 15-year follow-up period was determined, and the predictive validity of four demographic and historical risk factors reported in the literature to be consistently predictive of suicide in depressed patients was compared to the predictive validity of the DST results. RESULTS: Thirty-two of the 78 patients had abnormal DST results. Survival analyses showed that the estimated risk for eventual suicide in this group was 26.8%, compared to only 2.9% among patients who had normal DST results. None of the demographic and historical risk factors examined in the study significantly distinguished those who later committed suicide from those who did not. CONCLUSIONS: In efforts to predict and prevent suicidal behavior in patients with major depressive disorder, HPA-axis hyperactivity, as reflected in DST results, may provide a tool that is considerably more powerful than the clinical predictors currently in use. Research on the pathophysiology of suicidal behavior in major depressive disorder should emphasize the HPA axis and its interplay with the serotonin system.

4. Black, D. W., et al. (2002). “The relationship between DST results and suicidal behavior.” Ann Clin Psychiatry 14(2): 83-88.
The authors assessed the relationship between dexamethasone suppression test (DST) results and suicidal ideations and behavior. Four-hundred-twenty-three mood disorder patients admitted to a tertiary care medical center were administered the DST from 1978 to 1981. The patients were subsequently followed up to determine death status using a record-linkage method. More than 44% had abnormal cortisol suppression (nonsuppressors) at the index admission. Suppressors and nonsuppressors did not differ significantly with respect to frequency of suicidal ideations or completed suicides. Suppressors were significantly more likely than nonsuppressors to have a history of suicide attempts or to have a suicide attempt following hospital discharge. Using logistic regression, and controlling for several important variables including diagnosis, maximum postdexamethasone cortisol was not significantly associated with suicide, suicidal ideation, or suicide attempts. We conclude that an abnormal DST is not useful as a predictor of suicidal behavior.

5. Goldstein, R. B., et al. (1991). “The prediction of suicide: Sensitivity, specificity, and predictive value of a multivariate model applied to suicide among 1906 patients with affective disorders.” Archives of General Psychiatry 48(5): 418-422.
• Stepwise multiple logistic regression was utilized in an attempt to develop a statistical model that would predict suicide in a group of 1906 lowans with affective disorders admitted to a tertiary care hospital. The risk factors identified by this approach included the number of prior suicide attempts, suicidal ideation on admission, bipolar affective disorder (manic or mixed type), gender, outcome at discharge, and unipolar depressive disorder in individuals with a family history of mania. However, the model failed to identify any of the patients who committed suicide. The results appear to support the contention that, based on present knowledge, it is not possible to predict suicide, even among a high-risk group of inpatients.

6. Mark, J., et al. (2004). “The Use of Mindfulness-Based Approaches for Suicidal Patients.” Archives of Suicide Research 8(4): 315-329.
7. Williams, J. M. G., et al. (2006). “Mindfulness-Based cognitive therapy for prevention of recurrence of suicidal behavior.” Journal of Clinical Psychology 62(2): 201-210.
Once suicidal thoughts have emerged as a feature of depression they are likely to be reactivated as part of a suicidal mode of mind whenever sad mood reappears. This article reviews the methods and the usefulness of mindfulness-based cognitive therapy (MBCT) as a treatment for the prevention of the reactivation of the suicidal mode. MBCT integrates mindfulness meditation practices and cognitive therapy techniques. It teaches participants to develop moment-by-moment awareness, approaching ongoing experience with an attitude of nonjudgment and acceptance. Participants are increasingly able to see their thoughts as mental events rather than facts (metacognitive awareness). A case example illustrates how mindfulness skills develop with MBCT and how they relate to the cognitive processes that fuel suicidal crises. An ongoing controlled trial will provide further evidence, but pilot work suggests that MBCT is a promising intervention for those who have experienced suicidal ideation in the past. © 2005 Wiley Periodicals, Inc. J Clin Psychol: In Session 62: 201–210, 2006.

Announcement: 14th Annual International Survivors of Suicide Day

This is a short announcement post about the American Foundation for Suicide Prevention’s 14th Annual International Survivors of Suicide Day, which will be on Saturday, November 17, 2012 at the Coralville Public Library , Meeting Room B in Coralville, Iowa on 401 5th Street. Admission is free and includes lunch.

For information or to pre-register, contact Keri Neblett at or call 319-351-2726 ext. 114. Walk-ins are welcome; pre-registering helps for planning.


9:45 AM-10:00 AM      Check in and registration

10:00 AM-10:15 AM     Welcome and Introduction

10:15 AM-11:30 AM       Guest Speaker (TBA)

11:30 AM-12:00 PM       Lunch

12:00 PM-1:30 PM         AFSP’s broadcast

1:30 PM-2:30 PM           Discussion of Broadcast

2:30 PM-2:45 PM           Closing ceremony

Parking is free in the underground parking garage.

Around the world, thousands of survivors gather together on this day for mutual support and practical guidance on coping with grief.

Working Together to Prevent Suicide Means Slowing to a Listening Pace

“(With people), if you want to save time, don’t be efficient. With people, slow is fast and fast is slow.”–Stephen Covey during a seminar in Bangkok in 2004, A Key Insight That I Got From Stephen Covey | The Care Guys

A recent item in AMA MorningRounds caught my eye about suicide prevention and it’s been in the print news a lot, I gather. The Obama administration is emphasizing a focus on preventing suicides, especially in the military and even Facebook is involved, partnering with the National Suicide Prevention Lifeline. Important links to check out:

Feds create new strategy to fight suicide – The Chart – Blogs

It reminds me of what I do every day, which is suicide risk assessment. Too often I’m trying to assess suicide risk in the aftermath of a suicide attempt. At least they’re alive. Frequently I’m asked to assess suicide risk in persons referred from med-surg clinics. A psychiatric consultation service is an extremely busy enterprise and moving fast often gets to be automatic–except when it comes to suicide risk. It’s hard to trust someone who seems in a hurry. I slow down for this, and try to find a chair to sit down with the patient and go over what’s happening in their lives, listen to pain, eschew the dropping of diagnostic labels, get a sense of the context of their suffering, and help them work on a safety plan:


There’s no quick way to listen to someone’s suffering and pain. Slow is fast, and fast is slow.



When Slow is Better than Fast

Fast food, gobbled down, makes you bloated, full and fat.
But food savored slowly with friends is comforting and nourishing.

Money spent too quickly is wasteful.
Saving for something helps you reach your dreams.

Scribbled handwriting can be hard for even the writer to decipher
But calligraphy has grace and clarity.

Fast snickering is mean.
But slow deep chuckles are kind.
(Massage therapist Laura says, “lymph loves laughter”).

Distorted voices talk fast (trying to sell you death)
Careful questioning slows them to a halt.

Self-destructive impulses come on in a rush
Slowly sensing and  knowing you are loved
By all that is God and all that is Good
Protects body, mind and soul.

Fast, sloppy exercise can lead to injury;
Slow, deliberate Tai Chi postures bring peace and balance.–Margalea Warner, part of her comment in Prozac Monologues, Prozac Monologues: Seventeen Keys to Recovery

Depression can lead to suicide and it’s one of the most common psychiatric disorders associated with suicide. Persons suffering psychosis, from disorders like schizophrenia or drug abuse, can hear voices “selling death.” Psychiatrists can help with these, although preventing suicide is a community effort. We all need to work together.

Nasal Spray, the New Suicide Prevention Tool?

Here’s one to wonder about. CNN posted a story about Thyrotropin Releasing Hormone (TRH) being an effective antisuicide agent (Can nasal spray help prevent military suicides? – This Just In – Blogs). The gist is that the U.S. Military is reaching for every conceivably feasible solution to stem the rising rate of suicides in the Army. There were 38 confirmed or suspected suicides in July and there’s no end in sight. The Army has recently given a research grant to Indiana University of Medicine Associate Professor of Neurobiology Dr. Michael Kubek to study whether a nasal spray could be a safe and effective way to deliver TRH to the brain to “help calm suicidal thoughts.” According to the article, Dr. Kubek helped discover TRH. I don’t know if that’s true or not. I’m not a neurobiologist nor a historian of neurobiological research nor a huge fan of Wikipedia (though I did add a couple of external links for the American Delirium Society (ADS) and the European Delirium Association (EDA) to the pretty good entry for delirium,  Delirium – Wikipedia, the free encyclopedia), but I didn’t find Kubek’s name in the Wikipedia TRH entry, Thyrotropin-releasing hormone – Wikipedia, the free encyclopedia.

In any case, the idea for delivering TRH to the brain quickly via a nasal spray probably does get its impetus from Dr. Kubek’s impressive work on developing ways to deliver neuropeptides by this route using nanoparticles. He and his colleagues have received a patent for their discoveries and he’s looking into forming his own company to develop this technology for use in direct patient care, Fund Research: Success Stories: About: IURTC.

More power to him, and I’m all for doing everything possible to help veterans.The challenge to health care professionals to do what they can to stem the tide of suicide is clear:

PsychiatryOnline | Psychiatric News | News Article

PsychiatryOnline | Psychiatric News | News Article

NIMH · Army STARRS Preliminary Data Reveal Some Potential Predictive Factors for Suicide

However, I could not find any recent literature about the use of TRH as an antidepressant, much less an antisuicide agent. Much of the literature seems to be from the 1970s, although there are a couple from my quick search that are more recent (see reference list below). There are some obvious methodological issues, including small numbers of patients and confounders; for example, how do you know the patients in the Furlong study didn’t get better just from the electroconvulsive therapy (ECT) alone?

I contacted a couple of research psychiatrists in our department and asked them about their thoughts on this issue, and their comments were:

“This is the first I’ve seen anything on this.  Don’t even recall seeing stuff presented at conference poster sessions on this.  On first blush makes me a little uncomfortable.”

“Light years from clinical practice – and a need for more thyroid is only the tiniest fraction of our veterans problems.”

I think the most telling part of the CNN story was the quote from a high-ranking Army officer who reportedly told Deputy Washington Bureau Chief Mark Thompson, “there are promising techniques that the military could deploy against suicide, but they involve an initial two-hour screening, a sit-down, a one-on-one with a psychiatrist that this nation is just not willing to pay for.”

What this probably means is that somebody thinks we can’t afford to pay for the application of a standard intervention involving a psychiatric diagnostic evaluation in which a psychiatrist sits down and listens to a soldier, tries to understand the pain, asks general and specific questions in a systematic suicide risk assessment, identifies the modifiable risk factors for suicide and puts them into the spiritual, psychological, emotional, cultural, social, and medical context of a suffering human being–and proposes a safe, practical, and effective treatment plan (Amos, J. J., M.D. (2010). Suicide risk assessment. Psychosomatic Medicine: An Introduction to Consultation-Liaison Psychiatry. J. J. Amos, M.D., and R. G. Robinson, M.D. New York, Cambridge University Press: 51-57; Fiedorowicz, J. G., K. Weldon, et al. (2010). “Determining suicide risk (hint: a screen is not enough).” J Fam Pract 59(5): 256-260).

But it looks like somebody is willing to pay for nasal spray. In my opinion, I think we need to ask ourselves and our soldiers whether we can afford not to apply what we already know to be effective, evidence-based, interventions available right now to address the suffering that leads to suicide for sons and daughters who are laying it on the line for us in battle. And we need to stop stigmatizing mental illness and mental health issues.


Callahan, A. M., M. A. Frye, et al. (1997). “Comparative antidepressant effects of intravenous and intrathecal thyrotropin-releasing hormone: Confounding effects of tolerance and implications for therapeutics.” Biological Psychiatry 41(3): 264-272.
A significant amount of preclinical and human data indicate that thyrotropin-releasing hormone (TRH) has antidepressant effects. Although early studies showing these effects using intravenous TRH were not consistently replicated, it has been suggested that this could be explained by its poor blood—brain barrier penetration. For this reason we compared the antidepressant effect of intrathecal and intravenous TRH administered in a double-blind design to 2 treatment-refractory patients with bipolar II disorder. Each experienced a robust antidepressant response by both routes; subsequent open trials of intravenous TRH also were effective until apparent tolerance developed. Intrathecal TRH was readministered and both subjects again experienced robust antidepressant responses. These preliminary data suggest a differential mechanism of tolerance to the two routes of administration and raise the possibility that a subgroup of patients may be responsive to the antidepressant effects of TRH independent of its route of administration.

Eugene Pekary, A., K. F. Faull, et al. (2005). “TRH-like antidepressant peptide, pyroglutamyltyroslyprolineamide, occurs in rat brain.” Journal of Mass Spectrometry 40(9): 1232-1236.
We have previously reported the occurrence of pGlu-Glu-Pro-NH2(Glu-TRH, EEP), Val-TRH, Tyr-TRH, Leu-TRH, Phe-TRH, and Trp-TRH in rat brain using a combination of HPLC and radioimmunoassays with antibodies that cross-react with the general structure pGlu-X-Pro-NH2 where ‘X’ maybe any amino acid residue (Peptides 2004; 25 : 647). This new family of TRH-like peptides, along with TRH (pGlu-His-Pro-NH2), has neuroprotective, anticonvulsant, antidepressant, euphoric, anti-amnesic, and analeptic effects. We now report that a combination of affinity chromatography using a rabbit antibody specific for Tyr-TRH and Phe-TRH, along with HPLC and tandem mass spectrometry operating in the multiple reaction monitoring (MRM) mode, provide conclusive evidence for the presence of Tyr-TRH in rat brain. Furthermore, synthetic Tyr-TRH is active in the Porsolt Swim Test suggesting that it is a fourth member of this family of in vivo neuroregulatory agents that have psychopharmacotherapeutic properties. Copyright © 2005 John Wiley & Sons, Ltd.

Furlong, F. W., G. M. Brown, et al. (1976). “Thyrotropin-releasing hormone: differential antidepressant and endocrinological effects.” The American Journal of Psychiatry 133(10): 1187-1190.
In a double-blind study, three depressed subjects received thyrotropin-releasing hormone (TRH) on three successive days, and one subject similarly received placebo; all subjects were then given ECT. Two of the patients given TRH responded to ECT. One patient’s reaction is of special significance because of her response to ECT, diminished thyroid-stimulating hormone response to TRH, increased growth hormone and prolactin response to stress, and antidepressant effect of TRH. These findings raise the possibility that previous conflicting reports about TRH’s antidepressant effects stem from the combined study of endocrinologically distinct depressive subgroups and strongly suggest that there may be a specific subgroup that is responsive to TRH.

Five patients with mental depression received thyrotropin (T.S.H.)-releasing hormone (T.R.H.) for 3 days as part of a double-blind, cross-over study. All patients showed improvement in the symptoms of depression. The plasma-T.S.H. response to T.R.H. was distinctly diminished in four of the five patients, suggesting an abnormality in the hypothalamic/pituitary axis.

Koranyi, L., V. Tamásy, et al. (1976). “Effect of thyrotropin-releasing hormone (TRH) and antidepressant agents on brain stem and hypothalamic multiple unit activity in the cat.” Psychopharmacology 49(2): 197-200.
The EEG and MUA (multiple unit activity) of mesencephalic reticular formation (MRF), area hypothalami posterior (PH), and area hypothalami anterior (AH) were studied in chronically implanted freely moving cats. The effects of thyrotropin-releasing hormone (TRH) and some antidepressant agents were tested on neuronal activity. Desipramine and imipramine resulted in a dose-dependent decline of MUA of all structures with the most significant decrease of activity in PH. A single injection of TRH resulted in slight or moderate gross behavioral changes and vegetative excitation lasting for 30–50 min with variable MUA levels. In the course of repetitive TRH treatment on consecutive days the gross behavioral changes and the vegetative symptoms failed to develop by the 3rd or 4th day. By that time the MUA changes of PH and MRF showed similar characteristics in response to TRH administration which was observed following the injection of desipramine and imipramine. The drugs, except for TRH, induced a suppression of paradoxical sleep cycles.

Metcalf, G. (1982). “Regulatory peptides as a source of new drugs — the clinical prospects for analogues of TRH which are resistant to metabolic degradation.” Brain Research Reviews 4(3): 389-408.
The biological properties of several analogues of TRH (Pyr-His-Pro-NH2) are reviewed. Analogues discussed include those with modifications to the Pyr moiety (e.g. DN-1417, CG 3509 and CG 3703), the Pro moiety (e.g. RX 77368) and MK-771 which has both terminal residues modified. The analogues have enhanced biological half-lives compared to TRH because of their resistance to enzymatic degradation. Neuropharmacological evaluation indicates the analogues to be active in antidepressant screening tests, to reverse the effects of diverse CNS depressants and to promote arousal when given alone. The analogues all exhibit enhanced potency compared to TRH in such tests. In contrast they appear equipotent to TRH in endocrine tests. An explanation is offered for this paradox in terms of metabolic stability and bioavailability to the requisite sites of action. The prospects for clinical utilization of the neuropharmacological properties common to TRH and its analogues are considered.

Plotnikoff, N. P., A. J. Prange, Jr., et al. (1972). “Thyrotropin releasing hormone: enhancement of dopa activity by a hypothalamic hormone.” Science 178(4059): 417-418.
Thyrotropin releasing hormone potentiates the behaviorial effects of dopa plus pargyline in mice. Because the potentiation occurs in hypophysectomized mice, as well as in normal mice, the phenomenon is independent of the release of thyroid stimulating hormone from the pituitary. Possible mechanisms and clinical implications are discussed.

Sattin, A., A. E. Pekary, et al. (1994). “TRH Gene Products Are Implicated in the Antidepressant Mechanisms of Seizuresa.” Annals of the New York Academy of Sciences 739(1): 135-153.

Szuba, M. P., J. D. Amsterdam, et al. (2005). “Rapid Antidepressant Response After Nocturnal TRH Administration in Patients With Bipolar Type I and Bipolar Type II Major Depression.” Journal of Clinical Psychopharmacology 25(4): 325-330.
Background: Thyrotropin-releasing hormone (TRH) is a tripeptide that produces endocrine and behavioral effects in animals and humans. Some studies have shown transient antidepressant activity after morning administration of TRH. We hypothesized that nocturnal administration of TRH, when the circadian sensitivity of the TRH receptor is at its peak, may result in a more robust antidepressant effect. Methods: Twenty patients with bipolar (BP) type I or BP type II major depressive episode (MDE) were given nocturnal intravenous TRH 500 [mu]g (n = 10) or saline (n = 10) at midnight in a randomized, double-blind fashion. Antidepressant activity was assessed using the Hamilton Depression Rating (HAM-D), Young Mania Rating (YMR), and Profile of Mood (POMS) scales over a 48-hour period. Thyrotropin (TSH), total T4, and free T3 concentrations were measured before and after TRH administration. Data were analyzed using [chi]2 test, Fisher exact test, and repeated-measures ANOVA. Results: Sixty percent of the TRH group and 10% of the saline group showed a >=50% reduction in baseline total HAM-D score within 24 hours (P = 0.03). HAM-D ratings fell by an average of 52% after TRH administration versus 12% after saline administration (P = 0.038). There was a modest increase in YMR scores after TRH compared with saline (P < 0.032). No manic or hypomanic episodes were observed. Antidepressant effects of TRH lasted up to 48 hours. There was no correlation between [DELTA]TSH, [DELTA]T4, or [DELTA]T3 measures after TRH (or saline) administration and the change in HAM-D scores. Conclusions: Nocturnal TRH administration may produce a rapid antidepressant effect in some patients with BP I and BP II MDE. (C) 2005 Lippincott Williams & Wilkins, Inc.

Takahashi, S., H. Kondo, et al. (1973). “Antidepressant Effect of Thyrotropin-Releasing Hormone (TRH) and the Plasma Thyrotropin Levels in Depression.” Psychiatry and Clinical Neurosciences 27(4): 305-314.
Twenty-four patients with mental depression received thyrotropin-releasing hormone (TSH). 14 patients in Group A were treated with a series of TRH injections 500 μg three times a week, for two to three weeks, and 150 mg/day of imipramine administration in a cross-over comparison. Only three patients showed mild improvement in their depressive symptoms, while imipramine, which was administered in place of TRH, revealed to have more effect on their depression. Antidepressant effect of TRH can be evaluated as not exceeding that of the tricyclics. A single dose of 500 μg TRH in Group B, consisting of 10 depressed inpa-tients, caused neither subjective feelings of improvement nor behavioral changes. Twenty-five percent of depressed patients showed an inadequate TSH response to TRH injection, although all the patients were euthyroid in their thyroid function tests. Three of four neurotic-depressives, with pro longed mental symptoms of several years, revealed a distinctly diminished plasma TSH response to TRH injection. These findings suggest an abnormality in the hypothalamic-pituitary axis, which may cause the fixation of mental symptoms. Neurotic-depressive symptomatology protracted for many years may be based on an unknown neuroendocrine dysfunctions. The implications of these findings remain to be explored.