Remission of suicidal ideation by magnetic seizure therapy? Neuro-nonsense in JAMA: Psychiatry

A recent article in JAMA: Psychiatry:

Sun Y, Farzan F, Mulsant BH, Rajji TK, Fitzgerald PB, Barr MS, Downar J, Wong W, Blumberger DM, Daskalakis ZJ. Indicators for remission of suicidal ideation following magnetic seizure therapy in patients with treatment-resistant depression. JAMA Psychiatry. 2016 Mar 16.

Was accompanied by an editorial commentary:

Camprodon JA, Pascual-Leone A. Multimodal Applications of Transcranial Magnetic Stimulation for Circuit-Based Psychiatry. JAMA: Psychiatry. 2016 Mar 16.

Together both the article and commentary can be studied as:

  • An effort by the authors and the journal itself to promote prematurely a treatment for reducing suicide.
  • A pay back to sources of financial support for the authors. Both groups have industry ties that provide them with consulting fees, equipment, grants, and other unspecified rewards. One author has a patent that should increase in value as result of this article and commentary.
  • A bid for successful applications to new grant initiatives with a pledge of allegiance to the NIMH Research Domain Criteria (RDoC).

After considering just how bad the science and reporting:

We have sufficient reason to ask how did this promotional campaign come about? Why was this article accepted by JAMA:Psychiatry? Why was it deemed worthy of comment?

I think a skeptical look at this article would lead to a warning label:

exclamation pointWarning: Results reported in this article are neither robust nor trustworthy, but considerable effort has gone into promoting them as innovative and even breakthrough. Skepticism warranted.

As we will see, the article is seriously flawed as a contribution to neuroscience, identification of biomarkers, treatment development, and suicidology, but we can nonetheless learn a lot from it in terms of how to detect such flaws when they are more subtle. If nothing else, your skepticism will be raised about articles accompanied by commentaries in prestigious journals and you will learn tools for probing such pairs of articles.

 

This article involves intimidating technical details and awe-inspiring figures.

figure 1 picture onefigure 1 picture two

 

 

 

 

 

 

 

 

 

Yet, as in some past blog posts concerning neuroscience and the NIMH RDoC, we will gloss over some technical details, which would be readily interpreted by experts. I would welcome the comments and critiques from experts.

I nonetheless expect readers to agree when they have finished this blog post that I have demonstrated that you don’t have to be an expert to detect neurononsense and crass publishing of articles that fit vested interests.

The larger trial from which these patients is registered as:

ClinicalTrials.gov. Magnetic Seizure Therapy (MST) for Treatment Resistant Depression, Schizophrenia, and Obsessive Compulsive Disorder. NCT01596608.

Because this article is strikingly lacking in crucial details or details in places where we would expect to find them, it will be useful at times to refer to the trial registration.

The title and abstract of the article

As we will soon see, the title, Indicators for remission of suicidal ideation following MST in patients with treatment-resistant depression is misleading. The article has too small sample and too inappropriate a design to establish anything as a reproducible “indicator.”

That the article is going to fail to deliver is already apparent in the abstract.

The abstract states:

 Objective  To identify a biomarker that may serve as an indicator of remission of suicidal ideation following a course of MST by using cortical inhibition measures from interleaved transcranial magnetic stimulation and electroencephalography (TMS-EEG).

Design, Setting, and Participants  Thirty-three patients with TRD were part of an open-label clinical trial of MST treatment. Data from 27 patients (82%) were available for analysis in this study. Baseline TMS-EEG measures were assessed within 1 week before the initiation of MST treatment using the TMS-EEG measures of cortical inhibition (ie, N100 and long-interval cortical inhibition [LICI]) from the left dorsolateral prefrontal cortex and the left motor cortex, with the latter acting as a control site.

Interventions The MST treatments were administered under general anesthesia, and a stimulator coil consisting of 2 individual cone-shaped coils was used.

Main Outcomes and Measures Suicidal ideation was evaluated before initiation and after completion of MST using the Scale for Suicide Ideation (SSI). Measures of cortical inhibition (ie, N100 and LICI) from the left dorsolateral prefrontal cortex were selected. N100 was quantified as the amplitude of the negative peak around 100 milliseconds in the TMS-evoked potential (TEP) after a single TMS pulse. LICI was quantified as the amount of suppression in the double-pulse TEP relative to the single-pulse TEP.

Results  Of the 27 patients included in the analyses, 15 (56%) were women; mean (SD) age of the sample was 46.0 (15.3) years. At baseline, patients had a mean SSI score of 9.0 (6.8), with 8 of 27 patients (30%) having a score of 0. After completion of MST, patients had a mean SSI score of 4.2 (6.3) (pre-post treatment mean difference, 4.8 [6.7]; paired t26 = 3.72; P = .001), and 18 of 27 individuals (67%) had a score of 0 for a remission rate of 53%. The N100 and LICI in the frontal cortex—but not in the motor cortex—were indicators of remission of suicidal ideation with 89% accuracy, 90% sensitivity, and 89% specificity (area under the curve, 0.90; P = .003).

Conclusions and Relevance  These results suggest that cortical inhibition may be used to identify patients with TRD who are most likely to experience remission of suicidal ideation following a course of MST. Stronger inhibitory neurotransmission at baseline may reflect the integrity of transsynaptic networks that are targeted by MST for optimal therapeutic response.

Even viewing the abstract alone, we can see this article is in trouble. It claims to identify a biomarker following a course of magnet seizure therapy (MST) ]. That is an extraordinary claim when a study only started with 33 patients of whom only 27 remain for analysis. Furthermore, at the initial assessment of suicidal ideation, eight of the 27 patients did not have any and so could show no benefit of treatment.

Any results could be substantially changed with any of the four excluded patients being recovered for analysis and any of the 27 included patients being dropped from analyses as an outlier. Statistical controls to control for potential confounds will produce spurious results because of overfit equations ] with even one confound. We also know well that in situation requiring control of possible confounding factors, control of only one is really sufficient and often produces worse results than leaving variables unadjusted.

Identification of any biomarkers is unlikely to be reproducible in larger more representative samples. Any claims of performance characteristics of the biomarkers (accuracy, sensitivity, specificity, area under the curve) are likely to capitalize on sampling and chance in ways that are unlikely to be reproducible.

Nonetheless, the accompanying figures are dazzling, even if not readily interpretable or representative of what would be found in another sample.

Comparison of the article to the trial registration.

According to the trial registration, the study started in February 2012 and the registration was received in May 2012. There were unspecified changes as recently as this month (March 2016), and the study is expected to and final collection of primary outcome data is in December 2016.

Primary outcome

The registration indicates that patients will have been diagnosed with severe major depression, schizophrenia or obsessive compulsive disorder. The primary outcome will depend on diagnosis. For depression it is the Hamilton Rating Scale for Depression.

There is no mention of suicidal ideation as either a primary or secondary outcome.

Secondary outcomes

According to the registration, outcomes include (1) cognitive functioning as measured by episodic memory and non-memory cognitive functions; (2) changes in neuroimaging measures of brain structure and activity derived from fMRI and MRI from baseline to 24th treatment or 12 weeks, whichever comes sooner.

Comparison to the article suggests some important neuroimaging assessment proposed in the registration were compromised. (1) only baseline measures were obtained and without MRI or fMRI; and (2) the article states

Although magnetic resonance imaging (MRI)–guided TMS-EEG is more accurate than non–MRI-guided methods, the added step of obtaining an MRI for every participant would have significantly slowed recruitment for this study owing to the pressing

need to begin treatment in acutely ill patients, many of whom were experiencing suicidal ideation. As such, we proceeded with non–MRI-guided TMS-EEG using EEG-guided methods according to a previously published study.

Treatment

magnetic seizure therapyThe article provides some details of the magnetic seizure treatment:

The MST treatments were administered under general anesthesia using a stimulator machine (MagPro MST; MagVenture) with a twin coil. Methohexital sodium (n = 14), methohexital with remifentanil hydrochloride (n = 18), and ketamine hydrochloride (n = 1) were used as the anesthetic agents. Succinylcholine chloride was used as the neuromuscular blocker. Patients had a mean (SD) seizure duration of 45.1 (21.4) seconds. The twin coil consists of 2 individual cone-shaped coils. Stimulation was delivered over the frontal cortex at the midline position directly over the electrode Fz according to the international 10-20 system.36 Placing the twin coil symmetrically over electrode Fz results in the centers of the 2 coils being over F3 and F4. Based on finite element modeling, this configuration produces a maximum induced electric field between the 2 coils, which is over electrode Fz in this case.37 Patients were treated for 24 sessions or until remission of depressive symptoms based on the 24-item Hamilton Rating Scale for Depression (HRSD) (defined as an HRSD-24 score ≤10 and 60% reduction in symptoms for at least 2 days after the last treatment).38 These remission criteria were standardized from previous ECT depression trials.39,40 Further details of the treatment protocol are available,30 and comprehensive clinical and neurophysiologic trial results will be reported separately.

The article intended to refer the reader to the trial registration for further description of treatment, but the superscript citation in the article is inaccurate. Regardless, given other deviations from registration, readers can’t tell whether any deviations from what was proposed. In in the registration, seizure therapy was described as involving:

100% machine output at between 25 and 100 Hz, with coil directed over frontal brain regions, until adequate seizure achieved. Six treatment sessions, at a frequency of two or three times per week will be administered. If subjects fail to achieve the pre-defined criteria of remission at that point, the dose will be increased to the maximal stimulator output and 3 additional treatment sessions will be provided. This will be repeated a total of 5 times (i.e., maximum treatment number is 24). 24 treatments is typically longer that a conventional ECT treatment course.

One important implication is for this treatment being proposed as resolving suicidal ideation. It takes place over a considerable period of time. Patients who die by suicide notoriously break contact before doing so. It would seem that a required 24 treatments delivered on an outpatient basis would provide ample opportunities for breaks – including demoralization because so many treatments are needed in some cases – and therefore death by suicide

But a protocol that involves continuing treatment until a prespecified reduction in the Hamilton Depression Rating Scale is achieved assures that there will be a drop in suicidal ideation. The interview-based Hamilton depression rating scales and suicidal ideation are highly correlated.

eeg-electroencephalogrphy-250x250There is no randomization or even adequate description of patient accrual in terms of the population from which the patients came. There is no control group and therefore no control for nonspecific factors. The patients are being subject to an elaborate, intrusive ritual In terms of nonspecific effects. The treatment involves patients in an elaborate ritual, starting with electroencephalographic (EEG) assessment [http://www.mayoclinic.org/tests-procedures/eeg/basics/definition/prc-20014093].

The ritual will undoubtedly will undoubtedly have strong nonspecific factors associated with it – instilling a positive expectations and considerable personal attention.

The article’s discussion of results

The discussion opens with some strong claims, unjustified by the modesty of the study and the likelihood that its specific results are not reproducible:

We found that TMS-EEG measures of cortical inhibition (ie, the N100 and LICI) in the frontal cortex, but not in the motor cortex, were strongly correlated with changes in suicidal ideation in patients with TRD who were treated with MST. These findings suggest that patients who benefitted the most from MST demonstrated the greatest cortical inhibition at baseline. More important, when patients were divided into remitters and nonremitters based on their SSI score, our results show that these measures can indicate remission of suicidal ideation from a course of MST with 90% sensitivity and 89% specificity.

Pledge of AllegianceThe discussion contains a Pledge of Allegiance to the research domain criteria approach that is not actually a reflection of the results at hand. Among the many things that we knew before the study was done and that was not shown by the study, is to suicidal ideation is so hopelessly linked to hopelessness, negative affect, and attentional biases, that in such a situation is best seen as a surrogate measure of depression, rather than a marker for risk of suicidal acts or death by suicide.

 

 

Wave that RDoC flag and maybe you will attract money from NIMH.

Our results also support the research domain criteria approach, that is, that suicidal ideation represents a homogeneous symptom construct in TRD that is targeted by MST. Suicidal ideation has been shown to be linked to hopelessness, negative affect, and attentional biases. These maladaptive behaviors all fall under the domain of negative valence systems and are associated with the specific constructs of loss, sustained threat, and frustrative nonreward. Suicidal ideation may represent a better phenotype through which to understand the neurobiologic features of mental illnesses.In this case, variations in GABAergic-mediated inhibition before MST treatment explained much of the variance for improvements in suicidal ideation across individuals with TRD.

Debunking ‘a better phenotype through which to understand the neurobiologic features of mental illnesses.’

  • Suicide is not a disorder or a symptom, but an infrequent, difficult to predict and complex act that varies greatly in nature and circumstances.
  • While some features of a brain or brain functioning may be correlated with eventual death by suicide, most identifications they provide of persons at risk to eventually die by suicide will be false positives.
  • In the United States, access to a firearm is a reliable proximal cause of suicide and is likely to be more so than anything in the brain. However, this basic observation is not consistent with American politics and can lead to grant applications not being funded.

In an important sense,

  • It’s not what’s going on in the brain, but what’s going in the interpersonal context of the brain, in terms of modifiable risk for death by suicide.

The editorial commentary

On the JAMA: Psychiatry website, both the article and the editorial commentary contain sidebar links to each other. Is only in the last two paragraphs of a 14 paragraph commentary that the target article is mentioned. However, the commentary ends with a resounding celebration of the innovation this article represents [emphasis added]:

Sun and colleagues10 report that 2 different EEG measures of cortical inhibition (a negative evoked potential in the EEG that happens approximately 100 milliseconds after a stimulus or event of interest and long-interval cortical inhibition) evoked by TMS to the left dorsolateral prefrontal cortex, but not to the left motor cortex, predicted remission of suicidal ideation with great sensitivity and specificity. This study10 illustrates the potential of multimodal TMS to study physiological properties of relevant circuits in neuropsychiatric populations. Significantly, it also highlights the anatomical specificity of these measures because the predictive value was exclusive to the inhibitory properties of prefrontal circuits but not motor systems.

Multimodal TMS applications allow us to study the physiology of human brain circuitry noninvasively and with causal resolution, expanding previous motor applications to cognitive, behavioral, and affective systems. These innovations can significantly affect psychiatry at multiple levels, by studying disease-relevant circuits to further develop systems for neuroscience models of disease and by developing tools that could be integrated into clinical practice, as they are in clinical neurophysiology clinics, to inform decision making, the differential diagnosis, or treatment planning.

Disclosures of conflicts of interest

The article’s disclosure of conflicts of interest statement is longer than the abstract.

conflict of interest disclosure

The disclosure for the conflicts of interest for the editorial commentary is much shorter but nonetheless impressive:

editorial commentary disclosures

How did this article get into JAMA: Psychiatry with an editorial comment?

Editorial commentaries are often provided by reviewers who either simply check the box on the reviewers’ form indicating their willingness to provide a comment. For reviewers who already have a conflict of interest, this provides an additional one: a non-peer-reviewed paper in which they can promote their interest.

Alternatively, commentators are simply picked by an editor who judges an article to be noteworthy of special recognition. It’s noteworthy that at least one of the associate editors of JAMA: Psychiatry is actively campaigning for a particular direction to suicide research funded by NIMH as seen in an editorial comment of his own that I recently discussed. One of the authors of this paper currently under discussion was until recently a senior member of this associate editor’s department, before departing to become Chair of the Department of Psychiatry at University of Toronto.

Essentially the authors of the paper and the authors of the commentary of providing carefully constructed advertisers for themselves and their agenda. The opportunity for them to do so is because of consistency with the agenda of at least one of the editors, if not the journal itself.

The Committee on Publication Ethics (COPE)   requires that non-peer-reviewed material in ostensibly peer reviewed journals be labeled as such. This requirement is seldom met.

The journal further promoted this article by providing 10 free continuing medical education credits for reading it.

I could go on much longer identifying other flaws in this paper and its editorial commentary. I could raise other objections to the article being published in JAMA:Psychiatry. But out of mercy for the authors, the editor, and my readers, I’ll stop here.

I would welcome comments about other flaws.

Special thanks to Bernard “Barney” Carroll for his helpful comments and encouragement, but all opinions expressed and all factual errors are my own responsibility.

Getting realistic about changing the direction of suicide prevention research

A recent JAMA: Psychiatry article makes some important points about the difficulties addressing suicide as a public health problem before sliding into the authors’ promotion of their personal agendas.

Christensen H, Cuijpers P, Reynolds CF. Changing the Direction of Suicide Prevention Research: A Necessity for True Population Impact. JAMA Psychiatry. 2016.

This issue of Mind the Brain:

  • Reviews important barriers to effective approaches to reducing suicide, as cited in the editorial.
  • Discusses editorials in general as a form of privileged access publishing by which non-peer-reviewed material makes its way into ostensibly peer reviewed journals.
  • Identifies the self-promotional and personal agendas of the authors reflected in the editorial.
  • Notes that the leading means of death by suicide in the United States is not even mentioned, much less addressed in this editorial. I’ll discuss the politics behind this and why its absence reduces this editorial to a venture in triviality, except that it is a call for the waste of millions of dollars.

Barriers to reducing mortality by suicide

stop suicidePrevention of death by suicide becomes an important public health and clinical goal because of suicide’s contribution to overall mortality, the seeming senselessness of suicide, and its costs at a personal and social level. Yet as a relatively infrequent event, death by suicide resists prediction and effective preventive intervention.

Evidence concerning the formidable barriers to reducing death by suicide inevitably clashes with the strong emotional appeals and political agendas of those demanding suicide intervention programs.

Skeptics encounter stiff resistance and even vilification when they insist that clinical and social policy concerning suicide should be based on evidence.

Robin WilliamsA skeptic soon finds that trying to contest emotional and political appeals quickly becomes like trying to counter Ted Cruz or Donald Trump with evidence contradicting their proposals for dealing with terrorism or immigration. This is particularly likely after suicides by celebrities or a cluster of suicides by teenagers in a community. Who wants to pay attention to evidence when emotions are high and tears are flowing?

See my recent blog post, Preventing Suicide in All the Wrong Ways for some inconvenient truths about suicide and suicide prevention.

The JAMA: Psychiatry article’s identification of barriers

The JAMA: Psychiatry article identifies some key barriers to progress in reducing deaths due to suicide [bullet points added to direct quotes]:

  • Suicide rates in most Western countries have not decreased in the last decade, a finding that compares unfavorably with the progress made in other areas, such as breast and skin cancers, human immunodeficiency virus, and automobile accidents, for which the rates have decreased by 40% to 80%.
  • Preventing suicide is not easy. The base rate of suicide is low, making it hard to determine which individuals are at risk.
  • Our current approach to the epidemiologic risk factors has failed because prediction studies have no clinical utility—even the highest odds ratio is not informative at the individual level.
  • Decades of research on predicting suicides failed to identify any new predictors, despite the large numbers of studies.
  • A previous suicide attempt is our best marker of a future attempt, but 60% of suicides are by persons who had made no previous attempts.
  • Although recent studies in cognitive neuroscience have shed light on the cognitive “lesions” that underlie suicide risk, especially deficits in executive functioning, we have no biological markers of suicide risk, or indeed of any mental illness.
  • People at risk of suicide do not seek help. Eighty percent of people at risk have been in contact with health services prior to their attempts, but they do not identify themselves, largely because they do not think that they need help.
  • As clinicians, we know something about the long-term risk factors for suicide, but we are much less able to disambiguate short-term risk or high-risk factors from the background of long-term risk factors.

How do editorials come about? Not peer review!

 Among the many privileges of being editor-in-chief or associate editors of journals is the opportunity to commission articles that do not undergo peer review. Editors and their friends are among the regular recipients of these gifts that largely escape scrutiny.

Editorials often provide a free opportunity for self-citation and promotion of agenda. Over the years, I’ve noticed that editorials are frequently used to increase the likelihood that particular research topics will become a priority for funding for the particular ideas will be given advantage in competition for funding.

Editorials of great opportunities for self citation. If an editorial in a prestigious journal cites articles published in less prestigious places, readers will often cite the article, without bothering to examine the original source. This is a way of providing false authority  to poor quality or irrelevant evidence.

Not only do authors of commissioned articles get to say what they wish without peer review, they can restrict what can be said in reply. Journals are less willing to publish letters to the editor about editorials rather than empirical papers. They often give the writers of the editorial veto power over what criticism is published. Journals always give the writers of the editorial last word in any exchange.

So, editorials and commentaries can be free sweet plums if you know how to use them strategically.

The authors

Helen Christensen, PhD Black Dog Institute, University of New South Wales, Randwick, New South Wales, Australia.

Pim Cuijpers, PhD Department of Clinical, Neuro, and Developmental Psychology, Vrije Universiteit Amsterdam, the Netherlands

Charles F. Reynolds III, MD Department of Psychiatry and Neurology, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

The authors’ agendas

Helen Christianson

Helen Christianson is the Chief Scientist and Director of the Black Dog Institute, which is described at its website:

Our unique approach incorporates clinical services with our cutting-edge research, our health professional training and community education programs. We combine expertise in clinical management with innovative research to develop new, and more effective, strategies for people living with mental illness. We also place emphasis on teaching people to recognise the symptom of poor mental health in themselves and others, as well as providing them with the right psychological tools to hold the black dog at bay.

A key passage in the JAMA: Psychiatry editorial references her work.

Modeling studies have shown that if all evidence-based suicide prevention strategies were integrated into 1 multifaceted systems approach, about 20% to 25% of all suicides might be prevented.

Here is the figure from the editorial:

suicide prevenino strategies

The paper that is cited  would be better characterized as an advocacy piece, rather than a balanced systematic review.

Most fundamentally, Christiansen makes the mistake of summing attributable risk factors  to obtain a grand total of what would be accomplished if all of  a set of risk factors were addressed.

The problem is that attributable risk factors are dubious estimates derived from correlational analyses which assume that the entire correlation coefficient represents a modifiable risk. Such estimates ignore confounding. If one adds together attributable risk factors calculated in this manner, one gets a grossly inflated view of how much a phenomenon can be controlled. The attributable risk factors are themselves correlated and they share common confounds. That’s why it is bad science to combine them.

Christiansen identifies the top three modifiable risk for suicide as (1) training general practitioners in detection and treatment of suicidal risk, and notably depression; (2) training of gatekeepers such as school personnel, police, (and in some contexts, clergy) who might have contact with persons on the verge of dying by suicide; and (3) psychosocial treatments, namely psychotherapy.

Training of general practitioners and gatekeepers has not been shown to be an effective way of reducing rates of suicide. #Evidenceplease. I’ve been an external scientific advisor to over a decade of programs in Europe which emphasized these strategies. We will soon be publishing the last of our disappointing results.

Think of it: in order to be effective in averting death by suicide, training of police requires that police be on the scene in circumstances where they could use that training to prevent someone from dying by suicide, say, by jumping from a bridge or self-inflicted gun wounds. The likelihood is low that it would be a police officer with sufficient training being in the right place at the right time, with sufficient time and control of the situation to prevent a death. A police officer who had received training would unlikely encounter only a few, if any situations in an entire career.

The problem of death by suicide being an infrequent event that is poorly predicted again rears its ugly head.

Christiansen also makes a dubious assumption that more readily availability of psychotherapy will substantially reduce the risk of suicide. The problem is that persons who die by suicide are often in contact with professionals, but they either break the contact shortly before death or never disclose their intentions.

Christiansen provides a sizable estimate for the reduction in risk for suicide by means restriction.

]. Yet, I suspect that she underestimates the influence of this potentially modifiable factor.

She focuses on restricting access to prescription medications used in suicides by overdose. I don’t know if death-by-overdose data holds for even Australia, but the relevant means needing restriction in the United States is access to firearms. I will say more about that later.

So, Christiansen makes use of the editorial to sell her pet ideas and her institute markets training.

Pim Cuijpers

Pim Cuijpers doesn’t cite himself and doesn’t need to. He is rapidly accumulating a phenomenal record of publications and citations. But he is an advocate for large-scale programs incorporating technology, and notably the Internet to reduce suicide. His interests are reflected in passages like

Large-scale trials are also needed. Even if we did all of these things, large-scale research programs with millions of people are required, and technology by itself will not be enough. Although new large trials show that the effects of community programs can be effective,1,6 studies need to be bigger, combining all evidence-based medical and community strategies, using technology effectively to reduce costs of identification and treatment.

And

Help-seeking may well be assisted by using social media. Online social networks such as Facebook can be used to provide peer support and to change community attitudes in the ways already used by marketing industries. We can use the networks of “influencers” to modify attitudes and behavior in specific high-risk groups, such as the military, where suicide rates are high, or “captive audiences” in schools.

Disseminating effective programs is no longer difficult using online mental health programs. Although some early suicide apps and websites have been tested, better online interventions are needed that can respond to temporal fluctuations in suicide risk. The power of short-term prediction tools should be combined with the timely delivery of unobtrusive online or app personalized programs. However, if these development are not supported by government or industry and implemented at a population level, they will remain missed opportunities.

suicide is preventable
100% PREVENTABLE BY WHOM?

Pim Cuijpers is based the Netherlands and writing at a time when enthusiasm of  the European Research Council  is waning in funding large-scale suicide prevention programs, especially expensive ones requiring millions of participants. Such studies have been going on for over a decade and the yield is not impressive.

The projects on which I consulted adopted the reasonable assumption that because suicide is a rare event, a population of 500,000 would not be sufficient to detect a statistically significant reduction in suicide rates of less than 30%. Consider all the extraneous events that can impinge on comparisons between intervention and control sites in the time period in which the intervention could conceivably be influential. this is too low an estimate of the sample that would be needed.

The larger the sample, the greater the likelihood of extraneous influences, the greater the likelihood that the intervention wouldn’t prove effective at key moments when it was needed to avert a death by suicide, and the greater the cost. See more about this here.

Pim Cuijpers has been quite influential in developing in evaluating web-based and app-based interventions. But after initial enthusiasm, the field is learning that such resources are not effective if left unattended without users being provided with a sense that they are in some sort of a human relationship within which they are consistent use of this technology is being monitored and appreciated, as seen in appropriate feedback. Pim Cuijpers has contributed the valuable concept of supportive accountability.  I have borrowed it to explain what is missing when primary care physicians simply give depressed patients a password to an Internet program and leave it at that, expecting they will get any benefit.

Evaluations of such technology have been limited to whether they reduce depressive symptoms. There is as much a leap from evidence of such reductions, when they occur, claims about preventing suicide, as there is from leaping from evidence that psychotherapy reduces the depressive symptoms to a case that psychotherapy prevents suicide.

Enlisting users of Facebook to monitor and report expressions of suicidality is not evidence based, It is evaluated by some as a disaster and a consumer group is circulating a petition   demanding  that such practices stop. A critical incident  was

man gets arrested for fake suicide messageCharles F. Reynolds

Although Charles Reynolds does not reference his paper in the text of the editorial, but nonetheless cites it.

I have critiqued the study elsewhere. It was funded in a special review only because of political pressure from Senator Harry Reid. The senator’s father had died by suicide shortly after a visit to a primary care physician. Harry Reid required that Congress fund a study showing that improving the detection and treatment of suicidality in the elderly by primary care physicians would reduce suicide.

I was called by an NIMH program officer when I failed to submit a letter of intent concerning applying for that initiative. I told her it was a boondoggle because no one could show a reduction in suicides by targeting physician behavior. She didn’t disagree, but said a project would have to funded. She ended up a co-author on the PROSPECT paper. You don’t often see program officers getting authorship on papers from projects they fund.

The resulting PROSPECT study involved 20 primary care practices in three regions of the Northeastern United States. In the course of the intervention study, one patient in the intervention group died by suicide and two patients, one in each of the intervention and control group, made serious attempts. A multimillion dollar study confronted the low incidence of suicide, even among the elderly. Furthermore, the substantial baseline differences among the practices dwarfed any differences in suicidal ideation in the intervention versus control group. And has of discussed elsewhere [  ], suicidal ideation is a surrogate end point that can be changed by factors that do not alter risk for suicide. No one advocating more money for these kind of studies would want to get into the details of this one.

 

So, the editorial acknowledges the difficulties studying and preventing suicide as a public health issue. It suggests that an unprecedented large study costing millions of dollars would be necessary if progress is to be made. There are formidable barriers to implementing an intervention in a large population of the complexity of the editorial suggests is necessary. Just look at the problems that PROSPECT encountered.

Who will set the direction of suicide prevention research?

The editorial opens with a citation of a blog by the then Director of NIMH

Insel T. Director’s Blog: Targeting suicide. National Institutes of Health website. Posted April 2, 2015.

The blog calls for a large increase in funding for the research concerning suicide and its prevention. The definition of the problem is shaped by politics more than evidence. But at least the blog post is more candid than the editorial in making a passing reference to the leading means of suicide in the United States, firearms.

51 percent of suicide deaths in the U.S. were by firearms. Research has already demonstrated that reducing access to lethal means (including gun locks and barriers on bridges) can reduce death rates.

Great, but surely death by firearms deserves more mentioned than a passing reference to locks on guns if the Director of NIMH is serious about asking Congress for a massive increase in funding for suicide research. Or is he being smart in avoiding the issue and even brave in the passing reference that he makes to firearms?

Firearms deserve not only mention, but thoughtful analysis. But in the United States, it is politically dangerous and could threaten future funding. So we talk about other things.

Banning research on the role of firearms in suicide

For a source that is much more honest, evidence-based, and well argued than this JAMA: Psychiatry editorial, I recommend A Psychiatrist Debunks the Biggest Myths Surrounding Gun Suicides.

In 1996, Congress imposed a ban on research concerning the effects of gun ownership on public health, including suicide.

In the spring of 1996, the National Rifle Association and its allies set their sights on the Centers for Disease Control and Prevention for funding increasingly assertive studies on firearms ownership and the effects on public health. The gun rights advocates claimed the research veered toward advocacy and covered such logical ground as to be effectively useless.

At first, the House tried to close down the CDC’s entire, $46 million National Center for Injury Prevention. When that failed, [Congressman Jay Dickey to whom the Dickey amendment is named] Dickey stepped in with an alternative: strip $2.6 million that the agency had spent on gun studies that year. The money would eventually be re-appropriated for studies unrelated to guns. But the far more damaging inclusion was language that stated, “None of the funds made available for injury prevention and control at the Centers for Disease Control and Prevention may be used to advocate or promote gun control.”

Dickey proclaimed victory — an end, he said at the time, to the CDC’s attempts “to raise emotional sympathy” around gun violence. But the agency spent the subsequent years petrified of doing any research on gun violence, making the costs of the amendment clear even to Dickey himself.

He said the law was over-interpreted. Now, he looks at simple advances in highway safety — safety barriers, for example — and wonders what could have been done for guns.

The Dickey amendment does not specifically ban NIMH from investigating the role of firearms in suicide, but I think Tom Insel and all NIMH directors before and after him get the message.

Recently an effort to repeal the Dickey amendment failed:

Just hours before the mass shooting in San Bernardino on Wednesday, physicians gathered on Capitol Hill to demand an end to the Dickey Amendment restricting federal funding for gun violence research. Members of Doctors for America, the American College of Preventative Medicine, the American Academy of Pediatrics and others presented a petition against the research ban signed by more than 2,000 doctors.

“Gun violence is probably the only thing in this country that kills so many people, injures so many people, that we are not actually doing sufficient research on,” Dr. Alice Chen, the executive director of Doctors for America, told The Huffington Post.

Well over half a million people have died by firearms since 1996, when the ban on gun violence research was enacted, according to a HuffPost calculation of data through 2013 from Centers for Disease Control and Prevention. According to its sponsors, the Dickey Amendment was supposed to tamp down funding for what the National Rifle Association and other critics claimed was anti-gun advocacy research by the CDC’s National Center for Injury Prevention. In effect, it stopped federal gun violence research almost entirely.

So, why didn’t the Associate Editor of the JAMA: Psychiatry, Charles Reynolds exercise his editorial prerogative and support this effort to repeal the Dickey amendment, rather than lining up with his co-authors in a call for more wasteful research that avoids this important issue?