Defining Suicide in Clinical Trials-How Do We Fare?

Sir,

“Suicide” comes from Latin sui (of oneself) and caedere (kill), and means “(to) intentionally kill oneself” (verb) or “action of killing oneself intentionally” (noun) (https://www.lexico.com/definition/suicide, accessed August 14, 2020: 0900). Suicide denotes an existential paradox—a significant departure from the natural instinct of self-preservation. As noted by Durkheim, an intent to die originates in major psychological and sociological upheavals, the likes of which have become more common in the 21st century, especially within the younger population.

Fortunately, not all suicidal attempts (SA) terminate in fatality. However, it is important—and difficult at the same time—to differentiate such attempts from a close clinical mimic, “in the absence of lethal intent.” Termed nonsuicidal self-injury (NSSI), these have been described in association with several psychiatric diagnoses, considered manifestations of poor impulse control, and recommended as a separate diagnostic category. DSM-5 describes NSSI with a clear absence of intent to die, and with an instrumental role in modifying psychosocial interactions of the individual; and contrasts this with suicidal behavior disorder—both under Section III. With significant resources being committed to suicidology all over the world, it is imperative that this differentiation is translated into research. With a fundamental difference in their nature3–5, it is expected that the efforts in identifying and managing acts with an intent to die would not be identical to those for NSSIs. Such contrasting is, thus, likely to generate focussed and rigorous recommendations .

We conducted a proof-of-concept search on PubMed for the term “‘Suicid*’ [Ti]” for Clinical Trials published in the previous year (accessed September 2, 2020: 1000). The rationale behind including trials was to understand the nature of recent studies, which would eventually add to level-I evidence in suicide interventions. A total of 25 articles were identified during the initial search, and after discarding three non-clinical-trials and one article in German, 21 papers were assessed for (a) clear a priori definition of “suicide” and (b) attempted differentiation from NSSI. The latter was done by searching for the term “self” in available texts—since mention of NSSI/deliberate self-harm (DSH)/self-harm/self-injury or self-injurious behavior would have this term contained within.

Only one study explicitly defined SAs; seven others used cut-off values on scales to define inclusion criteria, and one study possibly defined SA through a structured interview. All evaluated papers stated facts about suicide and/or SA, with an evident underlying assumption of a consensus on the nature and definition of such. Only two articles explicitly differentiated SAs from NSSIs, and one mentioned NSSI without going into any further details. Finally, almost all studies used a clinical scale to quantify “suicide,” as would be expected from their designs (Table 1).

Table 1.

DOIs of Studies Assessed and Relevant Data

DOI	Suicide/Suicidal Acts Defined a Priori	Attempted Differentiation from NSSI Behaviors
10.1001/jamanetworkopen.2019.17941	Yes—positive screen result for suicide risk on the ASQ tool	Yes—required intent to die as inclusion criteria for suicide
10.1177/1359104519843956	Yes—reported specific interviews, suicide probably defined in this; not explicit	Yes—explicitly differentiated suicide attempts from NSSI behaviors
10.1111/sltb.12568	Yes—no a priori definition, but used scale cut-off	No mention in the paper
10.1176/appi.ajp.2019.19030267	Yes—no a priori definition, but inclusion criteria required a score ≥3 on the Scale for Suicide Ideation, participants were free of suicidal plans or intent, as indicated by C-SSRS scores ≤3 on the ideation dimension.	No mention in the paper
10.1016/j.jaac.2018.12.013	Yes—no a priori definition, but inclusion criteria by endorsing severe suicidal ideation (≥31 on the Suicidal Ideation Questionnaire—Junior)	No mention in the paper
10.2196/14729	Yes—explicitly defined suicide ideations and acts	No mention in the paper
10.1093/tbm/ibz108	Yes—endorsed SI on the C-SSRS	No mention in the paper
10.1016/j.jagp.2019.08.018	Yes—but through HAM-D questions	No mention in the paper
10.1016/j.beth.2019.01.004	Yes—but through Beck Scale for Suicidal Ideation, item 6	No mention in the paper
10.1016/j.jad.2019.08.032	No clear a priori definition	No mention in the paper
10.1186/s12889-019-7996-2	No a priori definition, no agreed-upon and replicable definition	No mention in the paper
10.1016/j.psychres.2019.112493	No a priori definition	No mention in the paper
10.1002/da.22964	No a priori definition	No mention in the paper
10.1037/ccp0000457	No a priori definition	No mention in the paper
10.1002/da.22944	No a priori definition	No mention in the paper
10.1016/j.chiabu.2019.104126	No a priori definition	No mention in the paper
10.1017/S1352465819000122	No a priori definition	No mention in the paper
10.1111/sltb.12550	No a priori definition	No mention in the paper
10.2196/16253	No a priori definition	No mention in the paper
journal.pone.0222482. eCollection 2019	No a priori definition	No—used interchangeably
10.1186/s12889-019-7751-8	No a priori definition	Mentioned, but not differentiated from suicide
Studies not included
10.1024/1422-4917/a000712	English full text not available
10.1111/sltb.12530	Not a clinical trial
10.1002/da.22911.	Not a clinical trial
10.1016/j.jpsychires.2019.06.015	Not a clinical trial

ASQ: Ask Suicide-Screening Questions, C-SSRS: Columbia-Suicide Severity Rating Scale, HAM-D: Hamilton Scale for Depression, NSSI: nonsuicidal self-injurious.

This finding is marred by the brevity of search; but underscores an important issue in suicide research (in particular) and psychiatry (in general). An understandable reason for the lack of uniform definition is the non-availability of an official diagnostic category in the main texts of the two widely-used international classificatory systems in psychiatry. A further concern could be the fact that almost half of those with self-injurious thoughts or behaviors may go on to have a SA or have death as an outcome . One could argue that, given the lethality of those SAs, it might be wiser to err on the side of caution and consider all NSSIs as SAs. However, as Huang and colleagues have argued , it may be important to understand the innate differences between SA and NSSI in order to, ironically, discern the protective factors (readers may refer to Huang et al.’s for a discussion on the differences between NSSI and SA).

Recent estimates put rates of DSH classifiable as NSSI between 13% and 29% in community samples, going up to 40% in acute psychiatric inpatient populations. While some authors have argued that there might be little merit in differentiating the two, others such as Grandclerc et al. mention the possible differences in their outcomes, including the protective role of NSSI in “maintaining life by reducing and regulating negative emotions.” The latter is in agreement with the position taken by DSM-5.

Science calls for robustness and objectivity. Our exercise provides context to some of the recommendations around suicide and NSSI interventions, and, therefore, the evidence base. We feel that there is an urgent need for deliberation on this topic. We also believe that the researchers must endeavor to rigorously contrast SAs with NSSIs in clinical trials and strive to define suicide a priori. Interestingly, under present circumstances, whether there would be enough merit in this differentiation becomes a circular argument since we are not sure of the nature of “suicide” in most of these papers.