Managing the risk of suicide in people with treatment-resistant depression

Introduction

The management of suicide risk is often integral to the care of people with treatment-resistant depression (TRD). Suicide is a major public health concern worldwide, and yet it is a problem that remains poorly understood. Suicide occurs across a wide range of clinical presentations, including TRD, but the mechanisms accounting for suicide risk in TRD are not fully understood. Nevertheless, treatment guidelines for suicide risk in TRD are beginning to emerge, although more evidence is needed. In the sections that follow, we provide a brief overview of the phenomenology, risk, and treatment of suicidal thoughts and behaviors (STBs), and then we make recommendations for best practices for managing suicide risk for those with TRD.

Terms and definitions

Prior to considering management of suicide risk in TRD, it is worthwhile to define and clarify several key constructs related to suicide. Suicide, also referred to as suicide death, refers to the intentional ending of one’s own life. A discussion of STBs can be structured according to a recently developed theoretical model describing the pathway to suicide. This model begins with thoughts about suicide and identifies the sequence of thoughts and behaviors that culminate in a suicide attempt ( ). Suicidal ideation refers to thoughts about one’s own death or suicide. Suicidal ideation is often considered either passive (i.e., the wish to no longer be alive) or active (i.e., the wish to take one’s own life). Although active suicidal ideation is typically considered the more risky of the two, recent research suggests that passive and active ideation may be somewhat equivalent in terms of risk for suicide attempts, as well as other outcomes ( ). A suicide plan refers to the selection of a method and place to attempt suicide ( ). Suicide attempt refers to an intentional act undertaken with some intent to die as a result, regardless of whether death results. Nonsuicidal self-injury (NSSI; often referred to as “self-injury” or “self-harm”) refers to self-directed, harmful acts without intent to die as a result, most often performed for the benefit of reducing distressing psychological states, such as negative emotions ( ). NSSI is different than suicide, and is not the focus of this chapter, but NSSI is common among those with treatment-resistant depression ( ), and is a top risk factor for a future suicide attempts ( ).

Suicide prevalence

Suicide is a public health concern of enormous magnitude. In the United States, suicide is the 2nd leading cause of death among those ages 10–35, and the 10th leading cause of death among all age groups . In 2018, over 48,000 Americans died by suicide. Around the world, approximately 800,000 people die by suicide each year, according to the . Suicide accounts for 1.4% of all deaths worldwide, making it the 18th leading cause of death per year globally ( ). To put these numbers into perspective, suicide accounts for more global deaths each year than war, automobile accidents, AIDS, and homicide combined ( ). In addition to suicide death, there are also an estimated 25 million suicide attempts, and 140 million people engaging in suicidal ideation annualy around the world ( ).

Suicide prevalence rates vary between countries, and some data have suggested that suicide is more common in developed versus developing countries ( ). However, attempts to better understand this variation have not provided additional insights. Perhaps more illuminating is that several demographic characteristics seem to be commonly associated with suicide rates internationally. For example, males are more likely to die by suicide, whereas females are more likely to attempt and think about suicide ( ; ; ). In addition, younger individuals engage in STBs at a higher rate than older individuals ( ).

Some recent epidemiological data suggest that suicide may be on the rise, with rates in the United States increasing for both males and females between 2000 and 2016 ( ). This alarming statistic has drawn warranted attention from the media. However, considering a broader span of time adds nuance to the conclusion that suicide rates are increasing. During the 20 years prior to 2000, suicide rates in the US actually decreased ( Fig. 39.1 ).

Unlike many of the other leading causes of death worldwide, including cancer, heart disease, Alzheimer’s disease, stroke, and violence, we have not been able to effect a meaningful reduction in suicide rates. Our ability to generate knowledge about suicide and suicide prevention has been hampered in at least three ways. First, suicide is an extremely low base-rate phenomenon, with fewer than 11 out of every 100,000 people dying by suicide annually ( ). From a statistical perspective, as discussed in greater detail below, predicting the occurrence of such a rare phenomenon requires very large samples of research participants. Second, those who die by suicide cannot be directly studied using the tools most common in mental health research. Although we can examine morphological or biochemical abnormalities in the brains of suicide victims, these approaches have not revealed major insights about the phenomenology of suicide, or how we may prevent it. Third, suicide has not been studied systematically for very long, and research efforts have largely focused on a small number of constructs theorized to cause suicide ( ). A primary goal of this chapter is to highlight what we do know about suicide generally and among those with treatment-resistant depression, and to discuss future research priorities to better understand and prevent this enigmatic tragedy.

Suicide risk factors

Identifying risk factors for suicide is one approach toward better understanding the phenomenology of suicide, as well as more effectively predicting suicide and intervening before it occurs. A risk factor refers to a prospective predictor of an outcome of interest. Risk factors precede the outcome in time, and they predict whether the outcome is likely to occur by dividing people into high- and low-risk categories ( ). This is different than a correlate, which is associated with the outcome of interest, but the nature of that association is unclear. For example, if a cross-sectional study identified sleep loss as a correlate of suicidal ideation, it would be possible that suicidal ideation caused sleep loss—or vice-versa. Longitudinal data collection methods are therefore necessary to identify risk factors by establishing temporal precedence. It is important to note that identifying a risk factor does not necessarily indicate that the risk factor is causal. Causal risk factors are a specific type of risk factor in which manipulation of the risk factor creates an observable change in the likelihood of the outcome ( ). Very few studies have attempted to influence risk factors to determine causal relationships with suicide, and thus our current knowledge of suicide risk is largely informed by risk factors not yet known to be causal.

A recent meta-analysis of the past five decades of suicide research, which included data only from longitudinal studies of suicide risk factors, has provided some of the most compelling evidence to date about risk for suicide ( ). This meta-analysis examined the prospective relationship between risk factors and STBs (suicidal ideation, suicide attempt, and suicide) across 365 separate studies. The relationship between each risk factor and STB outcome was quantified in this study with a weighted odds ratio. This weighted odds ratio provided an estimate of how much more likely the outcome is to occur for those who are high in the risk factor, while taking into account the size of the sample used for the original analysis. Odds ratios above one indicate that outcome is more likely to occur for those higher in the risk factor, whereas the opposite is true for odds ratios less than one. An odds ratio of one indicates that the outcome is just as likely to occur for those who are higher vs lower in the risk factor (i.e., the outcome is predicted at chance level by the risk factor).

Depression has long been considered a risk factor for suicide, and indeed, countless studies have demonstrated an association between depression and STBs. However, found that depression was one of the five strongest risk factors only for suicidal ideation. For suicide attempt and suicide death, depression (categorized together with other forms of internalizing psychopathology) was rated sixth and ninth among the strongest risk factors, respectively. Data from other studies (some of which were included in the meta-analysis) have suggested that the effect of depression on increased suicide risk may not result from depression itself, but rather from the conditions that are commonly comorbid with depression. For example, two studies that included large, representative samples (one from the United States, one international) found that depression was one of the strongest risk factors for suicidal ideation. However, among those with suicidal ideation, depression predicted future suicide attempt and suicide death no better than chance, whereas other common mental disorders, especially those characterized by anxiety and agitation (panic disorder, posttraumatic stress disorder) or by poor impulse control (substance use disorders), were far better predictors than depression of whether ideators would go on to make a suicide attempt ( ). Moreover, the likelihood of making a suicide attempt was shown in each of these studies to be higher for those with greater numbers of comorbid mental disorders ( ). In other words, individuals with one mental disorder were less likely to attempt suicide than those with two mental disorders, who were less likely than those with three, and so on. Together, this body of evidence suggests that depression alone often leads to thoughts about death and suicide, but other conditions lead depressed individuals to act on these thoughts. This may be particularly important for TRD, wherein comorbid mental disorders are particularly common ( ).

According to the meta-analysis, prior self-injurious thoughts and behaviors (including suicidal ideation, suicide attempt, and NSSI) were among the strongest risk factors for all STBs outcomes, as shown in Table 39.1 .

Prior psychiatric treatment, including inpatient hospitalization, is another top risk factor for suicide ( ). The week following inpatient hospitalization is one of the highest risk periods for suicide attempts ( ). Although the factors that contribute to the significantly elevated risk of suicide in those recently discharged have not been adequately delineated, the nature of the reasons for inpatient hospitalization (e.g., STBs, emotional distress), and other challenges posthospitalization (e.g., persistent symptoms, disappointment with lack of greater improvement during hospitalization) are plausible contributors to risk.

Additional categories of risk factors, including physical illness and demographic characteristics were shown by to be poor predictors of suicide. In fact, their effects on suicidal ideation were close to chance. In practical terms, this means that by flipping a coin, one could predict a person’s suicidal ideation almost as accurately as one could by knowing that person’s ethnicity or their history of asthma.