1.1. DIAGNOSIS

Suicide occurs in the presence of any psychiatric diagnosis, but studies repeatedly show that suicide is most common in the mood disorders, major depressive disorder and bipolar disorder [4]. Many other disorders have elevated rates of suicide, such as mixed drug abuse, alcohol and opioid abuse, eating disorders, schizophrenia and personality disorders, and even acute stress disorders [4,5]. It may be that suicide is related to the occurrence of mood depression, severe anxiety, and increased trait impulsivity that occur in the course of the entire range of psychiatric disorders [6]. The increased risk of suicide has particularly been emphasized in bipolar disorder [7]. More recently, the role of early child abuse in suicide has been recognized as a factor in elevated suicide risk [8]. Child abuse has been considered to be associated with both early onset mood disorders and the trait of impulsivity [8].

1.2. TRAITS

The presence of behavioral traits that mediate the risk of suicidal behavior has been a recent theme in studies of suicidal behavior. There is strong evidence for familial-genetic transmission of suicidal behavior and increasing evidence for certain behavioral traits mediating this risk [8–12].

The trait of angry impulsivity has been repeatedly identified as a risk factor for suicidal behavior [6,8–12]. The trait of impulsivity is distributed across the range of diagnoses but is known to be highly associated with bipolar disorder, substance abuse, and cluster B personality disorders as well as a history of early child abuse [6,9]. One study reported elevated scores for neuroticism and hostility as well as impulsivity in prisoners with a positive family history of suicide [13].

Suicide risk factors can be grouped into chronic high-risk factors and immediate or acute high-risk factors. A prior suicide attempt is the most commonly found risk factor for suicide by many studies [4,14], while the rate of actual suicide in subjects with prior suicide attempts is about 5%–10%. A prior suicide attempt could be an indicator that the risk factor of impulsivity is present. Past suicidal behavior is sometimes not helpful in a suicide risk assessment, since Isometsa and Lonnqvist [15] have reported from a large group of studied suicides that about 62% of male suicides and 38% of female suicides died on their first suicide attempt.

While suicidal ideation and particularly a suicide plan is considered a strong predictor of suicide risk, but as it is often erroneously assumed, the opposite, a denial of suicidal ideation or plan, is a very poor predictor by itself that the risk of suicide is low. This is aptly demonstrated by Isometsa et al.’s [16] report on 100 cases of suicide that occurred on the day that the patients had seen their psychiatrist. It was reported that only 22% of the patients who committed suicide endorsed suicidal thoughts at their last visit. In 76 cases of inpatient suicide reported by Busch et al. [17], it was reported that 76% of inpatients had a nursing note quoting the patient as denying suicidal ideation as the last noted communication from the patient prior to their suicide. It is quite humane to assume that if a positive indicates risk, a negative indicates low risk. Such does not appear to be the case for suicide, since a patient at high risk for suicide may be subject to suicidal impulses subsequent to denying suicidal intent or may be lying since they have decided to end their life and do not want to be interfered with. A denial of suicidal intent or plan should be taken as a neutral factor to be considered along with the patient’s past history, life situation, and current clinical state.

Angry impulsivity has been repeatedly found to be chronic high suicide risk factor, which in the presence of certain situations [6,8,18–20], mood states, or anxiety can become a precipitant of suicidal behavior. Other chronic risk factors for suicide include being of male gender, living alone, owning a hand gun, or a history of significant chronic pain [21–24].

Therefore, in assessing a patient for suicide risk, it is not uncommon that the patient could be considered a high chronic risk for suicide but not at acute risk for suicide at the time of the assessment. The presence of chronic risk factors may color the clinician’s assessment as to whether a patient is currently in a high-risk group. The term high-risk group indicates the fact that suicide is not individually predictable, but certain risk factors may lead the clinician to consider the patient in a high-risk group and manage the patient as such. While chronic risk factors for suicide may be useful in an actuarial prediction of a group of individuals more likely to manifest suicidal behaviors at some future point, the patient’s clinical state and current life situation at the time of assessment will (along with a consideration of chronic risk factors) be the clinician’s best source of information in assessing whether a patient should be managed like a patient in an acute high-risk group for suicide.

The patient’s clinical state at the time of clinical assessment in the context of the clinical state over the recent past as well as knowledge of recent losses or stresses occurring in their life situation is a crucial factor in assigning risk group status and planning treatment.

1.3. CLINICAL STATE

A careful assessment of the patient’s current clinical state and life situation is the most important source of information concerning whether or not the patient should be managed as patient is at high acute risk for suicide. The occurrence of recent clinical worsening of symptoms of depression or anxiety is of great importance and merits a full suicide assessment. The presence of a mixed state (or mixed features with depressive symptoms co-occurring with manic or even hypomanic features) is often associated with increased activity, impulsiveness, and severe anxiety/agitation resulting in increased risk of suicidal behavior.

Critical occurrences associated with high risk include being recently admitted or discharged to/from a psychiatric inpatient facility and the risk is elevated by the recentness of discharge up to a year following the event [15,25–27]. The recent occurrence of a loss of a loved one or divorce, a major financial setback, job loss, serious medical diagnosis (e.g., a recent diagnosis of cancer), or legal problem can precipitate a suicidal state, particularly in the presence of depression or in a highly impulsive individual [5,28–30]. It is important to assess how a patient is coping with the “bludgeonings of chance” when such events have occurred.

An assessment of the current clinical state should take into account how they are coping with life stress as well as whether their negative traits (such as negative affect) have recently increased. Has the patient increased the use of alcohol, which can further increase angry impulsivity, for instance [25,31]? Is the patient manifesting increased comorbid anxiety, agitation, or substance abuse [25,31]?

1.4. COMORBID ANXIETY: DYSPHORIC AROUSAL

It is not yet determined whether “comorbid” anxiety in mood disorders is really a comorbid anxiety disorder or is an intrinsic aspect of the symptomatology found in mood disorders. Our current diagnostic system separates symptoms of mood disorders such as major depression and bipolar depression from anxiety disorder. One study using the schedule for affective disorders and schizophrenia, current (SADS-C), a scale that rates both the presence and severity of each symptom in a major depression population, found that anxiety was present to a moderate degree in 62% of patients and panic attacks occurred in 29% [32]. A study by Clayton et al. [33] reported anxiety levels in over 300 patients with primary (no prior diagnosis) depression and showed a high frequency of anxiety symptoms and a wide severity level. The frequency of both anxiety occurring after the onset of a depression and the frequency of depression occurring in a patient already diagnosed as having a generalized anxiety disorder (GAD) (Diagnostic and Statistical Manual-IV [DSM-IV] requires 6 months of criteria symptoms for GAD and 2 weeks of criteria symptoms for major depressive episode) raises the question whether anxiety should not be considered a criterion symptom for major depression and bipolar depression with or without a mixed state.

In 1990, Fawcett et al. [25] reported a prospective study of 13 suicides over the first year and 34 suicides over 10 years in a largely hospitalized sample of patients with major affective disorders (N = 954) followed for 10 years. Prior suicide attempts (recent and past), severity of suicidal ideation, and severity of hopelessness were not significantly greater in 13 suicides over the first year of follow-up compared to the majority of non-suicides, but were significantly associated with suicide over a 2- to 10-year follow-up period [25]. However, the levels of psychic anxiety and panic attacks were significantly more severe or frequent at baseline in the 13 suicide patients compared with the majority of non-suicides. A subsequent study by Hall et al. [34] found elevated levels of psychic anxiety in 90% of a sample of 100 patients hospitalized for suicide attempts and then interviewed, as measured by their SADS-C psychic anxiety scores reflecting the month prior to their suicide attempt.

In 2003, Busch et al. [17] reported a review of 76 cases of inpatient suicide. Charts of these cases were stripped of identity and reviewed over the period of 1 week prior to their suicide. Seventy-nine percent of these cases showed the presence of severe anxiety and/or agitation for at least 3–7 days before their suicide (while the last communication noted by nursing staff prior to their suicide conveyed a denial of suicide thoughts of intent in 76% of cases) [17]. In 2007, Simon et al. [35] published a review of 32,000 cases of bipolar disorder from the combination of two managed care databases showing that the presence of comorbid diagnoses of GAD was associated with an elevated rate of suicide (odds ratio [OR] = 1.8) and suicide attempts (OR = 1.4). It was also found that while the suicide attempt rate was elevated with the presence of comorbid substance abuse, there was no increased risk of suicide found in this sample [35].

In 2008, a study by Stordal et al. [36] showed that 60,995 subjects in Norway, rating themselves monthly (except for July) on the Hospital Anxiety and Depression scale from 1995 to 1997, who committed suicide (N = 10,670 males and 3933 females) showed a simultaneous peak in the severity of depression and anxiety ratings during the month of their suicide (r = 0.72, p = .01), which occurred in the spring and early fall (p = .01). Finally, a study by Pfeiffer et al. [37] of over 887,000 veterans treated for depression showed that suicide was significantly associated with diagnoses of comorbid GAD, anxiety disorder not otherwise specified (NOS), and panic disorder, but not with post traumatic stress disorder (PTSD) or other anxiety disorders (OR = 1.8). In addition, a significant increase in suicide associated with taking antianxiety medication (OR = 1.8) was reported along with a further elevation in suicides in patients taking high-dose antianxiety medications (OR = 2.2). This would also suggest that anxiety severity, rather than anxiety disorder presence, might be associated with suicide as was found by the Fawcett et al. [32] study reviewed earlier.

While a study of suicidality in bipolar patients as opposed to suicide has not found the incidence of prior suicide attempts to be associated with the presence of comorbid GAD, it is argued that suicide attempts may not be totally equivalent to suicide and that these studies did not measure anxiety severity at the time of a suicide attempt, only a past history of suicide attempts, and therefore do not address the issues presented earlier [37].

A recent cross-national study by Nock et al. [6] of suicide attempts in a sample of over 100,000 subjects found suicide associated with the co-occurrence of anxiety. Nock postulated in this report that while depression was associated with suicidal thoughts, disorders characterized by anxiety and poor impulse control lead people to carry out a suicidal behavior [6]. This was reported by Brown et al. [38] in personality disorders as well as in mood disorders and found to be associated with low cerebrospinal fluid (CSF) 5-hydroxy indolacetic acid (5-HIAA) levels, suggesting a decreased turnover of serotonin in brain associated with impulsivity. Indeed, Swann et al. [20] have reported increased impulsivity associated with a history of more frequent suicide attempts and, more recently, Taylor et al. [39] reported that increased anxiety leads to increased impulsivity in bipolar patients.

In 1965, Bunney and Fawcett [40] reported three cases of suicide, which were found to have elevated excretion of 17-hydroxycorticosteroids (a urinary metabolite of cortisol in plasma) in 24h urine collections made the days leading up to their suicide (they were patients on a research unit at National Institute of Mental Health [NIMH]). This was followed by a second paper of several more such cases [41]. Subsequently, the dexamethasone suppression test, which measured an overactive hypophyseal pituitary adrenal system (HPA), was found to show HPA overactivity in patients who committed suicide [42–46]. None of these reports, except for a schizophrenic patient who committed suicide with elevated 17-hydroxycorticoid excretion reported by Sachar et al. [47], manifest anxiety or dysphoric hyperarousal. Sachar reported that his patient was not depressed but exhibiting “ego disintegration.” The question raised is whether patients who are on the verge of suicide are manifesting state anxiety or dysphoric hyperarousal as a clinical symptom, which correlates with HPA axis overactivity.

It may turn out that increased anxiety symptoms in patients with major depression or bipolar disorder may not be secondary to a comorbid anxiety disorder, but a feature of the primary mood disorder. It is hoped that an anxiety severity dimension will be added to all mood disorder diagnoses in DSM-V. This would draw attention to the significance of the role of anxiety in the outcome of mood disorders and focus more attention on the more successful treatment of severe anxiety symptoms in mood disorder patients.

It has been reported that in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study severe anxiety predicted poor response to antidepressant treatment [48,49]. Recent analyses by Coryell and coworkers [50,51] have demonstrated that elevated anxiety severity at base line predicts significantly more time spent in depression in a sample of major mood disorder patients followed over 16–20 years.

The presence of severe anxiety or dysphoric hyperarousal is one of the clinical state variables that should be assessed and addressed in the management of suicide risk. A state of increased impulsiveness related to increased anxiety/arousal in response to negative events should also be considered and addressed in the management of suicide risk. While this factor is certainly not present in all patients prior to suicide, the previously cited inpatient suicide study found it present in 76% of cases studied [17]. The authors’ experience from reviewing ∼100 additional outpatient suicide cases suggests that severe anxiety/dysphoric hyperarousal was present in more than half the cases. The presence of severe anxiety/dysphoric hyperarousal may be one of the most common clinical indicators of imminent suicide risk available to the clinician. A subgroup of patients who carefully plan their suicide over a period of days or weeks may show no signs of severe anxiety/hyperarousal and in fact appear calm and convey no signs of ambivalence, having made their decision. These patients will not indicate their plan to a clinician or significant other and are very difficult, if not impossible, to intervene with prior to their suicide.

1.5. COMORBID SUBSTANCE ABUSE

Another comorbid clinical factor that also requires assessment is the presence of increased substance abuse. It is well known that alcohol and other substance abuse are associated with suicidal behavior [31]. In the collaborative study, it was found that the recent onset of moderate alcohol abuse was seen in the weeks/days prior to suicide. It appeared that these patients were using alcohol as self-treatment of untreated severe anxiety and insomnia in these cases. The behavioral disinhibiting effects of alcohol and other substances are well known. Such substance abuse tends to increase impulsiveness and impair judgment, thereby increasing the risk of suicidal behavior.

The review of Harris and Baraclough [4] found elevated rates of suicide in patients suffering with mixed drug abuse, opioid abuse, and alcohol abuse. Increases in the severity of abuse may portend increased risk of suicidal behavior.

1.6. SHOULD THERE BE A DIAGNOSIS OF SUICIDAL BEHAVIOR?

Since suicide/suicidal behavior occurs across the entire spectrum of psychiatric diagnosis and seems to be transmitted independently in families, with a significant proportion of genetic risk, and can be predicted statistically by prior suicidal behavior, the question arises whether suicidal behavior should be a separate diagnostic category.

A diagnosis of suicidal behavior disorder would increase the clinical focus on interventions to prevent suicidal behavior in vulnerable patients. Currently, evidence suggests that patients with a history of suicidal behavior receive inadequate pharmacologic treatment, which is similar to treatment of other depressed patients [52].

There is a significant amount of scientific data supporting a suicidal behavior diagnosis including genetic factors in transmission found in twin studies, familial transmission independent of diagnosis, biological risk markers, and prediction of subsequent suicidal behavior from past suicidal behavior [53].

On the other hand, it could be argued that this diagnosis may have a stigmatizing effect and undermine the doctor–patient relationship. Also, since a significant proportion of suicides occur on the first attempt as noted earlier [14], such a diagnosis may add a modest amount to the clinical assessment of current suicide risk. Would the effect of a separate diagnosis of suicidal behavior disorder have the net effect of improving clinical care of suicidal patients? Such a category may help with research efforts to better detect and treat acute suicide risk. What would be the appropriate criteria for this disorder: prior suicide attempts, suicide plans or rehearsals, or immediate/chronic suicide ideation?

From the clinical practice point of view, the greatest lack is the relative dearth of clinical or biological markers to detect an individual at acute risk of suicide. Given the difficulty in predicting behavior in an individual, this may always be a limited area of knowledge. However, every piece of information relevant to detecting acute high-risk states for suicide is valuable in our efforts to prevent suicide in our patients.

1.7. SUMMARY AND CONCLUSIONS

It appears that suicide occurs across diagnoses and stems from mood depression, hopelessness, severe anxiety, and increased impulsivity, often but not always related to histories of early abuse and a past history of suicidal behavior, as well as situational factors such as clinical worsening of symptoms, not infrequently in the context of a real or anticipated major loss. Chronic risk factors such as early childhood abuse, impulsivity, a past history of substance abuse, living alone, and a history of past or recent suicide attempts are important to elicit and take into consideration. Acute risk factors such as severe anxiety, insomnia, evidence of increased impulsivity, clinical worsening of symptoms, and an admission of suicide plan or preparation for a suicide attempt and recognition of situational factors such as a recent or anticipated major loss may allow for an intervention prior to a lethal attempt. Biological trait factors such as impulsivity often relating to a history of early childhood abuse, substance abuse and changes in HPA, adrenergic response, and serotonin systems seem to occur across diagnoses. In the presence of mood depression, which is seen across diagnoses and always present in mood disorders, suicidal ideas may occur that are translated into suicide attempts in the presence of the aforementioned factors, often triggered by adverse events or symptom worsening.

Further development of understanding of these pathways to suicide will both increase our clinical knowledge of when to intervene to prevent suicide and enhance our capacity to intervene in ways to prevent the development of acute suicidal risk states in vulnerable individuals.

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