Ayal Schaffer, M.D., F.R.C.P.C. Mark Sinyor, M.Sc., M.D., F.R.C.P.C. The topic of suicide risk and prevention in bipolar II disorder (BD II) is very important from a number of perspectives. In recent years there has been increased clinical and research interest in this area, driven by the disheartening data showing high rates of suicide in patients with BD II. It is no longer reasonable to accept that suicide is an unavoidable outcome for some people. Initiatives such as the Zero Suicide Model have been at the forefront of a renewed effort to establish systems of care that systematically assess for suicide risk and implement appropriate management strategies. Solely focusing on treating the underlying illness is not enough, with a strong evidence base emerging to support broad-based use of suicide prevention strategies. In this chapter we first examine the available epidemiological data on suicide in bipolar disorder, and when available in BD II specifically. We follow this discussion with an introduction to a bipolar disorder–specific suicide risk assessment model, informed by the latest information on how specific clinical factors influence risk assessments for patients with BD II. Finally, we review management approaches. Because the focus of this chapter is on BD II, we highlight data specific to this subtype. Excluding data on combined bipolar I disorder (BD I) and BD II samples would leave too many gaps in the review, so we have also included these for context and comprehensiveness. There is widespread evidence that rates of suicide attempts and suicide deaths are elevated in people with bipolar disorder. In this section, we review the epidemiology of suicide in bipolar disorder in general, and then move to what is known specifically about those with BD II. The two most common outcomes studied are suicide attempts and suicide deaths. Although the former is of interest because attempts can cause substantial morbidity and are themselves a key risk factor for eventual death by suicide, there is also evidence that those who attempt suicide differ from those who die by suicide, and many suicide deaths are not preceded by a history of attempts. Therefore, when possible, we have emphasized data on suicide deaths rather than attempts as the most important outcome for informing prevention efforts. Numerous studies have reported on various aspects of the epidemiology of suicide in bipolar disorder, with results influenced by factors such as characteristics of the sample (e.g., population-based vs. clinical), duration of follow-up, and ascertainment of records of suicide death. In a seminal prospective study of a population-based Swedish sample, Osby et al. (2001) reported that suicide was the second most common cause of death among people with bipolar disorder after deaths from cardiovascular disease. Tondo et al. (2003) later conducted a pooled analysis of all published articles up to 2001 on bipolar disorder in general and reported an overall standardized mortality ratio (SMR) compared with the general population of 22.1 (95% CI=20.0–24.1). Although this ratio has been widely cited, it must be interpreted with caution, since important methodological aspects likely influenced the results. Even at face value, there is concern that an SMR of 22.1 may not be accurate. In the United States, suicide accounts for approximately 1.4% of all deaths. If those with bipolar disorder have a 22-fold increased likelihood of dying by suicide at any point in their lives, this would translate into an approximately 30% likelihood of dying by suicide (taking into account that those with bipolar disorder account for a portion of the overall 1.4% of deaths), a risk of suicide that is much higher than suicide rates in any reported study in bipolar disorder or indeed of any specific clinical population. This discrepancy may be largely due to the distinction between high-risk periods versus risk over an entire lifetime. Most population-based studies are not birth cohorts and track people from the time at which they have been identified as “patients” with bipolar disorder following contact with health care services. This selects for a subgroup of those with bipolar disorder who have come to clinical attention and may represent a more severe cohort, which may be especially relevant for those with BD II. Furthermore, the studies examine an epoch of monitoring that begins with active illness, and the period of time after a diagnosis of bipolar disorder and first contact with treatment services, such as hospitalization, is known to be associated with higher risk of suicide; therefore, extrapolation from this period to a lifetime will lead to an overestimate of risk. A large Swedish cohort study by Nordentoft et al. (2011) partially addressed this limitation by including an unusually long follow-up period. The epidemiological analysis included people with International Classification of Diseases, 10th Revision (ICD-10)–defined bipolar affective disorder and followed them for over 35 years from the time they were identified as a “patient” (i.e., entered into mental health treatment services). Cumulative incidence of suicide deaths among individuals with bipolar disorder was 7.77% of men and 4.78% of women. This provides a reasonable estimate of the long-term risk of suicide among patients with bipolar disorder and can provide a foundational level of risk onto which other modifying factors may be added (discussed below in the subsection “Identifying General Suicide Risk Factors”). Another avenue of study focuses on reporting rates of suicide during specific periods of follow-up rather than comparison with the general population. The International Society for Bipolar Disorders (ISBD) Task Force on Suicide in Bipolar Disorder (Schaffer et al. 2015b) conducted a pooled analysis of all publications from 1980 to 2012 that reported on rates of suicide in both BD I and II samples. When pooled data were weighted for duration of exposure, a suicide rate of 164 per 100,000 per year was identified (in contrast to the reported global average rate of 10.6 per 100,000 per year). The same limitations noted above apply to these data, given that the average duration of follow-up in the included studies was 8.5 years. An understanding of suicide deaths in people with bipolar disorder should also incorporate available information on specific methods of suicide. This has clear implications for potential suicide prevention strategies. Four large studies have reported on suicide methods among bipolar disorder samples in Sweden (Osby et al. 2001), Taiwan (Chen et al. 2009), the United Kingdom (Hunt et al. 2006), and Canada (Schaffer et al. 2014). Across the four studies there was surprising consistency of results, with 17.1%–32.5% deaths by hanging, 24.9%–33.5% by self-poisoning, and 13.7%–18.9% by jumping from a height. It is worth noting that these are common methods of suicide in general and that those with BD I and II constitute a small proportion of all suicide deaths. Nevertheless, means restriction strategies targeting these specific methods are likely to confer specific protection to those with bipolar disorder. There are limited epidemiological data on the impact of bipolar disorder subtype on rates of suicide deaths. In his seminal study of the Zurich cohort, Angst et al. (2002) compared mortality rates between 113 patients with BD I and 46 patients with BD II. Suicide deaths were recorded in 12 patients with BD I (SMR=11.53) and 6 patients with BD II (SMR= 14.15), a nonsignificant difference. Notably, he found that treatment reduced overall mortality rates in both groups and suicide mortality in particular. Within the BD II group, treatment reduced the suicide SMR from 27.63 to 9.51; however, a note of caution must be taken in interpreting these results because the sample size in both groups was small. In a follow-up study of a large Italian sample of 1,765 hospitalized patients (Sani et al. 2011), death by suicide occurred in 4.2% of patients with BD II and 2.8% of patients with BD I. This difference was nonsignificant, and the findings were notable for lower rates of suicide compared with the Zurich cohort, likely accounted for by a shorter follow-up window, and potentially attributable also to personal and/or clinical risk factors (other than bipolar disorder diagnosis and subtype) that may have differed between the samples. Overall, these studies point to an absence of consistent data supporting any difference in risk of suicide death in patients with BD II versus BD I. Although the limitations in the extant data prevent any definitive conclusions from being drawn, evidence suggests that the bipolar disorder subtype in and of itself is unlikely to have a meaningful impact on the suicide risk assessment in clinical settings. A much larger literature exists on the likelihood of a suicide attempt in BD I and II samples. A comprehensive review by Novick et al. (2010) included 24 studies reporting data on both retrospective and prospective suicide attempts during follow-up periods ranging from 18 months to 44 years. Among subjects with BD II (n=1,099), 30.1% had a retrospectively identified lifetime suicide attempt, a nonsignificant difference compared with BD I samples (36.3%). Using a random effects meta-analytic model, Novick et al. reported an odds ratio for BD I compared with BD II of 1.21 (95% CI=0.98–1.48), which came close to significance (P=0.073). When examining only prospective data, those authors found that 19.8% of subjects with BD II had made a suicide attempt during the follow-up period, compared with 23.8% of subjects with BD I—again a nonsignificant difference. Since 2010, there have been a number of additional studies comparing suicide attempts on the basis of bipolar disorder subtype. To revisit the question of potential differences in risk of suicide attempts, the ISBD Task Force (previously referred to) conducted a meta-analysis incorporating these newer data (Schaffer et al. 2015c). This analysis included a total of 6,047 BD I subjects and 2,407 BD II subjects, and found an OR of 0.96 (95% CI=0.64–1.44, P=0.83) for suicide attempts in BD I versus II samples. This finding further reinforced the conclusion that there do not appear to be significant differences based on subtype. Overall findings have repeatedly demonstrated no consistent, significant differences in rates of suicide attempts or suicide deaths between patients with BD II and those with BD I. However, the most important outcome of this area of research is that both groups, collectively, are at substantially higher risk of suicide compared with the general population. This suggests that rather than focusing solely on disorder subtype, future studies ought to aim to more precisely incorporate higher risk time periods and/or clinical presentations that may be amenable to targeted prevention strategies in both or either subtype. Case Vignette Sophia, a 31-year-old woman, was brought by her parents for assessment to the emergency department. She reports experiencing suicidal thoughts with a plan to ingest a large number of her prescribed medications. She has been drinking alcohol excessively over the past few days, following a major argument with her fiancé. She has a 10-year history of BD II and is followed in the outpatient department. She has a history of four to five past major depressive episodes, managed by a variety of pharmacological and psychotherapeutic approaches. Two months before this presentation she had a hospitalization for a depressive episode with psychotic features and suicidal ideation. Desvenlafaxine 50 mg was started in addition to her usual treatment with quetiapine 400 mg at bedtime. Since starting the antidepressant, she has noted increased irritability, with some racing thoughts and anxiety at night that interfere with her sleep. Sophia endorses a family history of suicide death in her paternal grandfather; he had been diagnosed with an alcohol use disorder. There is also suspicion of suicide death in her paternal aunt, who had been hospitalized and treated with lithium. There are numerous clinical issues involved in the care of a patient such as Sophia. In the following subsections, we explore a framework model for understanding Sophia’s risk of suicide attempts and family history of suicide death. We then review specific clinical factors that influence risk. In the final section of the chapter we move to an examination of management approaches for Sophia and other patients with BD II, specifically related to suicide prevention. There are a number of well-known models in the literature that explore factors associated with suicidal behavior (Hawton et al. 2013; Joiner et al. 2017; Mann 2002). A comprehensive review of these models is beyond the scope of this chapter, but for many patients across diagnostic groups, the various models provide important perspectives on the development and progression of suicidal thoughts and behaviors. Models specific to bipolar disorder have been proposed, with recent work by Malhi et al. (2018) being particularly notable for its emphasis on putative neurobiological mechanisms interacting with the clinical and environmental factors. Earlier work by Hawton et al. (2005) summarized meta-analytic results for specific clinical factors of interest. Our work within the ISBD Task Force on Suicide in Bipolar Disorder (Schaffer et al. 2015a, 2015b, 2015c) focused on a clinical model that grouped factors under distinct headings that would result in a bipolar disorder–specific suicide risk assessment (Figure 5–1). This rests on the premise not just that the diagnosis of bipolar disorder is relevant for a baseline estimation of elevated suicide risk, but that numerous relevant factors are inherent to the illness of bipolar disorder itself, with others being modified by the disorder’s presence. It then follows that understanding and incorporating the contribution of each of these factors into the risk assessment will result in a more individualized determination of risk. FIGURE 5–1.Clinical model for developing a suicide risk assessment specific to bipolar II disorder (BD II). From the general literature it is possible to identify a number of sociodemographic and clinical factors associated with suicide attempts and deaths. Factors discussed below such as age, race, psychosocial stressors, past and current suicidal ideation, prior suicide attempts or deliberate self-harm, contact with mental health services, and family history of suicide are important in understanding risk (McClatchey et al. 2017; Schaffer et al. 2015a, 2015c; Teti et al. 2014). These factors are relevant irrespective of diagnosis; for instance, capacity to harm the self, as evidenced by past suicide attempts, is a significant factor in suicide risk for patients with major depressive disorder (Hawton et al. 2013), schizophrenia (Gómez-Durán et al. 2012), and bipolar disorder (Guillaume et al. 2010; Valtonen et al. 2006). From a clinical perspective, these factors should always be incorporated into the suicide risk assessment. As new information is added to the model, a refinement of the overall risk is achieved. If we return to Sophia, simply based on the diagnosis of BD II in a female patient who had contact with mental health services, we understand that her longterm suicide risk is estimated at 4.8%. General risk factors can then be added. Some of these—namely, presence of suicidal ideation with a plan and a psychosocial stressor (argument with fiancé)—would increase her acute risk, whereas others, such as the absence of past suicide attempt and regular contact with treatment services, may reduce her risk. The fact that she has been brought to the emergency department by her parents could be an area of further exploration, because it may be evidence that Sophia has some strong social supports (potentially lowering her risk) and/or a sign that she lacks insight into her disorder or is reluctant to engage in further treatment (potentially increasing her risk). For some of the general risk factors, another layer of complexity results from the interaction between bipolar disorder and these factors. The most notable example is sex-based differences in suicide attempts and deaths. The general literature on suicide generally identifies a threefold or higher ratio of suicide deaths in men compared with women. This, however, is not the case in bipolar disorder, as several lines of research have reported a much narrower sex-based difference in risk. The Swedish studies by Nordentoft et al. (2011) and Osby et al. (2001) identified a 1.4–1.7 to 1 ratio of incidence of male to female suicide deaths. The ISBD Task Force on Suicide in Bipolar Disorder meta-analysis included 11 studies that identified 1,149 suicide deaths among 75,055 bipolar disorder subjects, and reported an odds ratio of 1.83 (95% CI=1.41–2.39) (P=0.00001) for males compared with females. Therefore, although males with bipolar disorder are certainly at higher risk of dying by suicide, the ratio is notably reduced compared with the general population. This implies that the impact of a BD II illness on suicide risk in women is relatively higher than the impact on men. So rather than applying the standard ratio of 3:1, males to females, in the context of BD II, the 1.8:1 ratio is more accurate, although it has been identified from mixed subtype samples. Returning to our proposed model, sex is therefore a factor that is impacted by the presence of BD II. The presence of psychosis is another example of this type of interaction, with psychotic symptoms or disorders identified as general risk factors for suicide attempts and deaths (Chan et al. 2018; Dutta et al. 2011). However, in the context of bipolar disorder, this does not appear to be the case. Large clinical and epidemiological studies of combined BD I and BD II samples did not find any association between the presence of lifetime psychosis and suicide attempts (Dennehy et al. 2011; Finseth et al. 2012; Ryu et al. 2010), with one exception being a Korean study that identified an association between lifetime auditory hallucinations and suicide attempts in a clinical combined (BD I and BD II) sample (Song et al. 2012). Similarly, the presence of psychotic features has also been quite consistently shown to not be associated with suicide deaths in bipolar disorder samples (Black et al. 1988; Tondo et al. 2007), with the exception of a Taiwanese study that found that the presence of mood-incongruent psychosis at onset of illness was significantly less common among those that eventually died by suicide (Tsai et al. 2002). Psychosis, therefore, provides another example of how general risk factors cannot simply be extrapolated to bipolar disorder without first exploring for the presence of an interaction. Furthermore, within the context of BD II, psychosis can only be present in the context of a depressive episode, with a paucity of data specifically examining this subsample of presentation. For factors such as sex and psychosis, the impact of the illness on these features can provide a refined and more accurate assessment of risk, but there remain gaps in data specific to BD II. The relationship between substance use disorders and risk of suicide attempts and death in bipolar disorder is also complex. The overarching suicide literature has mostly found an impact of alcohol and drug use disorders on suicide risk (Kim et al. 2012; Porsteinsson et al. 1997). The heterogeneity in the nature and specifics of substance use makes it difficult to come up with broad generalizations, but most studies have found an effect. The ISBD Task Force examined this in some detail by first conducting meta-analyses using a broadly defined substance use measure, with follow-up analyses specifically for alcohol use, any illicit substance use, and specifically cannabis use. Eighteen studies were included in the broad substance use analysis, with a total combined BD I and BD II sample size of 39,139 subjects. The presence of a lifetime substance use disorder was associated with an increased likelihood of suicide attempts (OR=1.81, 95% CI=1.31–2.50). Consistent results were obtained for the first two subanalyses, with lifetime alcohol use disorder (OR=1.60) and lifetime illicit substance use disorder (OR=1.72) both being significantly associated with lifetime suicide attempts. Four studies were available for the analysis of cannabis use, with the largest study reporting a positive association, but the other three finding no difference, resulting in an overall nonsignificant OR=1.29. The data on substance use and suicide deaths in bipolar disorder samples are also mixed. The ISBD Task Force meta-analysis found a small (OR=1.20) but nonsignificant association between lifetime substance use disorder and suicide death. The data were heavily weighted by large epidemiological samples that did not find an association, in contrast to data from the mixed BD I and BD II clinical sample in the Systematic Treatment Enhancement Program (STEP)–BD, which reported a strong association (Dennehy et al. 2011). Many questions remain, as the timing of substance use could not be consistently elucidated. Returning again to Sophia, we now have further information for the model. Factors such as the presence of psychosis in her last depressive episode are understood to not necessarily impact her long-term suicide risk. Unfortunately, no further conclusions can be drawn here, and this is indicative of the need for more high-quality information to include in the model. This includes further data not only on the impact of specific factors but also on how the synergy of individual risk factors may modify risk. One of the key limitations at present is the absence of an accurate risk calculator that can combine the numerous general and bipolar disorder–specific risk factors into a single risk assessment estimate. Although extensive data do exist for a number of individual factors, there are few examples of two-factor analyses. Any further calculations are necessarily only blunt approximations based on single-factor effects, and there has been insufficient separation of BD II subanalyses to develop a more specific data signature for this group. This does not negate the value of applying a model for estimating suicide risk, but it must be understood that the level of precision is fairly poor, and that it is still prudent to eschew broader categories such as “low,” “moderate,” and “high” risk to avoid pseudoprecision. There is a substantial and growing literature examining the impact of bipolar disorder–specific clinical factors on risk of suicide attempts and deaths. These include variables such as age at illness onset, duration of illness, polarity of first episode, predominant polarity, polarity of most recent/current episode, the presence of mixed features, frequency of episodes, anxious distress, and atypical depressive features. A few studies have tested for differences in impact of these variables in BD II compared with BD I samples. Undurraga et al. (2012) prospectively examined 290 patients with bipolar disorder (BD II: n=86) followed for a median of 9 years. Patients with BD II were numerically but nonsignificantly more likely to develop suicidal ideation (54% vs. 37%). Other than depressive predominant polarity being overrepresented in the BD II group, there were no differences in risk factors for developing suicidal ideation or suicide attempts between patients with BD II and those with BD I. Bobo et al. (2018) conducted a very well designed and comprehensive comparison of suicide attempt risk factors in a large (N = 1,465) clinical sample of BD II and I subjects. They found only modest differences, with binge-eating behavior and comorbid binge-eating disorder being significantly associated with suicide attempts only in the BD II group; however, comorbid bulimia nervosa was a significant risk factor in both BD II and I groups, underscoring the challenge in interpreting these findings. Using machine modeling, they ranked the contribution of each variable by percentage of the total risk within both BD II and BD I samples but found only minimal differences between groups. Finally, in a STEP-BD subsample (Stanford site only) comprising 240 BD I outpatients and 254 BD II outpatients, several differences were found in correlates of suicide attempts (Goffin et al. 2016). Factors associated with suicide attempts in the BD I, but not the BD II, sample included lifetime history of eating disorder, current antidepressant use, lifetime history of an anxiety disorder, and first-degree relative with a mood disorder. In contrast, factors associated with suicide attempts in the BD II, but not the BD I, sample included childhood onset of bipolar disorder and lifetime history of psychosis. Phase of illness is also an important aspect of suicide risk assessment in bipolar disorder. Within BD II, not surprisingly, there is no significant increased risk during periods of pure hypomania, but there is an additive contribution of both depression and hypomania during mixed periods (Persons et al. 2018). Of note, this analysis of data from the National Institute of Mental Health Collaborative Depression Study found that a past history of mixed states was associated with risk of suicidal behavior during periods of depression in the BD I, but not the BD II, group. Overall, these data comparing risk factors between BD I and II show modest and sometimes inconsistent results. To date, there is insufficient evidence to suggest that differential contribution of specific factors be considered in clinical settings. Inclusion of bipolar disorder–specific clinical variables into the model shown in Figure 5–1 would then provide a comprehensive estimate of suicide risk. As noted earlier, this process does not lead to an exact estimate, because the field does not have the equivalent of a Framingham risk score. However, these factors can be used to inform the assignment of a categorical level of risk both acutely and in the long term. A management plan can be then developed on the basis of the assigned risk categories. In the next section we explore the management approach for a patient such as Sophia. The management approach for suicide prevention in patients with BD II should ideally incorporate two aspects. First, effective treatment for the underlying symptoms of BD II will undoubtedly have a positive effect on reducing risk of suicide (Angst et al. 1998; Khan et al. 2013). Second, there are specific pharmacological and nonpharmacological approaches to reducing risk of suicide that can complement treatment focused on symptom and episode reduction as well as functional improvement. A detailed discussion of management of BD II is covered in other sections of this textbook (see Chapters 8, “Mood Stabilizers and Antipsychotic Medications in Bipolar II Disorder”; 9, “Antidepressant Medications in Bipolar II Disorder”; and 10, “Psychosocial Interventions in Bipolar II Disorder,” respectively) and in published treatment guidelines (Yatham et al. 2018). The vast majority of treatment studies in BD II focus on symptomatic treatment, with suicide-related outcomes at times included as secondary measures or most commonly only addressed in the context of serious adverse events. It has been very difficult to indirectly glean any specific clinically relevant findings, even from pooled analyses of psychopharmacological trials in bipolar disorder (Khan et al. 2013). This leaves a smaller but growing literature that analyzes the impact of various interventions, not just on symptom reduction but on a variety of suicide-related outcomes such as suicidal ideation, suicide attempts, and deaths by suicide. This line of research begins with the study of the overall impact of any treatment on suicide-related outcomes. In studies of combined bipolar disorder samples, treatment to reduce symptom burden has been consistently associated with a significant decrease in suicidal behavior (Rucci et al. 2002; Yerevanian et al. 2007a, 2007b, 2007c). Fewer data are available with regard to prevention of suicide deaths, but what data are available suggest that mood stabilizer treatment likely reduces the risk (Angst et al. 1998; Khan et al. 2013). From a clinician’s perspective, what is of utmost importance is to understand how the various evidence-based treatments for mood episodes in the context of bipolar disorder differ in terms of their effects on suicidality. Among treatments for bipolar disorder, lithium has been the best studied with regard to a reduction in suicide attempts and deaths. A recent meta-review of 16 systematic reviews (Smith and Cipriani 2017) summarized the putative antisuicidal effect of lithium treatment in bipolar disorder but also highlighted the limitation from the absence of large comparative randomized controlled trial (RCT) data. Although lithium treatment has been shown to be associated with a reduced rate of suicide in patients with bipolar disorder compared with treatment with placebo or with lithium discontinuation, and numerous epidemiological analyses have replicated the finding that suicide-related events are less frequent when patients are treated with lithium compared with other medications, there are no prospective RCT data showing lithium to be superior to other mood-stabilizing agents. One RCT analysis found lithium treatment to be associated with reduced risk of deliberate self-harm compared with carbamazepine, but this has yet to be replicated (Cipriani et al. 2013). This remains the one aspect of research on lithium and suicide in bipolar disorder that would confirm the extent and specificity of the antisuicidal effects of lithium in this disorder. Prospective studies are also needed to determine lithium’s effect within specific clinical situations and subgroups of patients such as those with BD II. In this context, there are again very limited data on the differential effects of treatment on reducing suicide across bipolar disorder subtypes. In a Swedish national registry study (Song et al. 2017), lithium treatment was associated with a reduction in rate of suicide-related events in both BD I and BD II groups. The BD II group had a numerically larger reduction in risk (hazards ratio=0.62, 95% CI=0.46–0.82) than the BD I group (hazards ratio=0.85, 95% CI=0.67–1.09); however, the confidence intervals overlapped. Apart from lithium, anticonvulsants have the next largest literature specifically on reduction of suicide-related behavior in bipolar disorder. Following a 2009 U.S. Food and Drug Administration warning on anticonvulsant medications being associated with an increased risk of suicide thoughts or actions, several studies investigated this potential but found no evidence to support this concern (Arana et al. 2010; Leon et al. 2012). Furthermore, epidemiological studies have reported evidence of lower rates of suicide attempts and/or suicides during the month after starting an anticonvulsant medication (Marcus et al. 2013) and repeat purchases of anticonvulsant medications (Søndergård et al. 2008). Patients who receive anticonvulsants have been consistently found to have higher rates of suicide-related behavior compared with patients who are receiving lithium (Collins and McFarland 2008; Goodwin et al. 2003), but again, these are nonrandomized studies. The findings may be biased by selective use of anticonvulsants for patients at increased risk of a suicide, related to the perception that this class may be more effective for “complicated” cases, including psychiatric comorbidities and rapid cycling. Additionally, the perception of higher lethality in lithium overdose may paradoxically lead clinicians to avoid lithium use in their highest-risk patients. After lithium and anticonvulsants, there is an enormous decline in the availability of data on antipsychotics or antidepressants and suicide-related events in bipolar disorder. Small clinical datasets and lack of RCT data make clinical interpretation of available data nearly impossible. Antipsychotic use has been associated with increased risk of suicide attempts (Ahearn et al. 2013; Yerevanian et al. 2007c), but these studies did not control for factors such as severity of illness and high-risk periods. Similarly, recent treatment with an antidepressant has been associated with increased likelihood of a suicide attempt (Marangell et al. 2008; Yerevanian et al. 2007b), yet for the same reasons as above, it is very difficult to interpret this finding with any confidence. Within the field of suicide prevention, significant attention has been given to the effectiveness of a variety of suicide prevention strategies. To date, there is a paucity of data exploring these interventions within bipolar disorder and certainly for subtypes such as BD II. We will therefore only review these briefly, because they can still serve as key components to a suicide prevention strategy for patients with BD II. Recent data suggest that the inclusion of a number of complementary strategies may be most advantageous. Prevention approaches that include coordinated aftercare, means restriction, publication of media guidelines on reporting of suicides, public awareness campaigns, gatekeeper training, general practitioner training, and availability of psychosocial treatments have each been shown to be effective, and when combined are estimated to have the potential to reduce suicide by 20%–25% (Krysinska et al. 2016). Specific psychotherapy modalities have also been shown to reduce suicide-related behaviors. Dialectical behavioral therapy (DBT; Linehan et al. 2015), cognitive-behavioral therapy for suicide prevention (Brown et al. 2005), and Collaborative Assessment and Management of Suicidality (CAMS; Jobes 2012) all show evidence of reducing suicide-related behaviors. Replicated data on novel interventions such as “caring contacts” after delivery of acute mental health services have also been shown to reduce risk of suicide-related behavior and even suicide deaths (Luxton et al. 2013). There has also been great interest in strategies to enhance coping, with different local versions developed based on the framework of the Stanley and Brown safety planning intervention (Boudreaux et al. 2017). A number of targeted management steps can be considered for patients such as Sophia. Table 5–1 below provides a summary of management options to consider. TABLE 5–1.Management options to consider for case vignette of patient with bipolar II disorder Standard treatment options Specific suicide prevention options Use evidence-based treatment to treat BD II depression. Institute means restriction with regard to access to a large amount of medications. Discontinue antidepressant in context of mixed features. Use psychotherapy modality with evidence for suicide prevention (i.e., CBT, DBT, CAMS). Consider use of lithium as monotherapy or in combination with an atypical. Initiate caring contacts after ED visit. Ensure appropriate follow-up. Develop written safety plan. Note.CAMS=Collaborative Assessment and Management of Suicidality; CBT=cognitive-behavioral therapy; DBT=dialectical behavior therapy; ED=emergency department. Bipolar II disorder is clearly associated with an increased risk of suicide attempts and death; however, epidemiological data suggest limited, if any, impact of bipolar disorder subtype on absolute risk. Models that incorporate both general and illness-specific clinical factors can enhance estimation of suicide risk in patients with BD II, yet these are inherently limited by large gaps in the data and the known poor predictive capacity of suicide prediction models. 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5
Suicide and Bipolar II Disorder
Epidemiology
Overall Suicide Rates in Bipolar Disorder
Suicide Methods
Suicide Rates in Bipolar II Disorder
Suicide Attempts in Bipolar I and II Disorders
Summary of Epidemiological Data
Clinical Factors
A Framework Model for Understanding Suicide Risk
Identifying General Suicide Risk Factors
Identifying the Impact of Bipolar Disorder on General Risk Factors
Identifying Impact of Factors Specific to Bipolar Disorder
Management
Overview
Pharmacological Treatments
Nonpharmacological Treatments
A Management Approach for Sophia
Conclusion
KEY POINTS
References
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