Open access peer-reviewed chapter
Risk factors of suicidal behavior in bipolar disorder patients.
Abstract
Bipolar disorder is a chronic, episodic illness that can cause functional impairment and has a variable course. Compared to other psychiatric disorders, bipolar disorder is linked to a more elevated risk of suicide. The incidence of fatal suicide methods was shown to be higher in these patients compared to the general population. Severe, pure, or mixed depression episodes are most commonly linked to thoughts and behavior of suicide. However, it is less prevalent in episodes of dysphoric mania and seldom during episodes of euphoric mania or euthymia. Various factors have been studied as risk factors for suicide in bipolar disorder. These include gender, history of suicide attempts, suicidal thought, family history of suicide, mood episodes, rapid cycling illness, age of onset, attack polarity, drug use, and personality traits. Lithium therapy is known to dramatically lower rates of self-harm and suicide behavior in patients with unipolar and bipolar depression. ECT has an effect on the prevention of suicide in unipolar and bipolar depression. Identifying protective factors is as important as identifying risk factors. Adaptive coping mechanisms and social support seem to have protective effects. It is crucial to remember that treatment and a good response to treatment are protective against suicide.
Keywords
- suicidal behavior
- mania
- hypomania
- risk factors
- treatment
1. Introduction
Approximately 800,000 deaths worldwide occur each year due to suicide. Therefore, suicide is considered a significant public health problem [1, 2, 3]. Bipolar disorder is an episodic, lifelong mood disorder in which manic/hypomanic or depressive episodes occur, sometimes separately and sometimes together and can also lead to functional impairment [4, 5, 6]. The all-cause mortality rate in bipolar disorder is twice as high as in the general population. Of the specific causes, the risk is highest in suicide. Patients with bipolar disorder have approximately 20–30 times higher suicide risk than the general population [7, 8].
Patients with bipolar disorder have been observed to have more lethal suicide attempts and methods compared to the general population [9]. Bipolar disorder carries the highest risk of suicide among other psychiatric disorders [10, 11, 12]. They are also at higher risk of completing suicide than both the general population and those with other mental illnesses [13]. Approximately one-third to one-half of patients with bipolar disorder attempt suicide at least once during their lifetime. Approximately 15–20% of patients die by suicide [14, 15, 16, 17]. Patients with bipolar disorder who have previously attempted suicide have a significantly impaired quality of life, even if they are clinically euthymic [12, 18, 19]. A history of previous suicide attempts is the strongest predictor of completed suicide [20].
There is evidence to suggest that completed suicides tend to occur disproportionately in depressive, dysphoric, and mixed episodes compared to manic or hypomanic episodes [21]. Bipolar disorder-II (BD-II) is associated with a comparatively elevated risk of suicide in comparison to bipolar disorder-I (BD-I). This disparity may be attributed to the longer duration of depressive episodes experienced by individuals with BD-II [8, 22]. Multiple studies have also shown comparatively elevated rates of completed suicide among BD-II compared to those with BD-I, therefore disproving the assertion that BD-II is a less severe form of bipolar disorder [23]. Reconsolidating the current data on suicide risk in BD-I and BD-II might enhance clinical evaluation, care planning, and therapy choices for individuals with bipolar illness [24].
This chapter is about suicidal behavior in patients with bipolar disorder. In particular, the relationship between suicidal behavior and hypomanic and manic episodes of bipolar disorder has been investigated. The history, epidemiology, risk factors, treatment and preventive approaches of suicidal behavior have been mentioned. It has been written in order to contribute to the literature by reviewing the studies on suicidal behavior in bipolar disorder. Suicidal behavior in bipolar disorder was first investigated by scanning the articles of the last 10 years in PubMed and Google Scholar. Since the resources on suicidal behavior in mania and hypomania were limited, the year criterion was removed and the search was expanded. In screening (1) bipolar disorder, (2) suicide, (3) suicidal behavior, (4) hypomania, (5) mania, (6) lithium, (7) ECT keywords were used. The reviewed articles and the sources of the articles were evaluated and the appropriate ones for this study were taken into consideration.
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2. Definition and history of suicidal behavior
Although there are several different definitions of suicide that mean the same thing, I think the definition that best explains it is “any death that is the direct or indirect result of a positive or negative action taken by a person knowing that it will result in death” by French sociologist Emile Durkheim [25]. Throughout human history, actions and views on suicide have changed. When we look at the history of suicide, some societies have called suicide the work of the devil and an attempt that would attract the wrath of the Gods.
In the past, some societies burned the houses of individuals who committed suicide and prevented their bodies from being buried [26]. The provision in the Attic Laws in Ancient Greece, which required a person wishing to end her life to notify the state in advance of her/his action, stating her/his reasons, shows that the State controlled the action rather than prohibiting suicide. In Roman society, society consisted of various classes and each class was subject to its own laws. Therefore, the treatment given to freemen, slaves, and soldiers differed from each other in terms of suicide. Free people who attempted suicide were punished severely, while slaves were deprived of all their rights. Many slaves were seen to commit suicide due to overwork and the behavior of their masters. A slave who attempted suicide was considered an immoral person. Later, the Romans, who learned the maxims of the Stoics and Greek philosophy, accepted suicide as a pleasant way to end one’s life [27, 28]. In the military, a soldier who ended his life due to fear or laziness was considered a dishonorable person. Since a soldier who was assigned to protect his country was obliged to serve his state in this capacity, the act of suicide was considered desertion from the army [27].
According to the Christian religion, suicide is not tolerated and there is a belief that the individual cannot voluntarily take the life given by God. Suicide is not tolerated in Islam too, and there is an opinion that no individual should kill himself/herself [28]. On the other hand, Buddha and Brahman religions do not see suicide as a sin [26].
The prosecution of the act of suicide, which was not tolerated and was punished severely, declined toward the end of the eighteenth century, particularly under the influence of Beccaria, Montesquieu and Voltaire [27]. In England, people who attempted suicide were punished until 1955. In six tribes living in Nigeria, Uganda and Kenya, it is believed that touching individuals who have committed suicide will bring bad luck. In contrast, in Trikopia, some types of suicide acts are respected and admired [26].
There are many approaches to explaining suicidal behavior from a psychosocial perspective [29]. One of the most important theories on suicide is Emile Durkheim’s socially oriented theory. Durkheim argued that suicide stems from conflicts between individuals and society and irregularities in the individual’s relationship with society. As the level of social integration increases in a society, suicide decreases. He stated that the suicide rates of those who cannot identify with social groups are higher than those who are committed to society. He explained that this rate is lower in married people than in single, separated, or divorced people, and lower in religious people than in non-religious people. He stated that suicide rates increase even more when there is a deterioration in social values such as a war defeat or economic depression. Durkheim seems to have concluded that the weakening of the bonds of individuals with the social groups they identify with is the main factor in suicidal behavior [27]. His theory is successful in explaining the distribution of suicide rates across societies and countries. In theories that focus on the relationship between suicide and internal factors, such as psychodynamic theories, which define suicide as “the desire to kill oneself as a result of directing one’s anger at others,” suicide is expressed as a means of communication, providing help, remorse, confession, threat, or revenge [29].
A behavioral process that begins with thought and ends in death is defined as “suicidal behavior.” The National Institute of Mental Health has identified three main concepts related to suicide. The first of these is completed suicide, which is a voluntary, self-directed behavior that results in death [30]. The second is called a suicide attempt. It describes behaviors that aim to end a person’s life but do not result in death [28, 30]. This term encompasses behaviors classified as nonfatal acts, such as incomplete suicide, failed suicide, suicide declaration, and contradictory attempt. Individuals who attempt suicide are known to attempt suicide multiple times later in life [30]. The last one is suicidal ideation. It is defined as the person constantly thinking about suicide, making plans in this direction, openly threatening to kill himself, openly expressing a desire to die but not having any observable behavior [30, 31].
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3. Epidemiology of suicide
Annually, approximately 800,000 fatalities occur globally due to suicide, underscoring its significance as a public health concern [1]. Suicide ranks among the top 10 leading causes of death worldwide, and in certain countries, it is the second most prevalent cause of death for individuals aged 15–34. This issue presents substantial challenges to both medical practitioners and society at large [32]. Notably, suicide rates exhibit geographical and national variations, influenced by factors such as age, gender, socioeconomic status, chosen methods, and access to healthcare services. While the incidence of suicide attempts is notably higher among women, completed suicides occur three times more frequently among men. Overall, suicide attempts are estimated to be 30 times more prevalent than completed suicides, with repeated attempts serving as significant predictors of eventual completion. The most common methods of suicide include hanging, chemical poisoning, and firearms [33].
Psychiatric disorders are identified as the primary contributors to the majority of suicides [33]. The mortality rate associated with suicide in patients with major affective disorders is estimated to be between 15% and 20% [17]. Furthermore, it is believed that this mortality rate may exceed 20% in patients with bipolar disorder [15]. Studies indicate that nearly 50% of these patients will have at least one suicide attempt. Bipolar disorder is recognized as one of the most prevalent mental disorders associated with suicidal behavior, with the risk of suicide mortality approximately 30 times higher than in the general population [12]. Bipolar disorder is one of the most common mental disorders that lead to suicidal behavior. Suicide mortality risk in bipolar disorder is approximately 30 times higher than in the general population [8, 34, 35]. Suicide attempters with bipolar disorder use more lethal methods than patients with unipolar depression. This may partly explain why bipolar disorder is frequently mentioned in completed suicides [36].
The correlation between bipolar disorder and the risk of suicidal behavior is well established. Some studies have indicated that rates of suicidal ideation among patients with bipolar disorder may be higher, comparable, or lower than those observed in individuals with major depression, suggesting challenges in distinguishing the relative risk of suicidal behavior between these disorders [34, 37].
Moreover, the literature reveals difficulty in determining whether specific subtypes of bipolar disorder (BD-I or BD-II) correlate with higher levels of suicidal ideation [8, 35, 37, 38]. Nevertheless, a consensus exists in many studies that individuals diagnosed with bipolar disorder, particularly those with the BD-II subtype, are at an increased risk for both suicide attempts and completion. This heightened risk in BD-II may be attributed to the increased prevalence of agitated depression and anxiety disorders within this subgroup compared to BD-I [24, 39, 40, 41].
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4. The relationship between suicide and mental disorders
A diagnosis of mental disorder is present in 95% of all individuals exhibiting suicidal behavior [42]. Depression, drug use, psychosis are the primary risk factors [43] and other conditions including anxiety disorders, eating disorders, trauma-related disorders, personality disorders, and organic mental disorders [44]. Depressive disorder accounts for 80% of these mental disorders. For both males and females, the psychiatric diagnosis that carries the greatest risk of suicide is mood disorders. Depressed men are more likely to attempt suicide [42].
Approximately 10% of patients with schizophrenia die by suicide. These patients are affected by social isolation and stigma. Suicide in schizophrenia is often due to depressed mood. Hallucinations influence suicidal behavior in a small percentage of patients with schizophrenia. Although the suicide rate among patients with schizophrenia is quite low throughout their inpatient treatment, 50% of suicides happen during the first weeks and months after their release from the hospital [42].
Suicidal behavior is seen in 15% of patients with alcohol dependence. Approximately 80% of these are male. Personality disorders, difficulties in relationships and social adaptation, excessive negative life events, decreased ability to cope with discomfort, conflicts with people around them such as family members and healthcare personnel, depressive disorder, and alcohol addiction may lead to suicidal tendencies. In addition, approximately 20% of completed suicide attempts were made by patients with panic disorder and social phobia [42].
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5. The relationship between mania and suicidal behavior
Data in the literature on suicidal behavior in mania are limited. Studies have shown that suicidal behavior is more common in mixed mania than in pure mania [45, 46, 47, 48]. A total of 26–55% of patients with mixed mania have suicidal ideation, compared with only 2–7% in patients with pure mania [49]. In patients with bipolar disorder, suicidal behavior occurs most frequently during severe, pure, or mixed depressive episodes. It is less common during dysphoric mania and very uncommon during euphoric mania or euthymia [50, 51, 52, 53]. Suicidality in mania is unclear if it is a categorical phenomena indicating dysphoria without major depression or whether it arises from many simultaneous depressed symptoms. The analysis of clinical and demographic features of dysphoric manic patients with and without suicidality revealed a notable increase in suicidal thoughts among individuals with a previous suicide attempt, those who had taken antidepressants in the week leading up to hospitalization, those with a history of alcohol abuse, and who were Caucasian. Suicidal thoughts occurred in approximately 50% manic patients whose concurrent depressive symptoms were not sufficient to constitute major depression. Suicidality is a clinically significant concern in most dysphoric manic patients. Dysphoric mania alone and no single emotional symptom or symptom pattern usefully distinguishes suicidal from nonsuicidal manic patients [45].
A hypothesis has been proposed that the higher prevalence of suicidal thoughts in Caucasians may be due to the higher rate of dysphoric mania in Caucasians compared to non-Caucasians [47]. There is an opinion that dysphoric manic patients who take antidepressants immediately before admission may have more severe psychopathology or depression than those who do not take antidepressants. This may be one reason why dysphoric manic patients who take antidepressants immediately before admission are approximately four times more likely to commit suicide than those who do not take antidepressants. Another possible explanation is that antidepressants may cause increased agitation in some dysphoric manic patients, which may lead to increased suicidal thoughts [45].
Mixed depression is a major risk factor for suicide, and mixed depression is especially linked to BD-II [50]. Mixed depression is three times more common in BD-II than in unipolar depression, and this may partially explain the higher suicide risk seen in BD-II compared to unipolar depression [54, 55]. Every manic patient displaying significant depressive symptoms should undergo a thorough assessment for suicidal tendencies. Current findings support that suicide is fairly prevalent in dysphoric mania and is often concurrently two additional depressed symptoms [45]. Additionally, the risk of suicide may increase due to the patient’s delusions during a manic episode [56]. There is one study that found that symptoms of mania and anxiety during a depressive episode do not increase the risk of suicidal behavior in patients with bipolar disorder and at least moderate depressive symptoms. However, it is unclear whether symptoms of mania and anxiety during a depressive episode increase suicidal behavior in patients with bipolar disorder [57].
Bipolar disorder patients who have previously attempted suicide also exhibit traits such as increased severity of mania, more frequent occurrence of suicidal ideation during manic or depressive episodes, and higher prevalence of medical illnesses [58].
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6. Suicidal behavior in hypomania
As with mania, there is limited data in the literature on suicidal behavior in hypomania. It is known that 8–55% of patients with major depression have subthreshold hypomanic symptoms. Several studies have shown an association between subthreshold bipolarity and elevated levels of suicidality. This shows that patients with major depression who have subthreshold hypomanic symptoms have some differences from patients with major depression who do not have subthreshold hypomanic symptoms [59, 60, 61]. The limited data on hypomania and the little known effect on suicide risk may indicate the need for further studies on this subject.
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7. Risk factors and warning signs
Although common suicide risk factors are applicable to patients with bipolar disorder, there exist distinct risk factors that are unique to the pathology. Characterizing the risk factors unique to bipolar disorder patients for suicide has been challenging. Research examining suicide risk factors in bipolar disorder over the last few decades has produced mixed findings. Gender, mood episodes, rapid cycling illness, age of initiation, episode polarity, polarity of initial emotional episode, familial suicide history, previous suicide attempts, suicidal thoughts, personality disorders, personality traits, traumatic experiences, and substance abuse have been examined as risk factors for suicide in bipolar disorder. These factors are listed in Table 1 [16, 38, 62]. Results on gender are contradictory. Research shows that women attempt suicide at a higher rate, especially at a younger age, while men have a higher rate of completed suicide [9, 53, 63]. However, there are also studies that show no significant difference between men and women [17, 51, 58, 63, 64].
| Sociodemographic factors |
|
| Clinical history |
|
| Psychiatric comorbidity |
|
| Genetic factors |
|
| Other |
|
Table 1.
In patients with bipolar disorder, having previously attempted suicide increases the likelihood of suicide by 37 times [65]. At least 50% of all suicides are seen in people who have previously attempted suicide [66, 67]. Suicidal thought is linked to despair, mixed depression, severe depression, psychotic symptoms, prior suicide attempts, alcohol use, symptoms of panic disorder, and an early onset [16, 68, 69].
In bipolar disorder, major depression episodes by themselves are an important risk factor for suicide, with the majority of suicide attempts and committed suicides taking place during depressed periods. Additionally, if the initial mood episode was of a predominantly depressive polarity, there was an eightfold increased risk for a suicide attempt. An elevated incidence of suicide actions and suicide attempts is linked to the prevalence of dominant depressive polarity in future episodes [15, 70, 71]. Suicidal thoughts and behaviors are quite common in mixed episodes and dysphoric mania. Specifically, suicidal thoughts are present in 26–55% of patients with dysphoric mania, but only in 2–7% of patients with pure mania [16, 49, 64]. However, patients with bipolar disorder tend to make suicide attempts most commonly (78–80%) during severe pure or mixed episodes, less often (11–20%) during mixed affective episodes or dysphoric mania, and quite rarely (0–7%) during euphoric mania or euthymia [16, 72]. Suicide attempts have also been linked to the bipolar disorder subtype known as rapid cycling [73, 74].
The onset of a first depressive episode, the early phases of illness, untreated illness, the frequency of past depressive episodes, prior hospitalizations, and concurrent medical comorbidities have all been related to suicide in mood disorders [75]. Furthermore, there is a correlation between the development of mood-incompatible psychotic symptoms and a higher likelihood of suicide [76]. Bipolar disorder onset age has been linked to the likelihood of suicide attempts; a lower diagnostic age corresponds to a greater risk [51, 73]. Borderline, antisocial, histrionic, and narcissistic types of comorbid personality disorders significantly increase the risk of suicide. These personality disorders are associated with greater impulsivity, aggressiveness, and raised levels of severe mood episodes [16].
There is insufficient evidence to conclude that drug, alcohol, or nicotine use problems increase the risk of suicide in people with bipolar disorder [16]. A number of risk variables, including childhood abuse and neglect [75], higher altitude [77], dysfunctional personality characteristics [78, 79], being single, widowed, or divorced, inadequate social support, spirituality, and religiosity [12] have not been well explored but are believed to play a role in suicide.
Studies consistently demonstrate that a past history of suicide attempts [16, 63, 73, 80, 81] and a family history of attempted or completed suicide [64], especially in first-degree relatives [63, 73] are the most dependable and potent risk factors for suicide attempts and completed suicide in bipolar disorder patients. This may be partially attributed to the inherent heredity of bipolar illness (40%) and the intra-family transfer of suicidal tendencies [82]. As shown in primary research and other twins, family and adoption studies, there is evidence that genetic risk factors contribute significantly to suicide in patients with bipolar disorder [38, 66, 76]. Strong associations were found between the risk of suicidal behavior and the serotonin-related genes 5-HT1–7 and 5-HTT, as well as the tryptophan hydroxylase genes TPH1 and TPH2. Suicidal attempts have been associated with several genes, such as AKT1, AKT1P, ADRA2, BDNF, COMT, CREB1, GSK3B, FOX03A, and MAPK1 [8, 83, 84, 85]. Three major genes linked to a higher risk of suicide attempt were identified in the biggest genome-wide association study (GWAS) conducted so far. Bipolar disorder has been linked to an intronic variation of non-coding RNA LOC105374524, an insertion-deletion polymorphism on chromosome 4 [86]. Genetic studies on suicide may guide us in determining the underlying biological mechanisms, developing suicide prevention strategies, and taking precautions against suicidal behavior in the future.
There exists data indicating that the presence of white matter hyperintensities in the brains of patients with bipolar disorder may raise the risk of suicide [87, 88, 89]. Nevertheless, the expansion of white matter hyperintensity volume in bipolar disorder may be associated with disease burden and may not have a direct connection to the risk of suicide [90]. Suicidal behavior in bipolar disorder has been linked to disruption of the hypothalamic-pituitary-adrenal (HPA) axis, according to evidence [91]. Nevertheless, a lot of studies on how the HPA axis functions in bipolar illness have not specifically looked at how it can affect suicidal behavior. Furthermore, there is presently no clinical evidence to support the use of salivary/plasma cortisol level testing or dexamethasone suppression testing in the assessment of suicide risk in bipolar disorder patients [92, 93, 94].
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8. Diagnosis of suicidal behavior
The assessment of suicide risk in people with bipolar disorder should be conducted by direct clinical questioning. Insufficient attention given to psychiatric emergencies in overcrowded institutions and the failure to routinely assess bipolar disorder patients may have adverse consequences for instances involving suicidal thoughts or suicide attempts. A thorough psychiatric assessment should be carried out while evaluating suicide, including analyzing the patient’s mood, irritability, presence or absence of psychosis, and suicidal thoughts. Particular attention should be given to ascertaining the duration of suicidal thoughts, the presence of a detailed plan, the intended method of death, the characteristics and severity of prior suicide attempts, and the availability of deadly methods [95]. An analysis of the patient’s emotional temperament (depressed, hyperthymic, cyclothymic, irritable, anxious) and personality characteristics may provide a more precise assessment of suicide risk [51].
There are no suicide risk assessment tools that have been specially developed and validated for bipolar disorder. However, there are general risk assessment methods that can help clinicians to detect patients at high risk of suicide and effectively begin treatment. These should, of course, not be used as a substitute for comprehensive clinical assessment, but rather as a guide. Columbia Suicide Severity Rating Scale (C-SSRS) [96], Columbia Classification Algorithm of Suicide Assessment (C-CASA) [97], The Tool for Assessment of Suicide Risk (TASR) [98], the Oxford Mental Illness and Suicide tool (OxMIS) [99] or the Modular Assessment of Risk for Imminent Suicide (MARIS) [100] may be used for this assessment.
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9. Therapeutic approaches
The best treatment method for bipolar disorder patients who have attempted suicide is to hospitalize them in a psychiatric clinic. In this way, these patients are both protected and treated. Knowing the patient’s medication history and compliance with treatment contributes to treatment planning. Obtaining information from family members and/or close friends during the initial evaluation may be important for treatment planning, follow-up and prevention. For outpatients at high risk of suicide, follow-up evaluations should be performed at regular intervals after the initial evaluation, and any alteration in clinical status should be closely monitored [8].
The clinician should not hesitate to ask about suicide because of concerns that it may trigger suicidal behavior or because of personal concerns about the idea. Because patients with suicidal ideation often have had suicidal thoughts for a long time, most patients are open to discussing these thoughts. It is important to note that a significant number of individuals who complete suicide (regardless of diagnosis) have had contact with mental health services in the months leading up to their death. It is estimated that 75–83% of individuals who commit suicide have had contact with a physician in the past year. In the month leading up to the death, only 46% of these individuals have visited a mental health professional, and 36% have done so in the week prior to death. Therefore, it is important to discuss suicide with patients. The most effective way to prevent suicide in patients with bipolar disorder is to recognize clinical and demographic risk factors [62].
9.1 Pharmacotherapy
Initially, the initial stage in managing bipolar disorder involves verifying the diagnosis and assessing the present condition of the patient. Treatment varies depending on the episode. Mood stabilizers and antipsychotics are the primary therapeutic regimen for managing mania and depression [5, 38]. Clinical experience spanning decades, many randomized controlled trials, and meta-analyses have consistently shown that lithium significantly decreases suicidal and self-harm behaviors in patients with bipolar and unipolar depression [16, 101, 102]. Lithium is a prophylaxis against suicidal behavior, not an acute intervention. Furthermore, lithium overdose can be fatal. The long-term usage of lithium decreases the mortality risk by 60–80% [101, 103]. Noncompliance with lithium increases the risk of suicide [104]. Early intervention with suicide-preventive drugs like lithium, along with vigilant monitoring and regular follow-up, is the most effective approach to decreasing suicide rates [62]. The Food and Drug Administration reported an increased risk of suicide after reviewing clinical trials of carbamazepine, divalproex, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, and zonisamide, but this report has been extensively reviewed over the past 15 years, showing that these drugs do not increase the risk of suicide in bipolar disorder [105, 106]. In addition, valproate, lamotrigine, and carbamazepine have been shown to have a suicide prevention effect, although less than that reported for lithium [107].
Antipsychotic drugs recommended for bipolar depression include quetiapine, lurasidone, and olanzapine (in combination with fluoxetine). Atypical antipsychotics, such as aripiprazole, olanzapine, and quetiapine, may have antidepressant effects and long-term mood-stabilizing effects in patients with bipolar disorder. However, there is no specific evidence for a suicide prevention effect [8, 108]. Clinical evidence indicates that clozapine decreases suicide attempts and hospitalizations for suicidal behavior in patients with schizophrenia. Although not well researched, it has preventive benefits against suicide in bipolar disorder [109].
Despite the substantial reduction in suicide risk among depressed individuals with prolonged therapy, no antidepressant drug has been shown to prevent suicide [110, 111]. There are concerns that antidepressant medications may worsen the course of the illness by causing agitation during mixed episodes or by triggering transitions to hypomanic or manic states and may contribute to suicidal behavior [112]. In addition, some studies have even suggested that antidepressant treatment may increase suicidality in a subgroup of bipolar disorder [75]. However, the International Society on Bipolar Disorders has recognized that some patients with bipolar disorder may benefit from antidepressant medications and that the risk of transition is minimal when bupropion is prescribed in addition to mood stabilizers [113]. Several studies suggest that intravenous and intranasal ketamine may expedite the treatment of suicidal tendencies in bipolar disorder. However, the availability of ketamine is limited [114, 115, 116].
9.2 Electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS)
ECT is effective in reducing the acute risk of suicide in severely depressed and suicidal adult patients [103, 117]. ECT has been shown to provide better suicide prevention outcomes than current pharmacological treatments in both unipolar and bipolar depression [118]. Nevertheless, the enduring impact of ECT on the management of suicidal tendencies in individuals diagnosed with bipolar disorder remains uncertain [51].
TMS is an approved treatment for treatment-resistant major depression. It may have a short-term potential reduction in suicide risk. However, TMS is not currently FDA-approved for bipolar depression. Although TMS and rTMS (repetitive transcranial magnetic stimulation) have been shown to have potential benefits for bipolar depression, there is a theoretical risk of transitioning to hypomania or mania [119, 120, 121].
9.3 Psychotherapy
There are few studies investigating the effects of psychological treatment on suicidal ideation in patients with bipolar disorder [8, 103]. In general, psychotherapy and other psychological approaches are used in addition to pharmacotherapy in the treatment of patients with suicidal ideation [103]. The problem of compliance with treatment for suicidal patients is the biggest obstacle in treatment [122]. While depression itself may cause problems with treatment compliance, other diagnoses such as lack of motivation and personality disorders and hopelessness about treatment may also be effective [122, 123]. Once the patient has attended the first therapy session, measures such as fixing the therapist and meeting times and calling the patient when he/she does not show up will increase compliance [124].
Psychotherapeutic techniques based on problem-solving, cognitive and behavioral methods may limit the risk of suicide in relatively mildly depressed patients [125]. A systematic review of observational studies investigating the effects of psychotherapeutic programs in preventing suicidal behaviors found that cognitive behavioral therapy (CBT) and dialectical behavioral therapy (DBT) were the most commonly used and effective psychotherapeutic interventions, even in the short term, for patients with suicidal ideation or suicide attempts [126].
Problem-solving therapy is based on the idea that individuals who encounter problems do not have sufficient problem-solving skills and therefore try to solve them through inappropriate means, such as suicide [127].
After identifying the problem, it leads to finding more functional ways to solve this problem. The therapist should discuss the patient’s way of thinking, expose them to the factors that cause negative emotions in a controlled manner, accompany the patient while producing new solutions, and help the patient evaluate himself/herself positively when he/she can produce healthy solutions [128].
Cognitive therapy used in suicidal behavior, although it originated from cognitive therapies used in the treatment of depression, shares many common techniques with problem-solving therapy. It states that thoughts and interpretations related to the event affect emotions and behavior. The thoughts and cognitive distortions that the individual automatically produces reveal unhelpful adaptive behaviors, including suicide. The patient’s basic beliefs include distortions about the outside world and himself. These basic beliefs affect cognitive content and processes. The therapist tries to change the patient’s suicidal behavior by focusing on the patient’s cognitive content and processes [129].
A brief intervention addressing suicidal behavior disorder with Acceptance and Commitment Therapy has shown a reduction in both the frequency and intensity of suicidal ideation [130].
Alongside these findings, there are also opinions that psychological interventions have little or no apparent benefit in bipolar disorder [8, 17, 103, 125, 131].
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10. Preventing suicidal behavior
Identifying protective factors is as important as identifying risk factors [8]. Prospective studies suggest that suicide attempts in bipolar disorder are predicted by long duration of untreated illness [132], smoking [133], rapid cycling [134], early onset of bipolar disorder [135], previous suicide attempts [80], severity of depression [110], alcohol or other substance abuse [136] and feelings of hopelessness [137]. Strong social support, good family structure, and the use of adaptive coping mechanisms may provide protective benefits. In addition, a hyperthymic temperament and a strong sense of perceived meaning in life are also protective elements [34, 138, 139]. It has been revealed that religiosity may play a protective role, but the results are not yet conclusive [12, 140, 141]. It is crucial to emphasize that treatment, and particularly a positive response to treatment, is protective against suicide. Given that treatment can reduce the risk of increased suicidality, it is not surprising that most suicides are untreated [8, 34, 142].
Pharmacologically speaking, lithium has the most potential to prevent suicide in patients with bipolar disorder [101, 143, 144]. Lithium treatment is likely to benefit suicide prevention by reducing impulsivity and aggression seen in depression or dysphoric-agitated, mixed states, which are especially linked to suicidal behavior [101, 145]. Some results suggest that lithium may contribute to suicide prevention even in patients with bipolar disorder who show limited or moderate response to its preventive properties. This finding may suggest that in a patient with a high risk of suicide who does not show improvement with lithium, the physician should either maintain lithium, even at a reduced dosage, or add it to another mood stabilizer instead of switching to a different mood stabilizer [143].
The International College of Neuropsychopharmacology clinical guidelines recommended ketamine as a fourth-line therapy for bipolar depression, only when used in combination with a mood stabilizer. The effects of ketamine on patients with bipolar depression have been the subject of few research. These investigations indicate that ketamine has antidepressant effects similar to those seen in unipolar depression [146, 147, 148].
Apart from its antidepressant properties, ECT is also regarded as a potent antisuicidal intervention. It has comparable effectiveness in treating bipolar depression to MDD. According to certain research, ECT has shown greater efficacy in treating bipolar depression compared to unipolar depression. Its antisuicidal effects are comparable to the psychopharmacological effects seen in bipolar mixed states and mania [8, 118, 143, 149].
11. Conclusions
Among mental diseases, bipolar disorder has the greatest association with suicide mortality. Predicting suicide is difficult, but some risk factors may be used to evaluate the risk of suicide in bipolar disorder. These include previous suicide attempts, family history of suicide, and a dominant depressive polarity. In order to reduce suicide in bipolar disorder patients, regular psychiatric controls, early intervention and treatment during attack periods, and close observation and follow-up are effective ways. Lithium’s effect in reducing the risk of suicidal behavior may be advantageous in treatment. In addition, ECT may be a prompt and efficient method to treat suicidal tendencies in bipolar disorder. Supportive social environments and psychological support may also provide further benefits.
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