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Clinical Professor of Psychiatry
Department of Psychiatry
Icahn School of Medicine at Mount Sinai
New York, New York
Joseph F. Goldberg, MD: consultant/advisor/speaker: AbbVie, Alkermes, BioXcel, Jazz, Lundbeck, Otsuka, Sage, Sunovion, Supernus.
The term “suicidality” broadly encompasses thoughts, behavioral gestures, attempts, and completed actions related to deliberately trying to cause one’s own death. More than one half of individuals with bipolar disorder attempt suicide at least once, and suicide completion rates in bipolar disorder range from 4% to 19% Of note, individuals with bipolar disorder are up to 30 times more likely than people in the general population to make a suicide attempt. It is rare for suicidal features to occur during phases of pure (euphoric) mania, leading some experts to believe that suicidal behavior in people with bipolar disorder is driven mainly by depression alone (both regarding current symptom severity as well as cumulative burden of depression over time). Others think it is more driven by the combination of depression, high trait impulsivity, and the “activated” state seen in bipolar disorder with mixed features vs “pure” depressed phases of bipolar disorder, where energy and urges to act on impulses may be relatively low. In some studies, risk for completed suicide in bipolar disorder appears to be substantially higher during the first few years after illness onset, whereas in others the risk remains constant throughout their lifetimes. One longitudinal follow-up study noted an approximate 14%/year risk of suicidal thoughts or acts after a first lifetime manic episode.
A handful of risk factors for suicidal behavior in people with bipolar disorder are well established, but it remains impossible to predict imminent risk with certainty. In addition to depressive symptom severity or mixed features, having a history of previous suicide attempts, comorbid alcohol or substance use disorders, depression polarity predominance, and childhood trauma are among the more well-recognized clinical features that increase the possibility of suicidal behavior. Other features that have been identified as possible risk factors for suicidality may be “intervening” variables linked with other characteristics more immediately associated with suicidality, such as early age at onset, duration of untreated illness, a rapid cycling course, the number of medications someone is taking (sometimes a proxy variable for illness severity), or past medication nonadherence. Demographically, a bimodal age distribution for suicidality peaks before the age of 35 years and again after age 75 years. Men tend to complete suicide more often than women by virtue of undertaking more lethal methods, but women tend to make more attempts overall. All mood disorders carry an increased risk for suicidal features, and there is presently no consensus from research findings as to whether risk for suicide completions is different in bipolar vs unipolar (major) depressive disorder or in bipolar I vs II disorder.
Most suicide attempts in people with bipolar disorder occur on impulse rather than with premeditation. In that sense, the oft-cited “antisuicide” properties of lithium carbonate in bipolar disorder may have as much (if not more) to do with reducing the impulse to act on suicidal thoughts than on directly altering suicidal thoughts. In fact, no studies have demonstrated that lithium reduces suicidal ideation, but meta-analyses show that it does reduce the likelihood of suicide attempts by approximately 10% and completions by approximately 20%. By contrast, IV ketamine has emerged as one of the few (if any) drugs that appears to have a direct effect in reducing suicidal ideation during major depressive episodes—at least partially independent of its effect on mood. Retrospective studies that report lower suicide attempt or completion rates with lithium vs other mood stabilizers such as divalproex or carbamazepine can be difficult to interpret because of so-called confounding bias. This means it is possible that lithium use may be less likely to lead to suicidal behavior, but it is equally possible that nonrandomized studies merely show that patients deemed at higher risk for overdose or suicidal behavior may be more likely to be prescribed other drugs that carry less risk for lethality in overdose, although prospective randomized studies have shown similarly low rates of suicidal behavior between lithium and divalproex.
Considering the many uncertainties that persist about suicidality in bipolar disorder, best practices include several basic tenets. First, early recognition and intervention for bipolar disorder remains a cornerstone of good care. Good care means recognizing and assessing suicide risk factors over time and sharing information with patients and involved family members, particularly when patients themselves can influence modifiable risk factors such as comorbid substance use or poor treatment adherence. At the same time, healthcare professionals should appreciate that, despite the best of care, some patients with bipolar disorder may still succumb to the lethality of suicide, making such tragic outcomes unfortunately as inevitable as in other fields of medicine, such as oncology. The use of evidence-based pharmacotherapies for bipolar disorder, especially during phases of depression, may be instrumental in helping to mitigate suicide risk over time. That said, comprehensive care for high-risk patients, especially those with chronic suicide risk, should go above and beyond pharmacotherapies, as pharmacotherapy alone cannot afford sufficient protection against suicidality and other very poor treatment outcomes in high-severity/high-risk patients. This comprehensive care often involves multimodal team-based treatments with periodic reassessment of level of care and the inclusion of structured psychotherapies, case management services, occupational therapists, and other members of the treatment team.
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