Suicide prevention requires a comprehensive approach with consideration given to brain function, psychological stressors, and pharmacologic options, according to research presented by Teena M. McGuinness, PhD, PMHNP-BC, FAANP, FAAN, at the 2021 American Association of Nurse Practitioners National Conference (AANP 2021).1

As of 2019, suicide was the 10th leading cause of death overall in the United States.2 While suicide rates have not risen during the COVID-19 pandemic in the general population, rates of suicide have risen among children and adolescents, noted Dr McGuiness, who is professor emerita at the University of Alabama at Birmingham School of Nursing.

“Alarmingly, suicide attempts have risen 50% for adolescent girls during COVID-19,” Dr McGuiness said in an interview. Colorado has declared a pediatric state of emergency due to this mental health crisis.

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“Another sad finding is that the rate of suicide among nurses is much higher than that among physicians pre-COVID-19,” Dr. McGuiness said. “The suicide incidence for nurses who were women was 17.1 per 100,000 compared to 8.6 per 100,000 for the general population of women. Nurses who are men have approximately the same incidence as the general population of men (13.9 per 100,000); men historically have been known to have significantly higher rates of suicide.”

In her presentation, Dr McGuiness discussed the role of different parts of the brain in suicidality, how adverse childhood experiences affect brain function, and how prescribing esketamine or lithium may be effective in preventing suicide.

Suicidality and Traumatic Brain Injury

Dr McGuiness noted that veterans are a special at-risk population for suicide. While this increased risk is often linked to psychological complications following service, such as post-traumatic stress disorder (PTSD), suicide is also the leading cause of death among people with chronic traumatic encephalopathy (CTE). In the interview, Dr McGuiness outlined several ways in which veterans may acquire a traumatic brain injury (TBI) while in service, including working as a paratrooper or encountering an improvised explosive device.

Citing the death by suicide of football player Aaron Hernandez at age 27 as an example, Dr McGuiness said that patients who have CTE may have problems with mood, behavior, and cognition, which increase the risk for suicide. For veterans who sustain a TBI, Dr McGuiness explained that long-term effects are not always easy to anticipate.

“For an obvious head injury, military health care provides excellent care,” Dr McGuiness said. “But long-term sequelae may be unpredictable. The military and Veterans Affairs provide a service called Traumatic Brain Injury Center of Excellence, and is a good place to start.”

The Role of the Limbic System in Suicidality

The hippocampus and amygdala play a key role in the limbic system for suicide. In a patient who is considering suicide, there is decreased gray matter volume in the right and left amygdala and prefrontal cortex (PFC), as well as diminished functional connectivity between the bilateral amygdalae and the ventral and medial PFC. Dr McGuiness noted that the amygdalae–ventral/medial PFC circuit should be a target for intervention, as it is related to the pathogenesis of suicidal behavior. In addition, hippocampal volume could be a marker for suicidality.

Although the mechanisms underlying suicidality are multifactorial, Dr McGuiness pointed out that childhood trauma can be a contributing factor. She explained the link between adverse childhood experiences and changes in the limbic system, as well as gray matter alterations in the auditory cortex and specific language pathway, which may increase the risk of suicide.

Use of a measurement-based assessment like the Patient Health Questionnaire (PHQ-9) is a “requisite part of ensuring safety” for patients who are considering suicide, Dr McGuiness stated.

“The PHQ-9 is the most common method of measurement-based care and is often used in primary care clinics as a routine method of assessing mental health. Completed by the patient, the clinician can review the questions with the patient and have a frank discussion about the patient’s mental well-being,” she said.

Treatment Options for Suicide Prevention

From a pharmacotherapy perspective, multiple options are available for suicide prevention in at-risk patients. Dr McGuiness focused specifically on lithium and esketamine as treatment options in her presentation.

Esketamine is an antagonist of the N-methyl-d-aspartate (NMDA) receptor. This agent is currently approved for treatment-resistant depression in conjunction with an oral antidepressant and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. However, adverse events including dissociation, nausea, vertigo, and dizziness are common, and improvements lasting longer than 1 month have not been systematically evaluated for esketamine.

Lithium has been underprescribed in patients who are at risk of suicide. It is linked to reduced suicide risk in minute doses, but is most effective when given at a therapeutic dose, Dr. McGuiness explained. Known for its capability to decrease mood instability, lithium has neurotropic and neuroprotective effects. It has been associated with increases in hippocampal and cortical volume, telomere length, and improved genetic expression of behavioral genes.3

Prior to starting treatment with lithium, laboratory tests including kidney function tests, thyroid function tests, electrocardiogram (EKG) for patients older than 50 years or with a history of cardiac disease, pregnancy test, liver function tests, and complete blood count with differential should be performed. The patient’s weight should also be monitored.

“While monitoring of lithium levels as well as health in general with a focus on renal function since it is excreted via the kidneys is required, these actions can often be accomplished every 6 months, [which is] reasonable, considering that many chronic disorders require regular monitoring; bipolar disorder and most mental illnesses are chronic disorders,” Dr McGuiness stated.

Dr McGuiness suggests a “start low and go slow” approach to lithium treatment, and noted that gradual titration may lead to better treatment adherence.

“Research with consumers, families, and clinicians should be conducted on exploring how lithium therapy could become more acceptable as a treatment,” Dr McGuiness said. “For example, could education of clinicians, consumers, and families lead to less stigma and greater adherence? What specific practices of monitoring lithium levels and potential side effects would work to decrease stigma? What are the important outcomes that lithium could reduce?”

Dr McGuiness emphasized the importance of a comprehensive approach to suicide prevention. In addition to understanding brain function and considering pharmacologic treatment options, there are also psychotherapy options including dialectical behavioral therapy (DBT), Collaborative Assessment and Management of Suicidality (CAMS), and cognitive behavioral therapy (CBT).

Any patient experiencing suicidality requires a safety plan, such as the evidence-based Attempted Suicide Short Intervention Program (ASSIP).

Dr McGuiness concluded her presentation by urging clinicians to visit the Suicide Prevention Resource Center, which provides the latest evidence-based guidance on suicide prevention.


1. McGuiness T. Prevention of suicide by understanding the suicidal brain. Presented at: American Association of Nurse Practitioners National Conference; June 15-June 20, 2021.

2. Suicide. National Institute of Mental Health. Updated May 2021. Accessed June 20, 2021.

3. Post RM. The new news about lithium: An underutilized treatment in the United States. Neuropsychopharmacology. 2018;43(5):1174-1179. doi:10.1038/npp.2017.238

This article originally appeared on Clinical Advisor