Suicide is the tenth leading cause of death in the United States claiming nearly 48,000 individuals in 2019 and is the second leading cause of death among individuals aged 10 to 34 years.1 From 1999 to 2019, the suicide rate increased by 33%.1 In a retrospective study evaluating suicide risk in > 29,000 men, veterans had a greater risk for suicide in all age groups except for the oldest when compared with nonveterans.2 Another study of > 800,000 veterans found that younger veterans were most at risk for suicide.3 Veterans with completed suicides have a high incidence of affective disorders comorbid with substance use disorders, and therefore it is imperative to optimally treat these conditions to address suicidality.4 Additionally, a retrospective case-control study of veterans who died by suicide matched to controls identified that the cases had significantly higher rates of mental health conditions and suicidal ideation. Given that the veteran population is at higher risk of suicide, research of treatments to address suicidal ideation in veterans is needed.5
Lithium and Antisuicidal Properties
Lithium is the oldest treatment for bipolar disorder and is a long-standing first-line option due to its well-established efficacy as a mood stabilizer.6 Lithium’s antisuicidal properties separate it from the other pharmacologic options for bipolar disorder. A possible explanation for lithium’s unique antisuicidal properties is that these effects are mediated by its impact on aggression and impulsivity, which are both linked to an increased suicide risk.7,8 A meta-analysis by Baldessarini and colleagues demonstrated that patients with mood disorders who were prescribed lithium had a 5 times lower risk of suicide and attempts than did those not treated with lithium.9 Lithium’s current place in therapy is in the treatment of bipolar disorder and major depressive disorder augmentation.10-12Smith and colleagues found that in a cohort study of 21,194 veterans diagnosed with mental health conditions and initiated on lithium or valproate, there were no significant differences in associations with suicide observed between these agents over 365 days; however, there was a significant increased risk of suicide among patients discontinuing or modifying lithium within the first 180 days of treatment.13
Currently, lithium is thought to be underutilized at the US Department of Veterans Affairs (VA) Michael E. DeBakey VA Medical Center (MEDVAMC) in Houston, Texas, based on the number of prescriptions of lithium in the large population of veterans seen by mental health clinicians. MEDVAMC is a 538-bed academic teaching hospital serving approximately 130,000 veterans in southeast Texas. The Mental Health Care Line has 73 inpatient beds and an outpatient clinic serving > 12,000 patients annually. By retrospectively evaluating changes in suicidality in a sample of veterans prescribed lithium, we may be able to better understand the role that lithium plays in a population that has a higher suicide rate than does the general population. The primary objective of this study was to evaluate the change in number of suicide attempts from 3 months prior to lithium initiation to 3 months following a 6-month duration of lithium use. The secondary objective was to determine the change in suicidal ideation from the period prior to lithium use to the period following 6 months of lithium use.
Methods
This was a single-site, retrospective chart review conducted between October 2017 and April 2018. Prior to data collection, the MEDVAMC Research and Development committee approved the study as quality assurance research. Patients with an active lithium prescription were identified using the VA Lithium Lab Monitoring Dashboard, which includes all patients on lithium, their lithium level, and other data such as upcoming appointments.
Inclusion criteria consisted of adults who were aged ≥ 18 years, had an active lithium prescription on the date of data extraction, and had an active lithium prescription for at least 6 months. Patients were excluded if they had < 3 months of data before and/or after lithium was used for 6 months, and if they were initiated on lithium outside MEDVAMC. Cumulatively, patients had to have at least 12 months of data: 3 months prior to lithium use, at least 6 months of lithium use, and 9 months after lithium initiation.
Suicide Attempt and Suicidal Ideation Identification
When determining the number of suicide attempts, we recorded 4 data points: Veterans Crisis Line notes documenting suicide attempts, hospital admissions for suicide attempts, suicide behavior reports within the indicated time frame, and mental health progress notes documenting suicide attempts. Suicidal ideation was measured in 4 ways. First, we looked at the percentage of outpatient mental health progress notes documenting suicidal ideation. Second, using the Patient Health Questionnaire-9 (PHQ-9) depression assessments, we looked at the percentage of patients that indicated several days, more than half the days, or nearly every day to the question, “Thoughts that you would be better off dead or of hurting yourself in some way.”14 Third, we recorded the percentage of suicide risk assessments that patients responded yes to both questions on current preoccupation with suicidal thoughts and serious intent and plan to commit suicide with access to guns, stashed pills, or other means. Finally, we noted the percentage of suicide risk assessments where the assessment of risk was moderate or high.
A retrospective electronic health record (EHR) review was performed and the following information was obtained: patient demographics, lithium refill history, concomitant psychotropic medications and psychotherapy, lithium levels, comorbidities at lithium initiation, presence of a high-risk suicide flag in the EHR, suicide risk assessments, suicide behavior reports, Veteran Crisis Line notes, PHQ-9 assessments, and hospital admission and mental health outpatient notes. The lithium therapeutic range of 0.6-1.2 mmol/L is indicated for bipolar disorder and not other indications where the dose is typically titrated to effect rather than level. Medication possession ratio (MPR) was also calculated for lithium (sum of days’ supply for all fills in period ÷ number of days in period). A high-risk suicide flag alerts clinicians and staff that a mental health professional considers the veteran at risk for suicide.15 Statistical analysis was performed using the paired t test for means to assess proportional differences between variables for the primary and secondary outcomes. Descriptive statistics were used to describe the baseline characteristics.