US Pharm. 2016;41(11):HS12-HS18.
ABSTRACT: In 2014, the Office of Suicide Prevention of the U.S. Department of Veterans Affairs reported that veterans have a 21% higher risk for suicide when compared to civilian adults. Greater prevalence of mental health conditions, such as depression and posttraumatic stress disorder (PTSD), as well as substance use disorders, place veterans at a higher risk for suicide. Early identification of high-risk patients allows for appropriate intervention and assistance to recovery. Understanding the unique risk factors associated with veterans, being aware of the warning signs of suicidality, possessing knowledge of medications associated with an increased risk of suicide, and being familiar with available suicide-related resources can better equip pharmacists with the tools needed to help prevent suicide in this population.
Veterans account for one of every five suicides.1 Compared to the general population, veterans are less likely to seek care for psychiatric disorders, are more likely to successfully complete suicide, and have a significantly higher suicide risk.2 In 2014, the Office of Suicide Prevention of the U.S. Department of Veterans Affairs (VA) reported that veterans have a 21% higher risk for suicide when compared to civilian adults.3 Combat exposure to trauma and death are associated with the development of various mental health conditions, such as posttraumatic stress disorder (PTSD) and major depression.4 Veterans suffering from such psychiatric disorders have up to a 5.7-fold increase in the risk of suicidal ideation as compared to those without.5 The FDA has identified medications and drug classes with increased suicidality, designating them with black box warnings (BBWs). Addition of such medications to a veteran’s drug regimen can further potentiate the risk of suicide.
In a recent study of veterans who served during the Iraq and Afghanistan wars between 2001 and 2007, the rate of suicide was greatest within 3 years of leaving service.4 In addition, the rate of suicide was highest in both male and female veterans who were 18 to 29 years old.3 Early recognition of the signs of suicide and identification of potential risk factors is crucial in preventing suicide in veterans. Recognizing the importance of suicide prevention in all veterans, regardless of gender and age, should also be acknowledged.
In 2013, the VA and the Department of Defense (DoD) released a joint clinical practice guideline for the assessment and management of patients at risk for suicide.6 Although no absolute method exists to assess suicide risk, the VA/DoD developed a three-tiered stratification system (high, intermediate, and low) to aid in determining acuity and the level of clinical intervention. The risk assessment should include evaluating suicidal ideation, suicidal intention, suicidal impulse, and suicidal attempt or preparatory behavior.6
Observed warning signs should be identified and immediately reported (TABLE 1).7 Those associated with the highest likelihood of suicidal behavior occurring in the near future include suicidal communication such as writing or talking about suicide, preparations for suicide or seeking access, and recent use of lethal means such as weapons, medications, or toxins. These behaviors are likely to put individuals at higher risk, particularly if they have previously attempted suicide, have a family history of suicide, or intent to use and have access to using a method that is lethal.6
A systematic review prepared for the VA evaluated 26 studies for risk factors associated with suicide attempts and completed suicides.8 This report concluded that there was adequate evidence supporting the relationship between PTSD, depression, and psychiatric conditions (e.g., psychotic disorder, personality disorder) with increased risk of suicide. Although evaluation of other risk factors such as substance use disorders (SUDs) and traumatic brain injury were limited, the significance of such concomitant conditions should not be dismissed. Medications associated with increased risk of suicidality should also be considered when evaluating the appropriateness of a patient’s drug regimen.8
Mental Health Conditions That May Increase Suicidality
Depression: Depression is a major mental health diagnosis within the veteran population. In a report published by the VA, the rate of depression is doubled in veterans aged ≥65 years as compared to the general population within the same age group.9 In a subset of Operation Iraqi Freedom (OIF)/Operation Enduring Freedom (OEF) veterans who were evaluated, 14.3% were diagnosed with depression.10
The most serious consequence of severe depression is suicidal ideation, so early detection and treatment of depression is essential. In a study conducted by the VA, 51% of patients with depression who died of suicide had seen a provider in the month preceding their suicide, highlighting the importance of periodic screening for suicidality during treatment of depression and appropriate referral to mental health programs.11
PTSD: In a survey of more than 3,000 veterans, the prevalence of PTSD was estimated to be 8%, with a notably higher prevalence in females as well as in younger veterans aged 21 to 29 years.12 Veterans who screened positive for PTSD were more than four times as likely to endorse suicidal ideation relative to non-PTSD veterans.13 PTSD has been found to be a particularly significant risk factor for suicidal ideation in OIF/OEF veterans, with up to 20% of veterans having PTSD in a given year.14
Veterans with PTSD are at high risk for developing suicidal behavior, depression, and SUDs.15 Therefore, early detection and treatment of PTSD is important. It is also important for clinicians to be aware of the resources available for veterans to ensure successful recovery. The VA has a National Center for PTSD, which offers resources to veterans, the general public, and professionals.16
SUD: Veterans in the 18- to 25-year-old age group are the most susceptible to SUD. The DoD has had a policy of zero-tolerance for illicit drug use, which accounts for the low rates of SUD in military personnel compared to civilians, 2.3% vs. 12%, respectively. Conversely, service members report higher misuse of prescription drugs than civilians. The most commonly abused prescription drugs are opioids.17 In addition, alcohol misuse has increased considerably over the years in service members.
In the 2010 Army Suicide Prevention Task Force Report, almost one third of all suicides involved alcohol or drug abuse.17 Therefore, prudent prescribing of prescription medications with abuse potential and early detection and treatment of SUD is significant. Utilization of resources such as prescription drug monitoring programs (PDMPs) is also key in preventing drug abuse.
Medications With Increased Risk of Suicidality
The FDA has identified over 125 drugs for potential increased risk of suicidal ideation and behavior and enforces BBW labels for these medications. Certain drug classes as a whole, such as antidepressants and antiepileptics, carry this labeling.18 In addition, the VA/DoD has identified medications with increased risk of suicide that may be of greater significance in the veteran population. Selected medications are highlighted in TABLE 2.6,19
Antidepressants: According to the latest VA Health Care Utilization Report among OIF/OEF veterans, it was determined that of veterans with a possible mental disorder, PTSD was the most prevalent diagnosis across four consecutive quarters, with depressive disorders ranked second.20 Antidepressants and antipsychotics play a pivotal role in helping veterans recover from these mental health disorders; however, recognizing the potential risks associated with their use is crucial.
Treatment of depression can present challenges and must be monitored appropriately. The BBW for antidepressants and suicidality was first introduced in 2004 when the FDA reported that children, adolescents, and young adults had higher rates of suicide when prescribed antidepressants, particularly during initiation or dose-titration periods.21 The association between antidepressants and suicidality is thought to be related to the medications’ effects on the physical symptoms of depression preceding the improvements in the emotional symptoms. Resulting mania or aggression can subsequently lead to self-harm. Although all patients on antidepressants should be monitored for suicidal ideation when titrating, younger veterans (18-24 years) in particular should also be monitored closely after initiation.22
Rate of initiation and titration of antidepressants, as well as drug selection, are also important in minimizing suicide risk. In a recent study of patients aged ≤24 years, higher initial doses of antidepressants were associated with a higher risk of suicide attempts, prompting a “start low, go slow” mentality for initiation and titration.18 In a series of four data reports collected in 2004 and 2005 from sponsors of antidepressants (including selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], and other antidepressants), the FDA concluded that the only notable observed differences of suicidal behavior and ideations between the drugs studied was an apparent lower risk of suicidality seen with sertraline.23 A retrospective study of patients undergoing treatment for depression at the VA from 1999 to 2004 suggested that sertraline and fluoxetine may be associated with a lower risk of suicide compared to other antidepressants.24 Despite these findings, it is important to recognize the importance of monitoring patients on all types of antidepressants.
Antipsychotics: Some atypical antipsychotics (e.g., aripiprazole, olanzapine) have been FDA approved for the treatment of depression or bipolar I disorder or as an adjunct for depression. As such, these antipsychotics also carry a BBW for increased suicidality and should be monitored closely in patients treated with these agents.25,26 Limited evidence suggests a positive relationship between some second-generation anti-psychotics (SGAs) and decreased suicidal behavior.27 The use of clozapine has been shown to reduce the risk for recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are considered at risk of reexperiencing suicidal behavior.28 Further research is necessary to clearly support the antisuicidal effects of antipsychotics.
Prescription Opioids: More than 50% of veterans in primary care suffer from chronic pain, resulting in the increased prescribing of opioid analgesics.6 The inherent risks of utilizing opioids in managing pain include dependency and overdose. Comorbid mental health conditions, such as PTSD, have been associated with high-dose opioid use, as well as coadministration with medications such as benzodiazepines. In August 2016, the FDA released a BBW regarding increased risk of extreme sleepiness, respiratory depression, coma, and death when taking opioids and benzodiazepines concomitantly.29 This combination of medications can result in an increased risk of overdose and further magnify the risk of opioid prescribing in the veteran population.30
Although the majority of fatal overdoses are thought to be unintentional, opioids can be “stockpiled” and used as a mode for suicide. For veterans with high suicide risk in particular, opioid therapy is not appropriate until further evaluation and stabilization occur.31
If opioids are warranted for a veteran, the monitoring of opioid use should be considered, which may include evaluating the prescribed dose (higher risk of overdose associated with >120 morphine equivalents/day), frequency of fills (also utilizing PDMPs), and appropriateness of concomitantly prescribed medications (e.g., benzodiazepines, antidepressants, antiepileptics, antiparkinsonian agents, antipsychotics/neuroleptics). Reduction in the quantity of pills per fill may also be considered in order to prevent the potential for intentional overdose.32
Varenicline: It is estimated that over 20% of veterans enrolled in the VA healthcare system currently smoke.33 For veterans interested in tobacco cessation, varenicline is an available treatment option. Early studies pointed toward the possible association of varenicline with suicidal ideation, suicide attempts, and completed suicide, prompting the BBW.34 Recent results from studies directly evaluating the risk of suicide with varenicline therapy are mixed. In a qualitative analysis by Hughes, varenicline was not associated with increased suicide outcomes.35 In addition, two recent, large observational studies and a meta-analysis of randomized controlled trials all failed to find significant associations between varenicline and suicidal behavior.36 Rather, it appears that tobacco use is associated with an increased risk for suicide.37
Nonetheless, in a series of case studies involving the use of varenicline in veterans, it was determined that as the veteran population has higher rates of comorbid psychiatric conditions, they may be at higher risk for serious adverse effects, such as suicidal behavior.38 Therefore, caution should still be exercised when prescribing varenicline in the veteran population. Close monitoring of any changes in behavior is also recommended.
VA-Specific Resources: In February 2016, the VA held the Veterans Suicide Prevention Call to Action Conference at which the Secretary of the VA, Robert McDonald, made a call to end the suicide crisis in the veteran population.39 The VA has actively begun to address the issue by implementing compre-hensive, broad-ranging suicide prevention initiatives, including a toll-free Veterans Crisis Line, placement of Suicide Prevention Coordinators at all VA Medical Centers and large outpatient facilities, and improvements in case management and tracking to address increasing rates of suicide in the veteran population.40
Best Practices for Pharmacists: Contrary to common belief, inquiring about suicidal intention does not increase the rate of suicide. A review of 13 studies examining this issue concluded that there was no statistically significant increase in suicidal ideation as a result of being asked about the presence of suicidal thoughts. In addition, the review suggested that inquiring about suicidal intention may possibly decrease rate of suicide and lead to improvements in mental health.41
Pharmacist Responsibilities: Pharmacists are uniquely positioned to identify at-risk patients and to engage in discussion regarding suicide due to their role in dispensing mental health medications. Many may consider pharmacists ill-prepared to appropriately respond to patients struggling with suicide. Developing a level of comfort that allows for empathetic and open-minded discussion is critical in preventing suicide.
Pharmacists should, at a minimum, have an understanding of common risk factors, particularly those specific to veterans, medications with BBW for suicidal ideation, and warning signs of suicidality. They should be cognizant of any changes in mood or behavior, such as feelings of hopelessness and encourage patients to immediately reach out to their mental health or primary care provider to discuss any suicidal thoughts. Collaboration with the healthcare team should also follow this consultation to ensure that the patient’s providers are aware of the current situation. Pharmacists should also be aware of the available suicide prevention resources and make appropriate referral to suicide hotlines (TABLE 3).42
Pharmacists can also monitor changes in how a mental health medication is taken or how it is prescribed. They should be encouraged to determine the reason behind recent changes in medications in an attempt to elucidate the patient’s current risk of suicide. The addition of medications to a patient’s regimen should also be evaluated to determine if high-risk drugs, such as those with BBW for suicidal ideations, have been prescribed, which can be brought to the attention of the patient and the provider. Above all, in consultations with patients, pharmacists should remember to be encouraging, listening attentively and helping connect patients with appropriate resources and providers.42
Set Appropriate Expectations: Patients should be made aware of when to expect antidepressants to improve mood and when to follow up with prescribers if their mood is not improving. Patients may expect physical symptoms to improve in the first 1 to 2 weeks of therapy, while mood symptoms may take 3 to 4 weeks before improvement is evident. At least 6 to 8 weeks is recommended to allow assessment of efficacy of a given dose and up to 12 weeks in geriatric patients. Patients may need to be on therapy for 6 to 12 months, even if symptoms improve. Those experiencing their first depressive episode after 60 years of age or experiencing three or more episodes within 5 years may require lifelong therapy due to the high risk of relapse.43,44
Stress Compliance: Patients need to understand the importance of compliance with antidepressants and be aware of the appropriate dialogue to have with providers if unwanted side effects occur from taking their medication. Studies supporting the importance of medication compliance have reported that the risk of suicide may increase five-fold after antidepressants are discontinued inappropriately.22
Create a Safe, Open Atmosphere for Discussion: Discussing suicide with patients can be uncomfortable; however, as frontline members of the healthcare team, pharmacists can be effective in preventing suicide. Being mindful of the way suicide is brought up and discussed can help to decrease the awkwardness. Asking open-ended questions in a nonjudgmental way can help to create an opportunity for patients to share, allowing for the provision of as many resources as possible to prevent a suicide attempt.45
It is estimated that up to 22 veterans die by suicide every day in the United States.46 When signing into law the Clay Hunt Suicide Prevention for American Veterans Act, President Obama recognized the magnitude of the issue, calling upon “every community, every American,” to make suicide prevention a national mission.39 As healthcare professionals, pharmacists can contribute to reaching out to our nation’s veterans. Understanding the unique risk factors associated with veterans, being aware of the warning signs of suicidality, possessing knowledge of medications associated with an increased risk of suicide, and being familiar with available suicide-related resources can help to better equip pharmacists with the tools needed to help prevent suicide. Taking the initiative to create a safe environment for open conversation and resisting hesitation in addressing the topic of suicide may aid in the first steps toward a veteran’s road to recovery.
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40. Office of Public Affairs. Remarks by Under Secretary for Health David J. Shulkin. VA conducts nation’s largest analysis of veteran suicide. U.S. Department of Veterans Affairs. July 7, 2016. www.va.gov/opa/pressrel/pressrelease.cfm?id=2801. Accessed October 4, 2016.
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46. Kemp J, Bossarte R. Suicide Data Report, 2012. Washington, DC: Department of Veterans Affairs; 2012. www.va.gov/opa/docs/Suicide-Data-Report-2012-final.pdf. Accessed August 10, 2016.
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