Navigating the Complex PTSD, Medication, and Suicide Risk Landscape for Veterans

Tony Clark, September 15, 2025

Post-Traumatic Stress Disorder (PTSD) is a prevalent wound of military service, that lingers long after active duty.  PTSD profoundly impacts the lives of countless veterans. While advancements in mental health care offer hope, the interplay between PTSD, its pharmacologic treatments, and the tragic risk of suicide presents a complex challenge, which demands careful consideration and nuanced solutions. Balancing the benefits versus the risks of using medication to treat PTSD is complex. While medications offer a proven pathway to reducing debilitating PTSD symptoms, the potential for an acute increase in suicidal thoughts, particularly in the early and end stages of treatment, should not be overlooked.

PTSD: A Significant Risk Factor for Suicide in Veterans

While veterans make up a small portion of the U.S. population, they face a disproportionately higher risk of suicide. The Department of Veterans Affairs (VA) has consistently highlighted this issue, with a 2023 report showing that the suicide rate for veterans was 1.5 times the rate for non-veteran adults in 2021. Unfortunately, this gap has widened in recent years [1].

PTSD is a major contributor to this increased vulnerability, often co-occurring with other mental health conditions like depression and substance use disorders, all of which amplify suicide risk. The constant psychological distress, social isolation, and impaired functioning that come with severe PTSD can lead to profound feelings of hopelessness and clinically significant distress—key precursors to suicidal thoughts [5].

The Role of SSRIs: A Double-Edged Sword?

When it comes to treating PTSD, SSRIs (Selective Serotonin Reuptake Inhibitors) are a key part of current treatment plans. Specifically, the FDA has only approved two medications for PTSD: sertraline (Zoloft) and paroxetine (Paxil).

These two drugs are consistently recommended as the first choice for medication by the VA and the Department of Defense (DoD) in their clinical practice guidelines. The guidelines suggest using SSRIs, sometimes in combination with other medications, to help reduce core PTSD symptoms like intrusive thoughts, a heightened state of alert (hyperarousal), and avoidance behaviors.

Given their approved status and guideline recommendations, it is not surprising that SSRIs like sertraline and paroxetine are the most prescribed medications for veterans with PTSD. 2-Dooz's direct discussions with veterans and its PTSD Clinical Study recruitment efforts suggest that the percentage of veterans prescribed SSRIs for their PTSD symptoms may be over 80%.

A critical concern with SSRIs is the well-known "black box warning" about an increased risk of suicidal thoughts and behaviors. This risk is most pronounced in younger adults (under 25) when they first start treatment or when their dose is adjusted. While this warning applies to all populations, its implications are especially significant for veterans. Since veterans already face a heightened risk of suicide due to their PTSD and other co-occurring conditions, a crucial question arises: are we inadvertently increasing risk while trying to mitigate suffering?

Symptom Reduction vs. Suicide Risk

To adequately address this, we must consider the clinical utility of SSRIs against their potential risks.

• Benefit: PTSD Symptom Reduction (PCL-5)

Numerous clinical trials and meta-analyses support the effectiveness of SSRIs in reducing PTSD symptom severity.  A 2020 study of VA Practices found that SSRIs significantly reduced overall PTSD symptom severity by an average of 6.8 to 10.1 points, as measured by the DSM-5 PTSD Checklist (PCL-5) [2].

In context, a meaningful clinical improvement for the PCL-5 is assumed to be 10 points [3].  A PCL-5 score decrease of 10 points from the use of SSRIs should equate to a decrease in the severity of re-experiencing, avoidance, negative cognitions, and hyperarousal symptoms; significantly improving a veteran's quality of life and functional capacity. 

• Cost: Increased Risk of Suicidal Ideation/Behavior

The "black box warning" for SSRIs highlights a small but statistically significant increased risk of suicidal ideation and behavior, especially in younger adults and at the start of and end of treatment. While the absolute risk remains low, any increase in a population already vulnerable to suicide, such as military veterans, warrants serious attention.

One meta-analysis on antidepressants and suicidality across various psychiatric conditions found that the increased risk of suicidal ideation or behavior associated with SSRI use in adults under 25 was approximately 2 to 3 times higher than placebo; though the absolute difference in adverse events was small [4].

Weighing Clinical Efficacy Against Potential Harm

Studies reveal a complex picture. While some data suggests that successfully treating depression—a common co-occurring condition with PTSD—can reduce long-term suicide risk, the initial phase of SSRI treatment and any changes to dosage are a concern. This is especially true for younger veterans with severe PTSD, who may experience heightened emotional volatility during these periods [7]. 

Furthermore, discontinuing SSRIs too quickly can cause a more severe rebound of PTSD symptoms across all age groups. It's also important to consider the risk of drug interactions, as veterans often take multiple medications for co-occurring conditions like chronic pain. The suicide risk isn't tied to a single drug; rather, it is the cumulative effect of everything a veteran may be consuming along with an SSRI.

In summary, the use of SSRIs for veterans with PTSD is a delicate balancing act. While these medications offer a proven way to reduce debilitating PTSD symptoms, the potential for an acute increase in suicidal thoughts—particularly at the beginning or end of treatment—cannot be overlooked.

• Consider this case study: A veteran with a PCL-5 score of 67 indicates severe PTSD. If the veteran experiences a significant 10-point reduction in symptom severity from using SSRIs, he could go from being incapacitated by flashbacks and hyperarousal to having the capacity to engage in daily life, work, and therapy. However, if the crucial initial and end phases of treatment exacerbate suicidal thoughts, even briefly, the consequences could be devastating. 

Enhancing Safety and Efficacy

This tricky balancing act underscores the need for the following:

1. Personalized Treatment: A "one-size-fits-all" approach is insufficient. Treatment decisions must be highly individualized, considering a veteran's specific symptoms, co-morbidities, previous treatment history, and unique risk factors for suicide.

2. Integrated Care: When used before evidence-based psychotherapies like Cognitive Processing Therapy (CPT) or Prolonged Exposure (PE), non-pharmacological adjunctive therapies, like the one currently being tested by 2-Dooz, could potentially reduce the need for medication and the risks that come with it. By lowering symptom severity, these adjunctive therapies could pave the way for follow-on psychotherapy, which remains the cornerstone of long-term PTSD recovery [6].

3. Enhanced Monitoring and Communication: Veterans who are beginning or adjusting their SSRI treatment need rigorous and consistent monitoring for any changes in mood, the emergence of suicidal thoughts, or shifts in behavior. It is crucial to have open and transparent discussions about the benefits and risks of all treatment options, so veterans can make informed decisions about their care.

Addressing PTSD and suicide risk in military veterans requires a comprehensive, compassionate, and continually evolving strategy. By understanding the intricate role of medication within this context, we can provide safer and more effective pathways to healing for those who have served our nation.

References:

[1] U.S. Department of Veterans Affairs. (2023). National Veteran Suicide Prevention Annual Report: 2023. Available at: https://www.mentalhealth.va.gov/docs/data-sheets/2023/2023-National-Veteran-Suicide-Prevention-Annual-Report-508.pdf (Note: This is a general VA report on suicide; specific PTSD-related rates are embedded within broader veteran suicide statistics.)

[2] Shiner, B., et al. (2020).  Comparing Medications for DSM-5 PTSD in Routine VA Practice.  J Clin Psychiatry 202;81(6):20m13244.

[3] Using the PTSD Checklist for DSM-5 (PCL-5). (Updated versions are regularly released. Accessed on September 11, 2025 at https://www.ptsd.va.gov/professional/assessment/documents/using-PCL5.pdf.

[4] Stone, M., et al. (2009). Antidepressants and suicidality in adults: a meta-analysis of placebo-controlled trials. British Medical Journal, 339, b2654. (Access via PubMed or BMJ website: https://www.bmj.com/content/339/bmj.b2654)

[5] Ilgen MA, Bohnert ASB, Ignacio RV, et al. Psychiatric Diagnoses and Risk of Suicide in Veterans. Arch Gen Psychiatry. 2010;67(11):1152–1158. doi:10.1001/archgenpsychiatry.2010.129.

[6] Descilo, T., et al. (2009).  Effects of a yoga breath intervention alone and in combination with an exposure therapy for post-traumatic stress disorder and depression in survivors of the 2004 South-East Asia tsunami.  Acta Psychiatr Scand 2009: 1-12.  DOI: 10.1111/j.1600-0447.2009.01466.x.

[7] Coupland C, Hill T, Morriss R, Arthur A, Moore M, Hippisley-Cox J. Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: cohort study using a primary care database. BMJ. 2015 Feb 18;350:h517. doi: 10.1136/bmj.h517. PMID: 25693810; PMCID: PMC4353276.

(Disclaimer: This article provides general information and does not constitute medical advice. Treatment decisions for PTSD and related conditions should always be made in consultation with a qualified healthcare professional.  If you are a veteran or you know of a veteran who is in crisis, please seek immediate help by calling or texting the Veterans Crisis Line at 988 and pressing 1.)