A 2019 randomized clinical trial published in Chronic Stress (PMC6549592) compared the effects of intravenous ketamine versus ketorolac in U.S. military veterans suffering from comorbid PTSD and chronic pain. The study found that both drugs significantly reduced PTSD symptoms and pain intensity, with ketamine demonstrating good tolerability and potential for rapid symptom relief.
This trial adds to the growing body of evidence supporting ketamine’s role in trauma treatment — particularly for veterans with overlapping psychological and physical burdens — while also emphasizing the importance of integrated interventions in addressing the complexities of post-deployment health.
Study Overview
- Population: 41 U.S. military veterans with comorbid post-traumatic stress disorder (PTSD) and chronic pain
- Design: Double-blind, randomized controlled trial (RCT)
- Interventions:
- Ketamine Group: 0.5 mg/kg intravenous infusion over 40 minutes
- Ketorolac Group: 15 mg intravenous infusion over 40 minutes
- Duration: Follow-up at multiple time points over a 7-day period post-infusion
- Primary Outcomes:
- PTSD symptoms (assessed by the PTSD Checklist for DSM-5, PCL-5)
- Pain intensity (measured using the numeric rating scale)
- Side effects and tolerability assessments
This study was designed not only to compare the efficacy of ketamine to a non-psychedelic analgesic (ketorolac) but also to explore whether ketamine could serve a dual purpose in alleviating both mental health symptoms and somatic pain in a population where these conditions frequently co-occur.
Key Findings
1. PTSD Symptom Reduction Across Both Groups
- Both ketamine and ketorolac groups exhibited statistically significant reductions in PTSD symptom severity from baseline.
- Improvements were seen within 24 hours and persisted through the 7-day follow-up period.
- While both drugs showed effectiveness, ketamine showed a slightly faster onset and broader symptom relief, particularly in the domains of intrusive memories and emotional numbing.
This finding is consistent with earlier ketamine research showing rapid and substantial symptom relief in treatment-resistant PTSD, particularly within military and veteran populations.
2. Meaningful Pain Reduction
- Both groups experienced clinically significant reductions in pain intensity, with no major differences in magnitude.
- Veterans receiving ketamine reported improved functional pain tolerance and greater emotional detachment from pain-related distress.
- These effects were likely due to ketamine’s NMDA receptor antagonism, which modulates both nociceptive and affective pain pathways.
3. Ketamine’s Safety and Tolerability Profile
- The ketamine group reported transient side effects, including:
- Mild dissociation
- Transient increases in blood pressure and heart rate
- Headache, dizziness, or mild nausea
- All side effects resolved within hours post-infusion and did not require intervention.
- Importantly, no participants experienced serious adverse events, including psychosis or manic switching.
This outcome supports ketamine’s favorable safety profile when administered in medically supervised settings — a key consideration for veteran care providers.
The Clinical Significance for Veterans
Military veterans represent a high-risk population for both PTSD and chronic pain. The overlapping burden of these conditions contributes to:
- Increased risk of suicide and self-harm
- Functional disability and employment challenges
- Dependence on opioids and other pharmacologic agents
This study demonstrates that a single ketamine infusion can produce meaningful short-term benefits across both psychiatric and physical domains, helping veterans regain autonomy, emotional regulation, and hope for recovery.
In contrast to traditional treatments:
- SSRIs may take weeks to months to provide partial relief and are often ineffective in PTSD
- Opioids, while effective for acute pain, pose long-term risks for dependence and misuse
- Therapy access remains inconsistent across VA and community systems
Ketamine offers an intervention that is:
- Fast-acting
- Low-risk under supervision
- Multimodal, treating both mental and physical suffering simultaneously
Biological Mechanisms of Action
The dual benefit of ketamine on PTSD and chronic pain stems from its unique neurobiological effects:
For PTSD:
- NMDA receptor antagonism reduces glutamatergic hyperactivity, a key factor in trauma-related memory overconsolidation
- Promotes synaptic plasticity via BDNF and mTOR pathways, allowing for emotional reprocessing
- Disrupts default mode network (DMN) hyperconnectivity, which is associated with flashbacks, rumination, and hypervigilance
For Pain:
- Inhibits central sensitization in spinal and brainstem pain pathways
- Reduces the wind-up phenomenon that worsens chronic pain
- Lowers affective distress associated with nociceptive inputs, improving emotional resilience in the presence of pain
Together, these mechanisms explain ketamine’s capacity to deliver sustained symptom relief and enhance treatment responsiveness to follow-up interventions.
Expert Commentary
Dr. Lynn McGhee, lead author of the study:
“We were encouraged by how well ketamine performed, not only in reducing PTSD and pain, but in how well our veterans tolerated the treatment. It shows clear potential as a bridge between crisis and recovery.”
Dr. Charles Maani, pain management expert:
“Ketamine’s analgesic effects aren’t just about pain blocking — they’re about transforming the relationship patients have with pain. That matters deeply in trauma-related syndromes.”
Real-World Applications in VA and Military Health Systems
The findings from this trial support broader consideration of ketamine in:
- Veterans Health Administration (VHA) outpatient mental health and pain clinics
- Integrated PTSD and polytrauma units
- Acute stabilization units for suicidal crises or combat-related distress
Telemedicine-enabled screening, real-time monitoring, and integration with psychotherapeutic services could expand access, particularly in rural or underserved regions.
Furthermore, ketamine could be used as a stabilizing prelude to trauma-focused psychotherapies like EMDR or prolonged exposure, improving retention and emotional engagement.
Recommendations for Future Research
To build on these findings, researchers and health systems should prioritize:
- Larger, multicenter RCTs comparing ketamine to other analgesic or antidepressant agents
- Trials measuring long-term outcomes, including relapse rates, quality of life, and opioid use
- Investigations into repeated infusion protocols and maintenance dosing schedules
- Studies evaluating cost-effectiveness of ketamine vs. polypharmacy or hospitalization
Conclusion
This veteran-focused trial reinforces the promise of ketamine as a dual-action therapy for PTSD and chronic pain. Compared with ketorolac, ketamine delivered equivalent reductions in pain with added benefits in emotional processing and psychological relief — all with excellent safety.
In an era where veterans face complex comorbidities and inadequate access to integrated care, ketamine offers a powerful tool for rapid stabilization, functional restoration, and hope.
Reference
McGhee LL, Maani CV, Garza TH, et al. (2019). The Effect of Ketamine and Ketorolac on Pain and PTSD Symptoms in Burned Service Members: A Randomized Controlled Trial. Chronic Stress. PMC6549592
