In the review article Ketamine as treatment for post-traumatic stress disorder: A Review by Liriano, Hatten, and Schwartz (2019), researchers examined the growing evidence behind ketamine’s potential as a rapid-acting intervention for post-traumatic stress disorder (PTSD). As conventional therapies often fail to provide full remission for many individuals, ketamine emerges as a hopeful alternative in cases of treatment-resistant PTSD.
PTSD is a chronic and debilitating condition marked by intrusive memories, hyperarousal, and emotional numbness, often following trauma. While selective serotonin reuptake inhibitors (SSRIs) remain the only FDA-approved class of medications for PTSD, they have limited efficacy for a significant subset of patients. This review explores how ketamine—already shown effective for treatment-resistant depression (TRD)—might offer similarly rapid, though short-term, relief for PTSD sufferers.
Why Standard PTSD Treatments Often Fall Short
SSRIs such as sertraline and paroxetine are the most commonly prescribed treatments for PTSD. While these drugs can offer modest symptom relief, their limitations are significant:
- Delayed onset of action, often requiring weeks before noticeable improvement
- Partial or non-response in many individuals
- Side effects that lead to poor adherence
As a result, there is a pressing need for therapies that act faster and help those who have not responded to traditional treatments.
The Mechanistic Rationale for Ketamine
Ketamine, a dissociative anesthetic and NMDA receptor antagonist, has gained recognition for its rapid antidepressant effects, especially in TRD. Its potential for PTSD likely stems from its action on glutamatergic transmission and synaptic plasticity—mechanisms believed to underlie trauma-related memory and emotional processing.
Animal studies and neuroimaging in humans suggest ketamine resets dysfunctional brain circuits, including:
- The amygdala, which is hyperactive in PTSD
- The prefrontal cortex, which is often underactive
- Default mode network components tied to rumination and flashbacks
These effects may facilitate more adaptive emotional responses to trauma and reduce the intensity of fear-based memories.
Review Findings: Short-Term Symptom Relief
The reviewed studies indicated that ketamine can result in near-complete symptom resolution in the short term. Similar to its use in major depressive disorder (MDD), the benefits were often noticeable within hours and persisted for several days to a week.
Key observations included:
- Rapid reduction in intrusive thoughts and hyperarousal
- Improved emotional regulation
- Temporary dissociative symptoms that faded shortly after infusion
While these effects are promising, they were often transient, emphasizing the need for strategies to maintain benefits over time.
Safety, Tolerability, and Limitations
Ketamine was generally well-tolerated in the short-term trials reviewed. Some patients reported:
- Mild dissociation or perceptual disturbances
- Transient elevation in blood pressure or heart rate
Importantly, no serious adverse events were noted when ketamine was administered in controlled clinical settings.
However, several limitations emerged:
- Small sample sizes across studies
- Lack of long-term data on safety and efficacy
- Uncertainty about optimal dosing or frequency
Implications for Future Treatment Models
The findings support the idea that ketamine may be a useful adjunctive treatment for individuals with PTSD who do not respond to conventional medications. As researchers refine treatment protocols, important areas of focus include:
- Combining ketamine with psychotherapy, especially exposure-based models
- Exploring repeated dosing schedules for sustained relief
- Evaluating alternative formulations, such as intranasal or oral ketamine
Conclusion
The review article Ketamine as treatment for post-traumatic stress disorder: A Review underscores ketamine’s potential in addressing treatment-resistant PTSD. While not yet a first-line treatment, ketamine may offer a lifeline to those unresponsive to traditional approaches, with the added advantage of rapid symptom reduction.
Ongoing research will be essential to establish safety, efficacy, and best practices, but the initial findings provide real hope for individuals struggling with the long-term consequences of trauma.
References
- Liriano, F., Hatten, C., & Schwartz, T. L. (2019). Ketamine as treatment for post-traumatic stress disorder: A Review. Drugs in Context, 8, 1–7. https://doi.org/10.7573/dic.2019-3-8
- Feder, A., Parides, M. K., Murrough, J. W., et al. (2014). Efficacy of intravenous ketamine for treatment of chronic PTSD: A randomized clinical trial. JAMA Psychiatry, 71(6), 681–688. https://doi.org/10.1001/jamapsychiatry.2014.62
- Duman, R. S., & Aghajanian, G. K. (2012). Synaptic dysfunction in depression: Potential therapeutic targets. Science, 338(6103), 68–72. https://doi.org/10.1126/science.1222939
- Abdallah, C. G., Averill, L. A., Akiki, T. J., et al. (2019). The neurobiology and pharmacotherapy of PTSD: Focusing on glutamate and ketamine. Neuroscience Letters, 693, 86–91. https://doi.org/10.1016/j.neulet.2018.01.019
- Krystal, J. H., Davis, L. L., Neylan, T. C., et al. (2017). It is time to address the crisis in the pharmacotherapy of posttraumatic stress disorder: A consensus statement of the PTSD psychopharmacology working group. Biological Psychiatry, 82(7), e51–e59. https://doi.org/10.1016/j.biopsych.2017.03.007
