Ketamine for Post-Traumatic Stress Disorder
Key Points:
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PTSD is a psychiatric disorder which follows a traumatic event.
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PTSD is thought to result from changes in neurotransmitters and key brain structures/regions.
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Ketamine has a long history of use in traumatic situations beginning with wartime injuries.
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Ketamine appears to be effective in the treatment of PTSD.
What is Post-Traumatic Stress Disorder?
Post-Traumatic Stress Disorder (PTSD) is one of the five major types of anxiety disorders and can develop after exposure to terrifying events where significant physical harm occurs or was threatened. Following the event, recurrent, involuntary, and intrusive distressing memories/dreams/reactions occur. The duration of these disturbances last more than 1 month long. Examples of traumatic events that could trigger PTSD include violent personal assaults, natural or human-caused disasters, accidents, or military combat.
The lifetime prevalence of PTSD among adults in the United States is about 6%. Along with PTSD comes a significant clinical, social, and economic burden.
What Causes PTSD?
PTSD can develop after extremely stressful, frightening, or distressing events or after prolonged traumatic experiences. Examples of events that can lead to PTSD include:
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Serious accidents
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Physical or sexual assault
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Abuse
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Life threatening health problems
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Childbirth experiences
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War and battlefield exposure
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Torture
When we look at the pathophysiology of PTSD, there are two major changes that occur:
1) Inappropriately high stress hormones
Although the precise pathophysiology of PTSD is not clear, studies have shown that those who suffer from PTSD have abnormally high levels of stress hormones. These hormones, like adrenaline, are usually released in short bursts known as the “fight or flight” response. Those with PTSD continue to produce these chemicals even when there is no danger.
2) Changes in brain structures:
Additionally, structures of the brain that process emotions appear different on brain scans. The hippocampus, responsible for memory and emotions, appears smaller in size. The literature suggests that these changes may relate to fear, anxiety, memory problems, and flashbacks. The poorly functioning hippocampus may cause inappropriate processing of these memories that lead to a sustained level of anxiety.
How Does Ketamine Treat PTSD?
It is believed that a neurotransmitter called glutamate plays a key role in the pathogenesis of PTSD.
Glutamate is important in several functions:
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Regulation of the brains ability to form and reorganize synaptic connections (neuroplasticity)
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Maintenance of dendrite density (dendrites are small branches on neurons that receive signals from other neurons)
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Modulation of brain function such as cognition, learning, memory, and mood
Chronic stress significantly impacts glutamate transmission.
Although the exact mechanism of action of ketamine is not fully understood, broadly speaking, there are two major ways in which ketamine exerts its effects.
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First, within the first couple hours of a ketamine infusion, the release of glutamate is effected in key areas of the brain including the hippocampus.
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Second, ketamine aids in the restoration of lost dendritic density (increasing dendritic spine number) through increasing brain-derived neurotrophic factor (BDNF). Significant increases in density begin to occur approximately 2-7 days after an infusion. It is believed that increases in dendrite density, especially in the hippocampus. This can lead to increased functionality of the hippocampus and cause more appropriate processing of memories.
How Effective is Ketamine Infusion Therapy for PTSD?
The literature suggests that current pharmacological treatments are ineffective in about 40% of patients. Ketamine appears to be a novel treatment for refractory and disabling cases of PTSD given its effectiveness in both decreasing the likelihood and symptoms of PTSD.
Ketamine’s use in war time on solders injured in battle have led to several studies examining the relationship between ketamine administration (by medics to provide pain relief during acute medical intervention) and decreased PTSD diagnoses following the injury. Several studies have shown that, when comparing ketamine administration compared to morphine administration to treat battle injuries, soldiers treated with ketamine had lower rates of PTSD diagnosis the following year.
This has led to further study of ketamine infusions to treat diagnosed and resistant cases of PTSD. The literature indicates that a single dose of ketamine produces rapid and significant decreases in PTSD symptoms that remain for at least 2 weeks. Ketamine was also associated with decreased depression symptom severity and overall improvement of the individuals’ clinical presentation.
It is important to note that receiving a loading dose of ketamine (6 infusions over a period of a few weeks) has been shown to be far more effective than just a single treatment of ketamine.
How Can I Find Out More Information?
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