Ketamine for the Treatment of PTSD

Currently only two medications are approved by the FDA for the treatment of PTSD which include Sertraline and Paroxetine. These medications are often associated with significant side effects and have limited efficacy. Consequently, the Department of Veteran Affairs have recommended psychotherapy as first-line treatment for PTSD over pharmacologic interventions. However, even despite psychotherapy, patients often chronically suffer from PTSD along with other often associated comorbid disorders such as depression and substance abuse. There is clearly a need for new treatment options for those suffering from PTSD.

A promising new approach to therapy for patients suffering with PTSD includes psychedelics such as 3,4-methylenedioxymethamphetamine (MDMA), ketamine, and classical psychedelics (psilocybin and lysergic acid diethylamide [LSD]). This new approach to therapy with the use of psychedelic compounds acts as an adjunct to the psychotherapeutic process. When combining psychedelics such as ketamine with psychotherapy, patients are capable of building trust and rapport with their therapist and strengthening their therapeutic potential for healing and long-term relief.

What causes PTSD?

PTSD can develop after exposure to a trauma that includes witnessing, experiencing, or even learning about a traumatic event. Approximately 1 in 3 people who experience a severely traumatic event will develop PTSD. There appears to be various risk factors for PTSD which includes:

• Poor social support
• History of other mental disorders such as excessive compulsive disorder
• History of physical injury such a traumatic brain injury
• Lower socioeconomic status
• History of trauma exposure prior to the PTSD causing event
• Childhood abuse
• Gender (females are twice more likely to develop PTSD than males

Symptoms of PTSD

The cardinal symptoms of PTSD include intrusive symptoms, avoidance symptoms, negative cognition and mood, and arousal and reactivity changes.

• Intrusive symptoms: Emotional distress or physical reactions to something that reminds the person of a traumatic event. This also may include nightmares, reliving the traumatic event as if it were happening again (flashbacks), and unwanted and upsetting memories of the traumatic event.
• Avoidance symptoms: Trying to avoid thinking, talking, or exposure to stimuli that is associated with traumatic events. Individuals with PTSD often try to avoid certain people, places, activities, or social situations that may remind them of the trauma.
• Negative cognition and mood: Symptoms may include having negative thoughts of oneself, feelings of hopelessness, poor memory, and lack of interest in activities they previously enjoyed. Others will experience feelings of guilt or shame that may lead to depressive thoughts and negative mood.
• Arousal and reactivity changes: Symptoms include irritability or aggressive physical or verbal behaviors. Individuals may experience an outburst, anger, or other form of aggression. Other symptoms may include sleep disturbances and poor concentration, while others may act recklessly such as driving too fast or maybe self-destructive (eg, substance use).

Current treatment options for PTSD

Psychotherapy is currently a first-line treatment for PTSD which includes trauma-focused therapies. Techniques include exposure to trauma related cues that are associated with negative responses such as fear. The goal is to desensitize the individual with repeated exposure to cues that they associate with a traumatic event.

Trauma-focused psychotherapies include:

• Prolonged Exposure (PE): This is a strategy that involves “Imaginal” exposure with visualization and talking about the trauma. The goals of therapy are to change thoughts and feelings surrounding the trauma. The process of engaging with real life situations is called “in vivo” exposure. This involves identifying activities or situations that have been avoided due to the trauma.
• Cognitive Processing Therapy (CPT): Involves discussing the trauma and symptoms along with helping individuals implement better thought and behavioral patterns. The goal is to reframe negative thoughts related to the trauma and make positive lifestyle changes.
• Eye Movement Desensitization and Reprocessing (EMDR): A type of therapy that encourages the patient to talk and focus on the trauma memory while simultaneously experiencing bilateral stimulation that typically involves eye movements. Talk therapy combined with back-and-forth eye movements may help people process upsetting memories, thoughts, and feelings related to the trauma
• Medications such as selective serotonin or norepinephrine reuptake inhibitors (SSRIs or SNRIs) may be used to treat PTSD along with other classes of drugs being used off label. Unfortunately, these medications are often associated with significant side effects, delayed onset (2+ weeks), and less than ideal efficacy.

Psychedelics for the treatment of PTSD

There has been a recent acceptance of the use of psychedelics for the treatment of various medical disorders such as depression, anxiety, and PTSD. Psychedelics are extremely safe with some having no known lethal dose or no significant side effects. Additionally, the response rates for patients using psychedelics as a form of therapy often are very efficacious and superior to currently used medications such as SSRIs and SNRIs. Psychedelic compounds include psilocybin (“magic mushrooms”), LSD, Ketamine, and MDMA. We will focus our discussion on ketamine.

Ketamine first synthesized in 1962 then approved by the FDA in 1970 is considered a “dissociative psychedelic.” Ketamine is a medication commonly used for anesthesia, although at low doses it has been found to be highly effective for the treatment of depression, anxiety, PTSD, suicidal ideation, and other mental disorders. Ketamine is safe and has very rapid effects that are often superior to currently used medications such as antidepressants.

Ketamine has been found to promote regrown of broken connections (synapses) in the brain that have resulted from traumatic stress or events. This process involves neuroplasticity and neurogenesis. Neuroplasticity is the ability of the brain to form new connections and pathways, while neurogenesis involves the ability of the brain to grow entirety new neurons. In relation to PTSD, ketamine may serve a role in how individuals process fear and memories related to a traumatic event. Given the ability to reform new pathways in the brain and change the way of thinking and processing information, ketamine has been shown to enhance receptiveness and effectiveness of various psychotherapies as we mentioned previously. Given at low, subanesthetic doses, ketamine may augment trauma-focused psychotherapy resulting in higher response rates with longer lasting effects.

How well does ketamine work for PTSD?

One randomized controlled trial using ketamine at an infusion dose of 0.5 mg/hr of body weight led to a significant and rapid reduction of PTSD symptoms. Other studies have suggested that the therapeutic effects of ketamine for PTSD can have prolonged and enhanced effects with repeated infusions administered via six infusions over a 12-day period. Remission rates of upwards to 80% have been reported with repeated infusions over a short period of time for PTSD.

Ketamine for PTSD in veterans

Ketamine infusion therapy may be an excellent treatment option specifically for combat veterans. Combat veterans are at high risk for developing PTSD and less than 40% seek help. The prevalence of PTSD ranges from 27% to 37% in Vietnam veterans, 18% for those deployed to Iraq, 11.5% for veterans deployed to Afghanistan, and 10.1% for Gulf War veterans. In one study using IV ketamine for the treatment of PTSD in combat veterans, participants experienced significant response rates and other than some occasional nausea, none experienced any significant adverse events or side effects. Assessment tools used to measure responses included the Patient Health Questionnaire (PHQ-9) and PTSD Checklist (PCL-5). Specifically assessing depression (PHQ-9), symptoms dropped significantly, from an average score of 18.9 to 9.5, a 50% reduction, while for PTSD, scores also dropped at a high rate from an average score of 56.2 to 31.3, a 44% reduction.

Conclusion

Given the alarming rates of PTSD, depression, and substance abuse, especially in our beloved veterans, the need for effective, safe, and rapid acting treatment modalities such as ketamine infusion therapy ought to be considered. Integration of ketamine offers a new opportunity for the treatment of PTSD and has been repeatedly shown to be a highly valuable treatment option that can augment other trauma-focused psychotherapies. Ketamine’s remarkable ability to alter how traumatic memories and fear are processed offers a novel and exciting opportunity for effective and long-lasting relief of symptoms. I have often said that ketamine should be considered as a catalyst or adjunct to help break negative thought patterns and behavior, while promoting a healthy lifestyle and mind. Ketamine once again is showing promise for various mental disorders and should be a seriously considered worthwhile option for people suffering or have failed other methods of therapy for PTSD.

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