Ketamine as a Treatment for Post-Traumatic Stress Disorder

Who does PTSD affect?

Post-traumatic stress disorder (PTSD) can occur in people exposed to a traumatic event such as a natural disaster, a serious accident, a terrorist act, war, rape, and those who have been threatened with death, sexual violence, or serious injury. Exposure does not have to be firsthand. For example, PTSD can occur from learning about the violent death of a close family or friend or because of repeated exposure to horrible details of trauma such as police officers exposed to facts of child abuse cases. Some studies have found a connection between those who have PTSD and their loved ones developing secondary symptoms of PTSD. The most common secondary symptoms were (sleep disturbances, anxiety, distress). This is thought mainly due to how tiring and disruptive to daily life it is to care for loved ones with PTSD.

PTSD is currently diagnosed in 8.7% of the general U.S adult population (1 in 11 people) and does not happen to just combat veterans but can occur in all people, of any ethnicity or culture, and at any age. Women are twice as likely as men to have PTSD. For reasons that are not entirely clear PTSD is slightly higher in Latinos, African Americans, and Native Americans. The highest rates are found among military veterans, firefighters, police officers, and emergency medical personnel.

PTSD – What does it look like?

PTSD can occur days or even years after the event and if untreated can last a lifetime. It creates recurrent, intense, and disturbing memories, nightmares, and flashbacks. These can be triggered by internal or external cues that somehow remind the person of the traumatic event1 Individuals often attempt to avoid reminders of trauma by controlling their thoughts, memories, and emotions or by avoiding people, places, conversations, and situations. A person’s memory of events may change, and they may also develop symptoms of serious depression including negative beliefs and expectations, negative emotional states, anhedonia (inability to feel pleasure), and social withdrawal.1 Those suffering from PTSD often exhibit irritability, self-destructive behavior, hypervigilance, sleep disturbance, and lack of concentration.

PTSD is often disabling, making it difficult for an individual to maintain employment and social wellness. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5 published by the American Psychiatric Association), in both community and veteran populations, PTSD is associated with poor social and family relationships, excessive absence from work, lower income, and lowered educational achievement. Individuals with PTSD are 80% more likely to have at least one other mental disorder.1 Conduct disorder, depression, anxiety, and substance use disorder are common.

Treatment

Antidepressant and cognitive-behavioral therapy are the most common treatments for PTSD but fail to work well for many patients.

The Veteran’s Administration/Department of Defense currently recommends treatment with the selective serotonin reuptake inhibitors (SSRIs) including Zoloft and Paxil2. Other drugs may also be tried, for example, Effexor, tricyclic antidepressants, and monoamine oxidase inhibitors. These medications take weeks to work if at all and need to be used with caution as they carry their own risk for creating suicidal thoughts and violent behavior. One novel treatment not typically included in guidelines is ketamine.

Research suggests that PTSD damages how information moves through the brain (synaptic connectivity). The success seen from ketamine treatments comes from ketamine’s ability to repair and improve damaged connections at the same time as building new healthy connections (neuroplasticity). This repair and rebuild happens almost immediately reversing the effects of PTSD damage. However, if ketamine therapy is discontinued with no ongoing support strategies, PTSD damage may reappear over time.

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Clinic controlled ketamine treatment.

Ketamine Studies

  1. In a double-blind, randomized, controlled trial 41 chronic PTSD patients were studied. Researchers found symptoms were significantly improved 24 hours post-infusion with multiple patients remaining significantly improved at 2 weeks.3 Additionally, ketamine was associated with a decrease in negative thinking and depression.
  2. In one of several case reports a 26-year-old combat veteran with diagnoses of PTSD and major depressive disorder4 reported a complete reduction of anxiety and depression from day 1 to day 14 after a single ketamine infusion. At day 14 effects from the single infusion began to diminish.
  3. A case report, by D’Andrea and colleagues, looked at a 23-year-old veteran who, following a 15-month deployment,5 had experienced symptoms of PTSD for 6 months including sleep terrors and nightmares. He frequently sat ‘guarding’ his home and crashed his car twice in response to gunshots heard during hunting season. The patient had tried multiple antidepressants, hypnotics, and antipsychotics. He tried psychotherapy had been hospitalized three times, including at facilities with PTSD treatment programs. The patient achieved only partial short-term improvements. Following IV ketamine he showed an immediate, drastic decrease in PTSD symptoms which led to improved functioning, remission of anxiety and hyperarousal, improved mood, normalized sleep without the use of sedatives, and no nightmares. His improvement lessened 15 days after the treatment.
  4. A case report by Donoghue and colleagues focused on a 7-year-old boy with a history significant of PTSD, and disruptive behavior disorder who displayed frequent episodes of severe emotional and behavioral outbursts involving destruction of property.6 He was tried on several medications with no significant improvement. After multiple hospitalizations, he was living in a long-term residential care facility. The patient received IV ketamine as an anesthesia for a tonsillectomy. His caregivers in the residential facility noted a significant improvement in his symptoms: decreased intensity and frequency of aggressive behaviors, and improved ability to control his emotions and behavior. When he did become upset, caregivers noted that his emotions did not escalate to the levels before receiving ketamine. The child also was able to speak about his past trauma for the first time. After 13 days, his symptoms began to return. Following a second ketamine infusion, the patient again displayed improvements in behavior, which lessened after 8 days.
  5. Another study7 aimed to examine the efficacy of oral ketamine therapy in an outpatient setting for PTSD and depression. It was found ketamine treatment reduced hospital admissions by approximately 70% per patient. There was a significant decrease in both the number of admissions and the length of stay in a psychiatric hospital for patients.
 

Safety

Existing data show little risk for routine significant side effects or drug-to-drug interactions related to the use of ketamine. It is recommended that patients be monitored closely during ketamine treatments. Side effects reported in the first 24 hours included blurred vision, dry mouth, restlessness, fatigue, nausea/vomiting, poor coordination, and headache. Ketamine can create a dose-dependent transient dissociative state (temporary disconnecting from one’s thoughts, feelings, memories, or sense of identity).

Summary

PTSD is a problematic condition that can be difficult to treat. SSRIs are the standard first-line treatment but, oftentimes, PTSD can be found to be resistant to these treatments. Many patients who have participated in trials of SSRIs, as well as other psychoactive drugs, have not achieved remission. Atypical antipsychotics and benzodiazepines are sometimes used in an attempt to control symptoms but should be used with caution as individuals suffering from PTSD are at heightened risk for addiction. Supplementing these standard treatments with psychotherapy and hospitalization has not been demonstrated to significantly improve outcomes.

Based on randomized controlled trials, and case reports, ketamine has shown a near-complete resolution of PTSD symptoms over the short term. These clinical improvements are immediate and typically last a minimum of 1–2 weeks after a single treatment.

References


  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5.Washington, DC: American Psychiatric Association; 2013. [Google Scholar]
  2. Office of Quality and Performance and the Veterans Affairs and Department of Defense Development Work Group. Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. Version 3.0.Washington, DC: Veterans Health Administration and Department of Defense; 2017. [Google Scholar]
  3. Feder A, Parides MK, Murrough JW, et al. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder. JAMA Psychiatry. 2014;71(6):681–688. doi: 10.1001/jamapsychiatry.2014.62. [PubMed] [CrossRef] [Google Scholar]
  4. Womble AL. Effects of ketamine on major depressive disorder in a patient with posttraumatic stress disorder. AANA J. 2013;81(2):118–119. [PubMed] [Google Scholar]
  5. D’Andrea D, Sewell RA. Transient resolution of treatment resistant posttraumatic stress disorder following ketamine infusion. Biol Psychiatry. 2013;74:e13–e14. doi: 10.1016/j.biopsych.2013.04.019. [PubMed] [CrossRef] [Google Scholar]
  6. Donoghue AC, Roback MG, Cullen KR. Remission from behavioral dysregulation in a child with PTSD after receiving procedural ketamine. Pediatrics. 2015;136(3):e694–e696. doi: 10.1542/peds.2014-4152. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  7. Hartberg J, Garrett-Walcott S, Gioannis AD. Impact of oral ketamine augmentation on hospital admissions in treatment-resistant depression and PTSD: a retrospective study. Psychopharmacology. 2017;235(2):393–398. doi: 10.1007/s00213-017-4786-3. [PubMed] [CrossRef] [Google Scholar]

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