A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder

Summary & key facts

Researchers ran a careful test with 30 people who had long-term posttraumatic stress disorder (PTSD). Half got six intravenous ketamine infusions over two weeks. The other half got a sedative called midazolam as a control. After the two weeks, people who received ketamine had bigger drops in clinician-rated PTSD symptoms and in depression symptoms than the control group. About two-thirds of the ketamine group responded to treatment, compared with about one in five in the control group. The benefit often faded over weeks, and no serious side effects were reported. The study is small and short, so more research is needed before we know how useful repeated ketamine treatment is for PTSD in the long run.

Key facts:

• Thirty people with chronic PTSD were randomly put into two groups for a controlled test.
• One group received six ketamine infusions (about 0.5 mg per kilogram of body weight) over two weeks.
• The other group received six infusions of midazolam, a sedative used here as a control.
• Clinician-rated PTSD symptoms fell more in the ketamine group than in the control group after two weeks.
• On the main PTSD measure, the ketamine group scored about 12 points lower than the control group at week two.
• About two-thirds of people given ketamine were classified as treatment responders, compared with about one in five given midazolam.
• Among people who responded to ketamine, the typical time until their symptoms returned was about 28 days after finishing the two-week course.
• Ketamine infusions were generally well tolerated in this study and there were no serious adverse events reported.
• The study was small and followed people for a short time, so the results need to be confirmed in larger and longer studies.

Abstract

OBJECTIVE: Posttraumatic stress disorder (PTSD) is a chronic and disabling disorder, for which available pharmacotherapies have limited efficacy. The authors' previous proof-of-concept randomized controlled trial of single-dose intravenous ketamine infusion in individuals with PTSD showed significant and rapid PTSD symptom reduction 24 hours postinfusion. The present study is the first randomized controlled trial to test the efficacy and safety of repeated intravenous ketamine infusions for the treatment of chronic PTSD. METHODS: Individuals with chronic PTSD (N=30) were randomly assigned (1:1) to receive six infusions of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) (psychoactive placebo control) over 2 consecutive weeks. Clinician-rated and self-report assessments were administered 24 hours after the first infusion and at weekly visits. The primary outcome measure was change in PTSD symptom severity, as assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), from baseline to 2 weeks (after completion of all infusions). Secondary outcome measures included the Impact of Event Scale-Revised, the Montgomery-Åsberg Depression Rating Scale (MADRS), and side effect measures. RESULTS: The ketamine group showed a significantly greater improvement in CAPS-5 and MADRS total scores than the midazolam group from baseline to week 2. At week 2, the mean CAPS-5 total score was 11.88 points (SE=3.96) lower in the ketamine group than in the midazolam group (d=1.13, 95% CI=0.36, 1.91). Sixty-seven percent of participants in the ketamine group were treatment responders, compared with 20% in the midazolam group. Among ketamine responders, the median time to loss of response was 27.5 days following the 2-week course of infusions. Ketamine infusions were well tolerated overall, without serious adverse events. CONCLUSIONS: This randomized controlled trial provides the first evidence of efficacy of repeated ketamine infusions in reducing symptom severity in individuals with chronic PTSD. Further studies are warranted to understand ketamine's full potential as a treatment for chronic PTSD.

Topics

Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes Posttraumatic Stress Disorder Research Treatment of Major Depression

Categories

Health Sciences Medicine Pharmacology

Tags

Administration (probate law) Anesthesia Chronic stress Clinical psychology Internal medicine Ketamine Law Medicine Political science Posttraumatic stress Psychology Randomized controlled trial

Substances

Ketamine

Conditions & symptoms

Depression PTSD Anxiety or worry Feeling disconnected from others Lack of energy or motivation Poor sleep Sadness or low mood