Posttraumatic Stress Disorder (PTSD)
Conditions
Keywords
Psilocybin, PTSD, Veterans, Psilocybin-assisted psychotherapy, Posttraumatic stress disorder, Psychotherapy
Brief summary
This study will evaluate the feasibility, safety and preliminary efficacy of psilocybin-assisted psychotherapy in military veterans with treatment-refractory posttraumatic stress disorder (PTSD).
Detailed description
Posttraumatic stress disorder (PTSD) is a severe and debilitating mental health condition that significantly impacts patients' lives, leading to functional impairments, strained relationships, and high healthcare costs. About half of the patients with PTSD do not benefit from current evidence-based psychotherapy and available pharmacological treatments offer only limited benefits. Therefore, there is a high need for novel therapeutic approaches in the treatment of PTSD. Psilocybin-assisted psychotherapy is a promising approach combining the pharmacological effects of psilocybin, a serotonergic psychedelic, with psychotherapy. Psilocybin-assisted psychotherapy has shown promising effects in several phase 2 studies in the treatment of mental health conditions such as depression and end-of-life anxiety, with two phase 3 studies underway for treatment-resistant depression. Building on these initial promising results, psilocybin-assisted psychotherapy is increasingly being studied for other psychiatric indications, including PTSD. Many of psilocybin's potential therapeutic mechanisms appear to be transdiagnostic in nature. For example, studies suggest that psilocybin can enhance introspection, emotional processing, and psychological flexibility, all of which could facilitate psychotherapeutic processes. Psilocybin has also been shown to reduce avoidance and promote neural plasticity and cognitive reappraisal, which could be particularly relevant for addressing core symptoms of PTSD, such as persistent avoidance and rigid negative thought patterns. Furthermore, its ability to foster a sense of connectedness aligns well with the therapeutic need of individuals with PTSD who face challenges related to social isolation. Preliminary findings from an initial Phase 2 trial suggest that psilocybin-assisted psychotherapy may be safe and associated with clinically meaningful improvements in PTSD symptoms. However, this study differed from the present study in several important aspects. Participants were not required to have had previous unsuccessful evidence-based psychotherapies for PTSD, and psilocybin administration was not embedded within psychotherapeutic treatment. The current open-label pilot study will focus on veterans with treatment-refractory PTSD, a patient population that frequently shows partial or no response to standard evidence-based PTSD treatment. In addition, psilocybin administration will be part of an extensive psychotherapeutic treatment protocol. This study aims to collect data on the feasibility, preliminary efficacy and safety of psilocybin-assisted psychotherapy in this population, to inform a potential future randomized controlled trial.
Interventions
Two psilocybin sessions (15 mg psilocybin in the first session; 25 mg psilocybin in the second session) embedded in a psychotherapeutic framework with three preparatory sessions and six integrative sessions.
Sponsors
ARQ National Psychotrauma Centre
National Healthcare System for Veterans / Landelijk Zorgsysteem voor Veteranen (LZV)
Leiden University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Are between 18 and 70 years old. * Able to provide written informed consent. * Fluent in speaking and reading Dutch. * Is a veteran of the Dutch Armed Forces. * Able to swallow pills. * Have a body mass index (kg/m2) of \>18.0. * Meet DSM-5 criteria for current PTSD. * Meet criteria for treatment-refractory PTSD. * Agree to have study visits audiovisually recorded. * Able to provide a contact (relative, spouse, close friend, or other support person) who is willing and able to be reached by the investigators in the event of the participant becoming unwell or unreachable.
Exclusion criteria
* Has a history of any medical condition that could make receiving psilocybin harmful because of temporary increases in blood pressure and heart rate. * Has a medical or psychiatric condition that could interfere with study participation or pose a risk to the participant's safety or well-being. * Has uncontrolled hypertension. * Unable or unwilling to safely taper-off prohibited psychiatric medication. * Has been exposed to electroconvulsive therapy (ECT) within 12 weeks of enrollment. * Has any current problem which, in the opinion of the investigator, might interfere with study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinician-Administered PTSD Scale for DSM-5 Revised (CAPS-5-R) | From Baseline to 1 month after final integrative psychotherapy session | The last month CAPS-5-R is a semi-structured interview that assesses index history of DSM-5-defined traumatic event exposure, including the most distressing event and time since exposure, and rates intrusion symptoms (intrusive thoughts or memories), avoidance, cognitive and mood symptoms, arousal and reactivity symptoms, duration and degree of distress and dissociation. The CAPS-5-R will be administered by a study independent CAPS-5-R rater. |
| Semi-structured interview | One month after final integrative psychotherapy session | Comprehensive qualitative information about participants' evaluation of the feasibility, acceptability and efficacy of psilocybin-assisted psychotherapy for PTSD will be collected through a semi-structured interview. |
| Treatment Acceptability/Adherence Scale Modified (TAAS-M) | One month after final integrative psychotherapy session | A modified 10-item version of the Treatment Acceptability and Adherence Scale (TAAS-M) will be used to describe acceptability and adherence to psilocybin-assisted psychotherapy. |
| Feasibility of participant screening and study retention | From screening until one month after the final integrative psychotherapy session. | The feasibility of participant screening and study retention will be assessed by documenting the number and proportion of participants who fail screening, the number and proportion of enrolled participants who discontinue the intervention, and the reasons for screen failure and discontinuation. All measures will be summarized descriptively. |
| Concomitant medication use | From screening until one month after the final integrative psychotherapy session. | Concomitant medication use during study participation will be recorded. |
| Columbia Suicide Severity Rating Scale (C-SSRS) | Measured at several timepoints from screening to one month after the final integrative psychotherapy session. | The C-SSRS is a clinician-administered measure of suicidal behavior devised to detect potential suicidal thoughts or behaviors during a clinical trial. |
| Adverse events | From screening until one month after the final integrative psychotherapy session. | Severity, incidence and frequency of AEs and serious adverse events (SAEs). |
| Blood pressure | At several timepoints between screening and one month after the final integrative psychotherapy session, including during psilocybin administration. | Systiloc and diastolic blood pressure (mmHg) will be monitored. |
| Heart rate | At several timepoints between screening and one month after the final integrative psychotherapy session, including during psilocybin administration. | Heart rate (beats per minute) will be monitored. |
| Body temperature | At several timepoints between screening and one month after the final integrative psychotherapy session, including during psilocybin administration. | Body temperature (°C) will be monitored. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sheehan Disability Scale | Change from Baseline to one month after final integrative psychotherapy session | The Sheehan Disability Scale is a 3-item assessment of functional impairment. |
| Beck Depression Inventory-II (BDI-II) | Change from baseline to one month after final integrative psychotherapy session | The BDI-II is a 21-item self-report measure for depression symptom severity. |
Countries
Netherlands
Contacts
CONTACTAnnika Wirsching, MSc
PRINCIPAL_INVESTIGATOREric Vermetten, MD, PhD
Leiden University Medical Center
Outcome results
None listed