Burnout, Caregiver, Burnout, Professional, COVID-19, Depression, Post Traumatic Stress Disorder, Moral Injury
Conditions
Keywords
psilocybin, psychedelic assisted psychotherapy
Brief summary
This study aims to investigate the effects of a single dose of psilocybin, delivered in the contextof pre- and post-dose psychotherapy, on symptoms of depression and burnout suffered by healthcare clinicians as a result of frontline work in the COVID pandemic.
Detailed description
Aim 1: To assess short- and longer-term effects of psilocybin-assisted psychotherapy (PAP) on symptoms of depression experienced by physicians and nurses with frontline work exposure in the COVID pandemic. Hypothesis 1.1: Compared to active placebo, PAP will result in short term improvement in symptoms of depression 1 day and 1 week after the psilocybin dose session. Hypothesis 1.2: Compared to active placebo, PAP will result in longer term improvement of symptoms of depression 4 weeks after the medication dosing session. The primary outcome will be a comparison between the psilocybin 25 mg vs control groups of a combination of depression symptoms measured at 4 weeks post medication dose session. 1.1.2. Aim 2: To explore short- and longer-term effects of psilocybin-assisted psychotherapy (PAP) on symptoms of burnout experienced by physicians and nurses with frontline work exposure in the COVID pandemic. Hypothesis 2.1: Compared to active placebo, PAP will result in short term improvement in symptoms of burnout 1 day and 1 week after the psilocybin dose session.
Interventions
PAP + psilocybin 25 mg
DRUGActive placebo
PAP + niacin 250mg
Sponsors
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The investigators, study therapists, and outcomes assessors will all be blinded in the randomized phase of the study. Participants will be unblinded after the primary outcome, and those receiving placebo will be eligible to receive open label psilocybin.
Intervention model description
This study tests a hypothesis that a single session of psilocybin (the 'medication dosing' session) in the context of pre- and post-dose psychotherapy will result in improvement of symptoms of depression and burnout measured 4 weeks post-dose. This study hypothesis will be tested in a single site, double-blind, randomized controlled design involving 30 clinician participants that will compare effects of a single 25mg oral dose of psilocybin to a 250 mg of niacin (active placebo). The primary outcome measurements will be collected 4 weeks after the psilocybin dose, after which the participant group assignment will be unblinded, and participants who received niacin will be offered the opportunity to have a second dose session with a 25 mg dose (with pre- and post-dose psychotherapy).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants must be physicians or nurses with at least 1 month of frontline clinical experience during the COVID pandemic who rate at least 2 of 4 items from the COVID Exposure index as 'more than half the days' during their peak 2 week period of exposure: i. Caring for someone critically ill with COVID-19, or who became critically ill while you were involved; ii. Working longer hours than usual in order to provide assistance or care to individuals with COVID-19; iii. Witnessing or responding to a death related to COVID-19, or losing a patient you had been caring for to COVID-19; iv. Caring for patients who have died without family physically present due to COVID-19 precautions 2. Have a Montgomery-Asberg Depression Rating Scale (MADRS) clinician-administered depression score \>21, indicating moderately severe symptoms. 3. Have had persistent symptoms despite at least one medication and/or therapy trial of standard care treatment for depression. 4. English speaking - able to understand the process of consent and the risk and benefits associated with the study, and able to give written informed consent. 5. Must be willing to sign a medical release for the investigators to communicate directly with their therapist and doctors to confirm a medication and/or medical history. This is decided on a case-by-case basis upon the discretion of the PI. 6. Must be driven home after the medication dosing session by a driver (which could be a friend, family, rideshare or taxi). 7. Must provide at least one adult to have continuous contact with the participant, provide participant transportation, monitor changes in the participant's behavior, and notify research staff of behavior changes. 8. Has been off selective serotonin inhibitors (SSRIs) for at least five half-lives of the drug plus 2 weeks. 9. Must avoid taking any psychiatric medications or starting a new psychiatric medication during the study. Should participant's doctor recommend starting a new psychiatric medication, participant will be required to notify the study team and the subject would withdraw from the study 10. Must provide a contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the Clinical Investigators in the event of a participant becoming suicidal. 11. If able to bear children, must have a negative pregnancy test at study entry. 12. Are willing to commit to preparation sessions, medication dosing sessions, integration sessions, to complete evaluation instruments and commit to be contacted for all necessary telephone contacts.
Exclusion criteria
1. Personal or immediate family history of schizophrenia, bipolar affective disorder, delusion disorder, paranoid disorder, or schizoaffective disorder. 2. Suicidal ideation with a Columbia Suicide Severity Rating Scale (C-SSRS) \> 3 3. Current substance abuse disorder (except in the case of mild alcohol use ) 4. Neuroleptic and SSRI medications that cannot be tapered and discontinued in conjunction with the participant's prescribing physician. 5. Unstable neurological or medical condition; history of seizure, chronic/severe headaches. 6. Positive urine pregnancy test at the time of screening 7. Any unstable medical condition that my render study procedures unsafe. 8. Any use of psychedelic drugs within the prior 12 months. 9. Use of tramadol, due to the potential for serotonin syndrome with concomitant use of psilocybin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale | 4-weeks post psilocybin-assisted psychotherapy | Assesses symptoms of depression (clinician-assessed): minimum score 0, max 60; higher score indicates more severe symptoms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale | 24 weeks post-psilocybin in the randomized phase psilocybin arm | Assesses symptoms of depression (clinician-assessed): minimum score 0, max 60; higher score indicates more severe symptoms |
| Stanford Fulfillment Index | 1,4,8,12,24 -weeks post psilocybin-assisted psychotherapy | Assesses professional burnout in 3 components that are scored separately (professional fulfillment, interpersonal disengagement, work exhaustion) |
| PTSD Checklist for DSM-5 (PCL5) | 4 weeks post-psilocybin or placebo session | Assesses symptoms of post-traumatic stress disorder; minimum score 0, max 80; higher scores indicate more severe symptoms of PTSD |
| Moral Injury Symptom Scale | 4, 24 weeks post-psilocybin-assisted psychotherapy | Assesses symptoms of moral injury: minimum score 10, max 100; higher score indicates more severe symptoms |
| Beck Depression Index | 1, 4, 8, 12, 24-weeks post-psilocybin-assisted psychotherapy | Assess self-reported symptoms of depression: minimum score 0, max 63; higher score indicates more severe symptoms of depression |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Psilocybin Arm psychedelic assisted psychotherapy + 25mg psilocybin
Psilocybin (Usona Institute): PAP + psilocybin 25 mg | 15 |
| Placebo Psychedelic assisted psychotherapy + 250mg niacin
Active placebo: PAP + niacin 250mg | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Placebo | Total | Psilocybin Arm |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 30 Participants | 15 Participants |
| Age, Continuous | 36 years | 38 years | 40 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 26 Participants | 13 Participants |
| Region of Enrollment United States | 15 Participants | 30 Participants | 15 Participants |
| Sex: Female, Male Female | 7 Participants | 15 Participants | 8 Participants |
| Sex: Female, Male Male | 8 Participants | 15 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 0 / 12 |
| other Total, other adverse events | 0 / 15 | 0 / 15 | 0 / 12 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 12 |
Outcome results
Primary
Montgomery-Asberg Depression Rating Scale
Assesses symptoms of depression (clinician-assessed): minimum score 0, max 60; higher score indicates more severe symptoms
Time frame: 4-weeks post psilocybin-assisted psychotherapy
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Psilocybin Arm | Montgomery-Asberg Depression Rating Scale | 21.33 score on a scale | Standard Deviation 7.84 |
| Placebo | Montgomery-Asberg Depression Rating Scale | 9.33 score on a scale | Standard Deviation 7.32 |
Comparison: The null hypothesis was that the mean change in MADRS score from the preparation 1 session to day 28 would be the same in both niacin and psilocybin groups. The alternative hypothesis was that the change in the psilocybin group would be greater than the change in the niacin group, with an assumed true effect size of 1.06 SD units based on findings in prior studies. With 15 participants per group, this study had 80% power to observe a statistically significant difference between groups.p-value: <0.001t-test, 2 sided
Secondary
Beck Depression Index
Assess self-reported symptoms of depression: minimum score 0, max 63; higher score indicates more severe symptoms of depression
Time frame: 1, 4, 8, 12, 24-weeks post-psilocybin-assisted psychotherapy
Secondary
Montgomery-Asberg Depression Rating Scale
Assesses symptoms of depression (clinician-assessed): minimum score 0, max 60; higher score indicates more severe symptoms
Time frame: 24 weeks post-psilocybin in the randomized phase psilocybin arm
Population: Participants in the placebo arm were not followed with the MADRS score after Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psilocybin Arm | Montgomery-Asberg Depression Rating Scale | 3.67 score on a scale | Standard Deviation 4.48 |
Secondary
Moral Injury Symptom Scale
Assesses symptoms of moral injury: minimum score 10, max 100; higher score indicates more severe symptoms
Time frame: 4, 24 weeks post-psilocybin-assisted psychotherapy
Secondary
PTSD Checklist for DSM-5 (PCL5)
Assesses symptoms of post-traumatic stress disorder; minimum score 0, max 80; higher scores indicate more severe symptoms of PTSD
Time frame: 4 weeks post-psilocybin or placebo session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psilocybin Arm | PTSD Checklist for DSM-5 (PCL5) | 16.67 score on a scale | Standard Deviation 15.04 |
| Placebo | PTSD Checklist for DSM-5 (PCL5) | 6.74 score on a scale | Standard Deviation 10.69 |
Secondary
Stanford Fulfillment Index
Assesses professional burnout in 3 components that are scored separately (professional fulfillment, interpersonal disengagement, work exhaustion)
Time frame: 1,4,8,12,24 -weeks post psilocybin-assisted psychotherapy