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TITLE PAGE
Title
Ketamine-assisted psychotherapy provides lasting and effective results in the treatment of depression,
anxiety and post traumatic stress disorder at 3 and 6 months: Findings from a large single-arm
retrospective effectiveness trial
Authors
Ryan Yermus MD, Michael Verbora MBA, MD, Sidney Kennedy MD, Robert McMaster MD, Sarah Kratina
BScN, RN, Elizabeth Wolfson PhD, Ben Medrano MD, Nathan Bryson PhD, Nabid Zaer MD, John Bottos,
Varun Setlur, Chris Lo PhD
Author Affiliations
Field Trip Health, Toronto, Ontario (Yermus, Verbora, Wolfson, Zaer, Bottos, Setlur); Family Medicine,
Faculty of Health Sciences, McMaster University, Hamilton, Ontario (Verbora); Department of Psychiatry,
Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario (Kennedy, McMaster, Lo); Institute
of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto,
Toronto, Ontario (Kratina); Social and Behavioural Health Sciences Division, Dalla Lana School of Public
Health, University of Toronto, Toronto, Ontario (Lo); Psychology, College of Healthcare Sciences, James
Cook University, Singapore (Lo); Field Trip Health NY & DC, New York, NY & Washington, District of
Colombia, (Medrano); Nue Life Medical Group, Delaware (Medrano); Reunion Neuroscience, Toronto,
Ontario (Bryson), School of Biological Sciences and Applied Chemistry, Seneca College, Toronto, Ontario
(Zaer).
Corresponding Author
Ryan Yermus MD, Field Trip Health, 30 Duncan St Suite 400, Toronto, Ontario, Canada, M5V 2C3.
Email: ryan@fieldtriphealth.com.
Telephone Number: 647-281-0082
Manuscript Word Count
2,881
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is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted January 17, 2023. ; https://doi.org/10.1101/2023.01.11.23284248doi: medRxiv preprint
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
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Key Points
Question What are the lasting effects of Ketamine-Assisted Psychotherapy on psychological distress?
Findings In this retrospective single-arm effectiveness trial that included 1806 adults, there were large
effect sizes at 3 months on depression, anxiety, and post traumatic stress (d’s=0.75-0.86) that were
sustained at 6 months.
Meaning These findings suggest that Ketamine-Assisted Psychotherapy is an effective treatment option
with substantial clinical benefits detected up to half a year.
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Abstract
IMPORTANCE Ketamine-Assisted Psychotherapy (KAP) is an emerging treatment option to alleviate
treatment resistant affective disorders, but its long term effectiveness remains unclear.
OBJECTIVE To examine the treatment effects of KAP on anxiety, depression, and post traumatic stress
disorder (PTSD) at 1, 3, and 6 months post treatment.
DESIGN, SETTING, AND PARTICIPANTS This retrospective single-arm effectiveness trial included self-
reported outcomes from 1806 adults with a history of depression, anxiety, or PTSD who had not
responded to prior treatment interventions and received KAP administered across 11 Field Trip Health
clinics in North America between March 13, 2020 and June 16, 2022.
INTERVENTION KAP consisting of 4-6 guided ketamine sessions (administered via intramuscular
injection or sublingual lozenge) with psychotherapy-only visits after doses 1 and 2 and then after every 2
subsequent doses. Mean number of doses administered was 4, SD=3, and mean number of
psychotherapy sessions was 3, SD=2.
MAIN OUTCOMES AND MEASURES Primary outcomes were changes in depression, anxiety, and
PTSD at 3 months relative to baseline, assessed respectively using the 9-item Patient Health
Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder measure (GAD-7), and the 6-item PTSD
Checklist (PCL-6). Secondary outcomes were changes at 1 and 6 months relative to baseline.
RESULTS Large treatment effects were detected at 3 months (d’s=0.75-0.86) that were sustained at 6
months (d’s=0.61-0.73). Case reductions (identified based on cut-off values) ranged from 39-41% at 3
months and 29-37% at 6 months. 50-75% reported a minimal clinically important difference at 3 months
and 48-70% at 6 months.
CONCLUSIONS AND RELEVANCE KAP produced sustained reductions in anxiety, depression, and
PTSD, with symptom improvement lasting well beyond the duration of dosing sessions. These effects
extended to as much as 5 months after the last KAP session. Given the growing mental health care crises
and the need for effective therapies and models of care, especially for intractable psychiatric mood
related disorders, these data would support the consideration of KAP as a viable alternative. Further
prospective clinical research should be undertaken to provide further evidence on the safety and
effectiveness of ketamine within a psychotherapeutic context.
TRIAL REGISTRATION Clinicaltrials.gov Identifier NCT05604794
Keywords: Anxiety, Depression, Ketamine, Psychedelic, Psychotherapy, Post Traumatic Stress Disorder
Word Count: 2,881
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Introduction
Over the past two decades, ketamine has demonstrated the potential to produce rapid and sustained
antidepressant effects and therapeutic outcomes for several psychiatric conditions.1 Most studies to date
have looked at the administration of ketamine via intravenous (IV) administration2 however, ketamine’s
application has evolved to include psychotherapeutic practices to reduce its unwanted dissociative effects
while bolstering positive antidepressant, anxiolytic, anti-stress, and other positive mood effects.3
Ketamine-Assisted Psychotherapy (KAP) has borrowed from earlier research on psychedelic substances
such as lysergic acid diethylamide (LSD) to facilitate deep and rapid introspective work within an
organized psychotherapeutic framework.4
Currently, ketamine is the only legal psychedelic medicine to treat persistent and severe
psychological distress in North America, making it well-suited for widespread psychotherapeutic
implementation. Preliminary clinical trial data are increasingly supportive of the safety and efficacy of KAP
to alleviate anxiety, depression, and post traumatic stress disorder (PTSD),5,6 with more trials underway
worldwide. In a recent study of patients with moderate to severe depression or anxiety, ketamine-assisted
therapy was found to have immediate effects on depression and anxiety; outcomes showed persistent
efficacy to 2 and 4 weeks in most treated subjects.7 However, the impact on post-treatment quality of life
is understudied, and there remains a need to clarify the long term effectiveness of KAP for a variety of
mood related disorders.
In this study, we conducted a retrospective analysis of outcomes from patients who were treated
with KAP at Field Trip Health centres across North America and agreed to participate in an open label
evaluation of outcomes up to 6 months after the intervention. Ketamine was administered via
intramuscular injection or sublingual lozenge. Primary outcomes were changes in depression, anxiety,
and post traumatic stress at 3 months from baseline. Secondary outcomes were changes at 1 and 6
months from baseline.
Methods
Ethics and Design
Ethics approval for this study was granted by Veritas Independent Review Board (#2022-3067-11240-5).
The study was a retrospective single-arm effectiveness trial of KAP involving chart review of patient self-
reported mental health outcomes assessed at baseline, 1, 3, and 6 months.
Participants and Procedure
Data was collected from clients treated across 11 Field Trip Health clinics in North America: 1) Toronto,
ON, Canada; 2) Vancouver, BC, Canada; 3) Fredericton, NB, Canada; 4) New York City, NY, USA; 5)
Atlanta, GA, USA; 6) Chicago, IL, USA; 7) Houston, TX, USA; 8) Seattle, WA, USA; 9) Santa Monica, CA,
USA; 10) San Diego, CA, USA; 11) Washington, DC, USA; between March 13, 2020, and June 16, 2022.
Participants included in the analysis had a documented history of depression or anxiety that showed lack
of adequate response to previous treatment(s) or presented with PTSD as assessed by the Structured
Clinical Interview for DSM 5 (SCID 5).8 Patient assessments were performed using a proprietary digital
platform (PortalTM) through the Electronic Medical Records (EMR) system at 1, 3, and 6 months. The
completion of measures was voluntary after the collection of signed written informed consent.
Treatment
Prospective clients were either self-referred in the United States or referred for treatment by a health care
provider to one of the 3 Canadian clinic locations. All clients were assessed by a psychiatrist or
psychiatric nurse practitioner to determine the appropriateness for treatment. Inclusion criteria included
signed written informed consent; being over the age of 18; and having a documented, prior diagnosis by a
psychiatrist of one or more of Major Depressive Disorder (MDD), Bipolar Depression, Generalized Anxiety
Disorder, Obsessive Compulsive Disorder (OCD), Eating Disorder, or a significant history of trauma
and/or a formal diagnosis of PTSD as per the DSM 5.
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Exclusion criteria included pregnant women and nursing mothers, although Postpartum
Depression (PPD) was considered on a case-by-case basis in consultation with the National Medical
Director; a relative (not absolute) contraindication for individuals with a Body Mass Index (BMI) above 35;
any individual who has met DSM 5 criteria for a Substance Use Disorder in the past 3 months and had
been unable to exhibit a reduction in use; Psychosis or psychotic symptoms; Active Mania: Bipolar 1
(chronic non-disruptive hypomania is an exception at the discretion of the treatment team); Borderline
Personality Disorder; uncontrolled medical disorders or physical conditions with negative interaction with
ketamine; individuals with symptomatic acute brain injury within 90 days of serious injury; individuals
diagnosed with moderate to severe sleep apnea; and individuals who were unable to identify a person or
service to assure their safe transport to home post treatment.
Upon medical approval, clients met with a licensed therapist to discuss preparation for KAP and
to initiate a therapeutic relationship. Dosing with ketamine was completed via intramuscular injection in
the United States and Vancouver and via sublingual lozenge in Toronto and Fredericton. Clients were
offered personalized treatment recommendations consisting of 4-6 guided ketamine sessions with
psychotherapy-only integration visits after doses 1 and 2 and then after every 2 subsequent doses.
Initial dosing via intramuscular injection was of 25-35mg with the option to titrate to 50-70mg at
visit 2 and up to 100mg for subsequent visits. The initial dose for lozenges was 200mg with the option to
increase by 50-100mg per visit up to 500mg. Ketamine doses were not scheduled on consecutive days
and could be interspersed by 1 week or more. Some participants completed additional sessions beyond
dose 6. Integration sessions were based on motivational interviewing and behavioural activation, but
therapists had the option to incorporate other modalities depending on their assessment of the client's
needs and goals.
Ketamine dosing was completed in Field Trip Health clinics using an approach consistent with
psychedelic studies in a setting designed to be aesthetically and functionally conducive with a state of
relaxation. Clients were dosed while seated in a comfortable reclining chair, wearing an eye shade and
listening to curated music playlists. Therapists were present to support clients during dosing sessions
while medical staff monitored heart rate, blood pressure, respiration rate and oxygen saturation
throughout the session.
Outcome Measures
Symptoms of depression were assessed by the 9-item Patient Health Questionnaire (PHQ-9).9 PHQ
scores may range from 0-27 with higher scores indicating more severe depressive symptoms. A PHQ cut-
off score of 15 has been validated to identify cases with at least moderately-severe depression.9 A
change of 3 points has been considered a minimal clinically important difference (MCID).10,11
Symptoms of anxiety were assessed by the 7-item Generalized Anxiety Disorder measure (GAD-
7).12 GAD scores may range from 0-21 with higher scores indicating more severe anxiety symptoms. A
GAD cut-off score of 10 has been validated to identify cases with at least moderate anxiety.12 A change of
3 points has been considered an MCID.10,11
Symptoms of post traumatic stress were assessed using the 6-item PTSD Checklist (PCL-6).13
PCL scores may range from 6-30, with higher scores indicating more severe stress symptoms. A PCL
cut-off score of 14 has been validated to identify cases of PTSD.13 A change of 5 points may be
considered an MCID.14
Statistical Analysis
We report descriptive statistics for the sample and analyze the extent of loss to follow-up. The primary
analysis was by Intention to Treat (ITT). We used linear mixed modelling to fit growth curves describing
the normative patient trajectory on each outcome.15 The main analysis involved fitting linear and
curvilinear trends over time and estimating mean differences at each endpoint compared to the baseline.
Cohen’s d was reported as a standardized measure of effect size for mean differences (d=0.2 is a small
effect, 0.5 medium, and 0.8 large).
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We reported secondary analyses on the effect of doses administered, controlling for age, gender,
and site differences; case reductions in depression, anxiety, and PTSD based on cut-offs; and
proportions of treatment responders based on MCIDs. As a sensitivity analysis, we used the Expectation-
Maximization (EM) and Markov Chain Monte Carlo (MCMC) algorithms to multiply impute missing follow-
up data.16 We simulated 1000 datasets per outcome measure, calculated the effects per imputation, and
combined the findings across imputations to achieve the best estimates for comparison to the initial
estimates.
Results
Descriptive Statistics
In total 1806 participants entered treatment (see Table 1 for sample characteristics). The mean age was
42 years, SD=12, and 52% of participants were female. Most individuals had a primary diagnosis of
depression (24%), anxiety (28%), or PTSD (25%). The mean number of assessments completed per
participant was 2.26, SD=2.01. 18% of baseline participants provided a 3-month assessment, and 5%
provided a 6-month assessment (see Figure 1 for patient flow diagram).
The mean number of doses was 4, SD=3, with 12% (210/1806) receiving more than 6 doses and
24% (440/1806) receiving 1 dose. Ketamine was administered sublingually to 32% (579/1806) of the
sample and intramuscularly to 68% (1227/1806). The mean number of (psychotherapeutic) integration
sessions was 3, SD=2, with 20% (365/1806) receiving more than 4 sessions.
Lost to Follow-up Analyses
Lost to follow-up refers to individuals who did not provide a follow-up assessment and is separate from
treatment status. Lost to follow-up was associated with less pretreatment psychological distress.
Compared to those who provided a 3-month assessment, those who did not had lower baseline scores on
PHQ, MDiff=-1.83, CI.95 (-1.09, -2.58), p<.0001, d=0.28, and PCL, MDiff=-1.56, CI.95 (-0.86, -2.25), p<.0001,
d=0.28. Compared to those who provided a 6-month assessment, those who did not had lower baseline
scores on GAD, MDiff=-1.58, CI.95 (-0.26, -2.90), p=0.02, d=0.28, and PCL, MDiff=-1.86, CI.95 (-0.51, -3.22),
p=0.007, d=0.33. Overall, the frequency of missing assessments had a tendency to be negatively
correlated with baseline scores on the PHQ, r=-0.13, p<.0001; the GAD, r=-0.06, p=0.02; and the PCL,
r=-0.10, p<.0001.
Primary and Secondary Outcomes
The primary outcomes were changes at 3 months from baseline, and secondary outcomes were changes
at 1 and 6 months from baseline. There was a significant reduction on the PHQ at 1 month, d=0.50, which
was amplified at 3 months, d=0.85, and remained detectable at 6 months, d=0.73. There was a reduction
on the GAD at 1 month, d=0.47, which was amplified at 3 months, d=0.86, and remained detectable at 6
months, d=0.73. There was a reduction on the PCL at 1 month, d=0.38, which was amplified at 3 months,
d=0.75, and remained detectable at 6 months, d=0.61. See Table 2 for details.
Dose and Other Predictive Factors
We entered dose as a predictive factor, controlling for age, gender, and site. Dose referred to the number
of doses administered at the time of assessment and was a within-subjects, time-varying factor. There
was a significant effect of dose on PHQ, b=-1.20, se=0.061, p<.0001, on GAD, b=-0.97, se=0.055,
p<.0001, and on PCL, b=-0.92, se=0.055, p<.0001. These coefficients indicate that per administered
dose, there was a reduction of 1.20 points on the PHQ and approximately 1 point reductions on the GAD
and PCL.
There were main effects of site, age, and gender. There were medium to large site differences
due to the requirement for clinician treatment referral in Canada. Overall, Canadian sites treated cases
with more intense symptomatology than American sites (which permitted self-referral): d=0.80, MDiff=5.19,
CI.95 (4.19, 6.20) on PHQ; d=0.43, MDiff=2.43, CI.95 (1.58, 3.28) on GAD; d=0.58, MDiff=3.27, CI.95 (2.41,
4.14) on PCL; all p’s<.0001. There were some small age effects. Compared to younger clients (estimated
at 30 years or mean age – 1SD), older clients (estimated at 54 years or mean age + 1SD) had lower
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overall PHQ scores, d=0.23, MDiff=-1.53, CI.95 (-2.09, -0.98), p<.0001, lower overall GAD scores, d=0.31,
MDiff=-1.73, CI.95 (-2.20, -1.25), p<.0001, and lower overall PCL scores, d=0.14, MDiff=-0.78, CI.95 (-1.27, -
0.30), p=0.002. There was one marginally significant gender difference. Compared to men, women had a
slight tendency to report higher overall PHQ scores, d=0.08, MDiff=0.54, CI.95 (-0.005, 1.08), p=0.05.
Caseness
There were statistically significant reductions in the proportions of depressed, anxious, and PTSD cases
as identified by scoring above or equal to clinical cut-off values on each outcome measure (see Table 3).
Case reductions showed similar patterns of change across outcomes as in the growth curve models, with
the largest case reductions at the primary 3-month endpoint.
In the 315 patients who provided a 3-month PHQ assessment, the depression case rate dropped
from 56% at baseline to 17% at 3 months. In the 305 patients who provided a 3-month GAD assessment,
the anxiety case rate dropped from 67% at baseline to 26% at 3 months. In the 299 patients who provided
a 3-month PCL assessment, the PTSD case rate dropped from 84% at baseline to 45% at 3 months.
In the 92 patients who provided a 6-month PHQ assessment, the depression case rate dropped
from 51% at baseline to 16% at 6 months. In the 72 patients who provided a 6-month GAD assessment,
the anxiety case rate dropped from 69% at baseline to 32% at 6 months. In the 69 patients who provided
a 6-month PCL assessment, the PTSD case rate dropped from 87% at baseline to 58% at 6 months.
Treatment Responders
See Table 4. In the 315 patients who provided a 3-month PHQ assessment, 75% reported a 3-point
MCID compared to baseline. In the 305 patients who provided a 3-month GAD assessment, 68%
reported a 3-point MCID compared to baseline. In the 299 patients who provided a 3-month PCL
assessment, 50% reported a 5-point MCID compared to baseline.
In the 92 patients who provided a 6-month PHQ assessment, 70% reported a 3-point MCID
compared to baseline. In the 72 patients who provided a 6-month GAD assessment, 65% reported a 3-
point MCID compared to baseline. In the 69 patients who provided a 6-month PCL assessment, 48%
reported a 5-point MCID compared to baseline.
Simulations
We multiply imputed 1000 datasets per outcome measure in which missing values were filled in with
simulated values, achieving relative efficiencies of 0.999. This method allows us to evaluate what would
have happened if individuals who were lost to follow-up were retained in the data analysis and is meant to
mitigate the poor retention rate. For each imputation, we specified linear mixed models to directly
estimate mean differences at each endpoint from baseline. These parameters were combined across
imputations to achieve best estimates of mean differences (see Table 2). There were no apparent
differences between imputed estimates and those based on the analysis of available cases only. Many
imputed estimates indicated a slightly larger effect than initially detected.
Discussion
This single-arm effectiveness trial examined the largest dataset to date of long term outcomes in clients
who received Ketamine-Assisted Psychotherapy. KAP aimed to alleviate symptoms of depression,
anxiety, and post traumatic stress. We found evidence of large to moderately large treatment effects at 3
and 6 months, d’s ranging from 0.61-0.86 and corresponding to 5-6 point reductions on the PHQ, 4-5
point reductions on GAD, and 3-4 point reductions on PCL. There was a consistent pattern of change
across measures characterized by reductions in psychological distress that were most apparent at 3
months. There were approximately 40% reductions in caseness for depression, anxiety, and PTSD at this
primary endpoint, and treatment responders ranged from 50-75%. This clinical benefit was sustained at 6
months.
Gender and age differences in outcomes were small to minimal, indicating the broad suitability of
KAP. Over 90% of individuals entered treatment within 3 months of intake, and 76% completed more than
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1 ketamine dose. Each ketamine dose was associated with 1-point reductions on the PHQ, GAD, and
PCL, in support of the current program, which recommends 4-6 ketamine sessions. This can be
anticipated to produce an estimated 4-6 point reduction across outcome measures over time, larger than
the MCID thresholds of 3-5 points for indicating treatment response. However, we caution that the effects
of dose must be interpreted within the context of KAP, which involved integration sessions that occurred
in lock step with ketamine dosing to activate and reinforce the psychological gains from this experience.
Occasional side effects included nausea, vomiting, and increases in blood pressure, not requiring medical
intervention nor requiring patients to be taken to a hospital. Findings may be most generalizable to
populations with treatment-resistant depression, anxiety, or PTSD eligible for KAP treatment according to
Fieldtrip Health guidelines. Given the lack of novel treatment options in the behavioral health space, KAP
represents a viable alternative that should be more widely considered.
Limitations
The main limitation of this study is the substantial attrition during the 6 month follow-up period. The
importance of completing the follow-up assessments was not made clear to patients and increased efforts
are needed to improve survey completion rates moving forward. The treatment effects demonstrated here
are based on those who provided follow-up data. These individuals tended to have more pretreatment
distress and may be considered a clinical priority. The estimates of treatment effect at 6 months are less
reliable than at 3 months. To the extent possible, we examined these issues using multiple imputation of
missing data. The estimates of treatment effect from these simulation analyses were stable and
consistent with the analysis of only available cases.
Although promising, a future prospective clinical trial with improved data collection is needed.
Other limitations include the retrospective nature of the study and lack of a randomised control group.
Further study is also needed to clarify the indications and contraindications of KAP for patient
subpopulations and the tailoring of treatment to further improve upon individual outcomes.
Conclusion
This large retrospective single-arm trial found that Ketamine-Assisted Psychotherapy is an effective
treatment achieving sustained and clinically meaningful reductions in depression, anxiety, and post
traumatic stress for up to half a year.
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ARTICLE INFORMATION
Corresponding Author: Ryan Yermus MD, Field Trip Health, 30 Duncan St Suite 400, Toronto, Ontario,
Canada, M5V 2C3. Email: ryan@fieldtriphealth.com.
Author Affiliations: Field Trip Health, Toronto, Ontario (Yermus, Verbora, Wolfson, Zaer, Bottos, Setlur);
Family Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario (Verbora);
Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario (Kennedy,
McMaster, Lo); Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public
Health, University of Toronto, Toronto, Ontario (Kratina, Lo); Social and Behavioural Health Sciences
Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario (Lo); Psychology,
College of Healthcare Sciences, James Cook University, Singapore (Lo); Field Trip Health NY & DC, New
York, NY & Washington, District of Colombia, (Medrano); Nue Life Medical Group, Delaware (Medrano);
Reunion Neuroscience, Toronto, Ontario (Bryson), School of Biological Sciences and Applied Chemistry,
Seneca College, Toronto, Ontario (Zaer).
Author Contributions: Drs Yermus and Lo had full access to all of the data in the study and take
responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Yermus, Verbora, Lo.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Setlur, Bottos, Yermus, Lo.
Obtained funding: Yermus, Lo.
Administrative, technical, or material support: Setlur, Zaer, Bottos.
Supervision: Yermus, Lo.
Conflict of Interest Disclosures: Dr Yermus is a co-founder of Field Trip Health and formerly served as
Chief Clinical Officer. He received a salary and stock options for his work in this regard. Dr Verbora, is the
Medical Director of Field Trip Health & Wellness, and he receives a salary and stock options for his work
in this regard. Dr Kennedy has received funding for Consulting or Speaking engagements from Abbvie,
Boehringer-Ingelheim, Janssen, Lundbeck, Lundbeck Institute, Merck, Otsuka Pfizer, Sunovion and
Servier. He has received Research Support from Abbott, Brain Canada, CIHR (Canadian Institutes of
Health Research), Janssen, Lundbeck, Neurocrine, Ontario Brain Institute, Otsuka, Pfizer, SPOR
(Canada's Strategy for Patient-Oriented Research). He has stock/stock options in Field Trip Health. Dr
McMaster was an advisor to Field Trip Health, and owns shares in Field Trip Health and Wellness and
Reunion Neuroscience. Ms Kratina has no disclosures to report. Dr Wolfson is the Vice President of
Clinical Services at Field Trip Health and Wellness. She receives a salary and stock options for her work
in this regard. Dr Medrano was the Medical Director of Field Trip Health. He is the current Medical
Director of Nue.Life Medical Group that provides medical and therapy services for Field Trip At Home. He
receives salary and stop options for all of these from both Field Trip and Nue.Life. Dr Bryson was Chief
Scientific Officer of Field Trip Discovery, formerly a division of Field Trip Health, but now known as
Reunion Neuroscience, and he continues to own shares in Field Trip Health and Wellness, and further, as
Chief Scientific Officer of Reunion Neuroscience has an on-going mutual service agreement with Field
Trip Health and Wellness. Mr Zaer is a clinical consultant at Field Trip Health and receives a salary for his
work. Mr Bottos is the Manager of Health Platforms at Field Trip Health. He receives a salary and stock
options for his work in this regard. Mr Setlur was the Director of Data at Field Trip Health. He received a
salary and stock options for his work in this regard. Dr Lo received an initial consultation fee from Field
Trip Health.
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Funding/Support: This publication of this study was supported by the Field Trip Health & Wellness
Research Grant.
Role of Funder/Sponsor: Employees of the funder of this research were involved in the design and
conduct of the study; collection, management, analysis, and interpretation of the data; preparation,
review, or approval of the manuscript; and decision to submit the manuscript for publication.
Data Sharing Statement: There is no plan to share data, although requests may be made for access.
Trial Protocol: Trial protocol will be available at clinicaltrials.gov after the results are published.
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is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted January 17, 2023. ; https://doi.org/10.1101/2023.01.11.23284248doi: medRxiv preprint
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is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted January 17, 2023. ; https://doi.org/10.1101/2023.01.11.23284248doi: medRxiv preprint
12
Table 1. Sample Characteristics
Baseline and Time
-
Invariant Variables N Mean SD
Age
1806
42.12
11.60
Frequency of Ketamine
Doses Administered
1806
4.04
2.70
Frequency of
Integration Sessions
Delivered
1711
3.21
2.03
N
Frequency
Percent
Gender
Female
1806
948
52.49
Male
1806
850
47.07
Non
-
Binary
1806
8
0.44
Primary Diagnosis
Anxiety
1745
488
27.97
Bipolar Disorder
1745
16
0.92
Depression
1745
418
23.95
Eating Disorder
1745
27
1.55
Obsessive
-
Compulsi
ve
Disorder
1745
47
2.69
PTSD
1745
442
25.33
Substance Abuse
1745
85
4.87
Other
1745
222
12.72
Caseness at Baseline
T0 PHQ
≥
15
1805
821
45.48
T0 GAD
≥
10
1802
1137
63.10
T0 PCL
≥
14
1797
1364
75.90
Time
-
Dependent
Variables
N
Mean
SD
T0 PHQ
1805
13.60
6.51
T1 PHQ
331
10.26
6.78
T3 PHQ
316
8.29
6.02
T6 PHQ
92
8.92
6.06
T0 GAD
1802
11.86
5.60
T1 GAD
334
8.79
5.84
T3 GAD
306
6.73
5.03
T6 GAD
72
8.39
5.84
T0 PCL
1797
17.98
5.63
T1 PCL
328
15.30
5.49
T3 PCL
300
13.88
4.98
T6 PCL
69
15.22
5.48
T0 = baseline; T1 = 1-month assessment; T3 = 3-month assessment; T6 = 6-month assessment.
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted January 17, 2023. ; https://doi.org/10.1101/2023.01.11.23284248doi: medRxiv preprint
13
Table 2. Predicted Mean Differences from Linear Mixed Model Analyses of Available Cases and Multiple Imputation
T0 = baseline; T1 = 1-month assessment; T3 = 3-month assessment; T6 = 6-month assessment.
***p<.0001.
Outcome
M1
Time
point
M2
Time
point M1 M2 diffM1-M2
Lower
CL-.95 Upper
CL.95 d Imputed
diffM1-M2 ImputedLower
CL-.95
Imputed
Upper
CL
.95
Imputed
d
PHQ
T1
T0
10.38
13.62
-
3.23***
-
3.57
-
2.90
0.50
-
3.88***
-
4.49
-
3.28
0.60
T3
T0
8.06
13.62
-
5.56***
-
5.96
-
5.15
0.85
-
5.96***
-
6.57
-
5.34
0.92
T6
T0
8.88
13.62
-
4.74***
-
5.68
-
3.80
0.73
-
4.79***
-
5.83
-
3.75
0.74
GAD
T1
T0
9.24
11.89
-
2.65***
-
2.95
-
2.34
0.47
-
3.16***
-
3.71
-
2.61
0.56
T3
T0
7.09
11.89
-
4.80***
-
5.17
-
4.44
0.86
-
5.27***
-
5.80
-
4.74
0.94
T6
T0
7.78
11.89
-
4.10***
-
5.02
-
3.18
0.73
-
4.04***
-
5.24
-
2.84
0.72
PCL
T1
T0
15.85
17.99
-
2.14***
-
2.44
-
1.83
0.38
-
2.72***
-
3.26
-
2.18
0.48
T3
T0
13.75
17.99
-
4.24***
-
4.60
-
3.87
0.75
-
4.53***
-
5.08
-
3.98
0.80
T6
T0
14.55
17.99
-
3.44***
-
4.38
-
2.50
0.61
-
3.57***
-
4.71
-
2.42
0.63
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted January 17, 2023. ; https://doi.org/10.1101/2023.01.11.23284248doi: medRxiv preprint
14
Table 3. Proportions scoring above cut-off by outcome and timepoint.
Outcome
Pr1
Time-
point
Pr2
Time-
point Pr1 Pr2 diffPr1-Pr2 Lower
CI.95 Upper
CI.95 n
PHQ
≥
15
T0
T1
0.52
0.27
0.25***
0.20
0.31
330
T0
T3
0.56
0.17
0.39***
0.33
0.45
315
T0
T6
0.51
0.16
0.35***
0.24
0.46
92
GAD
≥
10
T0
T1
0.64
0.41
0.23***
0.17
0.29
333
T0
T3
0.67
0.26
0.41***
0.35
0.47
305
T0
T6
0.69
0.32
0.37***
0.23
0.52
72
PCL
≥
14
T0
T1
0.79
0.59
0.20***
0.15
0.25
327
T0
T3
0.84
0.45
0.39***
0.33
0.45
299
T0
T6
0.87
0.58
0.29***
0.17
0.41
69
T0 = baseline; T1 = 1-month assessment; T3 = 3-month assessment; T6 = 6-month assessment.
***p<.0001.
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted January 17, 2023. ; https://doi.org/10.1101/2023.01.11.23284248doi: medRxiv preprint
15
Table 4. Proportions reporting MCIDs at endpoint compared to baseline.
Outcome
Endpoint
Pr
Lower CI
.95
Upper CI
.95
n
PHQ
T1
0.53***
0.47
0.58
330
T3
0.75***
0.70
0.79
315
T6
0.70***
0.60
0.79
92
GAD
T1
0.50***
0.44
0.55
333
T3
0.68***
0.62
0.73
305
T6
0.65***
0.54
0.76
72
PCL
T1
0.32***
0.26
0.37
327
T3
0.50***
0.44
0.56
299
T6
0.48***
0.36
0.60
69
Note. MCID = 3 points for PHQ and GAD. MCID = 5 points for PCL.
T1 = 1-month assessment; T3 = 3-month assessment; T6 = 6-month assessment.
***p<.0001.
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted January 17, 2023. ; https://doi.org/10.1101/2023.01.11.23284248doi: medRxiv preprint
1
6
Figure 1. Patient Flow Diagram
6
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is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted January 17, 2023. ; https://doi.org/10.1101/2023.01.11.23284248doi: medRxiv preprint
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted January 17, 2023. ; https://doi.org/10.1101/2023.01.11.23284248doi: medRxiv preprint
