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Psilocybin-assisted psychotherapy for the treatment of Major Depressive Disorder: Preliminary results from a randomized controlled trial

Authors:

Abstract

Background: Major Depressive Disorder (MDD) is a prevalent condition that confers substantial public health burden. Current approved treatments, including pharmacotherapy and psychotherapy, are limited in effectiveness and adherence. Recent evidence suggests that one or two administrations of psilocybin under psychologically supported conditions produces antidepressant effects in cancer and treatment-resistant depression populations. Further examination of the efficacy of this intervention among patients with MDD is warranted. Method: This is a randomized waitlist control trial investigating the immediate and enduring antidepressant effects of two psilocybin administration sessions (20mg/70kg and 30mg/70kg) given in the context of supportive psychotherapy in patients diagnosed with MDD. Outcome measures include the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at Baseline (>=17 required for enrollment) and 1- and 4-weeks after the second psilocybin session. Twelve participants (as of December 2018) completed the intervention and the 1- and 4-week assessments (n=12; Mean age=39, SD=14; female=67%; Mean GRID-HAMD=22.8, SD=3.1; Mean Years w/Depression=16.8, SD=13.7). In this preliminary analysis we combined Baseline and 1- and 4-week follow-up data from the waitlist and immediate treatment groups to examine overall treatment effect of the psilocybin intervention. Results: Compared to Baseline, the mean reduction in depression scores was 63% at 1-week and 62% at 4-weeks. Across the entire sample, 83% of participants had a clinically significant response (>50% reduction in depression scores) at both 1- and 4-weeks. Moreover, at 1- and 4-weeks, respectively, 58% and 58% of participants met criteria for remission of depression (<= 7 on the GRID-HAMD). Paired samples t-tests revealed a significant decrease in depression scores from Baseline (M=22.8; SD=3.1) to 1-week follow-up (M=8.3, SD=6.9), t(11)=6.04, p<.001, Cohen’s d = 2.7, and a significant decrease from Baseline to 4-week follow-up (M=8.0, SD=5.9), t(11)=6.91, p<.001, Cohen’s d = 3.1. There was no significant difference in depression scores between the 1- and 4-week follow-up, t(11)=0.27, p=.795. These preliminary data extend previous studies in depressed cancer patients and patients with treatment-resistant depression by suggesting that psilocybin-assisted psychotherapy may be efficacious for treatment of MDD in the general population. The overall effect of this intervention across conditions is 3-4 times above the threshold considered a “large” effect (>0.80). Furthermore, the trend of changes in depression scores by condition suggests that these effects are not accounted for by the passage of time. Future analyses of a larger patient sample (n=24) will include statistical comparison of waitlist and immediate treatment conditions as well as assessment at long-term follow-up time points at 3, 6, and 12-months.
Background Results
Psilocybin-assisted psychotherapy for the treatment of Major Depressive Disorder:
Preliminary results from a randomized controlled trial
Major Depressive Disorder (MDD) is a prevalent condition that
confers substantial public health burden. Current approved
treatments, including pharmacotherapy and psychotherapy, are
limited in effectiveness and adherence. Recent evidence suggests
that one or two administrations of psilocybin under psychologically
supported conditions produces antidepressant effects in cancer
and treatment-resistant depression populations.
Aims and Method
This is a randomized waitlist control trial investigating the immediate
and enduring antidepressant effects of two psilocybin administration
sessions (20mg/70kg and 30mg/70kg) given in the context of
psychotherapy in patients diagnosed with MDD.
Outcome measures include the GRID-Hamilton Depression Rating
Scale (GRID-HAMD) scores at Baseline (>17 required for
enrollment) and 1-and 4-weeks after the second psilocybin
session.
As of December 2018, a total of 12 participants completed the
intervention and the 1- and 4-week assessments:
Mean age = 39, SD = 14
Female = 67%
Mean Years with depression = 16.8, SD = 13.7
Conclusions
Alan K. Davis PhD, Darrick G. May MD, Mary Cosimano MSW,
Matthew W. Johnson PhD, Frederick S. Barrett PhD, Roland R. Griffiths PhD
Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, Psychedelic Research Unit
These preliminary data extend previous studies in depressed cancer patients and patients with treatment-resistant depression by
suggesting that psilocybin-assisted psychotherapy may be efficacious for treatment of MDD in the general population. The overall effect of
this intervention across conditions is 3-4 times above the threshold considered a “large” effect (>0.80). Furthermore, the trend of changes in
depression scores by condition suggests that these effects are not accounted for by the passage of time. Future analyses of a larger patient
sample will include statistical comparison of waitlist and immediate treatment conditions as well as assessment at long-term follow-up time
points at 3, 6, and 12-months.
*** p<.001; ^^^ Effect size: Cohen’s d = 2.7; +++ Effect size: Cohen’s d = 3.1
Funding
The study was supported by a crowdsourced funding campaign organized by Tim Ferriss and by a grant from the Riverstyx Foundation.
Dr. Davis and Dr. May were supported by a NIDA T32 postdoctoral training grant (#DA007209). Drs. Griffiths and Johnson were supported
by a NIDA grant (R01DA003889). The funding sources had no role in the design/execution of this study or the interpretation or
communication of findings.
Contact email for corresponding author: alan.kooi.davis@gmail.com
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Change in mean depression score
from Baseline to 1-wk
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Change in mean depression score
from Baseline to 4-wk
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Mean GRID-HAMD scores: Baseline = 22.8 (SD = 3.1), 1-wk = 8.3 (SD = 6.9), 4-wks = 8.0 (SD = 5.9)
For primary statistical analysis we combined Baseline and 1- and 4-
week follow-up data from the waitlist and immediate treatment
groups to examine overall treatment effect of the psilocybin
intervention. We combined groups because only 3 participants had
completed the waitlist condition at time of analysis.
We calculated the reduction in depression scores (% decrease) at
1-wk and 4-wks, the proportion of participants with a clinically
significant response (>50% decrease in GRID-HAMD scores) at 1-
wk and 4-wks, and the proportion of participants meeting criteria for
remission (<7 on the GRID-HAMD) at 1-wk and 4-wks. Additionally,
we used a paired samples t-test to compare mean depression
scores from baseline to 1-wk and 4-wks.
Lastly, we plotted mean GRID-HAMD scores at all time points in
two separate figures (bottom of results), one for each condition, to
present trend data for the treatment effect.
Data Analyses
Baseline 1-wk Baseline 4-wks
Change in depression scores over time
as a function of treatment condition
83%83%
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1-wk 4-wks
Proportion of participants meeting criteria for
clinically significant response (>50% decrease
in depressions scores)
at 1-wk and 4-wks
58%58%
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1-wk 4-wks
Proportion of participants meeting criteria
for remission (>7 on GRID-HAMD)
at 1-wk and 4-wks
Article
Full-text available
The medium to long term consequences of COVID-19 are not yet known, though an increase in mental health problems are predicted. Multidisciplinary strategies across socio-economic and psychological levels may be needed to mitigate the mental health burden of COVID-19. Preliminary evidence from the rapidly progressing field of psychedelic science, shows that psilocybin assisted psychotherapy (PAP), offers a promising trans-diagnostic treatment strategy for a range of disorders with restricted and maladaptive habitual patterns of cognition and behaviour, notably depression, addiction and obsessive compulsive disorder (OCD). The COMPASS pathways, phase 2b double blind trial of PAP in antidepressant-free, treatment resistant depression (TRD) is underway across 19 research sites, to determine the safety, efficacy and optimal dose of psilocybin. Results from the Imperial College London Psilodep-RCT comparing the efficacy and mechanisms of action of PAP to the selective serotonin reuptake inhibitor (SSRI) escitalopram will soon be published. However, the efficacy and safety of PAP in conjunction with SSRIs in TRD is not yet known. A new COMPASS study, with a centre in Dublin, will answer this question, with implications for the future delivery of PAP. While at an early stage of clinical development, and notwithstanding the immense challenges of COVID-19, PAP is likely to play an important therapeutic role for certain disorders in post COVID-19 clinical psychiatry.
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