MD (Res) Scholarship 2019 (2): Dr Camilla Day; King’s College London

Project Title: Qualitative and Quantitative Study of Contextual Factors in Psilocybin-assisted Therapy for Treatment Resistant Depression.

Supervisors: Professor Anthony Cleare and Dr James Rucker

Project Summary

Treatment resistant depression leads to high rates of disability and mortality and a very high socioeconomic burden, being the leading cause of disability worldwide. Novel interventions are needed to meet this need and recent trials investigating the effect of psilocybin with psychological support for depressive symptoms have shown a good safety project with promising results.

This MD (Res) will form part of the tertiary outcomes of the Psilocybin in Depression Resistant to standard treatment (PsiDer) trial led by Dr James Rucker at the Centre for Affective Disorders, South London and Maudsley NHS Trust and King’s College London. The PsiDer trial is funded by the National Institute for Health Research to investigate the safety, feasibility and efficacy of psilocybin in treatment resistant depression, using the gold standard design of a randomised control trial. The study will recruit up to 60 participants with current depression unresponsive to usual treatments. The main outcome of the study will be to evaluate the feasibility of an RCT design in which a single dose of oral psilocybin 25mg vs placebo will be given to adult participants with treatment resistant major depressive disorder (TRD), under psychologically supportive conditions, with 3 weeks of follow up. At 3 weeks follow up all participants will be offered an open label extension consisting of a single dose of 25mg psilocybin, delivered under identical conditions with a further 12 weeks of follow up. Secondary outcomes will be changes in depressive symptoms on Quick Inventory for Depressive Symptoms (QIDS) between placebo and psilocybin groups. Currently the study protocol is about to go through ethics, having just finished contract negotiation.

There is a basic assumption that the context in which psilocybin is taken dramatically alters the dosing experience and outcome for the individual but there has been little research into this complex interplay. Using a mixed method approach this MD (Res) aims to investigate how these contextual and experiential factors influence outcome so that we can learn how to optimise the context to improve outcomes for people with depression. In particular I shall use a validated scale (STAR-P and STAR-C) to investigate if therapeutic relationship, from the point of view of participant as well as clinician, effects changes in depressive symptoms after psilocybin. I shall also be using another validated scale (Kristen Neff Self-Compassion Trait Scale) to investigate if changes in self-compassion before and after psilocybin effect changes in depressive symptoms. I shall then see if increases in self-compassion states mediate the relationship between baseline therapeutic relationship and changes in depressive symptoms. I also aim to develop my own compassion experience scale to quantify the types of dosing experiences that may be important for changes in depressive symptoms. In order to complement these quantitative methods, I shall carry out semi-structured interviews in 8 individuals (4 men and 4 women) at three time point for a longitudinal analysis (interpretative phenomenological analysis) of people’s lived experience of depression and psilocybin with psychological support. The main aims of this qualitative analysis, is to optimise outcomes for psilocybin interventions, and also to understand the aetiology and treatment of depression from the point of view of the participant.

Student:

Camilla is an ST6 General Adult Psychiatrist at South London and Maudsley NHS Trust and Honorary Research Associate at the Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King’s College London. She is currently working at St Thomas’ Hospital Liaison and Perinatal teams but is about to start working in a therapeutic community for personality disorders at the Maudsley Hospital in February 2020. She started out studying psychology and physiology at St Edmund Hall, Oxford University and went onto to do fast track medicine at Warwick Medical School where she won a research scholarship. She then did an academic foundation programme in psychiatry in West Midlands and then moved to London to do her psychiatric training at South London and Maudsley NHS Trust. She has always been involved in psychiatric research and over the years has developed an interest in psychotherapy. She started working in the field of psychedelic research in 2014 with the Imperial Psychedelic Research Group where she volunteered as a guide for 11 participants receiving psilocybin for depression and collaborated in qualitative research. She is currently doing a part-time mixed methods MD Res in psilocybin for treatment resistant depression, having been fortunate to receive the Tom Palmer award from Mental Health Research UK.

Progress Report year 1, 2021

Honorary Research Associate with Psychedelic Research Group, Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King’s College London

I had my second daughter, Oona in July 2020 and so I had officially taken an interruption to my MD(res) from July 2020 – August 2021 so I can focus on motherhood. However since my area of research is rapidly evolving I have continued to collaborate with my team and continued to develop my Psychedelic Compassion Experience Scale. This scale is aiming to quantify the healing experiences that people have on a psilocybin ‘trip’ that may predict outcome in improvements in depression. Although the scale will reduce experience to a number, this scale is not aiming to reduce experience to fit an assumed psychological or biological pathyway and instead aims to align with the phenomenology of the experience.

During the last year, I have completed the first four stages of scale development including Identification of Domain, Item generation, Content Validity and Pre-testing of questions. Using both inductive and deductive methods my domain has expanded from the three components of self-compassion being Self-Kindness, Common Hummanity and Mindfulness to Inner Therapist, Connection and Emotional Experiencing.

Initially 14 pairs of antithetical questions (each question asked negatively as well as positively) were developed and pre-testing found that this was too cumbersome and the negative questions were dropped.

There were then 15 questions (1 more question was added to Connection) and after content validity testing from 10 experts in UK and USA, fleiss kappa increased from 0.64 to 0.78 and content validity index from 0.92 to 0.97 after dropping 3 questions. Fleiss kappa increased further to 0.98 on dropping one more question from Inner therapist however from written feedback it was obvious that the wording of this question was ambiguous and therefore was changed and if content validity were repeated, fleiss kappa would most likely increase further. There are now 12 items, 4 in each component and there have been some further wording changes on feedback from experts.

I have presented these findings at the International Conference of Psychedelic Research on 26th September 2020 and at the Mental Health Research UK Scholars’ day on 22nd April 2021.

Further Plans

The NIHR feasibility RCT trial comparing psilocybin with psychological support against placebo with psychological support in which my aims form part of has just started dosing participants. We are now due to start giving the 12 item Compassion Experience Psychedelic Scale. There are 60 patients in this trial and I also aim to give the scale to 120 healthy psilocybin users in order to be able to fully validate the scale.

Self-Compassion Trait and State Scale and Therapeutic Relationship Scale Aims

As the trial has now started, participants are being given the self compassion state and self compassion trait questionnaires to fill out before and after dosing. The STAR-C (clinician rate therapeutic relationship) scales are being given to the trial guides, who are delivering the psychological support that surrounds the psilocybin dosing, to fill out after dosing. The STAR-P (patient rate therapuetic relationship) are being given to the participants after dosing. These will then be analysed at the end of dosing.

Qualitative Aims

Furthermore I shall be liaising with phenomenology experts in order to finalise my qualitative interview questions and then as soon as possible I shall soon start interviewing participants.

Progress Report Year 2, 2022

Qualitative and Quantitative Study of Contextual Factors in Psilocybin-assisted Therapy for Treatment Resistant Depression.

August 2021-2022 Progress Report

Dr Camilla Day BA MBChB MRCPsych

Honorary Research Associate with Psychedelic Research Group, Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King’s College London.
Consultant Psychiatrist in Eating Disorder Outpatient Service, Maudsley Hospital, South London and Maudsley NHS Trust.

I returned to my clinical duties as a psychiatrist registrar and to this MD (res) in August 2021 having had my second daughter Oona. The NIHR feasibility RCT trial in which my aims are part of start dosing patients in the latter part of 2021. My Compassion Experience Psychedelic Scale is being given to the participants on the trial to fill out after their dosing of psilocybin. I am also in the process of getting ethics approval from KCL to give this scale to 120 healthy psilocybin users to fully validate the scale.

The self-compassion trait and state scale and therapeutic relationship scale (STAR-P) are also being given to participants on the trial before and after dosing. The STAR-C (clinician rate therapeutic relationship) scales are being given to the trial guides, who are delivering the psychological support that surrounds the psilocybin dosing, to fill out after dosing.

Regarding my qualitative aims I have been refining my aims and have decided to do a longitudinal interpretative phenomenological analysis in 8 participants (4 female and 4 male) at 4 time points (1) before dosing, (2) after randomized dosing, (3) a few days after open label dosing, (4) done a lot more reading into qualitative methods including reading a book called Qualitative Research in Healthcare edited by Immy Holloway and Essentials in IPA by Jonathan Smith as well as Essentials in Consensual Qualitative Research by Clare Hill. I have also been watching online presentations from the experts who created these methods. I have been reflecting on my chosen methodology Interpretative Phenomenological Analysis as compared to a descriptive phenomenological analysis (which believes that we can observe phenomena in others by ‘bracketing’ or suspending our own judgements/presuppositions) but human beings we are immersed in our worlds, and it is not possible to observe without interpretation. I have also attended training in NVIVO, the software that is used to collate transcriptions to aid analysis. I attended specific IPA training on ‘how to supercharge your interview’ and reflected that I needed to pilot my interview schedules and so have done this with a previous psilocybin participant who is on the steering committee for this NIHR trial, and he has been reimbursed for this.

I have been working on a review paper on the Therapeutic Relationship in Psilocybin for Treatment Resistant Depression.

In terms of future goals, I am hoping to present my method on an IPA forum that I belong to and start my interviews shortly. I am also hoping to submit my paper on Therapeutic Relationship to an appropriate journal.