Exploratory trial to assess the efficacy and safety of Psilocybin-Assisted Psychotherapy (PAP) involving family-members compared to standard PAP, in adults with treatment-resistant major depressive disorder. (TRMDD).
Reset Mind Science
60 participants
Jan 17, 2024
Interventional
Conditions
Summary
Psilocybin is a natural compound found in some mushroom species known to act on the brain pathway involved in depression. It is administered orally as capsules and is usually given during a psychotherapy session. A growing number of studies have shown that psilocybin can be safely given to humans for the treatment of depressive symptoms and can induce a profound psychedelic experience (a temporary altered state of awareness and responsiveness to your surroundings). Major depressive disorder (MDD) is a very common chronic mental health illness that can interfere with social, occupational and family relations. It can lead to disability and can even have life-threatening consequences. Although very variable, some factors may influence MDD such as genetic risk factors, recent negative life events, alcohol abuse and lack of family and social support. It has been reported that most MDD patients have problems with multiple areas of family functioning that are not usually considered during treatment. Most people diagnosed with MDD will relapse after their first episode of depression, and that risk increases with every subsequent episode. The primary goal of any MDD treatment is to control its symptoms and restore the person’s functionality. It usually involves a combination of medication and psychotherapy. However, despite modern advances in drugs and psychotherapeutic treatments, approximately 1 in 3 people with MDD do not respond to antidepressant therapies. Treatment-resistant major depressive disorder (TRMDD) can be defined as a failure to achieve remission to at least two proven antidepressants with adequate dosing and duration. Psilocybin has been used in multiple studies in people with TRMDD for more than 10 years. It has a different way of interacting in the brain than the current available antidepressant medications and it has shown promise as an aide to psychotherapy, especially for those with TRMDD. It has been studied at various doses and there have been no significant serious side effects. This study aims to show that there is an increased benefit to TRMDD participants that receive PAP and to see if involving family members who can be defined as a person with a close relationship to the participant such as a friend, relative, significant other, and/or cohabitant, may provide a more effective treatment and fewer relapses.
Eligibility
Inclusion Criteria42
- Participant must be over 18 years of age inclusive, up to 65 years old at
- the time of signing the informed consent.
- Participant is able to read, understand and agree with the procedures of
- the study.
- Participants must be diagnosed with major depressive disorder and have
- moderate to severe depression (17+ on the 17-item Hamilton Depression
- Rating scale [HAM-D17]).
- Participants have failed to respond to two adequate courses of
- antidepressant treatment of different pharmacological classes lasting at least
- weeks within the current depressive episode and have not been subject to
- Electroconvulsive therapy (ECT) within 6 months prior to the study.
- Participants can confirm the involvement and willingness of a family
- member during the PAP sessions and duration of the study
- Male participants are eligible to participate if they agree to the following
- during the study intervention period and for at least 3 months after the
- last administration of study intervention:
- Refrain from donating sperm PLUS, either:
- Be abstinent from heterosexual intercourse as their preferred and
- usual lifestyle (abstinent on a long term and persistent basis) and
- agree to remain abstinent OR;
- Must agree to use contraception/barrier method (condom); the
- participant should also be advised of the benefit for a female partner
- to use a highly effective method of contraception.
- b. Female participants:
- A female participant is eligible to participate if she is not pregnant or
- breastfeeding, and one of the following conditions applies:
- Is a woman of nonchildbearing potential (WONCBP) such as a woman
- in postmenopausal state (has experienced no menses for 12
- consecutive months without an alternative medical cause); OR
- Has a documented permanent sterilization method such as:
- o Documented hysterectomy
- o Documented bilateral salpingectomy
- o Documented bilateral oophorectomy, OR
- Is a woman on childbearing potential (WOCBP) and agrees to use a
- contraceptive method that is highly effective (with a failure rate of
- <1% per year), with low user dependency.
- A WOCBP must have a negative highly sensitive pregnancy test (urine) during
- screening and prior to each psylocibin administration.
- Consent for study team to contact participant’s HCP team to notify them
- of trial participation and for the arrangement of follow-up care in the event
- of discontinuation from the trial (including discontinuation due to withdrawal
- of consent from trial participation
Exclusion Criteria70
- Participants unable to provide written informed consent.
- Participants with history of current or previously diagnosed psychotic
- disorder, or bipolar disorder.
- Immediate family member with a diagnosed psychotic disorder.
- Participants that are pregnant or breastfeeding. Positive pregnancy test
- at screening or prior to any psilocybin administration or refusal to have an
- on-site B-HCG pregnancy test prior to any psilocybin administration.
- Participants who may have sexual contact, without contraceptive
- measures, with a person who may become pregnant during or within 90 days
- (or 3 months) of cessation of the psilocybin IMP.
- Participants with history of serious suicide attempts or with a current
- Columbia-Suicide Severity Rating Scale (C-SSRS) positive (YES) for questions
- ,5 or 6, or deliberate self-harm within the last year.
- Participants with any of Cluster B personality disorder such as:
- Borderline personality disorder
- Histrionic personality disorder
- Antisocial personality disorder
- Narcissistic personality disorder
- Participants with eating disorders such as:
- Anorexia Nervosa
- Bulimia Nervosa
- Binge Eating Disorder
- Other Specified Feeding and Eating Disorder
- Pica
- Rumination Disorder
- Avoidant/Restrictive Food Intake Disorder
- Unspecified Feeding or Eating Disorder
- Other:
- o Muscle Dysmorphia
- o Orthorexia Nervosa
- Participants who are receiving any Selective Serotonin recapture Inhibitor
- (SSRI) during the last 4 weeks. A washout period of 4 weeks (5 weeks for
- fluoxetine) prior to the enrolment is permitted. Patients who have received an
- Inhibitor of Mono-amino-oxidase (MAOIs) or patients receiving any other agent
- that may precipitate a serotonin syndrome (such as, but not limited to: LTryptophan, Selective Serotonin Reuptake Inhibitors, Tricyclic antidepressants,
- Tramadol, Buspirone, Amphetamines and anorectics, Atypical antidepressants,
- St John’s wort, or Lithium) in the previous 4 weeks before the study enrollment.
- Participants with known history of serotonin syndrome, neuroleptic
- malignant syndrome or malignant hyperthermia.
- Moderate to severe systolic or diastolic hypertension, or uncontrolled
- mild hypertension, a previous hypertensive crisis or a known or suspected
- aneurysm or history of intracerebral haemorrhage.
- Participants with evidence of mild to severe moderate hepatic
- impairment (Child Pughclass A-C)
- Participants with evidence of mild to severe renal impairment
- (GFR <70mL/min)
- Hypersensitivity to any of the study interventions, including any
- constituents thereof, or drug or other allergy that, in the opinion of the
- Investigator, contraindicates participation in the study.
- Clinically significant abnormal ECG at screening/baseline or during the
- dosing period that may, in the judgement of the investigator, affect the
- conduct of the study.
- Participants with known history of prolonged QT interval conditions or
- taking other medications that can prolong QT interval (such as, but not
- limited to: amiodarone, astemizole, chlorpromazine, cisapride, erythromycin,
- papaverine, procainamide, quinidine, sotalol, terfenadine, vandetanib).
- Substance use disorder (excluding nicotine or caffeine) current or in the
- last year. Alcohol Use Disorder is as defined per DSM-5. Participants who do
- not anticipate being able to refrain from smoking or vaping for 12 hours are
- excluded.
- Participants not suitable for participation, whatever the reason, as
- judged by the Investigator, including medical or clinical conditions that might
- affect their safety or ability to complete the protocol or that may confound
- the efficacy or safety results of the trial.
- Participants who are employees of the clinical study site or other
- individuals directly involved in the conduct of the study, or immediate family
- members of such individuals.
- Individuals accommodated in an institution because of regulatory or
- legal order; prisoners or participants who are legally institutionalised.
- Any specific situation during study that may raise ethics considerations
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Interventions
All participants will receive two separate doses of 25 mg of psilocybin 3 weeks apart from each other. in the form of a capsule Which they will take orally with water in the presents of the approved treating team members. This is in line with the schedule 9 licence agreement. They will be asked to consent verbally before receiving each dose. To minimise the risk of PAP-related nausea and vomiting, they should fast eight hours prior to receiving the dose and not drink anything 30 minutes prior to receiving psilocybin. When administered the psilocybin, each participant will be accompanied and monitored at all times by the treating therapists for a minimum of 6 hours (until the acute psychological effects of the drug wear off) and a medically qualified person that will be available at all times. Group 1: The treating Clinical Psychologists (Two will be always present) will remain in the room with the participant. The supporting family member will only be present for the Preparation period of the study and will not be present during the treatment sessions. Active Psychotherapy will take place following medication administration. During the preparation session, the family member will get to meet the therapists that will be with them during the entire study. Throughout this session, the therapists will explain the study team’s expectations on how they are to conduct yourself during and after each PAP session. This baseline visit/visit 3 may take approximately 2.5 hours. They are encouraged and must feel free to ask any questions you feel like asking. Group 2: The treating Clinical Psychologists (Two will be always present) will remain in the room with the participant. Active Psychotherapy will take place following medication administration.
Locations(1)
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ACTRN12623000618651