What side effects are associated with this type of intervention?

Psilocybin, a serotonin 5-HT2A receptor agonist, can cause transient side effects such as headaches, nausea, dizziness, and transient anxiety or paranoia. SSRIs, another common treatment for Major Depressive Disorder, can cause jitteriness, restlessness, anxiety, agitation, headache, sexual dysfunction, gastrointestinal symptoms (diarrhea and nausea), and insomnia. Tricyclic antidepressants (TCAs) can cause dry mouth, constipation, fluid retention, weight gain, grogginess, and difficulty concentrating, with potential cardiotoxicity limiting their use in older patients.

What prior FDA approvals exist?

The FDA has approved several treatments for Major Depressive Disorder (MDD), primarily focusing on selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and sertraline, and serotonin-norepinephrine reuptake inhibitors (SNRIs) like venlafaxine and duloxetine. While psilocybin, a serotonin 5-HT2A receptor agonist, is currently being studied in trials such as COMP360 for its potential in treatment-resistant depression, it has not yet received FDA approval. Other treatments that modulate the serotonin system, such as esketamine (a nasal spray approved for treatment-resistant depression), have shown promise and received FDA approval.

What other types of research exist?

Promising novel alternatives to COMP360 (Psilocybin) for Major Depressive Disorder patients include pimavanserin, which has shown efficacy as an adjunctive therapy in MDD, and augmentation strategies with atypical antipsychotics. Additionally, cognitive-behavioral therapy (CBT) and St John's wort are potential options.

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Psychedelic

Psilocybin for Major Depressive Disorder - TRD

Verified Trial

Phase 3

Recruiting

Research Sponsored by COMPASS Pathways

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Major depression without psychotic features (single or recurrent episode as informed by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition [DSM-5])

TRD, defined as failure to respond to an adequate dose and duration of two, three, or four different pharmacological treatments for the current episode as determined through the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and using the supplementary advice on additional antidepressants not included in MGH-ATRQ

Must not have

Lifetime paranoid, schizoid, schizotypal, histrionic, narcissistic personality disorder, or any ongoing serious psychiatric comorbidity based on medical history and clinical judgement

Timeline

Screening 10 weeks

Treatment Varies

Follow Up 14 weeks

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing COMP360, a new treatment for adults who have not responded to other depression treatments. Participants will receive one of three doses of COMP360 along with psychological support. The goal is to see if this combination can help improve their depression symptoms.

Who is the study for?

This trial is for adults over 18 with treatment-resistant depression (TRD), which means their current major depressive episode hasn't improved after trying two to four different antidepressants. Participants must have a moderate severity of depression and agree to stop taking any prohibited medications.

What is being tested?

The study tests the effectiveness, safety, and tolerability of COMP360 psilocybin therapy in people with TRD. It involves two administrations of the drug to see if it can help alleviate symptoms in those who haven't responded well to standard treatments.

What are the potential side effects?

While not explicitly listed here, common side effects associated with psilocybin may include nausea, headache, dizziness, changes in perception or mood swings. The specific side effects will be monitored closely throughout the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with major depression without psychosis.

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I have tried 2-4 different depression medications without success.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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You have a history of certain personality disorders or ongoing serious mental health issues based on medical history and clinical judgement.

Timeline

Screening ~ 10 weeks20 visits

Treatment ~ Varies

Follow Up ~ 14 weeks4 visits

Screening ~ 10 weeks

Treatment ~ Varies

Follow Up ~14 weeks

This trial's timeline: 10 weeks for screening, Varies for treatment, and 14 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

COMP360 25 mg versus COMP360 1 mg for the change from baseline in MADRS total score.

Secondary study objectives

COMP360 25 mg versus COMP360 1 mg for the change from baseline in Sheehan Disability Scale (SDS) total score.

COMP360 25 mg versus COMP360 10 mg for the change from baseline in MADRS total score.

COMP360 25 mg versus COMP360 10 mg for the change from baseline in Sheehan Disability Scale (SDS) total score.

Side effects data

From 2021 Phase 2 trial • 95 Patients • NCT02061293

Nausea

Pain

Viral upper resp. tract infection

Back pain

Bronchitis

Diarrhea

Influenza

Headache

Sinus headache

Depressed mood

Depression

Insomnia

Suicidal Ideation

Lower resp. tract congestion

Oropharyngeal pain

Alcohol withdrawal syndrome

Migraine

Thrombocytosis

Constipation

Vomiting

Oedema

Peripheral swelling

Pyrexia

Dermatitis contact

Bronchitis bacterial

Eye infection

Fungal infection

Traumatic lung injury

Hyponatremia

Arthralgia

Musculoskeletal pain

Pain in extremity

Malignant melanoma

Dizziness

Hypoesthesia

Sedation

Anger

Anxiety

Restlessness

Cough

Rhinorrhea

Sinus congestion

Sexual abuse

Endodontic procedure

Mallory-Weiss Syndrom

Anemia

Influenza like Illness

Gingivitis

Arthoscopic surgery

100%

80%

60%

40%

20%

Study treatment Arm

Diphenhydramine

Psilocybin

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: 25 mg COMP360 PsilocybinExperimental Treatment1 Intervention

25 mg COMP360 Psilocybin

Group II: 10 mg COMP360 PsilocybinExperimental Treatment1 Intervention

10 mg COMP360 Psilocybin

Group III: 1 mg COMP360 PsilocybinActive Control1 Intervention

1 mg COMP360 Psilocybin, active comparator

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Psilocybin

2021

Completed Phase 2

~530

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Major Depressive Disorder (MDD) include pharmacological and psychotherapeutic approaches. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) work by increasing the levels of serotonin and norepinephrine in the brain, which helps improve mood and emotional stability. Psilocybin, a serotonin 5-HT2A receptor agonist, is being studied for its potential to produce rapid and sustained reductions in depressive symptoms by altering brain connectivity and promoting neuroplasticity. Psychotherapy, such as cognitive-behavioral therapy (CBT), helps patients by changing negative thought patterns and behaviors. Understanding these mechanisms is crucial for MDD patients as it informs treatment choices and helps tailor interventions to individual needs, potentially improving outcomes and quality of life.