What side effects are associated with this type of intervention?

Psilocybin, a serotonin 5-HT2A receptor agonist, can cause transient side effects such as headache, nausea, and anxiety. SSRIs, including citalopram, escitalopram, fluoxetine, and sertraline, commonly cause jitteriness, restlessness, anxiety, headache, sexual dysfunction, gastrointestinal symptoms, and insomnia. Tricyclic antidepressants, like amitriptyline, can lead to dry mouth, constipation, weight gain, and cardiotoxicity, particularly in older patients.

What prior FDA approvals exist?

The FDA has approved several treatments for Major Depressive Disorder (MDD), primarily focusing on pharmacotherapy with antidepressants such as SSRIs (e.g., fluoxetine, sertraline) and SNRIs (e.g., venlafaxine, duloxetine). While psilocybin, a serotonin 5-HT2A receptor agonist, is currently being studied in trials like COMP360 for its potential in treatment-resistant depression, it has not yet received FDA approval. Other novel treatments for MDD include esketamine, a nasal spray approved for treatment-resistant depression, which acts on the NMDA receptor rather than the serotonin system.

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. Other potential alternatives include augmentation strategies with atypical antipsychotics or other novel pharmacological agents currently under investigation for treatment-resistant depression.

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Psychedelic

Psilocybin for Treatment-Resistant Depression

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

Aged ≥18 years at Screening

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

Must not have

Use of electroconvulsive therapy, deep brain stimulation, or vagus nerve stimulation during the current depressive episode

Exposure to COMP360 psilocybin therapy prior to Screening

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 6

Awards & highlights

Pivotal Trial

Summary

This trial is testing a new medication called COMP360 to help people with severe depression that hasn't improved with other treatments. The study involves adults aged 18 and older. Researchers want to see if a single dose of COMP360 can reduce depression symptoms when given with psychological support.

Who is the study for?

Adults over 18 with treatment-resistant depression (TRD), who haven't responded to at least two different antidepressants, can join this trial. They must have moderate to severe depression without psychotic features and agree to stop taking any prohibited medications. The current depressive episode should be their first or ongoing for 3 months to 2 years.

What is being tested?

The trial is testing the effectiveness, safety, and tolerability of a single dose of COMP360 psilocybin in individuals with TRD. It aims to see if this one-time treatment can help where standard antidepressants have failed.

What are the potential side effects?

While not specified here, psilocybin may cause temporary side effects such as headaches, altered sensory experiences and perception changes, nausea, dizziness, and emotional shifts during administration.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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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.

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I am 18 years old or older.

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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.

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I am 18 years old or older.

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I have been diagnosed with major depression without psychosis.

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My depression hasn't improved after trying 2-4 different medications.

Exclusion Criteria

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

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I have not used ECT, DBS, or VNS for my current depression.

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I have previously undergone COMP360 psilocybin therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 6

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 6

This trial's timeline: 3 weeks for screening, Varies for treatment, and week 6 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 placebo for the change from baseline in MADRS total score

Secondary study objectives

COMP360 25 mg versus placebo for the change from baseline in 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

Pivotal Trial

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

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: 25 mg COMP360 PsilocybinExperimental Treatment1 Intervention

25 mg COMP360 Psilocybin

Group II: PlaceboPlacebo Group1 Intervention

Matched placebo

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Psilocybin

2021

Completed Phase 2

~530

0 / 11Eligibility 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

The most common treatments for Major Depressive Disorder (MDD) include pharmacotherapy and psychotherapy. Pharmacological treatments often involve antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), which work by increasing the levels of serotonin and norepinephrine in the brain to improve mood and emotional stability. Psilocybin, a serotonin 5-HT2A receptor agonist, is being studied for its potential to rapidly and sustainably reduce depressive symptoms by modulating serotonin pathways and inducing neuroplasticity. This is particularly relevant for MDD patients as it offers a novel mechanism of action that may benefit those who are resistant to traditional treatments. Psychotherapy, including cognitive-behavioral therapy (CBT), helps patients by addressing negative thought patterns and behaviors, providing long-term coping strategies. Understanding these mechanisms is crucial for tailoring treatment plans to individual patient needs and improving overall treatment outcomes.