~33 spots leftby Dec 2032

Ketamine + Perampanel for Depression

JK
NR
Overseen byNaomi R Driesen, Ph.D.
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Yale University
Must not be taking: Topiramate, Memantine, Barbiturates, others
Disqualifiers: Suicide risk, Neurological disorder, Psychosis, Diabetes, others
Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

The proposed study will assess the combined effect of perampanel and ketamine on the anti-depressant response in individuals with treatment resistant depression. The purpose of this study is to test the hypothesis that stimulation of Alpha-Amino-3-Hydroxy-5-Methyl-4- Isoxazole Propionic Acid receptors (AMPAR) is critical to the anti-depressant response of ketamine.

Will I have to stop taking my current medications?

Participants must continue their current depression medication and dose for at least 4 weeks before joining the trial and should plan to keep taking it throughout the study. However, if you are currently taking ketamine, topiramate, memantine, barbiturates, monoamine oxidase inhibitors, or using benzodiazepines during the day, you will need to stop these medications before joining the trial.

What data supports the effectiveness of the drug Ketamine for depression?

Research shows that ketamine, when given intravenously or subcutaneously, can quickly and effectively reduce depression symptoms, even in patients who have not responded to other treatments. Studies have reported rapid and significant improvements in depression symptoms with ketamine, making it a promising option for those with treatment-resistant depression.12345

Is the combination of Ketamine and Perampanel generally safe for humans?

Ketamine is known to have rapid antidepressant effects but can cause side effects like dissociation (feeling detached from reality) and increased blood pressure. It has been studied in various forms and routes, showing some promise with manageable side effects, but long-term safety still needs more research. Perampanel's safety in combination with ketamine specifically isn't detailed here, so consulting with a healthcare provider is recommended.36789

How is the drug Ketamine + Perampanel unique for treating depression?

Ketamine is unique for depression treatment because it acts rapidly and can be administered in various ways, including subcutaneously, which is convenient and cost-effective. It works through multiple pathways, including NMDA receptor blocking and σ1-receptor activation, potentially enhancing its antidepressant effects compared to other treatments.346910

Research Team

JK

John Krystal, MD

Principal Investigator

Yale University Medical School

NR

Naomi R Driesen, Ph.D.

Principal Investigator

Yale University Medical School

Eligibility Criteria

This trial is for right-handed individuals with treatment-resistant depression, scoring above 17 on the Hamilton Depression Scale. They must be undergoing or agree to start external therapy and maintain current medication doses throughout the trial. Participants should avoid caffeine, drugs, alcohol before MRI sessions and use birth control if applicable.

Inclusion Criteria

I am receiving treatment besides the ketamine given in this study.
My depression hasn't improved after trying at least one anti-depressant.
I have been in psychotherapy for 4 weeks and plan to continue during the trial.
See 10 more

Exclusion Criteria

I have not donated more than 500 mL of blood or lost a similar amount in the last 56 days.
Psychosis other than psychotic experiences congruent with depressed mood during a period of depression
I have not taken monoamine oxidase inhibitors in the last 4 weeks.
See 23 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks
1 visit (in-person)

Treatment

Participants receive either ketamine plus perampanel or ketamine plus placebo, followed by MRI scans and symptom assessments

2 days
2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 hours
1 visit (in-person)

Treatment Details

Interventions

  • Ketamine (Glutamate Receptor Modulator)
  • Perampanel (Glutamate Receptor Modulator)
  • Placebo (Placebo)
Trial OverviewThe study tests whether activating AMPAR receptors enhances ketamine's anti-depressant effects in those unresponsive to standard treatments. It involves combining perampanel with ketamine versus a placebo to see if this improves depressive symptoms more effectively.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: ketamine plus perampanelExperimental Treatment2 Interventions
A screening session is conducted to ensure that the subject can safely receive perampanel and ketamine (physical exam, blood and urine analyses, electrocardiogram, drug and alcohol testing). The participant will then receive 6 milligrams (mg) oral perampanel and intravenous ketamine. Participants will then undergo a 2-hour magnetic resonance imagining (MRI) scan. The following day, participants will return for an additional scan and symptom assessment.
Group II: ketamine plus placeboPlacebo Group2 Interventions
A screening session is conducted to ensure that the subject can safely receive perampanel and ketamine (physical exam, blood and urine analyses, electrocardiogram, drug and alcohol testing). The participant will then receive an oral placebo (in lieu of 6 mg oral perampanel) and intravenous ketamine. Participants will then undergo a 2-hour MRI scan. The following day, participants will return for an additional scan and symptom assessment.

Ketamine is already approved in Canada for the following indications:

🇨🇦
Approved in Canada as Spravato for:
  • Treatment-resistant depression

Find a Clinic Near You

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials
1,963
Recruited
3,046,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials
3,007
Recruited
2,852,000+

Findings from Research

In a study of 9016 patients receiving ketamine intravenous therapy (KIT) for depression, 53.6% showed a significant response (≥50% reduction in depression scores) within 14-31 days, indicating KIT's efficacy in real-world settings.
While most patients benefited from KIT, a small percentage (8.4%) experienced worsening depressive symptoms, highlighting the need for careful monitoring during treatment.
A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings.McInnes, LA., Qian, JJ., Gargeya, RS., et al.[2023]
A case series involving three hospice patients demonstrated that a single subcutaneous dose of ketamine (0.5 mg/kg) followed by daily oral ketamine (0.5 mg/kg) led to rapid improvement in depression symptoms, as measured by various assessment tools.
This approach offers a potentially effective and convenient method for managing depression in hospice patients, providing quicker relief compared to traditional antidepressant therapies, although further prospective studies are needed to optimize dosing strategies.
Single Subcutaneous Ketamine Dose Followed by Oral Ketamine for Depression Symptoms in Hospice Patients: A Case Series.Latuga, NM., Luczkiewicz, DL., Grant, PC., et al.[2021]
Subcutaneous (SC) administration of racemic ketamine and esketamine has shown rapid and robust antidepressant effects in both unipolar and bipolar patients, with response and remission rates ranging from 50% to 100% after single or multiple doses.
The studies indicated that SC ketamine is generally well-tolerated, with only transitory side effects, making it a promising and cost-effective treatment option for depression, especially in developing countries.
Subcutaneous Ketamine in Depression: A Systematic Review.Cavenaghi, VB., da Costa, LP., Lacerda, ALT., et al.[2021]

References

A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings. [2023]
Single Subcutaneous Ketamine Dose Followed by Oral Ketamine for Depression Symptoms in Hospice Patients: A Case Series. [2021]
Subcutaneous Ketamine in Depression: A Systematic Review. [2021]
Intravenous ketamine infusion for a patient with treatment-resistant major depression: a 10-month follow-up. [2018]
Intravenous ketamine therapy in a patient with a treatment-resistant major depression. [2022]
Influence of formulation and route of administration on ketamine's safety and tolerability: systematic review. [2021]
The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. [2023]
Pharmacotherapy: Ketamine and Esketamine. [2023]
Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses. [2022]
Activation of σ1-Receptors by R-Ketamine May Enhance the Antidepressant Effect of S-Ketamine. [2023]