Study on Perampanel and Ketamine for Suicidal Thoughts and Depression
This study is looking at how a drug called perampanel might affect the anti-suicidal and antidepressant effects of ketamine. Researchers want to see if blocking certain brain receptors (AMPA receptors) with perampanel changes how well ketamine works for people with depression, bipolar disorder, PTSD, or major depressive disorder who are also experiencing suicidal thoughts. You might be able to join if you are between 21 and 65 years old, have current depression and suicidal thoughts, and meet other health criteria. The main goal is to see if perampanel changes how much suicidal thoughts and depression improve 24 hours after a ketamine infusion. The study is currently unclear on its recruitment status and plans to enroll 30 participants.
- Study design
- This interventional study involves 30 participants who will receive either perampanel or a placebo before a ketamine infusion. The order of perampanel or placebo will be switched for each participant.
- What's involved
- You would undergo psychiatric interviews, rating scales, questionnaires, a physical exam, EKG, and lab tests. If eligible, you would receive perampanel or placebo, then a ketamine infusion, with at least three weeks between infusions, and complete follow-up assessments.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your suicidal thoughts and antidepressant response will be measured at baseline and 24 hours after each ketamine infusion. You will also complete follow-up assessments through interviews and an electronic diary.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT05786066
The Impact of AMPA Receptor Blockade on Ketamine's Anti-Suicidal Effects
Recruiting
PHASE2Ages 21–65InterventionalBasic scienceYale UniversityInvestigator-initiated
~30 participants
Updated 2026-05-06 on ClinicalTrials.gov
What's tested:Perampanel 6 MGKetaminePlacebo
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Change in suicidal ideations in response to Ketamine
Measured over Baseline and 24 hours post infusion
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesConnecticut1
Study leadership
- Naomi Driesen, PhD · PRINCIPAL_INVESTIGATOR · Yale University / VACHS West Haven
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Current depression as indicated by a score greater than 17 on the full Hamilton Depression Rating Scale (HDRS-17) AND current major depressive episode as determined by structured clinical interview (SCID-5)
Current suicidal ideation as indicated by a score ≥ 2 on the HDRS-17 Item #3 ("wishes to be dead (or any thoughts of possible death to self)")
Anti-depressant resistant depressive symptoms, defined by a history of failure of one or more adequate anti-depressant trials
Participants will meet DSM-5 Criteria for MDD, PTSD or Bipolar Disorder as determined by the SCID-5
All participants given Ketamine must be engaged in mental health treatment outside of the research protocol. Those who are not receiving treatment with a mental health provider at the time of the phone screen may be referred for treatment and will have their admission to the protocol deferred until they are receiving treatment with a mental health provider for at least 4 weeks, at which time they may re-apply for admission to the protocol.
Individuals who are receiving pharmacotherapy for depression must have been receiving the current medication and dose for 4 weeks before randomization. Those who are not stable on their current medication and dose for 4 weeks at the time of the phone screen may have their admission to the protocol deferred until they are stable on their current psychopharmacotherapy. In addition, all individuals admitted to the protocol should have a plan to continue the current regime of pharmacotherapy for the duration of the trial.
Individuals who are receiving psychotherapy must have been in treatment for four weeks and should have a plan to continue the current regime of psychotherapy for the duration of the trial. Those who are not stable on their current regime of psychotherapy for 4 weeks at the time of the phone screen may have their admission to the protocol deferred until they are stable on their current regime of psychotherapy.
Willing to refrain from caffeine, drug, and alcohol use for one week prior to each Ketamine infusion
Females will be included if they are not pregnant or breastfeeding and agree to utilize a medically accepted birth control method (to include oral, injectable, or implant birth control, condom, diaphragm with spermicide, intrauterine device, tubal ligation, abstinence, or partner with vasectomy). Women who are surgically sterile or post-menopausal with cessation of menses for at least one year are not required to use birth control. If a woman should become pregnant during the study, she will be excluded from the trial.
Females will receive Ketamine during the follicular phase, i.e., in the first week after the start of the menstrual period, if at all possible. If a prospective participant typically has significant menstrual cramps during this entire follicular phase, she will be studied during another part of her cycle. She will be studied during the same part of her cycle for each scan, if possible.
Able to read and write English
Have at least a 12th grade education level or equivalent
Exclusion
A score on the Columbia-Suicide Severity Rating Scale \[43\] in the "intent" or "intent with plan" categories within the last 3 months or judged by Dr. Krystal or Dr. Driesen to be at serious risk for suicide.
Psychiatric hospitalization in the past two months
Suicide attempt in the past two months
Neurological disorder excluding migraine headaches or mild head injury. More than mild head injury is indicated by the presence of any of the following:
More than half hour unconsciousness after trauma
More than one hour post-traumatic amnesia
Concussive symptoms such as headache, memory problems, nausea/vomiting, irritability, ringing in the ears, dizziness, balance problems, difficulty concentrating or visual disturbances lasting more than one week after injury.
Concussive symptoms as defined above in the first week after injury causing more than one day impairment in typical duties.
Four or more concussive events of less severity than the above will also be grounds for exclusion. These events would include post-trauma symptoms such as the individual being dazed, seeing stars, unconscious for less than one half hour, or post-traumatic amnesia of less than an hour.
Current therapeutic treatment with Ketamine
Previous trial of Ketamine without therapeutic benefit
Current treatment with topiramate, memantine, or barbiturates within two weeks of randomization
Daytime use of benzodiazepines
Current treatment with monoamine oxidase inhibitors within 4 weeks of randomization
Treatment with a vagal nerve stimulator, ECT or deep brain stimulation within two weeks of randomization
Psychosis other than psychotic experiences congruent with depressed mood during a period of depression. Individuals experiencing psychosis during the current depressive episode will be excluded.
Other major medical disorder unless cleared by a study physician
History of violence unless cleared by Dr. Driesen or Dr. Krystal because of extenuating circumstances. For example, an individual whose violent behavior was always coupled with substance abuse and had obtained stable sobriety with no violent incidents or an individual who had received successful pharmacotherapy for impulse control difficulties may be included.
Individual meets criteria for a diagnosis of substance or alcohol use disorder within the three months prior to screening date. Individuals who meet criteria for mild alcohol use disorder within three months prior to screening date may be included in the study at investigator discretion. The diagnosis of mild alcohol use disorder shall be per DSM-5 and involve 2-3 symptoms. The PI's discretion will be based on the symptoms that are reported and the judged consistency and accuracy of the subjects' self-report.
A positive on screening urine drug test or, at the study physicians' discretion, on any drug screens given before the infusion visits.
A positive screening alcohol breathalyzer or alcohol saliva test or, at the study physicians' discretion, on any alcohol breathalyzer or alcohol saliva test given before the infusion visits.
A 12-lead ECG at screening has clinically significant abnormalities as determined by the physician reading the ECG.
Abnormality on clinical chemistry or hematology examination at the pre-study medical screening. Subjects with laboratory parameters outside the reference range for this age group will only be included if the study physician considers that such findings will not introduce additional risk factors.
History of positive HIV or Hepatitis B
Has received either prescribed or over-the-counter (OTC) centrally active medicine or herbal supplements within the week prior to the Ketamine infusion visit. Subjects who have taken OTC medication or herbal supplements may still be entered into the study, if, in the opinions of the Principal/Co-Investigator, the medication received will not interfere with the study procedures or compromise safety.
Known sensitivity to Ketamine or heparin
Resting blood pressure lower than 85/55 or higher than 140/90, or resting heart rate lower than 45/min or higher than 100/min, unless cleared by study physician. If a subject meets these blood pressure entrance criteria, but is being treated for high blood pressure, the study team will check with the subject's primary care physician or treatment provider to confirm that the subject is stable and normotensive on their current treatment plan.
History of general intellectual disability
Donation of blood in excess of 500 mL within 56 days prior to dosing or similar loss of blood due to other causes.
Potential participants may be eliminated at the discretion of Dr. Krystal, Dr. Driesen, or the study physician.
What this trial measures
- Change in suicidal ideations in response to KetamineBaseline and 24 hours post infusion
Change in suicidal ideation will be assessed 24 hours post-Ketamine infusion using a Scale for Suicidal Ideation, composed of the first five items of the Beck Suicide Inventory + the Hamilton Depression Rating Scale (HAMD-7) suicidality item. The first five items of the Beck Suicide Inventory are rated on a scale of 0-2, and the suicidality item on the HAMD-7 is rated from 0-4. Scores are totaled and will be analyzed as the dependent variable in a mixed-effects model with drug condition (placebo/perampanel) and time (baseline, 24-hour follow up) as within-subject factors.
- Change in antidepressant response to KetamineBaseline and 24 hours post infusion
Changes in depressive symptoms will be assessed 24 hours post-Ketamine infusion using the full Hamilton Depression Rating Scale (HAMD-7), a 7-item survey to assess depression. Scores range from 0-26 with scores indicating full remission (0-3) and partial/non-response (4-26). Scores are totaled and will be analyzed as the dependent variable in a mixed-effects model with drug condition (placebo/perampanel) and time (baseline, 24-hour follow up) as within-subject factors.