SuicidePhase 3NCT04260607
Initiating Ketamine in Acutely Suicidal Patients in the Emergency Department
A Phase 3 study testing Ketamine Hydrochloride and Normal saline in people with Suicide and Suicide Threat, run by Naval Medical Center Camp Lejeune at 1 site in United States.
Trial summary
Current treatment for acutely suicidal patients are limited to hospitalization, psychotherapy, electro-convulsant therapy, or a combination of the aforementioned. However, this has added to the national boarding problem. Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- Suicide, Suicide Threat, Depression Severe
- What is being tested?
- Ketamine Hydrochloride and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jan 2020to 16 Feb 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Subject Inclusion and Selection Criteria
- Patient demographics will consist of Active, Reserve, or retired military personnel or their dependents. Subjects must meet the following inclusion criteria:
- Adult (18 to 89 years old)
- Present with active SI
- Deemed to being admitted to inpatient psychiatric unit
Subject Exclusion Criteria:
- Age < 18 years old or > 89 years old
- Currently presenting with psychosis as determined by mental health consultant
- Have a history of Cognitive disorder that would impair understanding of consent
- Have a personal/family history of Schizophrenia
- Currently pregnant or nursing
- Serious and unstable medical condition/problems
- Inability to medically clear
- Non-English Speakers
- Civilian Humanitarians
- Have previously enrolled in this study
Trial locations and contacts
1 site in 1 country.
United States1 site
Naval Medical Center Camp Lejeune
Marine Corps Base Camp Lejeune, North Carolina, 28547
About this study
Current treatment for acutely suicidal patients are limited to hospitalization, psychotherapy, electro-convulsant therapy, or a combination of the aforementioned. However, this has added to the national boarding problem. Long term pharmacologic treatment for suicidal behaviors and mood stabilization has been studied in specific populations. In these populations, the decreases in suicidal ideation results from stabilization of the underlying psychiatric illness. Ketamine is most commonly used as an anesthetic with analgesic properties. It has been used off-label for pain management, procedural sedation, status epilepticus, and treatment resistant depression. It has been safely administered intravenously and well tolerated for chronic Post Traumatic Stress Disorder. It increases norepinephrine, dopamine, and serotonin through adrenergic neuron stimulation and prevention of catecholamine uptake. There is a strong corollary between stress and the development of depression and suicidal behaviors. It is proposed that the use of low dose intravenous ketamine may have benefit on the suicidal ideation of patients presenting to the Emergency Department.
Read the detailed description
There is a strong corollary between stress and the development of depression and suicidal behaviors. The neurobiological mediators of stress are primarily controlled by the noradrenergic and corticotropin-releasing factor (CRF) median eminence systems. Furthermore, stress directly and indirectly, through the Hypothalamic Pituitary Axis, activates the Locus Coeruleus (LC), which is the primary producer of NE in the central nervous system (CNS). Directly, glutaminergic neurons send excitatory signals to the LC via interaction with N-Methyl-D-Aspartate (NMDA) receptors NMDA antagonists, such as ketamine, can dampen the glutaminergic system, which has been implicated during states of depression and low moods.
The neurobiological commonality between multiple psychiatric disorders and depression, suicide, and attempted suicide is a decrease in serotonergic activity. It has been shown that patients who died of suicide, have decreased serotonin transporter in the ventromedial prefrontal cortex and anterior cingulate, which are areas that control decision making or willful action. The prefrontal cortex is important for inhibitory behavioral control. A potential treatment modality of ketamine, is that it produces activation of this region.35 The anterior cingulate cortex has been shown to be associated with impulsive aggression compared to control. Clinical studies have shown that low CSF 5-HIAA, metabolite in serotonin system, has been implicated and positively correlated to aggression scores and impulsivity. This is interesting because, suicides in the military are thought to have an impulsivity component, triggered by one or more major life stressors.
Another region associated with suicide is the infralimbic cortex. A recent study, based on neuroimaging techniques, demonstrated that glucose metabolism in this region was associated with SI at baseline, and decreases in SI was observed after ketamine infusion. This is the same region target by deep brain stimulation, for depression treatment. Additionally, the infralimbic cortex has been implicated in behavioral flexibility. Implicating that ketamine's anti-suicidal properties may stem from its ability to promoting cognitive flexibility. Most likely due to its ability to increase brain-derived neurotrophic factor (BDNF), which is a major contributor to neuronal plasticity. BDNF also plays key roles in synaptic and long-term potentiation, which may counteract the decreased levels in Mood Disorder (MDD) patients. Furthermore, ketamine infusion has been shown to change sleep slow wave activity. This biomarker is functionally related to increased synaptic strengthening and cortical synchronization. These factors, combined, may be implicated in not only ketamine's antidepressant effects and counteraction of decreased synaptic plasticity seen mood disorders, but also its ability to have week long lasting effects.
This information leads us to hypothesize that treatment of acutely suicidal patients with ketamine would: 1) decrease suicidal ideationto a clinically significant degree, and 2) the effect of ketamine will be seen for as long as one-week post administration.
To the best of our knowledge, this study does not duplicate any ongoing work. Instead, it would strengthen power to past studies and current work. There are four clinical trials investigating ketamine's effect on SI. One has an unknown status. There are two that are investigating ketamine in relationship to psychiatric standard of care, whereas this study is investigating its effects against a saline placebo. Finally, the last clinical trial is investigating the Neurobiology of Suicide. Their phase 2 component, which utilizes a similar protocol, uses ketamine as a tool to identify potential biomarkers for suicide. Furthermore, this study differs from Janssen Research \& Development's clinical trial in administration route and study design. Their study focuses on using ketamine through intranasal administration. Their primary outcomes are the long-term safety and efficacy, and the design of their study is an open label multicenter trial.
This research does not duplicate any prior work. To date, there is only one study, from Iran, that evaluates the effectiveness of ketamine in high risk patients, or those that present as acutely suicidal to the ED. This was a single blinded trial that utilized 0.2mg/kg infused over one minute. The study indicated significant decrease in their measurement outcomes. However, they concluded that ketamine is not a good choice for treatment because it did not meet their cut off values. Their results might have been influenced by the rapid infusion over one minute, which differs from our study as well as the vast majority of the literature. We believe the slower 40-minute infusion is necessary for optimal results, as the larger dosage has produced more clinically meaningful results in prior studies, and the slower infusion produced less negative side effects. They chose the minimal dose shown to diminish SI41 200 ng/ml (0.2 mg/kg), which provokes lateral nystagmus.35 This protocol utilizes a higher dose, 0.5 mg/kg, which is the ED50 for narcosis. Our study is medically relevant because dosage effects on SI have not been studied. Comparison of our studies may address questions regarding the optimal dose and infusion rate.
The BSSI will measure the severity of SI. It is based on the interviewer rated version of the original Scale for Suicidal Ideation (SSI), which is one of the few document suicide assessment tools with predictive validity for suicide completion. The internal reliability, test and retest validity, as well as invariance over time has been demonstrated for the BSS. Furthermore, the first five items of the BSSI are a common clinical screening for the presence of suicidal thoughts. For these reasons, the BSSI was chosen as our primary outcomes measure. Two studies have indicated that the cut off between high and low risk is a BSS ≥ 2. A recent investigation has determined BSSI ≥ 6 is predictive of future suicide attempts. These two values will serve in our analysis.
The Montgomery- Åsberg Depression Rating Scale (MADRS) is a widely known 10 item clinician administered measure of depression severity. Since it's development in the late 1970s, it has become more popular than the gold standard, Hamilton rating scale for Depression (HAM-D). It is considered to be more sensitive to change, just as effective, and simpler to use clinically. However, the reliability depends on good interrater agreement. Difficulties in clinical trial to show signal detection for known effective drugs have implicated clinician administered measurement as a possible source of error. To avoid poor interrater reliability, rater bias, and variable interview quality, this trial will utilize the self-administered version of the MADRS-S. This has 9 items and a total score ranging from 0 to 27.50 The scoring of MADRS-S has shown to be similar to that of physician scoring.
The emotional pain of the suicidal patient requires empathetic care that may not always be possible with the time pressures, volume, and pragmatic nature of the ED environment. A pharmacologic intervention with rapid effects to decrease SI would play a vital role in improving the standard of care for this vulnerable population.
- Conditions
- Suicide, Suicide Threat, Depression Severe
- Being tested
- Ketamine Hydrochloride, Normal saline
- Keywords
- ketamine
- Medical subject headings
- Suicide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketamine HydrochlorideDrug
Also called Experimental Arm
Experimental Procedure
- Baseline evaluation of suicidal severity (BSSI) \& degree of depressive symptoms (MADRS-S) will be evaluated through self-administered questionnaires.
- The experimental and placebo arms will receive a single dose of IV ketamine, 0.5 mg/kg in 100 cc NS or 100 cc of NS infused over 40 minutes.
- Post ketamine re-evaluation of outcome measures at four and twenty-four hours will determine clinical effectiveness of ketamine intervention
- Inspection of admission and transfer time provides time measurement for LOS. This secondary measure is needed to determine efficiency of intervention.
- Post ketamine re-evaluation of outcome measure at one-week post infusion will elucidate ketamine's durability of effect.
Normal salineDrug
Also called Placebo Comparator
Experimental Procedure
- Baseline evaluation of suicidal severity (BSSI) \& degree of depressive symptoms (MADRS-S) will be evaluated through self-administered questionnaires.
- The placebo arms will receive a single dose of 100 cc of NS infused over 40 minutes.
- Post Placebo infusion re-evaluation of outcome measures at four and twenty-four hours
- Inspection of admission and transfer time provides time measurement for LOS. This secondary measure is needed to determine efficiency of intervention.
- Post Normal Saline re-evaluation of outcome measure at one-week post infusion.
| Study group | Role | What they receive |
|---|---|---|
| Experimental-Ketamine | Experimental | single dose IV Ketamine (Ketalar) 0.5mg/kg in 100ml Normal Saline infused over 40 minutes Receives: Drug: Ketamine Hydrochloride |
| Placebo-Saline | Placebo comparator | 100ml Normal Saline infused over 40 minutes Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Suicidal Severity - Clinical Efficacy
Suicidal severity is measured by the total score on the Beck Scale for Suicide Ideation (BSS or BSSI). The BSS is a 21-item scale, where each item contains a group of statements that are rated from 0 to 2. Items 1 to 5 comprise a screening subscale. If the patient scores 0 in total on items 4 and 5, items 6 to 19 are skipped. Item 21 is only asked if the patient has attempted suicide at least once. The screening subscale can range from 0 to 10 points, whereas the total score can range from 0 to 42 points. A high total score corresponds with an increased number of specific suicidal characteristics that require greater clinical scrutiny.
Measured: 4 hour+/1 after infusion completion (performed for placebo and drug arms)
Suicidal Severity - Clinical Efficacy
Suicidal severity is measured by the total score on the Beck Scale for Suicide Ideation (BSS or BSSI). The BSS is a 21-item scale, where each item contains a group of statements that are rated from 0 to 2. Items 1 to 5 comprise a screening subscale. If the patient scores 0 in total on items 4 and 5, items 6 to 19 are skipped. Item 21 is only asked if the patient has attempted suicide at least once. The screening subscale can range from 0 to 10 points, whereas the total score can range from 0 to 42 points. A high total score corresponds with an increased number of specific suicidal characteristics that require greater clinical scrutiny.
Measured: 24-36 hours after infusion completion (performed for placebo and drug arms)
Suicidal Severity - Efficacy at 1 Week
Suicidal severity is measured by the total score on the Beck Scale for Suicide Ideation (BSS or BSSI). The BSS is a 21-item scale, where each item contains a group of statements that are rated from 0 to 2. Items 1 to 5 comprise a screening subscale. If the patient scores 0 in total on items 4 and 5, items 6 to 19 are skipped. Item 21 is only asked if the patient has attempted suicide at least once. The screening subscale can range from 0 to 10 points, whereas the total score can range from 0 to 42 points. A high total score corresponds with an increased number of specific suicidal characteristics that require greater clinical scrutiny.
Measured: 1week+/-1 day after infusion completion (performed for placebo and drug arms)
Depression Symptoms - Clinical Efficacy
Depression symptoms are measured by the total score on the Montgomery Asberg Depression Rating Scale (MADRS). The MADRS scale consists of 9 items. Each item is scored between 0 and 3, in intervals of 0.5 The total scores range between 0 and 27, with higher scores indicating more severe depressive symptoms.
Measured: 4 hours +/-1 after infusion completion (Performed for placebo and drug arms)
Depression Symptoms - Clinical Efficacy
Depression symptoms are measured by the total score on the Montgomery Asberg Depression Rating Scale (MADRS). The MADRS scale consists of 9 items. Each item is scored between 0 and 3, in intervals of 0.5 The total scores range between 0 and 27, with higher scores indicating more severe depressive symptoms.
Measured: 24-46 hours after infusion completion (Performed for placebo and drug arms)
Depression Symptoms - Efficacy at 1 Week
Depression symptoms are measured by the total score on the Montgomery Asberg Depression Rating Scale (MADRS). The MADRS scale consists of 9 items. Each item is scored between 0 and 3, in intervals of 0.5 The total scores range between 0 and 27, with higher scores indicating more severe depressive symptoms.
Measured: 1 week +/-1 day after infusion completion, performed for placebo and drug arms
Secondary outcomes (1)
Length of Hospital Stay
Difference in time between date of hospital admission to transfer or hospital discharge.
Measured: Performed on medical record review at 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2020
- Study start14 Jan 2020
- Primary completion24 Apr 2021
- Study completion16 Feb 2022
Why it stopped: As a busy MTF we were unable to retain a health care provider with the appropriate expertise to buy-in to this study once the initiating PI left military service.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (45)Papers the sponsor has linked to this study.
- Other trials for SuicideStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Experimental versus Placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Naval Medical Center Camp Lejeune
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Nathan H Butler, DO, Principal investigator, Naval Medical Center Camp Lejeune
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04260607
- Sponsor's protocol ID
- NMCCL.2018.0011
- Status last verified
- May 2025
- First submitted
- 5 Feb 2020
- Last updated
- 14 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Armed Forces Health Surveillance Center (AFHSC). Deaths by suicide while on active duty, active and reserve components, U.S. Armed Forces, 1998-2011. MSMR. 2012 Jun;19(6):7-10.
PubMed 22779434Owens PL, Fingar KR, Heslin KC, Mutter R, Booth CL. Emergency Department Visits Related to Suicidal Ideation, 2006-2013. 2017 Jan. In: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006 Feb-. Statistical Brief #220. Available from http://www.ncbi.nlm.nih.gov/books/NBK442036/
PubMed 28722846Ting SA, Sullivan AF, Boudreaux ED, Miller I, Camargo CA Jr. Trends in US emergency department visits for attempted suicide and self-inflicted injury, 1993-2008. Gen Hosp Psychiatry. 2012 Sep-Oct;34(5):557-65. doi: 10.1016/j.genhosppsych.2012.03.020. Epub 2012 May 2.
PubMed 22554432Reinstatler L, Youssef NA. Ketamine as a potential treatment for suicidal ideation: a systematic review of the literature. Drugs R D. 2015 Mar;15(1):37-43. doi: 10.1007/s40268-015-0081-0.
PubMed 25773961Weiss AP, Chang G, Rauch SL, Smallwood JA, Schechter M, Kosowsky J, Hazen E, Haimovici F, Gitlin DF, Finn CT, Orav EJ. Patient- and practice-related determinants of emergency department length of stay for patients with psychiatric illness. Ann Emerg Med. 2012 Aug;60(2):162-71.e5. doi: 10.1016/j.annemergmed.2012.01.037. Epub 2012 May 2.
PubMed 22555337Hazlett SB, McCarthy ML, Londner MS, Onyike CU. Epidemiology of adult psychiatric visits to US emergency departments. Acad Emerg Med. 2004 Feb;11(2):193-5.
PubMed 14759965Baraff LJ, Janowicz N, Asarnow JR. Survey of California emergency departments about practices for management of suicidal patients and resources available for their care. Ann Emerg Med. 2006 Oct;48(4):452-8, 458.e1-2. doi: 10.1016/j.annemergmed.2006.06.026. Epub 2006 Aug 21.
PubMed 16997683Jick H, Kaye JA, Jick SS. Antidepressants and the risk of suicidal behaviors. JAMA. 2004 Jul 21;292(3):338-43. doi: 10.1001/jama.292.3.338.
PubMed 15265848Ribeiro JD, Gutierrez PM, Joiner TE, Kessler RC, Petukhova MV, Sampson NA, Stein MB, Ursano RJ, Nock MK. Health care contact and suicide risk documentation prior to suicide death: Results from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). J Consult Clin Psychol. 2017 Apr;85(4):403-408. doi: 10.1037/ccp0000178.
PubMed 28333538Betz ME, Wintersteen M, Boudreaux ED, Brown G, Capoccia L, Currier G, Goldstein J, King C, Manton A, Stanley B, Moutier C, Harkavy-Friedman J. Reducing Suicide Risk: Challenges and Opportunities in the Emergency Department. Ann Emerg Med. 2016 Dec;68(6):758-765. doi: 10.1016/j.annemergmed.2016.05.030. Epub 2016 Jul 21.
PubMed 27451339Betz ME, Boudreaux ED. Managing Suicidal Patients in the Emergency Department. Ann Emerg Med. 2016 Feb;67(2):276-82. doi: 10.1016/j.annemergmed.2015.09.001. Epub 2015 Oct 9. No abstract available.
PubMed 26443554Hickey L, Hawton K, Fagg J, Weitzel H. Deliberate self-harm patients who leave the accident and emergency department without a psychiatric assessment: a neglected population at risk of suicide. J Psychosom Res. 2001 Feb;50(2):87-93. doi: 10.1016/s0022-3999(00)00225-7.
PubMed 11274665Meltzer HY, Alphs L, Green AI, Altamura AC, Anand R, Bertoldi A, Bourgeois M, Chouinard G, Islam MZ, Kane J, Krishnan R, Lindenmayer JP, Potkin S; International Suicide Prevention Trial Study Group. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry. 2003 Jan;60(1):82-91. doi: 10.1001/archpsyc.60.1.82.
PubMed 12511175Brown GK, Ten Have T, Henriques GR, Xie SX, Hollander JE, Beck AT. Cognitive therapy for the prevention of suicide attempts: a randomized controlled trial. JAMA. 2005 Aug 3;294(5):563-70. doi: 10.1001/jama.294.5.563.
PubMed 16077050Linehan MM, Comtois KA, Murray AM, Brown MZ, Gallop RJ, Heard HL, Korslund KE, Tutek DA, Reynolds SK, Lindenboim N. Two-year randomized controlled trial and follow-up of dialectical behavior therapy vs therapy by experts for suicidal behaviors and borderline personality disorder. Arch Gen Psychiatry. 2006 Jul;63(7):757-66. doi: 10.1001/archpsyc.63.7.757.
PubMed 16818865
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Initiating Ketamine in Acutely Suicidal Patients in the Emergency Department
- ClinicalTrials.gov ID
- NCT04260607
- Acronym / sponsor ID
- NMCCL.2018.0011
- Conditions
- Suicide, Suicide Threat, Depression Severe
- Keywords
- ketamine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: As a busy MTF we were unable to retain a health care provider with the appropriate expertise to buy-in to this study once the initiating PI left military service.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Naval Medical Center Camp LejeuneUS federal agency
- Study start
- 14 Jan 2020 (actual)
- Primary completion
- 24 Apr 2021 (actual)
- Study completion
- 16 Feb 2022 (actual)
- First posted
- 7 Feb 2020 (actual)
- Results
- Posted 19 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Current treatment for acutely suicidal patients are limited to hospitalization, psychotherapy, electro-convulsant therapy, or a combination of the aforementioned. However, this has added to the national boarding problem. Long term pharmacologic treatment for suicidal behaviors and mood stabilization has been studied in specific populations. In these populations, the decreases in suicidal ideation results from stabilization of the underlying psychiatric illness. Ketamine is most commonly used as an anesthetic with analgesic properties. It has been used off-label for pain management, procedural sedation, status epilepticus, and treatment resistant depression. It has been safely administered intravenously and well tolerated for chronic Post Traumatic Stress Disorder. It increases norepinephrine, dopamine, and serotonin through adrenergic neuron stimulation and prevention of catecholamine uptake. There is a strong corollary between stress and the development of depression and suicidal behaviors. It is proposed that the use of low dose intravenous ketamine may have benefit on the suicidal ideation of patients presenting to the Emergency Department.
Detailed description
There is a strong corollary between stress and the development of depression and suicidal behaviors. The neurobiological mediators of stress are primarily controlled by the noradrenergic and corticotropin-releasing factor (CRF) median eminence systems. Furthermore, stress directly and indirectly, through the Hypothalamic Pituitary Axis, activates the Locus Coeruleus (LC), which is the primary producer of NE in the central nervous system (CNS). Directly, glutaminergic neurons send excitatory signals to the LC via interaction with N-Methyl-D-Aspartate (NMDA) receptors NMDA antagonists, such as ketamine, can dampen the glutaminergic system, which has been implicated during states of depression and low moods.
The neurobiological commonality between multiple psychiatric disorders and depression, suicide, and attempted suicide is a decrease in serotonergic activity. It has been shown that patients who died of suicide, have decreased serotonin transporter in the ventromedial prefrontal cortex and anterior cingulate, which are areas that control decision making or willful action. The prefrontal cortex is important for inhibitory behavioral control. A potential treatment modality of ketamine, is that it produces activation of this region.35 The anterior cingulate cortex has been shown to be associated with impulsive aggression compared to control. Clinical studies have shown that low CSF 5-HIAA, metabolite in serotonin system, has been implicated and positively correlated to aggression scores and impulsivity. This is interesting because, suicides in the military are thought to have an impulsivity component, triggered by one or more major life stressors.
Another region associated with suicide is the infralimbic cortex. A recent study, based on neuroimaging techniques, demonstrated that glucose metabolism in this region was associated with SI at baseline, and decreases in SI was observed after ketamine infusion. This is the same region target by deep brain stimulation, for depression treatment. Additionally, the infralimbic cortex has been implicated in behavioral flexibility. Implicating that ketamine's anti-suicidal properties may stem from its ability to promoting cognitive flexibility. Most likely due to its ability to increase brain-derived neurotrophic factor (BDNF), which is a major contributor to neuronal plasticity. BDNF also plays key roles in synaptic and long-term potentiation, which may counteract the decreased levels in Mood Disorder (MDD) patients. Furthermore, ketamine infusion has been shown to change sleep slow wave activity. This biomarker is functionally related to increased synaptic strengthening and cortical synchronization. These factors, combined, may be implicated in not only ketamine's antidepressant effects and counteraction of decreased synaptic plasticity seen mood disorders, but also its ability to have week long lasting effects.
This information leads us to hypothesize that treatment of acutely suicidal patients with ketamine would: 1) decrease suicidal ideationto a clinically significant degree, and 2) the effect of ketamine will be seen for as long as one-week post administration.
To the best of our knowledge, this study does not duplicate any ongoing work. Instead, it would strengthen power to past studies and current work. There are four clinical trials investigating ketamine's effect on SI. One has an unknown status. There are two that are investigating ketamine in relationship to psychiatric standard of care, whereas this study is investigating its effects against a saline placebo. Finally, the last clinical trial is investigating the Neurobiology of Suicide. Their phase 2 component, which utilizes a similar protocol, uses ketamine as a tool to identify potential biomarkers for suicide. Furthermore, this study differs from Janssen Research \& Development's clinical trial in administration route and study design. Their study focuses on using ketamine through intranasal administration. Their primary outcomes are the long-term safety and efficacy, and the design of their study is an open label multicenter trial.
This research does not duplicate any prior work. To date, there is only one study, from Iran, that evaluates the effectiveness of ketamine in high risk patients, or those that present as acutely suicidal to the ED. This was a single blinded trial that utilized 0.2mg/kg infused over one minute. The study indicated significant decrease in their measurement outcomes. However, they concluded that ketamine is not a good choice for treatment because it did not meet their cut off values. Their results might have been influenced by the rapid infusion over one minute, which differs from our study as well as the vast majority of the literature. We believe the slower 40-minute infusion is necessary for optimal results, as the larger dosage has produced more clinically meaningful results in prior studies, and the slower infusion produced less negative side effects. They chose the minimal dose shown to diminish SI41 200 ng/ml (0.2 mg/kg), which provokes lateral nystagmus.35 This protocol utilizes a higher dose, 0.5 mg/kg, which is the ED50 for narcosis. Our study is medically relevant because dosage effects on SI have not been studied. Comparison of our studies may address questions regarding the optimal dose and infusion rate.
The BSSI will measure the severity of SI. It is based on the interviewer rated version of the original Scale for Suicidal Ideation (SSI), which is one of the few document suicide assessment tools with predictive validity for suicide completion. The internal reliability, test and retest validity, as well as invariance over time has been demonstrated for the BSS. Furthermore, the first five items of the BSSI are a common clinical screening for the presence of suicidal thoughts. For these reasons, the BSSI was chosen as our primary outcomes measure. Two studies have indicated that the cut off between high and low risk is a BSS ≥ 2. A recent investigation has determined BSSI ≥ 6 is predictive of future suicide attempts. These two values will serve in our analysis.
The Montgomery- Åsberg Depression Rating Scale (MADRS) is a widely known 10 item clinician administered measure of depression severity. Since it's development in the late 1970s, it has become more popular than the gold standard, Hamilton rating scale for Depression (HAM-D). It is considered to be more sensitive to change, just as effective, and simpler to use clinically. However, the reliability depends on good interrater agreement. Difficulties in clinical trial to show signal detection for known effective drugs have implicated clinician administered measurement as a possible source of error. To avoid poor interrater reliability, rater bias, and variable interview quality, this trial will utilize the self-administered version of the MADRS-S. This has 9 items and a total score ranging from 0 to 27.50 The scoring of MADRS-S has shown to be similar to that of physician scoring.
The emotional pain of the suicidal patient requires empathetic care that may not always be possible with the time pressures, volume, and pragmatic nature of the ED environment. A pharmacologic intervention with rapid effects to decrease SI would play a vital role in improving the standard of care for this vulnerable population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Experimental versus Placebo
| Arm | Type | Receives |
|---|---|---|
| Experimental-Ketamine | Experimental | Drug: Ketamine Hydrochloridesingle dose IV Ketamine (Ketalar) 0.5mg/kg in 100ml Normal Saline infused over 40 minutes |
| Placebo-Saline | Placebo comparator | Drug: Normal saline100ml Normal Saline infused over 40 minutes |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketamine HydrochlorideAlso: Experimental ArmExperimental Procedure 1. Baseline evaluation of suicidal severity (BSSI) \& degree of depressive symptoms (MADRS-S) will be evaluated through self-administered questionnaires. 2. The experimental and placebo arms will receive a single dose of IV ketamine, 0.5 mg/kg in 100 cc NS or 100 cc of NS infused over 40 minutes. 3. Post ketamine re-evaluation of outcome measures at four and twenty-four hours will determine clinical effectiveness of ketamine intervention 4. Inspection of admission and transfer time provides time measurement for LOS. This secondary measure is needed to determine efficiency of intervention. 5. Post ketamine re-evaluation of outcome measure at one-week post infusion will elucidate ketamine's durability of effect. | Drug | Experimental-Ketamine |
| Normal salineAlso: Placebo ComparatorExperimental Procedure 1. Baseline evaluation of suicidal severity (BSSI) \& degree of depressive symptoms (MADRS-S) will be evaluated through self-administered questionnaires. 2. The placebo arms will receive a single dose of 100 cc of NS infused over 40 minutes. 3. Post Placebo infusion re-evaluation of outcome measures at four and twenty-four hours 4. Inspection of admission and transfer time provides time measurement for LOS. This secondary measure is needed to determine efficiency of intervention. 5. Post Normal Saline re-evaluation of outcome measure at one-week post infusion. | Drug | Placebo-Saline |
Primary outcome
Suicidal Severity - Clinical Efficacy
Time frame: 4 hour+/1 after infusion completion (performed for placebo and drug arms)
Suicidal severity is measured by the total score on the Beck Scale for Suicide Ideation (BSS or BSSI). The BSS is a 21-item scale, where each item contains a group of statements that are rated from 0 to 2. Items 1 to 5 comprise a screening subscale. If the patient scores 0 in total on items 4 and 5, items 6 to 19 are skipped. Item 21 is only asked if the patient has attempted suicide at least once. The screening subscale can range from 0 to 10 points, whereas the total score can range from 0 to 42 points. A high total score corresponds with an increased number of specific suicidal characteristics that require greater clinical scrutiny.
Suicidal Severity - Clinical Efficacy
Time frame: 24-36 hours after infusion completion (performed for placebo and drug arms)
Suicidal severity is measured by the total score on the Beck Scale for Suicide Ideation (BSS or BSSI). The BSS is a 21-item scale, where each item contains a group of statements that are rated from 0 to 2. Items 1 to 5 comprise a screening subscale. If the patient scores 0 in total on items 4 and 5, items 6 to 19 are skipped. Item 21 is only asked if the patient has attempted suicide at least once. The screening subscale can range from 0 to 10 points, whereas the total score can range from 0 to 42 points. A high total score corresponds with an increased number of specific suicidal characteristics that require greater clinical scrutiny.
Suicidal Severity - Efficacy at 1 Week
Time frame: 1week+/-1 day after infusion completion (performed for placebo and drug arms)
Suicidal severity is measured by the total score on the Beck Scale for Suicide Ideation (BSS or BSSI). The BSS is a 21-item scale, where each item contains a group of statements that are rated from 0 to 2. Items 1 to 5 comprise a screening subscale. If the patient scores 0 in total on items 4 and 5, items 6 to 19 are skipped. Item 21 is only asked if the patient has attempted suicide at least once. The screening subscale can range from 0 to 10 points, whereas the total score can range from 0 to 42 points. A high total score corresponds with an increased number of specific suicidal characteristics that require greater clinical scrutiny.
Depression Symptoms - Clinical Efficacy
Time frame: 4 hours +/-1 after infusion completion (Performed for placebo and drug arms)
Depression symptoms are measured by the total score on the Montgomery Asberg Depression Rating Scale (MADRS). The MADRS scale consists of 9 items. Each item is scored between 0 and 3, in intervals of 0.5 The total scores range between 0 and 27, with higher scores indicating more severe depressive symptoms.
Depression Symptoms - Clinical Efficacy
Time frame: 24-46 hours after infusion completion (Performed for placebo and drug arms)
Depression symptoms are measured by the total score on the Montgomery Asberg Depression Rating Scale (MADRS). The MADRS scale consists of 9 items. Each item is scored between 0 and 3, in intervals of 0.5 The total scores range between 0 and 27, with higher scores indicating more severe depressive symptoms.
Depression Symptoms - Efficacy at 1 Week
Time frame: 1 week +/-1 day after infusion completion, performed for placebo and drug arms
Depression symptoms are measured by the total score on the Montgomery Asberg Depression Rating Scale (MADRS). The MADRS scale consists of 9 items. Each item is scored between 0 and 3, in intervals of 0.5 The total scores range between 0 and 27, with higher scores indicating more severe depressive symptoms.
1 secondary outcome
Length of Hospital Stay
Time frame: Performed on medical record review at 1 week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22779434Armed Forces Health Surveillance Center (AFHSC). Deaths by suicide while on active duty, active and reserve components, U.S. Armed Forces, 1998-2011. MSMR. 2012 Jun;19(6):7-10.
- Background: PubMed 28722846Owens PL, Fingar KR, Heslin KC, Mutter R, Booth CL. Emergency Department Visits Related to Suicidal Ideation, 2006-2013. 2017 Jan. In: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006 Feb-. Statistical Brief #220. Available from http://www.ncbi.nlm.nih.gov/books/NBK442036/
- Background: PubMed 22554432Ting SA, Sullivan AF, Boudreaux ED, Miller I, Camargo CA Jr. Trends in US emergency department visits for attempted suicide and self-inflicted injury, 1993-2008. Gen Hosp Psychiatry. 2012 Sep-Oct;34(5):557-65. doi: 10.1016/j.genhosppsych.2012.03.020. Epub 2012 May 2.
- Background: PubMed 25773961Reinstatler L, Youssef NA. Ketamine as a potential treatment for suicidal ideation: a systematic review of the literature. Drugs R D. 2015 Mar;15(1):37-43. doi: 10.1007/s40268-015-0081-0.
- Background: PubMed 22555337Weiss AP, Chang G, Rauch SL, Smallwood JA, Schechter M, Kosowsky J, Hazen E, Haimovici F, Gitlin DF, Finn CT, Orav EJ. Patient- and practice-related determinants of emergency department length of stay for patients with psychiatric illness. Ann Emerg Med. 2012 Aug;60(2):162-71.e5. doi: 10.1016/j.annemergmed.2012.01.037. Epub 2012 May 2.
- Background: PubMed 14759965Hazlett SB, McCarthy ML, Londner MS, Onyike CU. Epidemiology of adult psychiatric visits to US emergency departments. Acad Emerg Med. 2004 Feb;11(2):193-5.
- Background: PubMed 16997683Baraff LJ, Janowicz N, Asarnow JR. Survey of California emergency departments about practices for management of suicidal patients and resources available for their care. Ann Emerg Med. 2006 Oct;48(4):452-8, 458.e1-2. doi: 10.1016/j.annemergmed.2006.06.026. Epub 2006 Aug 21.
- Background: PubMed 15265848Jick H, Kaye JA, Jick SS. Antidepressants and the risk of suicidal behaviors. JAMA. 2004 Jul 21;292(3):338-43. doi: 10.1001/jama.292.3.338.
- Background: PubMed 28333538Ribeiro JD, Gutierrez PM, Joiner TE, Kessler RC, Petukhova MV, Sampson NA, Stein MB, Ursano RJ, Nock MK. Health care contact and suicide risk documentation prior to suicide death: Results from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). J Consult Clin Psychol. 2017 Apr;85(4):403-408. doi: 10.1037/ccp0000178.
- Background: PubMed 27451339Betz ME, Wintersteen M, Boudreaux ED, Brown G, Capoccia L, Currier G, Goldstein J, King C, Manton A, Stanley B, Moutier C, Harkavy-Friedman J. Reducing Suicide Risk: Challenges and Opportunities in the Emergency Department. Ann Emerg Med. 2016 Dec;68(6):758-765. doi: 10.1016/j.annemergmed.2016.05.030. Epub 2016 Jul 21.
- Background: PubMed 26443554Betz ME, Boudreaux ED. Managing Suicidal Patients in the Emergency Department. Ann Emerg Med. 2016 Feb;67(2):276-82. doi: 10.1016/j.annemergmed.2015.09.001. Epub 2015 Oct 9. No abstract available.
- Background: PubMed 11274665Hickey L, Hawton K, Fagg J, Weitzel H. Deliberate self-harm patients who leave the accident and emergency department without a psychiatric assessment: a neglected population at risk of suicide. J Psychosom Res. 2001 Feb;50(2):87-93. doi: 10.1016/s0022-3999(00)00225-7.
- Medical care of the returning veteran. Up To Date.Link provided by the sponsor.
- Knesper DJ. Continuity of care for suicide prevention and research: Suicide attempts and suicide deaths subsequent to discharge from the emergency department or psychiatry inpatient unit. 2010. Newton, MA: Suicide Prevention Resource Center. 68(6):758-Link provided by the sponsor.
- Ketamine. Lexicomp; 31 January 2020.Link provided by the sponsor.
- Janssen Research \& Development, LLC. A Long-term, Safety and Efficacy study of Intranasal Esketamine in Treatment resistant depression (SUSTAIN-2). 2017. ClinicalTrials.gov.Link provided by the sponsor.
- Neurobiology of Suicide. 2018. ClinicalTrials.Gov.Link provided by the sponsor.
- Pearson, 2018. Administering the Beck Scale Suicidal Ideation® (BSS®) Via Telepractice.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nathan H Butler, DO principal investigator
Naval Medical Center Camp Lejeune
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ketamine Hydrochloride and Normal saline in people with Suicide and Suicide Threat, run by Naval Medical Center Camp Lejeune at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Suicidal Severity - Clinical Efficacy (time frame: 4 hour+/1 after infusion completion (performed for placebo and drug arms)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04260607, which also lists 45 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2025.