Ketamine for Opioid Use Disorder and Suicidal Thoughts

Overseen By Joji Suzuki, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must not be taking: St. John's Wort, Theophylline

Disqualifiers: Psychotic disorder, Bipolar, Hypertension, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 1 day

4 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a pilot, double-blind, placebo-controlled randomized clinical trial of individuals with opioid use disorder (OUD) with suicidal ideation in the emergency department (ED) to receive either a single infusion of ketamine 0.8mg/kg (n=25) or saline placebo (n=25). The primary aim is to evaluate the safety of the ketamine treatment. The secondary aim is to determine the preliminary efficacy of opioid- and suicide-related outcomes.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that have known interactions with ketamine, such as St. John's Wort, theophylline, and opioid painkillers other than buprenorphine and methadone. If you are on these medications, you may need to stop them to participate.

What data supports the effectiveness of the drug ketamine for opioid use disorder and suicidal thoughts?

Research shows that ketamine can quickly reduce suicidal thoughts in people with depression, with effects lasting up to a week. This suggests it might help those with opioid use disorder who also have suicidal thoughts. ^{1 2 3 4 5}

Is ketamine safe for treating opioid use disorder and suicidal thoughts?

Research on ketamine for depression and suicidality shows it can have side effects like psychiatric and cardiovascular issues, but it is generally considered safe for short-term use. Long-term safety is less understood, and more studies are needed to assess its safety over extended periods. ^{4 6 7 8 9}

How is the drug ketamine unique in treating opioid use disorder and suicidal thoughts?

Ketamine is unique because it can rapidly reduce suicidal thoughts within hours, unlike traditional treatments that take weeks to work. It is also effective in patients with opioid use disorder, as it works through non-opioid mechanisms, making it safe to use alongside opioid treatments like Buprenorphine. ^{2 4 8 10 11}

Eligibility Criteria

This trial is for English-speaking adults over 18 with moderate to severe opioid use disorder (OUD) who have had an overdose before and are currently having suicidal thoughts serious enough for psychiatric hospitalization. They must be medically cleared and able to understand the research study consent process.

Inclusion Criteria

Endorsing suicidal ideation sufficiently severe to meet criteria for referral to an inpatient psychiatric facility or a crisis stabilization unit

Any prior history of an opioid overdose

Diagnosed with DSM5 opioid use disorder, moderate or severe

Exclusion Criteria

I have heart or EKG issues.

Pregnant

Patients who are breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive a single infusion of ketamine or saline placebo in a double-blind fashion

1 day

1 visit (in-person)

Safety Monitoring

Safety assessments conducted during and after the infusion, including monitoring of vital signs

Throughout infusion and at the end

Continuous monitoring during infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of opioid craving, suicidal ideation, and substance use

28 days

Remote follow-ups at 7, 14, and 28 days

Treatment Details

Interventions

• Ketamine

Trial Overview The trial tests if a single ketamine infusion (0.8mg/kg) is safe and effective compared to a saline placebo in reducing opioid use and suicidal thoughts among OUD patients in the emergency department. It's double-blind, meaning neither doctors nor participants know who gets ketamine or placebo.

Participant Groups

Group I: Ketamine Experimental Treatment 1 Intervention

This arm will receive ketamine (n=25)

Group II: Saline Placebo Placebo Group 1 Intervention

This arm will receive the saline placebo (n=25)

Ketamine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in European Union as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in United States as Spravato for:

• Treatment-resistant depression

Approved in European Union as Spravato for:

• Treatment-resistant depression

Approved in Canada as Spravato for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Findings from Research

A single intravenous infusion of ketamine (0.5 mg/kg) significantly reduces suicidal ideation within 4 hours and this effect can last up to 72 hours after treatment, based on a systematic review of 15 trials involving 572 participants.

While ketamine shows promise for short-term relief of suicidal thoughts, there is limited data on its long-term effects and actual suicidal behaviors, indicating a need for further research to sustain its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for suicidal ideation in adults with psychiatric disorders: A systematic review and meta-analysis of treatment trials. Witt, K., Potts, J., Hubers, A., et al.[2020]

In a study involving 156 participants with suicidal ideation, ketamine treatment led to a significantly higher rate of full remission of suicidal thoughts at day 3 compared to placebo, with 63% of those receiving ketamine achieving remission versus 31.6% in the placebo group.

The study found that ketamine was safe in the short term, with limited side effects and no occurrences of manic or psychotic symptoms, suggesting it could be a rapid and effective option for acute care in suicidal patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial. Abbar, M., Demattei, C., El-Hage, W., et al.[2022]

A single dose of ketamine can significantly reduce suicidal thoughts within an hour of administration, with effects lasting up to a week, making it a promising option for patients with severe or treatment-resistant depression.

The antisuicidal effects of ketamine occur independently of its impact on overall depression severity, indicating a unique mechanism of action that warrants further investigation for crisis intervention in suicidal patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for Depression, 6: Effects on Suicidal Ideation and Possible Use as Crisis Intervention in Patients at Suicide Risk. Andrade, C.[2022]

In a real-world study of 70 patients with severe depression and suicidal ideation, repeated subcutaneous administration of esketamine significantly reduced suicidality scores within 24 hours, demonstrating a rapid onset of action.

Esketamine was found to be safe and well tolerated, with stable heart rates and manageable blood pressure increases, indicating its potential as a viable treatment option for patients with resistant major depressive disorder and bipolar depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Subcutaneous Esketamine in the Treatment of Suicidality in Major Depressive Disorder and Bipolar Depression. Surjan, J., Grossi, JD., Del Porto, JA., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings. McInnes, LA., Qian, JJ., Gargeya, RS., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. Cavenaghi, VB., da Costa, LP., Lacerda, ALT., et al.[2021]

This systematic review analyzed 60 studies on the safety of ketamine for treating depression, revealing that acute doses of ketamine led to more frequent side effects, including psychiatric and cardiovascular issues, compared to placebo.

There is a notable lack of data on the long-term safety and effects of repeated ketamine dosing, highlighting the need for large-scale clinical trials to better understand its safety profile over extended use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side-effects associated with ketamine use in depression: a systematic review. Short, B., Fong, J., Galvez, V., et al.[2019]

In a study involving 16 recent suicide attempters, a single intravenous dose of ketamine (0.5 mg/kg) led to rapid and significant reductions in suicidal thoughts within 24 hours, with effects lasting up to 6 months post-infusion.

The results indicate that ketamine is a safe and effective treatment for reducing suicidality in high-risk patients, suggesting it could be integrated into existing healthcare settings for those in acute psychiatric care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of Ketamine Infusion after Suicide Attempt: New Frontiers in Treating Acute Suicidality in a Real-World Medical Setting. Shivanekar, S., Gopalan, P., Pizon, A., et al.[2023]

In a randomized controlled trial involving 57 patients with treatment-resistant depression, intravenous ketamine significantly reduced explicit suicidal thoughts within 24 hours compared to a placebo (midazolam), with 53% of ketamine-treated patients showing no suicidal ideation at that time.

Ketamine also decreased implicit suicidal cognition, as measured by the Implicit Association Test, indicating its potential to rapidly alter both conscious and unconscious suicidal thoughts, particularly in those with higher baseline suicidal ideation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression. Price, RB., Iosifescu, DV., Murrough, JW., et al.[2022]

A case study of a patient with treatment-resistant depression and active suicidal ideations showed that intravenous ketamine significantly reduced suicidal thoughts, even while the patient was on Buprenorphine, an opioid partial agonist.

This suggests that ketamine's antisuicidal effects may not solely rely on opioid mechanisms, indicating its potential safety and efficacy for individuals with substance use disorders or chronic pain who are maintained on opioid treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine's rapid antisuicidal effects are not attenuated by Buprenorphine. Hosanagar, A., Schmale, A., LeBlanc, A.[2021]

A systematic review of 12 randomized controlled trials found that subanesthetic ketamine, particularly in intravenous form at a dose of 0.5 mg/kg, significantly reduces suicidal ideation in acutely depressed patients, with effects observed within hours.

The benefits of ketamine for reducing suicidal thoughts can last beyond 24 hours, with one study showing sustained improvement up to six weeks after a single dose, although further research is needed to confirm long-term efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The rapid anti-suicidal ideation effect of ketamine: A systematic review. Hochschild, A., Grunebaum, MF., Mann, JJ.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Ketamine for suicidal ideation in adults with psychiatric disorders: A systematic review and meta-analysis of treatment trials. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Ketamine for Depression, 6: Effects on Suicidal Ideation and Possible Use as Crisis Intervention in Patients at Suicide Risk. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Subcutaneous Esketamine in the Treatment of Suicidality in Major Depressive Disorder and Bipolar Depression. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Side-effects associated with ketamine use in depression: a systematic review. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

A Pilot Study of Ketamine Infusion after Suicide Attempt: New Frontiers in Treating Acute Suicidality in a Real-World Medical Setting. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Ketamine's rapid antisuicidal effects are not attenuated by Buprenorphine. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

The rapid anti-suicidal ideation effect of ketamine: A systematic review. [2021]