When Hours Matter: A Look at Ketamine’s Rapid Effects on Suicidal Thinking

🔬 Study Title:

“Rapid reduction in suicidal thoughts after ketamine infusion in treatment-resistant depression: A randomized controlled trial”

Published: The American Journal of Psychiatry, 2018
Authors: Michael F. Grunebaum, MD, et al.
Link (PubMed): https://pubmed.ncbi.nlm.nih.gov/29450579

🧠 When Hours Matter: A Look at Ketamine’s Rapid Effects on Suicidal Thinking

Published: August 1, 2025
Author: Flowstate Therapy Team
(For educational purposes only. This content does not constitute medical advice or imply the availability of any specific treatment at Flowstate Therapy.)

Introduction

Suicidal ideation remains one of the most urgent and challenging symptoms in mental health care. For individuals facing treatment-resistant depression (TRD), these thoughts often persist despite multiple trials of antidepressants, therapy, or hospitalization.

Traditionally, interventions for suicidal thinking can take weeks to begin working — an agonizing timeline when someone is in crisis. But in recent years, clinical research has started exploring whether certain medications might act within hours, not weeks.

A pivotal 2018 randomized controlled trial (RCT) published in The American Journal of Psychiatry, titled “Rapid Reduction in Suicidal Thoughts After Ketamine Infusion in Treatment-Resistant Depression,” explored this very question. The study investigated whether a single ketamine infusion could rapidly reduce suicidal thinking in patients who had not responded to standard antidepressant treatments.

Here, we break down what the researchers found — and why it matters in the broader conversation about mental health science and suicide prevention.

The Study at a Glance

Citation: Grunebaum MF, Galfalvy HC, et al. (2018). Am J Psychiatry.
Link: PubMed Abstract
Design: Randomized, double-blind, placebo-controlled trial
Participants: 80 adults with major depressive disorder and suicidal ideation
Intervention: Single infusion of ketamine vs. midazolam (active placebo)
Outcome: Suicidal thoughts measured using the Scale for Suicidal Ideation (SSI)

Key Findings

1. Rapid Reduction in Suicidal Thoughts

Within 24 hours, participants who received ketamine showed a significant reduction in suicidal ideation compared to those who received the placebo. This included both the severity and frequency of suicidal thoughts.

The effect was observed using multiple clinical scales, including:

• SSI (Scale for Suicidal Ideation)

• MADRS-SI (Montgomery–Åsberg Depression Rating Scale – Suicidal Item)

This rapid change is especially noteworthy because most antidepressants — including SSRIs — typically take 4–6 weeks to show meaningful results, and they often have limited effect on suicidal thinking specifically.

2. Improvement in Depressive Symptoms

Ketamine recipients also showed reductions in overall depression severity, suggesting that the change in suicidal thoughts was not isolated — it was part of a broader mood improvement.

This supports the hypothesis that ketamine may address core mechanisms of depression beyond neurotransmitter levels, such as cognitive rigidity, emotional numbness, and hopelessness.

3. Sustained, But Temporary Effects

The study followed participants for up to six weeks, and while the anti-suicidal effects were most pronounced in the first few days post-infusion, some participants maintained improvements beyond the first week.

However, effects generally diminished without additional treatment, suggesting that integration, ongoing support, or repeat interventions may be necessary to sustain changes — a common theme in neuroplasticity-enhancing therapies.

How Might This Work?

Although the study was focused on outcomes, the authors and related research suggest several mechanisms that may underlie these rapid effects:

🧠 Glutamate and AMPA Activation

Ketamine blocks NMDA receptors and increases glutamate signaling, which leads to the activation of AMPA receptors — a key trigger in the chain reaction that promotes synaptogenesis and rapid neural remodeling.

This is thought to help disrupt maladaptive patterns of thought, such as hopelessness and suicidal rumination.

🔄 Neural Flexibility and Cognitive Shift

The ability to “shift perspective” is often diminished in depression and suicidal states. By increasing neuroplasticity, ketamine may open a window of flexibility, giving individuals space to imagine alternatives to their suffering, even briefly.

🌐 Default Mode Network Modulation

As seen in other studies, ketamine appears to temporarily disrupt the Default Mode Network, a brain system linked to self-referential and ruminative thinking. This disruption may provide a break from the internal loops that reinforce suicidal ideation.

Why This Study Matters

⚡ Emergency-Level Interventions

This RCT was one of the first to show that a single treatment could rapidly reduce suicidal thinking in a high-risk population. The implications for suicide prevention are profound — especially in emergency room, crisis, or inpatient settings where time is critical.

🔬 A Shift in How We Understand Antidepressants

This study supports a neurobiological paradigm shift — moving away from slow, cumulative neurotransmitter modulation toward treatments that restructure brain function and connectivity within days or hours.

It also raises broader questions: What if suicidal thinking is not just a symptom of depression, but a targetable neural state in itself?

🧩 Still Many Questions

While the results were promising, the authors emphasized the need for further research:

• What is the optimal frequency of administration?

• How long do benefits last?

• Can these effects be sustained with psychotherapy or other supports?

• What are the risks of repeated or long-term use?

Ethical and Regulatory Considerations

This study was conducted under carefully controlled, medically supervised conditions. In Canada, ketamine is a controlled substance, and its use for mental health conditions remains tightly regulated.

While Health Canada has approved ketamine in certain formulations (e.g., as an anesthetic), its use in psychiatry — including treatment for suicidal ideation — is still considered off-label and must follow stringent medical and ethical guidelines.

This makes education, safety protocols, and ongoing research essential pillars of any discussion around ketamine and mental health.

Final Thoughts

The 2018 study by Grunebaum and colleagues marked a turning point in mental health research. By showing that a single intervention could reduce suicidal thoughts within 24 hours, it challenged long-standing assumptions about what’s possible in psychiatric care.

Though more research is needed, and the clinical application of these findings remains highly specialized, the study adds meaningful evidence to a growing field focused on neuroplasticity, healing, and hope.

At Flowstate Therapy, we remain committed to exploring high-quality research and sharing science that empowers individuals, reduces stigma, and invites deeper understanding of the human mind.

📚 Further Reading

• Grunebaum MF et al. (2018). Rapid Reduction in Suicidal Thoughts After Ketamine Infusion in Treatment-Resistant Depression. Am J Psychiatry.

• Zarate CA et al. (2006). A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry.

• Wilkinson ST et al. (2018). Ketamine for depression: Evidence, challenges and promise. World Psychiatry.

🛑 Disclaimer

This article is for educational purposes only. It does not constitute medical advice and does not imply the availability of any specific treatment or service at Flowstate Therapy. Always consult with a licensed healthcare provider for mental health support or treatment decisions.