Ketamine for Depression and Suicidal Ideation: What Therapists Need to Know in 2026

Originally published: May 23, 2026 | Category: Clinical Research

If you are a therapist in private practice, you have probably had at least one client ask about ketamine treatment this year. Maybe more than one. And if you are like most clinicians I talk to, you have questions: Does it actually work? How safe is it? And what is my role when a client is receiving ketamine from a separate provider?

A landmark meta-analysis published in JAMA Psychiatry in 2026 has given us the clearest picture yet. Let me walk you through what it says and what it means for your practice.

The Study That Changed the Conversation

The systematic review and meta-analysis led by Dr. Michael Bloomfield and colleagues pooled data from 26 randomized clinical trials examining intravenous ketamine for patients in a major depressive episode. The findings were striking: single and repeated IV ketamine infusions produced rapid, statistically significant reductions in both depressive symptoms and suicidal ideation, measurable within hours of administration.

The meta-analysis included 1,876 participants across 26 trials, making it the largest and most comprehensive synthesis of IV ketamine data for major depressive episodes to date. The authors reported that the number needed to treat for response at 24 hours was approximately 4.3, meaning that for every four to five patients treated, one additional patient achieves a clinically meaningful response compared to placebo. For suicidal ideation specifically, the number needed to treat was even more favorable at approximately 3.7. These numbers rival or exceed any other acute psychiatric intervention currently available.

Importantly, the meta-analysis found that repeated infusions (typically a course of six over two to three weeks) produced larger effect sizes than single infusions for both depressive symptoms and suicidal ideation. This supports the current clinical practice of induction courses rather than one-off treatments. The maintenance phase where patients return for booster infusions every two to six weeks is not yet supported by the same quality of evidence, and this is where the field needs more research.

Key findings at a glance:

Outcome	Effect Size (SMD)	Timeframe	Significance
Depressive symptom reduction (single infusion)	−0.85	24 hours post-infusion	p < 0.001
Depressive symptom reduction (repeated infusions)	−1.02	End of treatment course	p < 0.001
Suicidal ideation reduction (single infusion)	−0.67	24 hours post-infusion	p < 0.001
Suicidal ideation reduction (repeated infusions)	−0.81	End of treatment course	p < 0.001
Response rate (≥50% symptom reduction)	OR 4.21	Across treatment	p < 0.001
Remission rate	OR 3.14	Across treatment	p < 0.001

Source: Bloomfield MAP, et al. JAMA Psychiatry. 2026. PMID: 42090166

But here is the critical caveat that every therapist needs to understand: long-term outcomes are not well established. The acute-phase data are compelling. What happens at three, six, or twelve months? That question remains largely unanswered by the current evidence base. The meta-analysis included predominantly short-term follow-up data, with very few studies reporting outcomes beyond six weeks. This means we can tell our clients with confidence that ketamine works in the short term, but we must be honest about the uncertainty surrounding maintenance and durability of effect.

How Ketamine Works: The Mechanism in Plain Language

Unlike traditional antidepressants that target serotonin or norepinephrine, ketamine works through a fundamentally different mechanism. Understanding this mechanism helps you explain the treatment to clients and make sense of the clinical effects they may report.

NMDA Receptor Antagonism

Ketamine blocks the N-methyl-D-aspartate (NMDA) receptor, a glutamate receptor in the brain. This blockade triggers a cascade of effects that ultimately increase synaptic connectivity. Think of it as a reset button for neural circuits that have become stuck in depression-related patterns. Within minutes of IV administration, ketamine triggers a rapid surge in extracellular glutamate in the prefrontal cortex. This glutamate surge activates AMPA receptors, which in turn triggers intracellular signaling pathways including the mTOR pathway. The net effect is a rapid increase in the density and function of dendritic spines, the physical structures that allow neurons to communicate. In depressed brains, these spines are typically atrophied. Ketamine rebuilds them.

Rapid Neuroplasticity

Within hours of administration, ketamine stimulates the release of brain-derived neurotrophic factor (BDNF) and activates the mTOR pathway. This leads to the rapid formation of new synaptic connections, literally rebuilding the neural architecture that supports mood regulation. This is why patients often report feeling lighter or clearer within hours, not weeks. Interestingly, patients with a common Val66Met polymorphism in the BDNF gene show reduced response to ketamine, suggesting that BDNF signaling is a key downstream mediator of the treatment effect. If you have clients who do not respond to ketamine despite adequate dosing, this genetic variation may be relevant.

Impact on Suicidal Ideation

The meta-analysis found that the anti-suicidal effects appear partially independent of the antidepressant effects. In other words, ketamine may reduce suicidal thinking through distinct neural pathways, possibly by dampening hyperactivity in the anterior cingulate cortex and improving cognitive flexibility around problem-solving. This is clinically significant because it means a client could experience relief from suicidal thinking even before their mood noticeably improves. For crisis situations, this has profound implications.

Opioid System Involvement

This is a newer and more controversial piece of the puzzle. Some research suggests that a component of ketamine’s antidepressant effect may be mediated through the opioid system. In one noteworthy study, pretreatment with naltrexone, an opioid antagonist, partially blocked ketamine’s antidepressant effect. This has implications for patients on naltrexone for alcohol use disorder or other indications, as their response to ketamine may be blunted. If you have clients on naltrexone who are considering ketamine, this is an important conversation to have with their prescriber.

Comparison With Traditional Antidepressants

Feature	SSRIs/SNRIs	Ketamine (IV)
Onset of action	2–6 weeks	Hours to days
Mechanism	Monoamine modulation	Glutamate/neuroplasticity
Duration of effect	Continuous (daily dosing)	Days to weeks per infusion
Route	Oral	IV (typically)
Evidence for suicidal ideation	Moderate (delayed)	Strong (rapid)
Long-term data	Extensive	Limited
Side effect profile	Well-characterized	Dissociative, BP changes
Accessibility	Primary care	Specialty clinics only

Clinical Protocols: What Patients Actually Experience

Therapy clients considering ketamine treatment often have questions about what the procedure actually involves. Here is what a typical course looks like based on current clinical practice:

Pre-Screening Phase (One to Two Weeks Before)

• Psychiatric evaluation confirming treatment-resistant depression or major depressive episode diagnosis
• Medical clearance including EKG, baseline blood pressure monitoring, and basic laboratory work
• Screening for contraindications including uncontrolled hypertension, active substance use disorder, and history of psychosis
• Medication review to identify potential interactions
• Informed consent discussing risks, expected effects, and the off-label nature of IV ketamine

The Infusion Session (Two to Three Hours)

• Patient settles into a private room with a comfortable recliner
• IV line placed and vital signs monitored continuously throughout
• Ketamine infused over approximately 40 minutes at a typical dose of 0.5 mg/kg
• Patient typically wears eyeshades and listens to instrumental music
• Dissociative effects begin within minutes, peak around 30 to 60 minutes, and resolve within 60 to 90 minutes
• Patient monitored for 30 to 60 minutes after infusion before discharge
• Patient cannot drive for 24 hours following treatment

The Induction Phase (Two to Three Weeks)

• Typically six infusions scheduled two to three times per week
• Response assessed after each infusion using standardized measures like MADRS, PHQ-9, and C-SSRS
• Dose adjustments made based on response and tolerability

The Maintenance Phase (Ongoing)

• Responders transition to maintenance infusions every two to six weeks
• Dose and frequency titrated to maintain response
• Some patients taper off over months; others require ongoing maintenance
• Long-term data beyond six to twelve months are limited, which clinicians should discuss with their clients

Who Is a Candidate for Ketamine Treatment?

Not every depressed client is a candidate for ketamine. Current clinical practice typically reserves ketamine for specific populations:

• Treatment-resistant depression (TRD): Failure of two or more adequate trials of traditional antidepressants at therapeutic doses for sufficient duration
• Acute suicidal ideation: Particularly when the risk of self-harm is imminent and other interventions have not worked quickly enough
• Major depressive episode with severe functional impairment: When the person cannot wait four to six weeks for SSRIs to potentially work
• Bipolar depression: Some evidence supports use, though with additional monitoring for mood switching into hypomania or mania

Exclusion criteria typically include uncontrolled hypertension, active substance use disorders (particularly dissociative drugs), current or past psychotic disorders, uncontrolled bipolar I disorder without mood stabilization, severe hepatic impairment, pregnancy, and known allergy or prior adverse reaction to ketamine. Each clinic will have its own medical screening protocol, and these criteria may vary.

Special Populations

Adolescents and young adults: Evidence for ketamine in adolescent depression is growing but remains preliminary. The developing brain may respond differently to ketamine in terms of both efficacy and safety. Some early studies suggest adolescents may be more sensitive to dissociative side effects. If you work with adolescents considering ketamine, encourage a thorough discussion with a child and adolescent psychiatrist experienced in this area.

Bipolar depression: Ketamine appears effective for bipolar depression, but the risk of mood switching into hypomania or mania requires careful monitoring. The meta-analysis included some bipolar patients and found no significant signal for treatment-emergent mania, but clinical experience suggests this risk exists and warrants vigilance. Clients with bipolar disorder being treated with ketamine should have a mood stabilizer on board and be monitored closely by both their psychiatrist and their therapist. Any sudden improvement in mood accompanied by decreased need for sleep, grandiosity, or racing thoughts should be taken seriously.

Pregnancy and postpartum: Data on ketamine use during pregnancy and lactation are extremely limited. Current guidelines generally recommend avoiding ketamine during pregnancy unless the potential benefit clearly outweighs risk. For postpartum depression, where the urgency of treatment may be higher, individual risk-benefit decisions are made on a case-by-case basis. Clients in this situation should ideally be co-managed by a reproductive psychiatrist.

Older adults: Limited evidence suggests ketamine is effective and safe in older adults, but dosing adjustments may be needed due to age-related changes in metabolism and increased sensitivity to cognitive side effects. Baseline cognitive assessment is recommended. Coordination with the clients’ geriatrician or primary care provider is important given the higher rate of medical comorbidities in this population.

Risks and Side Effects

Your clients need to know about these before they book their first appointment. And you need to monitor for them afterward.

Common Side Effects (10 to 30 Percent)

• Transient dissociative symptoms during infusion: The out-of-body experience. For most people it resolves within 60 to 90 minutes. For some it is deeply unsettling. Normalize this experience in advance.
• Nausea: Managed with antiemetics. Usually resolves post-infusion.
• Dizziness and lightheadedness: Resolves within hours.
• Headache: Responds to standard analgesics.
• Blurred vision: Resolves within hours.

Less Common Side Effects (1 to 10 Percent)

• Significant blood pressure elevation: Clinics monitor and may treat with antihypertensives during infusion.
• Emergence phenomena: Vivid dreams, depersonalization lasting hours to days after infusion.
• Anxiety or panic during infusion: More common in patients with anxiety disorders. Can be managed with reassurance and dose adjustment.
• Transient cognitive impairment: Usually resolves within 24 hours. Clients should not drive or make important decisions on infusion days.

Rare but Serious Side Effects (Less than 1 Percent)

• Psychotic symptoms: Particularly in those with vulnerability. This is why careful screening for personal or family history of psychosis is essential.
• Hypomanic or manic switching: Especially in bipolar spectrum disorders. Monitor for decreased need for sleep, grandiosity, pressured speech.
• Urinary symptoms: Cystitis and bladder dysfunction are associated with chronic heavy use, though this is more relevant to recreational use than clinical protocols.
• Hepatotoxicity: Idiosyncratic and rare.
• Seizures: In those with lowered seizure threshold.

Your role as the therapist is to monitor for these effects outside the clinic setting and communicate with the ketamine provider. If a client reports persistent dissociative symptoms, worsening mood, or new psychotic-like experiences between infusions, this needs immediate attention. Have a clear protocol for who to contact and when.

Ketamine and Psychotherapy: Integration Work

The integration of ketamine treatment with ongoing psychotherapy represents one of the most promising frontiers in mental health care. Patients who receive ketamine alone without concurrent psychotherapy may experience symptom relief without the cognitive and behavioral restructuring needed for durable change. Here is what integration looks like in practice:

Pre-Infusion Preparation (One to Three Sessions)

Before a client begins ketamine treatment, your role includes:

• Setting realistic expectations: Ketamine is not a cure. It creates a window for therapeutic work. The goal is symptom reduction that enables engagement in therapy, not replacement of therapy.
• Addressing fear and anxiety: Many clients are anxious about the dissociative experience. Normalize this and help them develop coping strategies such as grounding techniques they can use during the infusion if needed.
• Intention setting: Help clients formulate a simple intention for their treatment. Not a specific outcome they must achieve, but a direction of attention. For example, “I want to understand my relationship with sadness” rather than “I want to stop being sad.”
• Coordinating with the clinic: Ensure releases are signed and communication channels are open with the ketamine provider. Some clinics welcome therapist input on treatment timing and adjunctive support.

Post-Infusion Integration (One to Two Sessions per Infusion)

The 48 to 72 hours following each infusion represent the neuroplasticity window. During this period:

• Schedule sessions within 24 to 48 hours of infusion. This is when the brain is most receptive to new learning. Cognitive restructuring, behavioral experiments, and exposure work may be more effective during this window.
• Process the infusion experience. Clients often have meaningful and sometimes confusing experiences during ketamine sessions. Help them make meaning. Ask: What came up for you? What felt significant? Is there anything that felt confusing or unsettling?
• Translate insight into action. What does this experience tell you about what you need? What is one small change you can make today based on this understanding?
• Monitor for vulnerability. Rapid relief can feel destabilizing. Some clients need help adjusting to feeling better. Others may experience grief about lost time or regret about not accessing this treatment sooner. Both responses are normal and need space in session.

Long-Term Integration (Ongoing Sessions)

• Relapse prevention: Help clients identify early warning signs of depressive relapse and develop a crisis plan that includes their ketamine provider.
• Rebuilding identity: Depression fundamentally shapes self-concept. As symptoms lift, clients need support in rebuilding a sense of self that is not organized around illness.
• Addressing treatment dependence concerns: Some clients worry about becoming dependent on ketamine. Help them differentiate between therapeutic dependence, which is common in many chronic conditions, and psychological addiction, which is rare in clinical settings.

What This Means for Your Practice

1. Know the Treatment Landscape

Standard IV ketamine protocols involve six infusions over two to three weeks, each session lasting about two hours including monitoring. After the initial series, maintenance infusions are scheduled based on response, often every two to six weeks. Some clients receive a single infusion for acute suicidal crises. Understanding this helps you plan your therapeutic work around their treatment schedule.

2. Coordinate Care With the Prescribing Provider

This is probably the most important thing you can do. Get a signed release from your client to speak with the ketamine prescriber. Ask about the specific protocol being used, any observed side effects or adverse reactions, whether the prescriber is monitoring for hypomanic or manic switching, and their long-term treatment plan and exit strategy. Document this coordination in your clinical notes.

3. Monitor for Safety and Stability

Your client might feel dramatically better after their first or second infusion. This is good, but it also carries risks. A rapid shift from severe depression to euthymia can destabilize relationships, decision-making, and self-concept. Clients may make impulsive life decisions, underestimate ongoing vulnerability to depression, struggle to integrate rapid relief into their self-narrative, or experience grief about why this treatment was not available sooner. Stay attuned to these dynamics.

4. Address Common Questions

Client Question	Suggested Response
“Can I stop my antidepressants when I start ketamine?”	Not without coordinating with the prescriber. Some clinics recommend continuing current meds. Never discontinue abruptly.
“Is it addictive?”	Clinical protocols are designed to minimize dependence risk. Outside clinical settings, yes, ketamine has abuse potential. The clinic setting with monitoring is different from recreational use.
“My friend tried it and it did not work. Why?”	Response rates are around 50 to 70 percent for treatment-resistant depression. Non-response happens. There may be another infusion protocol or alternative treatment to consider.
“Do I still need therapy if the ketamine works?”	Absolutely. Medications treat symptoms. Therapy treats the person. The neuroplasticity window is actually an opportunity to do deeper therapeutic work.
“How long will the effects last?”	Effects of a single infusion typically last days to a week. Maintenance is needed for sustained benefit. Long-term data beyond three to six months are limited.
“Will I have a bad trip?”	The dissociative experience can be intense but is monitored by medical staff. Preparation sessions help reduce anxiety and improve the quality of the experience.

When Ketamine Is Not Appropriate

It is equally important to know when ketamine is not the right path. Contraindications include: current or past psychotic disorders, uncontrolled hypertension, active substance use disorder especially with dissociative drugs, pregnancy (relative), severe hepatic impairment, and known allergy. If your client has any of these, ketamine treatment should not proceed until they are addressed or an alternative is found.

Building Your Referral Network

If you decide to incorporate ketamine coordination into your practice, here is how to identify reputable providers: Look for medical oversight by psychiatrists, anesthesiologists, or psychiatric nurse practitioners. Ask about their standardized dosing protocol, vital sign monitoring, and emergency procedures. Check their integration approach, whether they encourage or facilitate psychotherapy alongside treatment. Visit the clinic environment if possible. Get references from other therapists who have referred clients there. A good clinic will welcome these questions.

The Bottom Line for Therapists

Ketamine is not a magic bullet. But it is a genuinely new tool, one that works through mechanisms fundamentally different from everything that came before it. For the client with crushing treatment-resistant depression or acute suicidal ideation, it can be life-changing in a matter of hours rather than weeks. The evidence says it works in the short term. What happens long-term depends, at least in part, on the therapeutic framework we build around it.

Your job as a therapist is not to prescribe or administer ketamine. It is to understand the treatment, coordinate with the medical team, help your client make informed decisions, and leverage the neuroplasticity window for deeper therapeutic work. The clinicians who invest in understanding this modality now will be best positioned to help their clients access and integrate a treatment that is rapidly becoming mainstream.

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References:

1. Bloomfield MAP, et al. Ketamine Infusions and Rapid Reduction of Suicidal and Depressive Symptoms in Major Depressive Episode: A Systematic Review and Meta-Analysis. JAMA Psychiatry. 2026. PMID: 42090166
2. Wilkinson ST, et al. A Systematic Review of Ketamine for Treatment-Resistant Depression. Am J Psychiatry. 2025;182(4):345-358.
3. Fava M, et al. The Neuroplasticity Window: Ketamine-Assisted Psychotherapy for Depression. Biol Psychiatry. 2025;97(3):221-230.
4. Zarate CA, et al. Mechanisms of Ketamine’s Rapid Antidepressant Effects. Annu Rev Pharmacol Toxicol. 2024;64:123-145.

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This article is for educational purposes and does not constitute medical advice. Clients considering ketamine treatment should consult with a qualified healthcare provider.