Explore the Research Behind
Ketamine-Assisted Therapy (KAT)
Ketamine-assisted therapy is supported by a vast body of research, and new studies continue to expand our
understanding of how it can help people heal. On this page, you’ll find a collection of trusted journal articles covering a
wide range of conditions that ketamine-assisted therapy can help with—from depression and anxiety to PTSD, OCD,
addiction, eating disorders, and more. Whether you’re learning for yourself or supporting someone you care about,
these resources offer a clear look at the science behind this innovative treatment.
Depression
Anxiety
PTSD
OCD
Alcohol
Study
Findings
Conclusion
Antidepressant effects of ketamine in depressed patients
Ketamine produced rapid antidepressant effects within hours. By 72 hours post-infusion, depression ratings were significantly improved on ketamine compared to placebo. Some patients reported near remission of symptoms a day after ketamine, whereas none showed improvement on placebo.
This small pilot established proof-of-concept that subanesthetic IV ketamine can rapidly reduce depressive symptoms in patients with otherwise resistant depression. It paved the way for larger trials by demonstrating ketamine’s fast-acting antidepressant potential.
Within 24 hours, 71% of ketamine-treated patients showed a clinical response (≥50% improvement) and ~29% achieved remission, versus 0% on placebo . The ketamine group maintained a significant antidepressant effect through 1 week (35% still improved at 1 week) . Ketamine was generally well-tolerated aside from transient dissociative effects.
This pivotal trial was the first controlled evidence that a single ketamine infusion can induce rapid and robust antidepressant effects in TRD patients, with some effects lasting several days . It firmly established IV ketamine’s role as a rapid intervention for refractory depression.
Ketamine led to rapid improvement in bipolar depressive symptoms: within 40 minutes, ketamine reduced depression scores significantly more than placebo (effect size d≈0.5) . 71% of ketamine-treated patients met response criteria within the first 24–48 hours vs 6% on placebo . Antidepressant effects persisted for up to 3 days post-infusion . One ketamine recipient had a brief hypomanic episode (comparable to one placebo patient), and ketamine was well tolerated aside from transient dissociation.
Even in bipolar depression – a population often excluded from antidepressant trials – a single ketamine infusion produced a rapid and robust antidepressant response . This suggests IV ketamine’s efficacy extends beyond unipolar depression, though effects are time-limited. Appropriate mood-stabilizer coverage is important to mitigate switch risk.
Ketamine produced a greater reduction in MADRS depression scores than midazolam at 24 hours (effect size d≈1.0) . 63% of ketamine patients met response criteria within 24 hours, versus 0–18% in the midazolam group (in prior similar trials) . Some antidepressant effect persisted for several days (median ~3 days). No serious adverse events occurred; ketamine’s dissociative and blood pressure effects were transient.
Against an active benzodiazepine control, IV ketamine demonstrated a clear, rapid antidepressant effect in TRD . This study alleviated concerns that ketamine’s benefits were merely due to unblinding or sedation. It reinforced ketamine’s potential as a fast-acting option in severe depression, albeit with a temporary duration of benefit.
Both twice-weekly and thrice-weekly ketamine regimens produced significant antidepressant improvements; increasing frequency to three times/week did not substantially enhance outcomes over twice-weekly dosing . The 0.5 mg/kg dose was effective in most patients, with no clear benefit to the higher 1.0 mg/kg dose . By day 15, response rates were similar across dosing schedules, and most responders maintained improvement for at least a week post-treatment.
This dose-frequency trial showed that the standard 0.5 mg/kg IV dose given 2 times per week is an efficacious and practical regimen for extending ketamine’s antidepressant effects . More intensive dosing did not markedly improve depression outcomes, helping define protocols that balance efficacy with burden and safety.
A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes
Ketamine outperformed control on all timeframes. At 24 hours, ketamine had an odds ratio ~7 for achieving remission (NNT ~5) . Clinical response at 24 hours was ~9 times more likely with ketamine than placebo (NNT ~3) . Benefits persisted through 7 days (OR ~4 for remission at 1 week) . Pooled effect size was large (d≈0.90 at 24h). Notably, unipolar depression showed somewhat greater improvement than bipolar depression . Ketamine’s side effects (transient psychotomimetic symptoms) did not lead to lasting psychosis or significant safety events in these trials .
This meta-analysis solidified that single-dose IV ketamine provides rapid, clinically meaningful antidepressant effects in treatment-resistant major depression . Approximately 50%–70% of patients respond within hours, though the effect wanes by 1–2 weeks. These findings gave the psychiatric community confidence in ketamine’s efficacy and acceptable safety in controlled settings.
"Significant improvement in depression and anxiety within 1 hour of the first dose.
Improvements persisted at 2 weeks and 1 month after the final dose.
Only transient, mild side effects observed; resolved within 1 hour.
"
IV ketamine at subanesthetic doses produces rapid, robust, and sustained antidepressant and anxiolytic effects, with good short-term tolerability.
A single ketamine infusion showed significantly greater MADRS score reduction than midazolam at 24 hours (mean decrease 10.9 vs 2.8 points). Repeated infusions yielded cumulative antidepressant effect—59% response rate, 23% remission rate by week 2. Median 3 infusions required for response. Weekly maintenance infusions sustained improvement (91% maintained response). No serious adverse events; dissociative effects declined over time.
IV ketamine shows rapid, cumulative, and durable antidepressant effects in TRD. Maintenance dosing can prolong benefits, and repeated infusions double the response rate compared to a single dose. Treatment is well tolerated.
Mean BDI dropped from 32.6 ± 8.4 to 16.8 ± 3.1 at 24 hours (p < 0.001). Response rate 53.7 percent and remission rate 41.5 percent at 24 hours. About 75 percent of responders maintained responder status at 7 days. Well tolerated with occasional nausea or anxiety and mild transient blood pressure and heart rate changes. No serious adverse events reported.
In a real world TRD population with comorbidities and ongoing medications, a single subanesthetic IV ketamine infusion produced rapid and clinically meaningful antidepressant effects with good short term tolerability. Benefits often persist about a week in responders, which supports use as an acute intervention and argues for planning serial infusions or maintenance strategies to extend response.
54.9% of patients achieved clinical response. Significant reductions observed in depressive symptoms and suicidal ideation at treatment endpoint. 78.3% experienced only transient, mild side effects (e.g., dissociation, nausea, hemodynamic changes). Dropout rate was 11.3%. No significant impact of demographic variables (age, sex) on outcomes or tolerability.
Long-term real-world evidence confirms IV low-dose ketamine is an effective, fast-acting, and well tolerated treatment for TRD, significantly reducing both depression severity and suicidal ideation. This supports its scalability and feasibility in public outpatient clinical settings.
Ketamine (both doses) reduced depression and anxiety within 1 hour, with effects persisting up to 7 days. Response at 24 h: HADS-Depression 56% (14/25); HADS-Anxiety 72% (18/25) for either ketamine dose. After fentanyl: 1/25 (depression) and 3/25 (anxiety) responders. Dose effects: Similar mood benefit at 0.5 vs 1.0 mg/kg; greater/longer durability suggested for 1.0 mg/kg. Side effects: Dose-related transient dissociation and BP increases; mild AEs (blurred vision, lightheadedness, numb lips, nausea), resolving <2 h; no serious AEs.
IM ketamine is a practical, well-tolerated alternative to IV with rapid antidepressant and anxiolytic effects in TRD. 0.5 mg/kg IM is a reasonable starting dose; 1.0 mg/kg may extend effect duration. Active-control results (vs fentanyl) strengthen specificity. Consider serial/maintenance dosing to sustain benefits.
"Repeat IV ketamine: Consistently effective in sustaining response; best evidence supports 2x/week 0.5 mg/kg dosing. Mean response rates ~64%; relapse typically 16–24 days after last infusion.
Esketamine: Proven maintenance efficacy in RCTs (though focus was racemic ketamine).
Adjunct oral agents: Generally failed to prolong efficacy (e.g., riluzole, lithium, DCS, clonidine, lamotrigine). Only rapamycin pre-treatment showed benefit in one small RCT.
Psychotherapy (CBT): Open-label trial showed responders maintained remission up to 12 weeks when CBT followed ketamine, but evidence limited.
Neurostimulation: TMS combined with ketamine yielded sustained CGI improvement up to 2 years in retrospective data; ECT + ketamine showed faster onset and cognitive benefits vs thiopental, but results were mixed for long-term durability.
Safety: Repeat ketamine generally well tolerated, with side effects limited to transient dissociation and mild hemodynamic changes."
The strongest, most reliable method to prolong antidepressant efficacy is repeat IV ketamine infusions (2x weekly). Adjunctive strategies such as rapamycin, CBT, and TMS show promising early evidence, but require further study. Oral agents tested so far do not reliably extend ketamine’s benefits. Maintenance esketamine is validated in RCTs. For TRD patients, strategic repeat or maintenance dosing remains the standard evidence-based approach.
An Integrative Approach to Ketamine Therapy May Enhance Multiple Dimensions of Efficacy: Improving Therapeutic Outcomes With Treatment Resistant DepressionA
"Ketamine rapidly reduces depressive symptoms, including suicidality, often within 4 hours, sustained for days to weeks.
Mechanistic evidence: glutamate/AMPA receptor stimulation, BDNF/mTOR signaling, synaptogenesis in PFC/hippocampus, normalization of network connectivity, reduction of inflammatory cytokines.
Psychedelic/dissociative states may contribute meaningfully to efficacy, with intensity of acute experience sometimes correlating with better outcomes.
Integrative protocols (psychoeducation, optimized dosing to induce high-entropy states, supportive set/setting, curated music, psychotherapy timed 24–48h post-dose) may enhance and prolong efficacy.
Rodent and human evidence suggests ketamine selectively reverses stress-induced dendritic spine loss, restores connectivity, and induces plasticity during a therapeutic “window.”
Potential risks include transient dissociation, perceptual changes, and rare abuse liability—though clinical misuse is uncommon."
Ketamine’s efficacy in TRD is multi-dimensional, relying not only on receptor-level effects but also on plasticity, anti-inflammatory activity, altered states, and subjective experiences. Optimized treatment protocols should integrate biological, experiential, and psychotherapeutic components to maximize and sustain benefits. This supports the use of ketamine-assisted psychotherapy (KAP) and multimodal monitoring in clinical practice.
Both formulations showed significant antidepressant effects, but IV racemic ketamine appeared more efficacious than intranasal esketamine in direct comparisons . Pooled analyses found greater symptom reductions on depression scales with IV ketamine, and a trend toward higher response/remission rates, than with esketamine at comparable time points . For example, one analysis reported an advantage in clinical response for IV ketamine over intranasal esketamine (response rates ~63% vs ~53%) . In terms of safety, both had similar profiles: transient dissociation and blood pressure increases were common to each, and both were deemed safe and acceptable in controlled settings .
This meta-analysis suggests that IV ketamine may confer slightly stronger antidepressant effects than intranasal esketamine in TRD . The IV route delivers the full racemic mixture directly, potentially yielding more robust or rapid symptom improvements. However, intranasal esketamine (FDA-approved) has practical and logistical advantages. These findings support the continued use of IV ketamine in specialized clinics, as it might achieve higher efficacy in some patients, while underscoring that both treatments are effective options for difficult-to-treat depression .
A single ketamine infusion caused a significantly larger 24-hour antidepressant improvement than midazolam (acute phase endpoint) . Moreover, repeated ketamine infusions had cumulative benefits: after the 2-week series of six infusions, the overall response rate doubled to ~59% (versus ~30% after the initial single infusion) . The median patient required 3 infusions to reach response criteria . In the 4-week maintenance phase, responders’ depression scores remained stable with weekly ketamine, indicating that continued infusions prolonged the remission . No further symptom gains occurred during maintenance, but those achieved were sustained . Ketamine’s side effects were acute and did not accumulate over repeated doses, and no new safety issues emerged with longer treatment.
This controlled trial systematically demonstrated that repeated ketamine infusions can sustain and amplify antidepressant effects in TRD . A single infusion yielded rapid relief, but a multi-infusion course roughly doubled the proportion of patients achieving robust response. Importantly, once-weekly maintenance infusions helped maintain the antidepressant benefits, preventing early relapse in responders . These findings guide clinical practice on optimizing ketamine therapy: an initial infusion to gauge effect, a short induction series for maximal response, and possible maintenance infusions (or transitioning to another therapy) to extend the duration of remission .
Across studies, ketamine produced rapid, dose-dependent anxiolytic effects within hours, lasting up to 1–2 weeks. Repeated low-dose infusions (0.5–1 mg/kg) or subcutaneous injections showed the greatest reductions in generalized and social anxiety. Ketamine also improved depression and suicidality in comorbid TRD. Adverse effects were transient (dissociation, nausea, mild BP increases). The optimal regimen appeared to be 0.5 mg/kg administered once or twice weekly. Mechanistic evidence suggests NMDA antagonism, AMPA activation, and BDNF/mTORC1 signaling underlie benefits.
Ketamine demonstrates significant short-term relief for refractory anxiety and anxiety with TRD, with an excellent safety profile when dosed subanesthetically. Effects are rapid but transient, supporting its role as an adjunct or bridge therapy. Long-term efficacy, abuse potential, and comparative data on (R)- vs (S)-ketamine require further study.
Ketamine significantly reduced clinician-rated social anxiety (LSAS) scores versus placebo at days 2, 5, and 10 post-infusion (effect size 1.1–1.37). 33% met LSAS response criteria vs 0% on placebo. VAS-Anxiety self-ratings trended toward improvement but were not statistically significant. 89% of participants reported >50% reduction in self-rated anxiety post-ketamine vs 53% after placebo. Dissociative symptoms were transient, peaking during infusion and resolving within 2 hours. No serious adverse events occurred.
Single-dose IV ketamine (0.5 mg/kg) appears safe and rapidly effective in reducing social anxiety symptoms for up to 2 weeks, suggesting a potential glutamate-mediated mechanism. Benefits were strongest on clinician-rated scales, and dissociation was brief and self-limiting. Findings warrant larger, parallel-group studies with active controls to confirm efficacy and optimize dosing.
Four of six acute RCTs showed significant improvement in anxiety scores with ketamine versus controls. Pooled data demonstrated strong benefit for SAD (OR = 28.94; 95% CI 3.45–242.57; p = 0.002) and moderate for GAD (OR = 30.33; p = 0.03), but nonsignificant for PTSD (OR = 2.03; p = 0.21). OCD participants showed temporary symptom reduction lasting up to 7 days. A clear dose-response relationship emerged: doses ≥ 0.5 mg/kg produced stronger anxiolytic effects. Maintenance therapy (1 mg/kg SC weekly) sustained anxiety reduction and improved functioning over 14 weeks. Common transient side effects included dissociation, dizziness, nausea/vomiting, and mild hypertension.
Ketamine shows broad, rapid anxiolytic potential across anxiety spectrum disorders, especially SAD and GAD, with effects sustained through maintenance dosing. While generally safe and well tolerated, dissociation and sympathomimetic effects warrant monitoring. Evidence for PTSD remains mixed, emphasizing the need for larger, parallel-arm RCTs to refine dosing, safety, and duration of benefit.
Significant multivariate effect on anxiety+depression (F(1,14)=4.78; p=0.046; r=0.50). Anxiety decreased from T1→T2 in S-ketamine vs control (F(1,14)=10.14; p=0.007; r=0.65). Depression change not significant (F(1,14)=1.60; p=0.23; r=0.32). No durable analgesic effect detected beyond the infusion period. No randomization; small sample.
At analgesic dosing, a single S-ketamine infusion in palliative-care patients was associated with a rapid reduction in anxiety but no clear effect on depression. Results are preliminary (retrospective, non-randomized, small N); prospective randomized studies are needed before routine adoption for psychological distress in palliative care.
Effects of ketamine in patients with treatment-refractory generalized anxiety and social anxiety disorders: Exploratory double-blind psychoactive-controlled replication study
Rapid anxiolytic effects were seen with ketamine. Within 1 hour of dosing, patients experienced marked reductions in anxiety symptoms (across GAD and social anxiety scales) during each ketamine session, whereas midazolam’s effect was minimal and short-lived . Ketamine’s anti-anxiety benefits persisted for up to one week post-infusion in many cases . A positive dose-response trend emerged: higher ketamine doses (0.5–1.0 mg/kg) tended to produce more pronounced and longer-lasting anxiolysis (with dose-related transient dissociation and blood pressure changes that remained clinically manageable) . No serious adverse effects were noted; all patients tolerated the multiple doses well.
For severe, treatment-resistant GAD/SAD, repeated ketamine infusions yielded significant and lasting anxiety reduction even in the absence of concomitant depression . Notably, relief often endured about a week, suggesting an extended therapeutic window. These findings support ketamine as a potential rapid anti-anxiety agent in refractory anxiety disorders and informed optimal dosing (around 0.5 mg/kg) for future larger trials.
Across studies, ketamine showed significant anxiolytic effects in severe anxiety disorders. The meta-analysis found a large acute reduction in anxiety severity versus placebo (standardized mean difference >1 at <24 hours post-infusion) . Clinical improvement was observed in various diagnoses – ketamine reduced panic and irritability in PTSD/GAD and improved social interaction in SAD . Notably, some anxiolytic benefits lasted up to 1 week after a single infusion . Higher ketamine doses tended to yield more sustained anxiety relief (consistent with dose-response findings) . While data were fewer than in depression, results were consistently positive and no new safety signals emerged in anxious patients .
Evidence is rapidly accumulating that IV ketamine can alleviate refractory anxiety symptoms, with benefits often paralleling those seen in depression treatment . This 2021 meta-analysis concluded that ketamine’s efficacy likely extends to chronic anxiety disorders that have failed standard treatments. Patients experienced reduced anxiety and fear symptoms for days to a week post-infusion. These findings encourage further RCTs and suggest ketamine’s mechanism (NMDA antagonism) may disrupt pathological anxiety circuits in ways conventional anxiolytics do not .
Ketamine led to a rapid reduction in PTSD symptom severity. At 24 hours, Clinician-Administered PTSD Scale (CAPS) scores dropped more in the ketamine condition than placebo (about a 10-point greater improvement on CAPS) . Yale PTSD Rating scores similarly improved. About 40–50% of patients were responders 24 hours after ketamine, versus 0% after placebo in the first phase (due to crossover, placebo patients later received ketamine) . Some improvement persisted up to one week, though symptoms gradually returned. No serious adverse events occurred.
This pilot established that ketamine can produce swift, significant relief of PTSD symptoms, at least transiently . Patients experienced reductions in re-experiencing, avoidance, and hyperarousal within a day. Though short-lived, these findings opened a promising new avenue for treating refractory PTSD and set the stage for repeat-dose studies to extend the benefit.
Repeated ketamine infusions led to greater PTSD symptom improvement than the midazolam control . After 2 weeks (all 6 infusions), CAPS scores in the ketamine group were on average 11.9 points lower than in the midazolam group (a large effect, d≈1.13) . 67% of ketamine patients were treatment responders (clinically significant drop in PTSD symptoms) vs only 20% on midazolam . Comorbid depression also improved more with ketamine. The median time until symptoms returned among responders was 27 days after the final infusion . Ketamine was well tolerated with no drop-outs for side effects .
This was the first controlled evidence that a course of ketamine infusions yields substantial and sustained PTSD symptom relief, beyond a single dose . Roughly two-thirds achieved significant improvement after six infusions, and benefits lasted ~4 weeks in many. These results position IV ketamine (given in a series) as a promising intervention for chronic PTSD, warranting integration with psychotherapy to maintain gains.
"Indications: Effective for acute pain in perioperative care, trauma, sickle cell crises, renal colic, and opioid-tolerant patients
Dosing: Subanesthetic IV infusions recommended (similar ranges as chronic pain use)
Efficacy: Provides strong opioid-sparing effect, improved analgesia; evidence supports use as adjunct or stand-alone therapy
Other Routes: Limited but emerging data for patient-controlled IV and nonparenteral forms (e.g., intranasal)
Contraindications: Same as chronic pain (active psychosis, uncontrolled cardiovascular disease, pregnancy, ↑ICP, etc.)
Safety: Best delivered under acute pain/anesthesia service supervision with structured monitoring protocols"
Consensus guidelines support IV ketamine at subanesthetic doses as a safe and effective option for acute pain, particularly in opioid-tolerant or refractory cases, provided it is delivered with standardized patient selection, dosing, and monitoring.
Both ketamine and ketorolac produced significant reductions in PTSD and chronic pain symptoms lasting up to 7 days. No difference between treatments. CP + PTSD group had fewer dissociative effects; CP-only group showed unexpected dissociation with ketorolac.
Low-dose IV ketamine was safe and well tolerated in veterans with comorbid PTSD + chronic pain. Comparable benefit with ketorolac suggests inflammation may contribute to symptom relief. No cardiovascular complications observed.
Ketamine consistently demonstrated rapid symptom relief in PTSD with favorable safety and tolerability. Combination protocols (e.g., with TIMBER or exposure therapy) improved durability. Repeated IV infusions (0.5 mg/kg over 40 min) yielded stronger and longer effects than single doses. No increased PTSD risk post-procedural use. Esketamine showed benefit but was generally less effective than racemic ketamine.
Ketamine offers significant therapeutic potential for PTSD, especially treatment-resistant and comorbid depression cases. Safety profile is favorable; dissociation is transient. Optimal dosing, frequency, and psychotherapy integration require standardization. More longitudinal and diverse trials are needed to confirm best practices.
Ketamine acts as an NMDA receptor antagonist and increases brain-derived neurotrophic factor (BDNF), potentially reversing stress-induced synaptic loss. In animal models, ketamine reduced fear conditioning and enhanced stress resilience. In clinical studies, IV ketamine (0.5 mg/kg) produced rapid and significant PTSD symptom relief lasting 1–2 weeks, with concurrent antidepressant effects. Racemic ketamine showed benefit, while S-ketamine was linked to stronger dissociative symptoms. Oral ketamine decreased psychiatric hospital admissions in PTSD patients. Adverse events were mostly mild and transient (dissociation, BP elevation, headache).
Ketamine may offer rapid symptom reduction for treatment-resistant PTSD and comorbid depression with limited short-term risks. Effects are transient, and standardized dosing and safety protocols are needed. Racemic ketamine may be safer and more effective than S-ketamine. Adjunctive psychotherapy could extend benefits.
No OCD symptom response (>35% improvement) observed in any participant. Mean OCD improvement 50% improvement). Both OCD and depression improved transiently from baseline, but only depressive symptoms showed a meaningful short-term effect.
Single-dose IV ketamine produces short-lived antidepressant effects in OCD patients with comorbid depression but lacks efficacy for core OCD symptoms. Suggests ketamine’s glutamatergic modulation may not address OCD pathophysiology in isolation. Further controlled studies needed for maintenance or combination strategies.
Significant anti-obsessional effects occurred during and shortly after ketamine infusion compared with placebo. Fifty percent (4/8) of participants who received ketamine first met responder criteria (≥35% Y-BOCS reduction) at 1 week versus 0% in the placebo-first group. Carryover effects were observed—symptom relief persisted beyond the 1-week washout. No serious adverse events; transient dissociation and mild side effects noted.
A single IV ketamine dose (0.5 mg/kg) can produce rapid, short-term reduction in obsessive thoughts in treatment-resistant OCD, independent of serotonin reuptake inhibition. Supports the glutamatergic hypothesis of OCD and suggests a potential fast-acting mechanism for refractory cases. Larger, parallel-group studies are warranted.
Eight of nine studies reported rapid anti-obsessive effects, five with statistical significance. OCD symptom scores decreased by ~49.7% within the first hour post-infusion but returned to baseline within 7 days. Some studies noted temporary antidepressant and anti-suicidal benefits. Combined therapy with CBT prolonged the duration of effect. All studies were small-scale, with limited statistical power.
Evidence supports ketamine’s potential for rapid, short-lived symptom relief in OCD. The unsustained nature of these effects limits standalone clinical use but suggests possible adjunctive benefit to bridge the latency gap of SSRIs. Larger randomized trials are needed to confirm efficacy and safety.
Ketamine increased odds of abstinence, delayed relapse, and reduced heavy-drinking days vs midazolam over 21 days; modeled NNT ≈ 4 (observed ≈ 6). Infusions were well tolerated; acute dissociation higher with ketamine; no ketamine-arm dropouts vs six in midazolam.
For treatment-seeking AUD already engaged in MET, a single subanesthetic ketamine infusion can improve short-term drinking outcomes and support engagement. Evidence is preliminary (small, homogeneous sample; short follow-up); best positioned as an adjunct to structured psychotherapy, not stand-alone therapy.
Ketamine significantly improved abstinence outcomes. Over 6 months, patients who received ketamine had about 10% more abstinent days than those who received placebo infusions (an absolute mean difference of +10%, 95% CI 1.1–19%) . The best outcomes were observed in the ketamine + therapy group, which had ~16% more abstinent days than the placebo + education group (95% CI 3.8–28%) . By contrast, the relapse rate (any return to heavy drinking) did not differ significantly between ketamine vs placebo overall . Importantly, ketamine was well tolerated in this alcohol-dependent sample, with no serious adverse events and no increase in craving or depression .
This trial provides evidence that a regimen of three ketamine infusions can augment therapy to improve sobriety in alcohol use disorder . Ketamine recipients maintained longer periods of abstinence, especially when combined with psychological therapy, suggesting a synergistic effect. While ketamine alone didn’t significantly cut relapse incidence, the increased abstinent days indicate meaningful clinical benefit. These findings support ketamine with therapy as a novel approach to enhance outcomes in alcohol dependence, deserving further research into optimizing therapy integration and maintenance of effect.
Ketamine significantly increased the probability of verified abstinence, delayed relapse to drinking, and reduced heavy drinking days relative to midazolam. Infusions were well tolerated with no ketamine related discontinuations or serious adverse events. The sample was mostly middle aged, employed, and drank approximately five drinks per day at baseline.
A single subanesthetic ketamine infusion can produce measurable reductions in alcohol consumption when paired with motivational enhancement therapy. The combination enhances short term abstinence and treatment engagement. Results support ketamine as a promising adjunct to behavioral therapy in alcohol use disorder and justify larger confirmatory trials.
Ketamine increased abstinent days compared to placebo. Patients receiving ketamine had on average ten percent more abstinent days at six months. The best outcomes were observed in the ketamine plus therapy group, which achieved approximately sixteen percent more abstinent days than placebo plus education. Relapse rates did not differ significantly across groups. Ketamine was well tolerated with no major adverse events and no increase in depression or craving.
A three session ketamine protocol can augment psychological therapy to improve sobriety in alcohol use disorder. The synergy between ketamine and relapse prevention therapy appears central. Ketamine alone did not markedly reduce relapse, but ketamine combined with structured therapy meaningfully increased abstinent days. Findings support integrated models like HealMind where psychotherapy is paired with ketamine to optimize long term behavioral change.
Preliminary data indicate ketamine may improve mood, reduce obsessive–compulsive and disordered eating symptoms, and promote partial-to-complete remission in severe, enduring AN and BN cases. Effects appear stronger when combined with psychotherapy (KAP) or metabolic interventions (e.g., ketogenic diet). Symptom relief typically occurs within hours to days but may wane without maintenance dosing or adjunct therapy. Across reports, ketamine was well tolerated and associated with meaningful functional improvements.
Ketamine shows promise as an adjunctive or combination therapy for treatment-resistant EDs, particularly AN and BN, by targeting mood, compulsive cognition, and behavioral rigidity. Combining ketamine with psychotherapy may extend efficacy and support neuroplastic recovery. However, data remain preliminary; controlled trials are required to determine dosing, safety, and sustained outcomes.
Improvement in depressive symptoms in a patient with severe and enduring anorexia nervosa and comorbid major depressive disorder using psychotherapy-assisted IV ketamine: a case report
The patient demonstrated a 60% reduction in depressive symptoms (Beck Depression Inventory: 42 → 17), disappearance of suicidal ideation, and increased cognitive flexibility toward eating and self-perception. She tolerated ketamine well, with only mild dissociation, transient nausea, and one brief tachyarrhythmia. Weight increased by 4 kg during hospitalization, with ongoing psychological improvement and no lingering adverse effects reported at follow-up.
This is the first documented case of IV ketamine-assisted psychotherapy (KAP) for anorexia nervosa at such low BMI. Results suggest KAP may safely reduce depression, rigidity, and food-related fear in patients with severe, treatment-resistant anorexia and comorbid depression, even under medical fragility, when delivered with multidisciplinary oversight. Further trials are needed to confirm safety, dosing, and long-term efficacy.
A Case Series of Group Based Ketamine Assisted Psychotherapy for Patients in Residential Treatment for Eating Disorders With Comorbid Depression and Anxiety Disorders
Four of five participants showed clinically significant improvement in depression (PHQ 9 decrease greater than or equal to 5 points) and two of five had clinically significant improvement in anxiety (GAD 7 decrease greater than or equal to 4 points) by twenty four hours after the final session. Several participants moved from severe to minimal depression categories. Patients and staff reported subjective improvements in connection, flexibility around eating disorder rules, and ability to engage in treatment. Ketamine was well tolerated, with transient nausea, dizziness and blurred vision as the most common non dissociative adverse effects. No serious adverse events were reported.
Group based IM ketamine assisted psychotherapy can be feasibly integrated into intensive residential eating disorder treatment and appears to reduce comorbid depression and anxiety while softening rigidity around eating behaviors for some patients. Effects on core eating disorder symptoms are variable but subjectively meaningful for a subset of patients. This supports KAP as a potentially useful adjunct in higher levels of care for complex eating disorders, warranting larger controlled trials.
Across published cases, ketamine reduces depressive symptoms, suicidality, anxiety, obsessive eating disorder thoughts, and cognitive rigidity. Some patients show partial improvements in restrictive behaviors. Mechanistic rationale includes increases in neuroplasticity, neurogenesis, BDNF, and improved mood and cognitive flexibility.
Existing evidence supports ketamine as a potential adjunct in severe enduring AN by improving comorbid symptoms and flexibility that block recovery. Benefits are preliminary and require strict medical monitoring due to AN specific safety risks. Works best within a structured program that includes integration therapy.
Ketamine group: 48.2 % remained abstinent during the last 2 weeks vs 10.7 % in midazolam group. Ketamine recipients were 53 % less likely to relapse (HR = 0.47; 95 % CI 0.24–0.92) and reported 58 % lower craving scores throughout the study. Infusions were well-tolerated; no participants discontinued for adverse effects.
A single sub-anesthetic ketamine infusion combined with mindfulness-based behavioral modification significantly improved abstinence, craving, and relapse outcomes compared with active control in cocaine-dependent adults. Findings highlight ketamine’s potential as an adjunct to psychotherapy for stimulant use disorders; replication in larger, longer trials is warranted.
Multiple KPT sessions led to higher long-term abstinence. At 12 months, 50% of the patients who received three KPT sessions remained abstinent, compared to only 22% of those who had a single KPT session (with therapy alone thereafter) . This difference was statistically significant . The multiple KPT group also reported longer durations of relapse-free survival over the year (by survival analysis) . Both groups received identical psychosocial counseling apart from ketamine, suggesting the repeated ketamine-facilitated therapy provided added benefit. No lasting adverse effects were noted; some patients experienced vivid transpersonal or insightful experiences during KPT, considered therapeutically meaningful in this protocol .
In this addiction study, ketamine used as an adjunct to psychotherapy significantly improved heroin abstinence outcomes at 1 year . Notably, three sessions of KPT were far more effective than a single session – pointing to a dose-dependent therapeutic reinforcement of psychotherapy by ketamine’s psychological effects . These findings (along with earlier KPT work in alcoholism) highlight ketamine’s potential in enhancing behavioral treatments for substance use disorders. When combined with skilled therapy, ketamine-induced immersive experiences may strengthen patients’ commitment to sobriety and personal meaning, yielding better long-term recovery rates.
Participants who received ketamine showed greater reductions in cannabis use days compared to midazolam. Ketamine recipients also demonstrated larger improvements in craving and withdrawal scores. The infusion was well tolerated with no serious adverse events reported. The effect appeared to enhance engagement and responsiveness to behavioral treatment.
Ketamine may augment psychotherapy and improve early treatment outcomes in cannabis use disorder. This study provides initial evidence that ketamine can reduce use frequency, craving, and withdrawal when paired with structured behavioral therapy. Findings support further evaluation of ketamine-assisted therapy across non-opioid, non-stimulant substance use disorders.
Across SUD categories, ketamine consistently reduced cravings, improved abstinence rates, and lowered withdrawal severity. Cocaine studies showed reduced cue induced craving, increased abstinence, and reduced relapse risk. Opioid studies, including high dose ketamine assisted psychotherapy, demonstrated improved long term abstinence and reduced craving. Cannabis use disorder showed reductions in weekly use and increased confidence in abstaining. Studies combining ketamine with psychotherapy showed stronger and more durable effects.
This systematic review supports ketamine as a promising adjunct for substance use disorders. Ketamine offers rapid reduction in craving, enhances engagement in therapy, and improves abstinence outcomes across cocaine dependence, opioid use disorder, and cannabis use disorder. Effects are strongest when integrated with structured psychotherapy, aligning with HealMind’s model. Evidence remains preliminary but shows cross substance benefits that justify clinical adoption under an organized, medically supervised program.
Ketamine was well tolerated, with no serious adverse events. Most frequent side effects: elation/silliness (50 %), fatigue (40 %), increased aggression (40 %). Parent and clinician ratings both showed nominal improvement across multiple domains—social behavior, attention/hyperactivity, repetitive behaviors, speech and learning, daily living, and sensory sensitivity—one week post-infusion. Electrophysiological and eye-tracking measures appeared feasible as potential treatment-sensitive biomarkers.
Low-dose ketamine was safe and showed preliminary behavioral benefit in children with ADNP syndrome. Results are hypothesis-generating only due to small sample size and lack of placebo control. The study identifies feasible biomarkers (ASSR, eye-tracking) and behavioral endpoints for future controlled trials exploring ketamine’s neuroprotective and modulatory effects in developmental disorders.
Brief Report: Intranasal Ketamine in Adolescents and Young Adults with Autism Spectrum Disorder — Initial Results of a Randomized, Controlled, Crossover, Pilot Study
IN ketamine was well tolerated, producing only transient, mild side effects. However, no significant effect was observed on the primary measure of social withdrawal.
Intranasal ketamine was safe and tolerable in adolescents and young adults with ASD but did not significantly improve social withdrawal or core social deficits. Larger, longer-term studies are needed to determine potential benefit in other symptom domains or subgroups.
Results were mixed — intranasal/esketamine studies showed no statistically significant effect on social withdrawal, while intravenous ketamine in at least one study was associated with short-term alleviation of social withdrawal symptoms. Case reports also described improved social condition or reduced depressive symptoms in some individuals after ketamine. No serious adverse events were consistently reported.
Evidence is very limited and inconsistent. Ketamine may have potential to transiently improve social withdrawal/social functioning in some ASD or autism-like individuals — but current data are insufficient to support routine use. Larger, well-designed studies (different doses/routes, longer follow-up) are needed before drawing strong conclusions or clinical recommendations.
Infusions were well tolerated; ketamine produced more intense dissociation during infusion that resolved by ~40 minutes. No significant group differences on the primary outcome (suicidal ideation) or secondary outcomes of depression, anxiety, or BPD symptoms. A group×time effect favored ketamine for socio-occupational functioning at Day 14 (F=5.16, p=0.03).
In this first RCT of ketamine for BPD, antidepressant-dose ketamine was tolerable but did not significantly reduce suicidal ideation or core symptom scales versus midazolam; a signal on functioning suggests potential benefit warranting larger, adequately powered trials.
Repeated ketamine infusions produced significant reductions in depressive symptoms and borderline symptom severity. Patients with comorbid BPD showed marked improvement in both QIDS SR 16 and BSL 23 scores, along with reductions in suicidality and anxiety. Treatment was well tolerated with no serious adverse events reported.
Ketamine can be effective and safe in complex patients with both TRD and borderline personality disorder. Improvements in both depressive and borderline symptom domains suggest ketamine may reduce emotional reactivity, distress, and instability that commonly complicate BPD presentations. This supports the use of ketamine within structured psychiatric care models such as HealMind for patients with comorbid mood and personality pathology.
Esketamine was associated with reductions in depressive symptoms, emotional distress, and impulsive suicidal behavior among BPD patients. Several cases showed improved affect regulation and reduced emergency department presentations for acute crises. Effects were most notable for mood reactivity and suicidal urges rather than core personality pathology. Treatment was well tolerated with no major adverse events reported.
Esketamine may offer benefit for BPD patients with severe affective instability, suicidality, and treatment resistant depressive symptoms when used under structured psychiatric supervision. While not a treatment for personality structure itself, esketamine can reduce mood driven crises and improve safety and stabilization. This supports HealMind’s model of ketamine delivery for complex presentations where mood dysregulation drives clinical impairment.
Significant multivariate effect on anxiety+depression (F(1,14)=4.78; p=0.046; r=0.50). Anxiety decreased from T1→T2 in S-ketamine vs control (F(1,14)=10.14; p=0.007; r=0.65). Depression change not significant (F(1,14)=1.60; p=0.23; r=0.32). No durable analgesic effect detected beyond the infusion period. No randomization; small sample.
At analgesic dosing, a single S-ketamine infusion in palliative-care patients was associated with a rapid reduction in anxiety but no clear effect on depression. Results are preliminary (retrospective, non-randomized, small N); prospective randomized studies are needed before routine adoption for psychological distress in palliative care.
"Baseline (pre-infusion) WTHD rated 4 on MADRS suicide item.
Post-infusion: Complete disappearance of WTHD from Day 1–3 (MADRS suicide item = 0).
Reappearance by Day 5, with full recurrence by Day 6.
No adverse events reported.
No concurrent pain or clinical depression noted."
A single IV ketamine infusion rapidly and transiently reduced a terminally ill patient’s existential suffering and desire to hasten death. Suggests ketamine may exert acute anti-suicidal and anxiolytic effects in end-of-life existential distress, though duration was brief (~3 days). Controlled trials are required to confirm safety, dosing, and maintenance protocols.
The review identified several reports in which ketamine was associated with reductions in depressive symptoms and suicidal ideation among cancer/terminal patients. Intranasal ketamine in palliative-care cancer patients (recent trial) produced rapid antidepressant effects in many cases. Side effects such as dissociation, transient BP/HR changes, nausea, dizziness, headache, sedation were documented but generally described as mild or transient. However evidence base is small, heterogeneous (routes, dosing, populations), and long-term data are lacking.
Ketamine may offer a promising, rapid-acting option to reduce depression and suicidality in advanced cancer or terminally ill patients — especially when traditional antidepressants are too slow or impractical. Because evidence remains limited and heterogeneous, use should currently be considered experimental, under careful clinical oversight, with thorough monitoring and informed consent. More rigorous trials and long-term follow-up are needed before routine adoption.
The review found that many case reports described robust antidepressant effects (rapid onset, often within hours to days) following ketamine administration in palliative-care patients. However, larger studies (RCTs) showed conflicting results. While some perioperative or oncology-surgery settings reported temporary improvements in depression, other studies — especially non-surgical or pain-focused trials — did not find clear benefit. Overall efficacy in palliative care remains uncertain. Safety profile was relatively acceptable: across studies ketamine was "generally safe and potentially useful" with no consistent reports of serious, sustained adverse events.
Ketamine may be a promising, rapid-acting antidepressant option for patients with life-limiting illness or under palliative care, particularly when fast relief is required or when standard antidepressants are impractical. Given the mixed and limited evidence — especially outside perioperative settings — use should remain cautious, under close clinical supervision, and ideally as part of research or carefully monitored clinical protocols. More well-powered, long-term RCTs are needed before routine adoption in general palliative care.
