Inadequate response to first- and second-line pharmacological treatments for psychiatric disorders is commonly observed. Ketamine has demonstrated efficacy in treating adults with treatment-resistant depression (TRD), with additional off-label benefits reported for various psychiatric disorders. Herein, we performed a systematic review and meta-analysis to examine the therapeutic applications of ketamine across multiple mental disorders, excluding mood disorders.

We conducted a multidatabase literature search of randomized controlled trials and open-label trials investigating the therapeutic use of ketamine in treating mental disorders. Studies utilizing the same psychological assessments for a given disorder were pooled using the generic inverse variance method to generate a pooled estimated mean difference.

The search in OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), EBSCO CINAHL Plus, Scopus, and Web of Science yielded 44 studies. Ketamine had a statistically significant effect on PTSD Checklist for DSM-5 (PCL-5) scores (pooled estimate = ‒28.07, 95% CI = [‒40.05, ‒16.11], p < 0.001), Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) scores (pooled estimate = ‒14.07, 95% CI = [‒26.24, ‒1.90], p = 0.023), and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores (pooled estimate = ‒8.08, 95% CI = [‒13.64, ‒2.52], p = 0.004) in individuals with PTSD, treatment-resistant PTSD (TR-PTSD), and obsessive compulsive disorder (OCD), respectively. For alcohol use disorders and at-risk drinking, there was disproportionate reporting of decreased urge to drink, increased rate of abstinence, and longer time to relapse following ketamine treatment.

Extant literature supports the potential use of ketamine for the treatment of PTSD, OCD, and alcohol use disorders with significant improvement of patient symptoms. However, the limited number of randomized controlled trials underscores the need to further investigate the short- and long-term benefits and risks of ketamine for the treatment of psychiatric disorders.

Ketamine has been widely used in refractory pain as an opioid adjuvant. Evidence suggests that ketamine can also have an essential role in easing depressive symptoms. Its rapid onset of action makes it a valuable choice in palliative care.

We present a case of a 70-year-old man with stage IV renal carcinoma and bone metastasis. The main symptoms included neuropathic pain, depression, and a persistent and severe desire for death.

We started continuous subcutaneous infusion with morphine 30 mg and ketamine 100 mg/day. The dose of ketamine was incremented to the maximum of 250 mg/day. During the 28-day treatment, we observed an overall improvement in neuropathic pain, depressive symptoms, and other end-of-life psychological aspects of distress. Only minor psychological side effects were identified, which were controlled by using midazolam in the continuous subcutaneous infusion.

Some studies have already demonstrated the benefits of ketamine use in alleviating depression, using parental infusion or oral formulas, which are administered in hospice care. Our report enhances the benefit of the subcutaneous route for palliative patients cared for at home.

This study aims to explore the outcome with iv ketamine treatment in a real-world clinical setting, primarily measured as posttreatment days hospitalised.

The psychiatric medical records of 46 patients having received iv ketamine on a psychiatric treatment indication between 2015 and 2018 were retrospectively examined. Analysis comparing the number and duration of hospital admissions before and after ketamine treatment as well as logistic regression analysis to investigate clinical predictors of effectiveness, were performed. To assess patients’ severity of depressed symptoms records were screened for MADRS-S scores.

No significant difference between pre- and posttreatment hospital days (p = 0.170), or number of hospitalisations (p = 0.740) were found. The response rate was 31% and remission rate 21%. None of the predictors showed statistical significance in the logistic model.

Iv ketamine treatment showed effectiveness in reducing depressive symptoms even with complex patients in a real-world clinical setting. However, this did not translate to a reduction in hospitalisation. Highlighting the multifaceted challenges posed when implementing iv ketamine treatment in clinical practice.

Amygdala subregion-based network dysfunction has been determined to be centrally implicated in major depressive disorder (MDD). Little is known about whether ketamine modulates amygdala subarea-related networks. We aimed to investigate the relationships between changes in the resting-state functional connectivity (RSFC) of amygdala subregions and ketamine treatment and to identify important neuroimaging predictors of treatment outcomes.

Thirty-nine MDD patients received six doses of ketamine (0.5 mg/kg). Depressive symptoms were assessed, and magnetic resonance imaging (MRI) scans were performed before and after treatment. Forty-five healthy controls underwent one MRI scan. Seed-to-voxel RSFC analyses were performed on the amygdala subregions, including the centromedial amygdala (CMA), laterobasal amygdala (LBA), and superficial amygdala subregions.

Abnormal RSFC between the left LBA and the left precuneus in MDD patients is related to the therapeutic efficacy of ketamine. There were significant differences in changes in bilateral CMA RSFC with the left orbital part superior frontal gyrus and in changes in the left LBA with the right middle frontal gyrus between responders and nonresponders following ketamine treatment. Moreover, there was a difference in the RSFC of left LBA and the right superior temporal gyrus/middle temporal gyrus (STG/MTG) between responders and nonresponders at baseline, which could predict the antidepressant effect of ketamine on Day 13.

The mechanism by which ketamine improves depressive symptoms may be related to its regulation of RSFC in the amygdala subregion. The RSFC between the left LBA and right STG/MTG may predict the response to the antidepressant effect of ketamine.

An urgent need exists to identify neural correlates associated with differing levels of suicide risk and develop novel, rapid-acting therapeutics to modulate activity within these neural networks.

Electrophysiological correlates of suicide were evaluated using magnetoencephalography (MEG) in 75 adults with differing levels of suicide risk. During MEG scanning, participants completed a modified Life-Death Implicit Association Task. MEG data were source-localized in the gamma (30–58 Hz) frequency, a proxy measure of excitation-inhibition balance. Dynamic causal modeling was used to evaluate differences in connectivity estimates between risk groups. A proof-of-concept, open-label, pilot study of five high risk participants examined changes in gamma power after administration of ketamine (0.5 mg/kg), an NMDAR antagonist with rapid anti-suicide ideation effects.

Implicit self-associations with death were stronger in the highest suicide risk group relative to all other groups, which did not differ from each other. Higher gamma power for self-death compared to self-life associations was found in the orbitofrontal cortex for the highest risk group and the insula and posterior cingulate cortex for the lowest risk group. Connectivity estimates between these regions differentiated the highest risk group from the full sample. Implicit associations with death were not affected by ketamine, but enhanced gamma power was found for self-death associations in the left insula post-ketamine compared to baseline.

Differential implicit cognitive processing of life and death appears to be linked to suicide risk, highlighting the need for objective measures of suicidal states. Pharmacotherapies that modulate gamma activity, particularly in the insula, may help mitigate risk.

Clinicaltrials.gov identifier: NCT02543983, NCT00397111.

The evidence base for racemic ketamine treatment for treatment-resistant major depressive disorder (TRD) continues to expand, but there are major challenges translating this evidence base into routine clinical care.

To prepare guidelines for ketamine treatment of TRD that are suitable for routine use by publicly funded specialist mental health services.

We consulted with senior leadership, clinical pharmacy, psychiatrists, nursing, service users and Māori mental health workers on issues relating to ketamine treatment. We prepared treatment guidelines taking the evidence base for ketamine treatment and the consultation into account.

Ketamine treatment guidance is reported. This offers two treatment pathways, including a test of ketamine responsiveness with intramuscular ketamine and the dominant use of oral ketamine for a 3-month course to maximise the opportunity for the short-term benefits of ketamine to accumulate.

We have responded to the challenges of translating the evidence base for ketamine treatment into a form suitable for routine care.

Public and patient expectations of treatment influence health behaviours and decision-making.

We aimed to understand how the media has portrayed the therapeutic use of ketamine in psychiatry.

We systematically searched electronic databases for print and online news articles about ketamine for psychiatric disorders. The top ten UK, USA, Canadian and Australian newspapers by circulation and any trade and consumer magazines indexed in the databases were searched from 2015 to 2020. Article content was quantitatively coded with a framework encompassing treatment indication, descriptions of prior use, references to research, benefits and harms, treatment access and process, patient and professional testimony, tone and factual basis.

We found 119 articles, peaking in March 2019 when the United States Food and Drug Administration approved esketamine. Ketamine treatment was portrayed in an extremely positive light (n = 82, 68.9%), with significant contributions of positive testimony from key opinion leaders (e.g. clinicians). Positive research results and ketamine's rapid antidepressant effect (n = 87, 73.1%) were frequently emphasised, with little reference to longer-term safety and efficacy. Side-effects were frequently reported (n = 96, 80.7%), predominantly ketamine's acute psychotomimetic effects and the potential for addiction and misuse, and rarely cardiovascular and bladder effects. Not infrequently, key opinion leaders were quoted as being overly optimistic compared with the existing evidence base.

Information pertinent to patient help-seeking and treatment expectations is being communicated through the media and supported by key opinion leaders, although some quotes go well beyond the evidence base. Clinicians should be aware of this and may need to address their patients’ beliefs directly.

Ketamine is an effective short-term treatment for a range of psychiatric disorders. A key question is whether the addition of psychotherapy to ketamine treatment improves outcomes or delays relapse.

To identify all studies combining psychotherapy with ketamine for the treatment of psychiatric disorders to summarise their effects and make recommendations for future research.

The review protocol was prospectively registered with PROSPERO (registration number CRD42022318120). Potential studies were searched for in MEDLINE, Embase, PsycINFO, SCOPUS, the Cochrane library and Google Scholar. Eligible studies combined ketamine and psychotherapy for the treatment of psychiatric disorders and did not use case reports or qualitative designs. Key findings relating to psychotherapy type, diagnosis, ketamine protocol, sequencing of psychotherapy and study design are reported. Risk of bias was assessed using modified Joanna Briggs critical appraisal tools.

Nineteen studies evaluating 1006 patients were included in the systematic review. A variety of supportive individual and group, manualised and non-manualised psychotherapies were used. The majority of studies evaluated substance use disorders, post-traumatic stress disorder and treatment-resistant depression. Ketamine protocols and sequencing of ketamine/psychotherapy treatment varied substantially between studies. Outcomes were largely positive for the addition of psychotherapy to ketamine treatment.

The combination of psychotherapy and ketamine offers promise for the treatment of psychiatric disorders, but study heterogeneity prevents definitive recommendations for their integration. Larger randomised controlled trials using manualised psychotherapies and standardised ketamine protocols are recommended to clarify the extent to which the addition of psychotherapy to ketamine improves outcomes over ketamine treatment alone.

Although ketamine can rapidly decrease suicidal ideation (SI), its neurobiological mechanism of action remains unclear. Several areas of the cingulate cortex have been implicated in SI; therefore, we aimed to explore the neural correlates of the anti-suicidal effect of ketamine with cingulate cortex functional connectivity (FC) in depression.

Forty patients with unipolar or bipolar depression with SI underwent six infusions of ketamine over 2 weeks. Clinical symptoms and resting-state functional magnetic resonance imaging data were obtained at baseline and on day 13. Remitters were defined as those with complete remission of SI on day 13. Four pairs of cingulate cortex subregions were selected: the subgenual anterior cingulate cortex (sgACC), pregenual anterior cingulate cortex (pgACC), anterior mid-cingulate cortex (aMCC), and posterior mid-cingulate cortex (pMCC), and whole-brain FC for each seed region was calculated.

Compared with non-remitters, remitters exhibited increased FC of the right pgACC–left middle occipital gyrus (MOG) and right aMCC–bilateral postcentral gyrus at baseline. A high area under the curve (0.91) indicated good accuracy of the combination of the above between-group differential FCs as a predictor of anti-suicidal effect. Moreover, the change of SI after ketamine infusion was positively correlated with altered right pgACC–left MOG FC in remitters (r = 0.66, p = 0.001).

Our findings suggest that the FC of some cingulate cortex subregions can predict the anti-suicidal effect of ketamine and that the anti-suicidal mechanism of action of ketamine may involve alteration of FC between the right pgACC and left MOG.

The suffering experienced by some patients at the end of their lives can lead to a wish to hasten death (WTHD). It is sometimes an existential suffering, refractory to palliative care even if well conducted, which leads to this desire. Since several years, in psychiatry, the rapid anti-suicidal effects of a single injection of ketamine have been proven. WTHD and suicidal ideation have similarities. The injection of a single dose of ketamine could have an efficiency on the desire to hasten death.

We report the case of a woman with advanced breast cancer expressing a WTHD, treated by ketamine.

A 78-year-old woman expressed a WTHD (request for euthanasia) because of existential suffering following a loss of autonomy related to cancer. The suicide item was 4 on the Montgomery–Åsberg Depression Rating Scale (MADRS). She had no associated pain or depression. A single dose of intravenous ketamine 1 mg/kg over 40 min plus 1 mg of midazolam was injected. She had no adverse effects. From D1 post-injection to D3, the WTHD disappeared completely with a MADRS suicide item at 0. At D5, the WTHD started to reappear, and at D6, the previous speech was completely back.

These results suggest an effect of ketamine on WTHD. This opens up the possibility of treating existential suffering at the end of life. The optimal dosage of this treatment would have to be determined as well as a maintenance of efficacy scheme.

We aimed to identify factors independently associated with the need for inotropic support for low cardiac output or haemodynamic instability after pulmonary artery banding surgery for CHD.

We performed a retrospective chart review of all neonates and infants who underwent pulmonary banding between January 2016 and June 2019 at our institution. Bivariate and multivariable analyses were performed to identify factors independently associated with the use of post-operative inotropic support, defined as the initiation of inotropic infusion(s) for depressed myocardial function, hypotension, or compromised perfusion within 24 hours of pulmonary artery banding.

We reviewed 61 patients. Median age at surgery was 10 days (25%,75%:7,30). Cardiac anatomy was biventricular in 38 patients (62%), hypoplastic right ventricle in 14 patients (23%), and hypoplastic left ventricle in 9 patients (15%). Inotropic support was implemented in 30 patients (49%). Baseline characteristics of patients who received inotropic support, including ventricular anatomy and pre-operative ventricular function, were not statistically different from the rest of the cohort. Patients who received inotropic support, however, were exposed to larger cumulative doses of ketamine intraoperatively – median 4.0 mg/kg (25%,75%:2.8,5.9) versus 1.8 mg/kg (25%,75%:0.9,4.5), p < 0.001. In a multivariable model, cumulative ketamine dose greater than 2.5mg/kg was associated with post-operative inotropic support (odds ratio 5.5; 95% confidence interval: 1.7,17.8), independent of total surgery time.

Inotropic support was administered in approximately half of patients who underwent pulmonary artery banding and more commonly occurred in patients who received higher cumulative doses of ketamine intraoperatively, independent of the duration of surgery.

Treatment-resistant depression (TRD) presents a significant challenge in clinical practice. Besides antidepressant medications, neurostimulation methods (ECT, rTMS) and ketamine are viable treatment options.

To objectively evaluate the real effectiveness of treatments within interventional psychiatry in the maintenance treatment.

The extensive literature review of the efficacy of ECT, rTMS, and ketamine treatment in the maintenance treatment of TRD and the author’s clinical and research experience will be included in this presentation.

Neurostimulation, particularly ECT and ketamine treatment are usually effective treatments for patients with TRD. However, both of these treatment modalities do not have sustained benefits and after discontinuing treatment the majority of patients relapse. Ketamine has rapid therapeutic effects in depression, but these effects are short-lived. Continuation treatment with ketamine in the form of intranasal ketamine is an option, but concerns over cognitive impairment, interstitial cystitis and significant addictive potential related to longer use of ketamine are significant limiting factors. rTMS is a first-line treatment option for patients with TRD according to the Canadian CANMAT guidelines. However, the majority of patients may relapse following the course of rTMS. The maintenance rTMS over an extended period of time is usually not feasible as it may significantly affect the waiting time for newly referred patients. Portable TMS machine for home use would be an alternative option for a limited number of patients.

Maintenance treatment has been always a big clinical challenge in mood disorder psychiatry. Only well-established multimodal treatment is a realistic option for getting long-term benefits in treating patients with TRD.

No significant relationships.

Ketamine is routinely used for anesthetic induction because of its dissociative properties. Recently, it has attracted attention as a rapid-acting anti-depressant, but other studies have also reported its efficacy in the management of diverse psychiatric pathologies previously resistant to treatment.

We aimed to review the efficacity of ketamine in the management of mental disorders.

We conducted a litterature review through pubmed database, using the following keywords: “mental illness”; “ketamine”;”depression”;”anxiety disorders”;”eating disorders”;”substance use disorders”.

Ketamine has primarily been used in psychiatry for people with treatment-resistant depression. Its efficacy in reducing suicidal ideation has been previously reported. Furthermore, Ketamine may be a potential therapeutic option for patients with treatment-resistant anxiety disorders, especially obsessive compulsive disorder (OCD) and post-traumatic stress disorder. It has recently been reported a rapid onset anxiolytic activity in treatment-resistant social anxiety disorder and generalized anxiety disorder. Besides, Ketamine use in subjects suffering from eating disorders was associated with a complete remission of severe anorexia nervosa with a return to normal weight and a decrease in body preoccupations. The use of ketamine alone or in combination with other therapies was effective in reducing alcohol and substance use, prolonging abstinence, reducing craving and enhancing motivation. ketamine in combination with motivational enhancement therapy may be an effective pharmacotherapy for initiating and sustaining abstinence from alcoholics

ketamine shows great promise as a treatment for several mental disorders. However, its possible side effects and short duration of efficacy limit its use. Further studies exploring longer-term outcomes and administration protocols are needed.

No significant relationships.

Identifying a feasible model of chronic schizophrenia would be valuable for studying the possible underlying mechanism and to investigate emerging treatments. Our hypothesis starts from the observation that combining ketamine with isolation could result in long-lasting neuro-psychological deficits and schizophrenia-like features; thus, it could probably be used as the first model of chronic schizophrenia that emphasizes the characteristic of having a multifactorial etiology

creation of a complex animal model capable of exhibiting the multifactorial origin and manifestation of schizophrenia.

we investigated the effects of ketamine administration combined with isolation in inducing schizophrenia-like symptoms in male albino rats and the brain reactive oxygen species levels.

Our results showed that the number of lines crossings in the open field test, the number of open arm entries in the elevated plus maze, and the spontaneous alternations percentage in the Y-maze were significantly lower in the ketamine + isolation group compared to both the control and ketamine + social housing group (p < 0.05). Furthermore, the ketamine + isolation intervention significantly increased the MDA levels and decreased the GPx levels both in the hippocampus and the cortex of the rats. In addition, our premise of creating a model capable of exhibiting both positive and negative symptoms of schizophrenia was also based on adding the aripiprazole treatment to a group of rats

combining ketamine with isolation could result in long-lasting neuro-psychological deficits and schizophrenia-like features

No significant relationships.

Major depressive disorder (MDD) is a highly prevalent clinical condition with a leading cause of disability worldwide. The currently available therapeutic agents have important limitations regarding side effects, partial or non-responsiveness. Patients are considered to have treatment-resistant depression (TRD) if there is no effect or minimal effectiveness after receiving adequate dose-duration use of antidepressants from two different categories. For this patients, electroconvulsive therapy (ECT) can be a treatment option and new therapies appear to tackle TRD like ketamine, a dissociative anesthetic and analgesic.

The authors elaborate a narrative literature review to understand if ketamine might enhance the antidepressant efficacy of ECT.

PubMed database searched using the terms “Electroconvulsive therapy”, “ketamine” and “treatment-resistant depression”.

ECT is currently recommended as an end-line therapy for TRD. Memory impairment after ECT could be a consequence of indiscriminate activation or saturation of glutamate receptors during the treatment, disrupting hippocampal plasticity involved in memory. Ketamine inhibits N-methyl-d-aspartate (NMDA) receptors, while stimulating glutamate release and was proposed as an ECT adjuvant, might reduce cognitive adverse effects, time until response/ remission and inclusively improve response rates to ECT.

However, response and remission rates of ketamine in ECT showed no significant difference from the comparator groups and was associated with higher rates of psychiatric and cardiovascular adverse events.

The results did not support the use the combination of ketamine and propofol as anesthetic agents for ECT in patients with MDD. However, further studies are needed to investigate the beneficial clinical and cognitive effects of ketamine alone in ECT settings.

No significant relationships.