Since physician-assisted dying (PAD) has become a part of the clinical dialogue in the United States (US) and other Western countries, it has spawned controversy in the moral, ethical, and legal realm, with significant cross-country variation. The phenomenon of PAD includes 2 practices: Euthanasia and medical aid in dying (MAiD). Although euthanasia has been allowed in different parts of the world, in the US it is illegal. MAiD has been enacted into law in some jurisdictions. As the practice involves people at the end of life (EOL), often with cancer, and sometimes struggling with psychiatric symptoms; they gain added salience in the field of Consultation-Liaison (CL) Psychiatry in general and Psycho-Oncology in particular.

The current paper reviews a case where a patient did request for MAiD and successfully carried it through, this case became more salient, as the CL Psychiatry department was intimately linked at various stages of care for the patient.

In describing the case several other aspects of EOL care issues were touched upon, and the various debates as well as treatment modalities, for an individual requesting for medical aid in dying were described.

MAiD will possibly remain a sensitive and controversial topic of discussion across the spectrum of healthcare, and as responsible and compassionate advocates for the patients, clinicians need to engage more with the debate surrounding it and facilitate informed decision making. We believe that the present case will throw light on to this enigmatic practice and help in furthering the dialogue surrounding MAiD.

Improving functioning in adults with major depressive disorder (MDD) and bipolar disorder (BD) is a priority therapeutic objective.

This retrospective post hoc secondary analysis evaluated 108 patients with MDD or BD receiving the antidepressants vortioxetine, ketamine, or infliximab. The analysis aimed to determine if changes in objective or subjective cognitive function mediated the relationship between depression symptom severity and workplace outcomes. Cognitive function was measured by the Perceived Deficits Questionnaire (PDQ-5), the Digit Symbol Substitution Test (DSST), and the Trail Making Test Part B (TMT-B). Depression symptom severity was measured by the Montgomery–Åsberg Depression Rating Scale (MADRS). Workplace function was measured by the Sheehan Disability Scale (SDS) work–school item.

When co-varying for BMI, age, and sex, the association between MADRS and SDS work scores was partially mediated by PDQ-5 total scores and DSST total scores, but not DSST error scores and TMT-B time.

This study was insufficiently powered to perform sub-group analyses to identify distinctions between MDD and BD populations as well as between antidepressant agents.

These findings suggest that cognitive impairment in adults with MDD and BD is a critical mediator of workplace function and reinforces its importance as a therapeutic target.

Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties.

To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD.

The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active (midazolam)-controlled trial. The study initially used fixed low dose ketamine (0.5 mg/kg, cohort 1), before protocol revision to flexible, response-guided dosing (0.5–0.9 mg/kg, cohort 2). This secondary analysis assessed anxiety using the Hamilton Anxiety (HAM-A) scale (primary measure) and ‘inner tension’ item 3 of the Montgomery–Åsberg Depression Rating Scale (MADRS), at baseline, 4 weeks (end treatment) and 4 weeks after treatment end. Analyses of change in anxiety between ketamine and midazolam groups included all participants who received at least one treatment (n = 174), with a mixed effects repeated measures model used to assess the primary anxiety measure. The trial was registered at www.anzctr.org.au (ACTRN12616001096448).

In cohort 1 (n = 68) the reduction in HAM-A score was not statistically significant: −1.4 (95% CI [−8.6, 3.2], P = 0.37), whereas a significant reduction was seen for cohort 2 (n = 106) of −4.0 (95% CI [−10.6, −1.9], P = 0.0058), favouring ketamine over midazolam. These effects were mediated by total MADRS and were not maintained at 4 weeks after treatment end. MADRS item 3 was also significantly reduced in cohort 2 (P = 0.026) but not cohort 1 (P = 0.96).

Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses.

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.