Music as an Intervention to Improve the Hemodynamic Response of Ketamine in Depression: A Randomized Clinical Trial.

This randomized clinical trial explores whether music improves the hemodynamic response of ketamine among patients with treatment-resistant depression in Canada.

The Montreal model: an integrative biomedical-psychedelic approach to ketamine for severe treatment-resistant depression.

Background: Subanesthetic ketamine has accumulated meta-analytic evidence for rapid antidepressant effects in treatment-resistant depression (TRD), resulting in both excitement and debate. Many unanswered questions surround ketamine's mechanisms of action and its integration into real-world psychiatric care, resulting in diverse utilizations that variously resemble electroconvulsive therapy, conventional antidepressants, or serotonergic psychedelics. There is thus an unmet need for clinical approaches to ketamine that are tailored to its unique therapeutic properties. Methods: This article presents the Montreal model, a comprehensive biopsychosocial approach to ketamine for severe TRD refined over 6 years in public healthcare settings. To contextualize its development, we review the evidence for ketamine as a biomedical and as a psychedelic treatment of depression, emphasizing each perspectives' strengths, weaknesses, and distinct methods of utilization. We then describe the key clinical experiences and research findings that shaped the model's various components, which are presented in detail. Results: The Montreal model, as implemented in a recent randomized clinical trial, aims to synergistically pair ketamine infusions with conventional and psychedelic biopsychosocial care. Ketamine is broadly conceptualized as a brief intervention that can produce windows of opportunity for enhanced psychiatric care, as well as powerful occasions for psychological growth. The model combines structured psychiatric care and concomitant psychotherapy with six ketamine infusions, administered with psychedelic-inspired nonpharmacological adjuncts including rolling preparative and integrative psychological support. Discussion: Our integrative model aims to bridge the biomedical-psychedelic divide to offer a feasible, flexible, and standardized approach to ketamine for TRD. Our learnings from developing and implementing this psychedelic-inspired model for severe, real-world patients in two academic hospitals may offer valuable insights for the ongoing roll-out of a range of psychedelic therapies. Further research is needed to assess the Montreal model's effectiveness and hypothesized psychological mechanisms.

Intravenous ketamine for benzodiazepine deprescription and withdrawal management in treatment-resistant depression: a preliminary report.

We present the first evidence that sub-anesthetic ketamine infusions for treatment resistant depression (TRD) may facilitate deprescription of long-term benzodiazepine/z-drugs (BZDRs). Long-term BZDR prescriptions are potentially harmful yet common, partly because of challenging withdrawal symptoms. Few pharmacological interventions have evidence for facilitating BZDR discontinuation, and none in patients actively suffering from TRD. In this ambi-directional cohort study, discontinuation of long-term (>6 month) BZDRs was attempted in 22 patients with severe unipolar or bipolar TRD receiving a course of six subanesthetic ketamine infusions over four weeks. We investigated the rates of successful BZDRs deprescription, trajectories of acute psychological withdrawal symptoms, and subsequent BZDRs abstinence during a mean follow-up of 1 year (primary outcome). Clinically significant deteriorations in depression, anxiety, sleep, and/or suicidality during the acute BZDR discontinuation phase were measured by repeated standardized scales and analyzed by latent growth curve models and percent correct classification analysis. Of the 22 eligible patients, all enrolled in this study and 91% (20/22) successfully discontinued all BZDRs by the end of the 4-week intervention, confirmed by urinary analyses. Less than 25% of discontinuers experienced any significant worsening of anxiety, depression, sleep difficulties, or suicidality during treatment. During follow-up (mean [range] duration, 12 [3-24] months), 64% (14/22) of patients remained abstinent from any BZDRs. These preliminary results suggest that ketamine infusions for TRD may facilitate the deprescription of BZDRs, even in patients with active depressive symptoms and significant comorbidity. Further investigation is warranted into this potential novel application of ketamine.

Imprinting: expanding the extra-pharmacological model of psychedelic drug action to incorporate delayed influences of sets and settings.

Background: Psychedelic drug experiences are shaped by current-moment contextual factors, commonly categorized as internal (set) and external (setting). Potential influences of past environments, however, have received little attention. Aims: To investigate how previous environmental stimuli shaped the experiences of patients receiving ketamine for treatment-resistant depression (TRD), and develop the concept of "imprinting" to account for such time-lagged effects across diverse hallucinogenic drugs. Methods: Recordings of treatment sessions and phenomenological interviews from 26 participants of a clinical trial investigating serial intravenous ketamine infusions for TRD, conducted from January 2021 to August 2022, were retrospectively reviewed. A broad literature search was undertaken to identify potentially underrecognized examples of imprinting with both serotonergic and atypical psychedelics, as well as analogous cognitive processes and neural mechanisms. Results: In naturalistic single-subject experiments of a 28-year-old female and a 34-year-old male, subjective ketamine experiences were significantly altered by varying exposures to particular forms of digital media in the days preceding treatments. Higher levels of media exposure reduced the mystical/emotional qualities of subsequent psychedelic ketamine experiences, overpowering standard intention-setting practices and altering therapeutic outcomes. Qualitative data from 24 additional patients yielded eight further spontaneous reports of past environmental exposures manifesting as visual hallucinations during ketamine experiences. We identified similar examples of imprinting with diverse psychoactive drugs in past publications, including in the first-ever report of ketamine in human subjects, as well as analogous processes known to underly dreaming. Conclusions/interpretation: Past environmental exposures can significantly influence the phenomenology and therapeutic outcomes of psychedelic experiences, yet are underrecognized and understudied. To facilitate future research, we propose expanding the contextual model of psychedelic drug actions to incorporate imprinting, a novel concept that may aid clinicians, patients, and researchers to better understand psychedelic drug effects. Clinical trial registration: ClinicalTrials.gov, identifier NCT04701866.

[Family-focused practices among adult mental health professionals: A portrait of the situation in Quebec]. / Pratiques centrées sur la famille chez les professionnels en santé mentale adulte : un portrait de la situation au Québec.

Context Children living with a mentally ill parent are a vulnerable population, at higher risk of various psychosocial and mental health problems. They are overrepresented in youth mental health and child protection services. Adult mental health services that treat parents have the opportunity to identify and support children in these families. However, to date, there is still little knowledge on the extent of family-centered practices offered by professionals from different disciplinary fields in Quebec. Objective This study aims to document the family-focused practices of adult mental health professionals according to different disciplines (social work, nursing, psychoeducation, psychology, and special education). Method A total of 524 participants, from all regions of Quebec and working with adult mental health clients, responded to an online provincial survey. A subsample of 380 participants, members of a professional order or association, was retained for the present study. These come from five discipline: social work (n=127), nursing (n=99), psychoeducation (n=57), psychology (n=56) and special education (n=41) A MANCOVA analysis was performed to compare groups on the five subscales of the French version of the Family Focused Mental Health Practice (FFMHPQ-FR, Piché et al., in press), controlling for gender, years of experience working in mental health services and estimated proportion of clients with a parental role. Results Significant differences were found between social workers and psychologists in reported family-focused practices. Participants also reported very different levels of facilitating factors such as workplace support, openness to training, perceived knowledge and skills, and attitudes towards these practices. Discussion This study helps to increase knowledge on the use of family-focused practices by professionals from different disciplinary fields, in the context of adult mental health services in Quebec. The results allow to better support the adoption of such practices in mental health services.

The effects of walking in nature on negative and positive affect in adult psychiatric outpatients with major depressive disorder: A randomized-controlled study.

BACKGROUND: While walking in nature has been shown to improve affect in adults from the community to a greater extent than walking in urban settings, it is unknown whether such benefits apply to individuals suffering from depression. Using a parallel group design, this randomized controlled trial examined the effects of a single walk in nature versus urban settings on negative and positive affect in adult psychiatric outpatients diagnosed with major depressive disorder (MDD). METHOD: Participants recruited from a psychiatric outpatient clinic for adults with MDD were randomly assigned to a nature or urban walk condition. Thirty-seven adults (mean age = 49 years) completed a single 60-minute walk. Negative and positive affect were assessed using The Positive and Negative Affect Schedule or PANAS at 6 time points: before the walk, halfway during the walk, immediately post-walk, at home before bedtime, 24 h post-walk, and 48 h post-walk. RESULTS: Controlling for baseline levels of affect before the walk, individuals who walked in nature experienced overall lower levels of negative affect, F(1, 35.039) = 4.239, p = .047, compared to those who walked in urban settings. Positive affect did not differ across walk conditions. LIMITATIONS: The generalizability of results are limited by the small sample size and the presence of more female than male participants. CONCLUSIONS: Walking in nature might be a useful strategy to improve negative affect in adults with MDD. Future research should investigate different ways to integrate the beneficial effects of nature exposure into existing treatment plans for psychiatric outpatients with MDD.

Efficacy of ketamine intervention to decrease alcohol use, cravings, and withdrawal symptoms in adults with problematic alcohol use or alcohol use disorder: A systematic review and comprehensive analysis of mechanism of actions.

BACKGROUND: Alcohol use disorder is highly prevalent and has important economical, societal, psychiatric, and medical consequences. All currently approved therapeutic approaches targeting alcohol dependence have relatively modest effects and high relapse rates. Recent evidence suggests that ketamine may be an effective intervention to treat alcohol use disorder and alcoholic withdrawal. This systematic review aimed to assess the current level of evidence for this intervention. METHODS: This systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered on the international database of systematic reviews PROSPERO. Medline(Ovid), CINAHL Complete(EBSCOhost), PsycINFO(Ovid), EBM Reviews(Ovid), EMBASE(Ovid), and Google Scholar were searched for studies using ketamine to treat harmful alcohol use, craving, or withdrawal states in humans. Studies of any methodology that evaluated ketamine in isolation or combination with other interventions were included. The risk of bias was assessed using specific Cochrane critical appraisal tools. RESULTS: Of 1922 abstracts identified, 8 full-text articles were eligible for inclusion, yielding a total sample size of 634 participants. Five studies investigated the impact of ketamine on alcohol use and/or cravings and/or withdrawal in outpatient settings. Three studies looked at the effect of adding ketamine to conventional treatment of withdrawal symptoms in participants admitted to intensive care unit for severe alcohol withdrawal. Results on primary outcomes were mixed within and across trials. CONCLUSIONS: Despite promising results, the current evidence does not permit definitive conclusions about the efficacy of ketamine in alcohol use disorders or withdrawal. Future studies are warranted.

Mindfulness-based cognitive therapy vs. a health enhancement program for the treatment of late-life depression: Study protocol for a multi-site randomized controlled trial.

Background: Late-life depression (LLD) affects up to 18% of older adults and has been linked to elevated dementia risk. Mindfulness-based cognitive therapy (MBCT) holds promise for treating symptoms of depression and ameliorating cognitive deficits in older adults. While preliminary findings are promising, a definitive RCT investigating its effects on late life depression and cognition have not yet been conducted. We present a protocol describing a multi-site blinded randomized controlled trial, comparing the effects of MBCT and of an active control, a Health Enhancement Program (HEP), on depressive symptoms, executive functioning, and brain biomarkers of LLD, among several other exploratory outcomes. Methods: Two-hundred and thirteen (n = 213) patients with LLD will be recruited at various centers in Montreal, QC, Canada. Participants will undergo stratified randomization to either MBCT or HEP intervention groups. We will assess changes in (1) depression severity using the Hamilton Depression Rating Scale (HAM-D17), (2) processing speed and executive functioning, (3) brain biomarkers of LLD (hippocampal volume, default network resting-state functional connectivity and executive network resting-state functional connectivity), and (4) other exploratory physiological and mood-based measures, at baseline (0 weeks), post intervention (8 weeks), and 26 weeks after baseline. Discussion: The proposed study will assess the clinical potential of MBCT to improve symptoms of depression, as well as examine its impact on cognitive impairments and neurobiological markers, and thus inform its use as a promising adjunct in the treatment of LLD. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT05366088.

Clinical Dimensions Associated With Psychological Pain in Suicidal Patients: One-Year Follow-up Study.

Objective: Psychological pain is a transdiagnostic factor in mental health and a key clinical dimension to understand suicide in patients with mood disorders. However, less is known about the clinical characteristics that predict high psychological pain. The aim of this study was to fill this gap in a sample of patients with mood disorders.Methods: Inpatients admitted for a major depressive episode, according to DSM-IV criteria, from 2010 to 2017 were divided into 3 groups: 178 recent suicide attempters (within the last 7 days), 101 past suicide attempters (lifetime history of suicide attempt), and 93 nonattempters (no lifetime history of suicidal act). At inclusion, current psychopathology, medication, personality traits (impulsivity, anxiety, hopelessness), and childhood trauma were assessed. At inclusion and at 1-year follow-up, depressive symptomatology and current and maximal (within the 15 last days) psychological and physical pain were assessed.Results: At baseline, maximal psychological pain was higher in recent than in past suicide attempters (odds ratio [OR] = 1.18 [1.04-1.35]) and nonattempters (OR = 1.32 [1.16-1.50]). In the multivariate model, depression severity (OR = 1.11 [1.08-1.16]) and worst physical pain (OR = 2.53 [1.28-5.02]) predicted high psychological pain, whereas bipolar disorder (OR = 0.54 [0.29-0.98]) predicted low psychological pain. During the follow-up, the change in maximal psychological pain was predicted by changes in depressive symptomatology (ß = 0.46, P < .001) and maximal physical pain (ß = 0.42, P < .003). Finally, among depressive symptoms, guilt, lack of initiative, and loss of appetite better explained maximal psychological pain, both at inclusion and at 1 year (all P < .050).Conclusions: Psychological pain is associated with a recent suicidal act and depressive severity. Due to the strong link between psychological pain and physical pain, future studies should investigate whether psychotropic drugs with analgesic effects protect from psychological pain and therefore from suicide.

Saccadic Eye Movements in Elderly Depressed Patients With Suicidal Behaviors: An Exploratory Eye-Tracking Study.

Suicidal behaviors (SBs) are often associated with impaired performance on neuropsychological executive functioning (EF) measures that encourage the development of more specific and reliable tools. Recent evidence could suggest that saccadic movement using eye tracking can provide reliable information on EF in depressive elderly. The aim of this study was to describe oculomotor performances in elderly depressed patients with SB. To achieve this aim, we compared saccadic eye movement (SEM) performances in elderly depressed patients (N = 24) with SB and with no SB in prosaccade (PS) and antisaccade (AS) tasks under the gap, step, and overlap conditions. All participants also underwent a complete neuropsychological battery. Performances were impaired in patients with SB who exhibited less corrected AS errors and longer time to correct them than patients with no SB. Moreover, both groups had a similar performance for PS latencies and correct AS. These preliminary results suggested higher cognitive inflexibility in suicidal patients compared to non-suicidal. This inflexibility may explain the difficulty of the depressed elderly in generating solutions to the resurgence of suicidal ideation (SI) to respond adequately to stressful environments. The assessment of eye movement parameters in depressed elderly patients may be a first step in identifying high-risk patients for suicide.

Low MoCA performances correlate with suicidal ideation in late-life depression.

Late-life depression remains an underdiagnosed clinical entity, mainly because the presence of cognitive impairment in the elderly leads clinicians to suspect dementia rather than depression. Our objective was to analyze the cognitive abilities of elderly depressed patients using the Montreal Cognitive Assessment (MoCA) in relation to the presence or absence of suicidal ideation. The MoCA, Beck Scale of Suicidal Ideation, Hamilton Anxiety Scale, and Hamilton Depression Scale were administered to 72 patients with a recent history of late life depression: 43 with suicidal ideation and 29 non-suicidal controls. The results show that suicidal patients demonstrated significantly worse performance on the MoCA total score and the delayed recall subtest in comparison to non-suicidal controls. In addition, after adjusting for age and depression, poorer performance on the MoCA total score correlated to the presence of suicidal ideation. We found that the MoCA total score is able to predict the presence of suicidal ideation in depressed elderly patients in a fair-to-good manner. As late-life depression is already established as a potential prodrome of dementia, longitudinal follow-up may determine whether depressed individuals with suicidal ideation are at higher risk of converting to dementia.

Adjunctive music improves the tolerability of intravenous ketamine for bipolar depression.

Intravenous ketamine is an effective treatment of bipolar depression. One of its most important side-effects is a transient altered state of consciousness commonly referred to as dissociation. These states can be anxiety-provoking, distressing and even treatment-limiting, warranting research into mitigation strategies. In this article, we present two cases that demonstrate the potential of adjunctive music to diminish the distress associated with ketamine-induced dissociation - though not necessarily its degree - in bipolar 1 disorder. Both patients suffering from severe depression underwent their first ketamine infusion without music and opted for music with subsequent infusions. They reported that music significantly improved the tolerance of their dissociative symptoms, thereby reducing distress and facilitating subsequent treatments. Both patients achieved remission from their highly treatment-resistant depressive episodes following six ketamine infusions. This is the first report of music's benefits on ketamine for bipolar 1 depression, though there is precedence in the scientific literature on 'psychedelics' where the use of music in combination with medication-induced altered states has been studied. The principles regarding music selection that have resulted from this paradigm may be applicable to the use of ketamine in unipolar and bipolar depression. The optimal use of music with ketamine warrants further research.

Functional network alterations differently associated with suicidal ideas and acts in depressed patients: an indirect support to the transition model.

The transition from suicidal ideas to a suicide act is an important topic of research for the identification of those patients at risk of acting out. We investigated here whether specific brain activity and connectivity measures at rest may be differently associated with suicidal thoughts and behaviors. A large sample of acutely depressed patients with major depressive disorder was recruited in three different centers (Montreal/Canada, Stanford/USA, and Jena/Germany), covering four different phenotypes: patients with a past history of suicide attempt (n = 53), patients with current suicidal ideas but no past history of suicide attempt (n = 40), patients without current suicidal ideation nor past suicide attempts (n = 42), and healthy comparison subjects (n = 107). 3-T resting-state functional magnetic resonance imaging (fMRI) measures of the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) were obtained and examined in a whole-brain data-driven analysis. Past suicide attempt was associated with a double cortico-subcortical dissociation in ALFF values. Decreased ALFF and DC values mainly in a frontoparietal network and increased ALFF values in some subcortical regions (hippocampus and thalamus) distinguished suicide attempters from suicide ideators, patient controls, and healthy controls. No clear neural differences were identified in relation to suicidal ideas. Suicide attempters appear to be a distinct subgroup of patients with widespread brain alterations in functional activity and connectivity that could represent factors of vulnerability. Our results also indirectly support at the neurobiological level the relevance of the transition model described at the psychological and clinical levels. The brain bases of suicidal ideas occurrence in depressed individuals needs further investigations.

Childhood cognitive skill trajectories and suicide by mid-adulthood: an investigation of the 1958 British Birth Cohort.

BACKGROUND: Poor cognitive abilities and low intellectual quotient (IQ) are associated with an increased risk of suicide attempts and suicide mortality. However, knowledge of how this association develops across the life-course is limited. Our study aims to establish whether individuals who died by suicide by mid-adulthood are distinguishable by their child-to-adolescence cognitive trajectories. METHODS: Participants were from the 1958 British Birth Cohort and were assessed for academic performance at ages 7, 11, and 16 and intelligence at 11 years. Suicides occurring by September 2012 were identified from linked national death certificates. We compared mean mathematics and reading abilities and rate of change across 7-16 years for individuals who died by suicide v. those still alive, with and without adjustment for potential early-life confounding factors. Analyses were based on 14 505 participants. RESULTS: Fifty-five participants (48 males) had died by suicide by age 54 years. While males who died by suicide did not differ from participants still alive in reading scores at age 7 [effect size (g) = -0.04, p = 0.759], their reading scores had a less steep improvement up to age 16 compared to other participants. Adjustments for early-life confounding factors explained these differences. A similar pattern was observed for mathematics scores. There was no difference between individuals who died by suicide v. participants still alive on intelligence at 11 years. CONCLUSIONS: While no differences in tests of academic performance and IQ were observed, individuals who died by suicide had a less steep improvement in reading abilities over time compared to same-age peers.

A systematic review of older adults' request for or attitude toward euthanasia or assisted-suicide.

OBJECTIVES: Prevalence rates of death by euthanasia (EUT) and physician-assisted suicide (PAS) have increased among older adults, and public debates on these practices are still taking place. In this context, it seemed important to conduct a systematic review of the predictors (demographic, physical health, psychological, social, quality of life, religious, or existential) associated with attitudes toward, wishes and requests for, as well as death by EUT/PAS among individuals aged 60 years and over. METHOD: The search for quantitative studies in PsycINFO and MEDLINE databases was conducted three times from February 2016 until April 2018. Articles of probable relevance (n = 327) were assessed for eligibility. Studies that only presented descriptive data (n = 306) were excluded. RESULTS: This review identified 21 studies with predictive analyses, but in only 4 did older adults face actual end-of-life decisions. Most studies (17) investigated attitudes toward EUT/PAS (9 through hypothetical scenarios). Younger age, lower religiosity, higher education, and higher socio-economic status were the most consistent predictors of endorsement of EUT/PAS. Findings were heterogeneous with regard to physical health, psychological, and social factors. Findings were difficult to compare across studies because of the variety of sample characteristics and outcomes measures. CONCLUSION: Future studies should adopt common and explicit definitions of EUT/PAS, as well as research designs (e.g. mixed longitudinal) that allow for better consideration of personal, social, and cultural factors, and their interplay, on EUT/PAS decisions.

The network structure of core depressive symptom-domains in major depressive disorder following antidepressant treatment: a randomized clinical trial.

BACKGROUND: Network analysis (NA) conceptualizes psychiatric disorders as complex dynamic systems of mutually interacting symptoms. Major depressive disorder (MDD) is a heterogeneous clinical condition, and very few studies to date have assessed putative changes in its psychopathological network structure in response to antidepressant (AD) treatment. METHODS: In this randomized trial with adult depressed outpatients (n = 151), we estimated Gaussian graphical models among nine core MDD symptom-domains before and after 8 weeks of treatment with either escitalopram or desvenlafaxine. Networks were examined with the measures of cross-sectional and longitudinal structure and connectivity, centrality and predictability as well as stability and accuracy. RESULTS: At baseline, the most connected MDD symptom-domains were fatigue-cognitive disturbance, whereas at week 8 they were depressed mood-suicidality. Overall, the most central MDD symptom-domains at baseline and week 8 were, respectively, fatigue and depressed mood; in contrast, the most peripheral symptom-domain across both timepoints was appetite/weight disturbance. Furthermore, the psychopathological network at week 8 was significantly more interconnected than at baseline, and they were also structurally dissimilar. CONCLUSION: Our findings highlight the utility of focusing on the dynamic interaction between depressive symptoms to better understand how the treatment with ADs unfolds over time. In addition, depressed mood, fatigue, and cognitive/psychomotor disturbance seem to be central MDD symptoms that may be viable targets for novel, focused therapeutic interventions.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Réseau Canadien Pour Les Traitements De L'humeur Et De L'anxiété (Canmat) Concernant L'utilisation De La Kétamine Racémique Chez Les Adultes Souffrant De Trouble Dépressif Majeur.

OBJECTIVE: Patients with major depressive disorder often have limited response to first-line and second-line medications; hence, novel pharmacological treatments are needed for treatment-resistant depression (TRD). Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has demonstrated rapid antidepressant effects in patients with TRD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence for efficacy and safety of racemic ketamine and to provide recommendations for its use in clinical practice. METHODS: A systematic review was conducted with computerized search of electronic databases up to January 31, 2020 using combinations of search terms, inspection of bibliographies, and review of other ketamine guidelines and consensus statements. The level of evidence and lines of treatment were assigned according to CANMAT criteria. Recommendations were given in question-answer format. RESULTS: Intravenous (IV) racemic ketamine given as a single infusion has Level 1 evidence for efficacy in adults with TRD. The evidence for multiple infusions, given as an acute series or as ongoing maintenance treatment, is limited to Level 3. Adverse events associated with ketamine infusions include behavioral (e.g., dissociative symptoms) and physiological (e.g., hypertension) events. There is only Level 3 or 4 evidence for non-IV formulations of racemic ketamine. Consensus recommendations are given for clinical administration of IV ketamine including patient selection, facility and personnel issues, monitoring, and maintaining response. CONCLUSIONS: Single-dose IV racemic ketamine is a third-line recommendation for adults with TRD. The need for repeated and maintenance ketamine infusions should be carefully assessed on a case-by-case basis with consideration of potential risks and benefits. Because of limited evidence for efficacy and risk for misuse and diversion, the use of oral and other formulations of racemic ketamine should be limited to specialists with ketamine-prescribing expertise and affiliations with tertiary or specialized centers.

Psychological pain and depression: it's hard to speak when it hurts.

OBJECTIVE: To investigate the neuropsychological features of depressed patients reporting high level of psychological pain. METHODS: Sixty-two inpatients were included and divided into two groups according to the level of psychological pain assessed by a Likert scale. Cognitive abilities were assessed using the Trail Making Test, the Stroop test, and Verbal Fluency Test (semantic and phonemic verbal fluency). Univariate and multivariate analyses were performed to determine neuropsychological factors associated with a high level of psychological pain. RESULTS: The median level of psychological pain was 8/10. High level of psychological pain was associated with poor phonemic verbal fluency performance in men (p = 0.009), but not in women, even after controlling for confounding factors (age, level of depression, anxiety). Groups did not differ on the Trail Making Test, the Stroop test, or the semantic verbal fluency measure. CONCLUSION: Psychological pain is a specific clinical entity that should be considered to be more significant than just a symptom of depression. High level of psychological pain appears to be associated with a deficit of phonemic verbal fluency in depressed men. This finding could help to target psychotherapeutic treatments and improve screening.Key pointsPatients with high psychological pain do not differ on the Trail Making Test, the Stroop Test or the Sematic Verbal Fluency Measure to patients with low psychological painHigh psychological pain is associated with a deficit in phonemic verbal fluency in depressed menFuture research should aim to clarify gender differences in psychological pain in participants with and without major depressive disorder, as well as explore the complex relationship between cognition and the different forms of pain (psychological, physical and psychosomatic).

A systematic review and meta-analysis of the efficacy of intravenous ketamine infusion for treatment resistant depression: January 2009 - January 2019.

BACKGROUND: Sub-anaesthetic administration of ketamine is an emerging practice in patients presenting treatment resistant depression (TRD), however several outstanding questions have yet to be answered. OBJECTIVE: To evaluate the effect of intravenous ketamine infusion for patients presenting TRD on depression scores, clinical remission and response rates, and to assess its efficacy over both time and frequency. METHODS: Five databases were searched up to January 4th 2019 to include primary studies evaluating the use of sub-anaesthetic dose of ketamine in adults presenting TRD. Two reviewers independently performed the study selection, quality assessment and data extraction. Results were summarised in a narrative synthesis. A meta-analysis using a random effects model was performed when possible to examine changes in standardized mean differences and odds ratios of outcome measures at 4 hours, 24 hours, or 7 days post-infusion. RESULTS: Twenty-eight studies in 35 publications were included. A strong ketamine effect was observed within 4 hours following a single infusion, and peaked at 24 hours. Ketamine's effectiveness was still present, yet somewhat diminished, 7 days post-infusion. Multiple infusions resulted in an enhanced and prolonged ketamine effect. LIMITS: Due to insufficient data, long-term safety and efficacy of ketamine utilisation in patients presenting TRD are yet to be investigated. CONCLUSIONS: Results provide support for the use of ketamine in the rapid management of depressive symptoms. While ketamine appears promising in the short-term treatment of TRD, more clinical and experimental data is needed with regards to the efficacy, tolerance and security of long-term administration of ketamine.

Childhood-maltreatment subtypes in bipolar patients with suicidal behavior: systematic review and meta-analysis

Objective: Patients with bipolar disorders have a high risk of suicidal behavior. Childhood maltreatment is a well-established risk factor for suicidal behavior. The objective of this study was to examine the association between childhood-maltreatment subtypes and vulnerability to suicide attempts in bipolar disorder using the Childhood Trauma Questionnaire (CTQ). Methods: A literature review was performed using the MEDLINE, Embase, and PsycINFO databases. Thirteen studies met the selection criteria. In the meta-analysis, the Childhood Trauma Questionnaire (CTQ) was used to assess a wide range of childhood maltreatment subtypes, which were analyzed by using a random-effects model to account for the likely variations of true effect sizes between the included studies. Results: In the systematic review, 13 studies met the selection criteria. The CTQ was selected for the meta-analysis to increase the homogeneity of assessment and to encompass a wide range of childhood-maltreatment subtypes. The data were analyzed using a random-effects model. Compared to bipolar non-attempters, bipolar suicide attempters had experienced childhood maltreatment with a significantly higher frequency and had higher total CTQ scores (Hedges' g = -0.38, 95%CI -0.52 to -0.24, z = -5.27, p < 0.001) and CTQ sub-scores (sexual abuse: g = -0.39, 95%CI -0.52 to -0.26, z = -5.97; physical abuse: g = -0.26, 95%CI -0.39 to -0.13, z = -4.00; emotional abuse: g = -0.39, 95%CI -0.65 to -0.13, z = -2.97; physical neglect: g = -0.18, 95%CI -0.31 to -0.05, z = -2.79; emotional neglect: g = -0.27, 95%CI -0.43 to -0.11, z = -3.32). Conclusions: Childhood maltreatment, as assessed by the CTQ, may contribute to an increased risk of suicidal behavior among people with bipolar disorders. Recognizing maltreatment as an etiological risk factor is a crucial step toward furthering science-based preventive psychiatry.