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Ketamine: stimulating antidepressant treatment?
SUMMARY: The appeal of ketamine - in promptly ameliorating depressive symptoms even in those with non-response - has led to a dramatic increase in its off-label use. Initial promising results await robust corroboration and key questions remain, particularly concerning its long-term administration. It is, therefore, timely to review the opinions of mood disorder experts worldwide pertaining to ketamine's potential as an option for treating depression and provide a synthesis of perspectives - derived from evidence and clinical experience - and to consider strategies for future investigations. DECLARATION OF INTERESTS: G.S.M. Grant/research support: National Health Medical Research Council, NSW Health, Ramsay Health, American Foundation for Suicide Prevention, AstraZeneca, Eli Lilly & Co, Organon, Pfizer, Servier, and Wyeth; has been a speaker for Abbott, AstraZeneca, Eli Lilly & Co, Janssen Cilag, Lundbeck, Pfizer, Ranbaxy, Servier, and Wyeth; consultant: AstraZeneca, Eli Lilly & Co, Janssen Cilag, Lundbeck, and Servier. M.A.F. Grant support: AssureRx, Janssen Research & Development, Mayo Foundation, Myriad, National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institute of Mental Health (NIMH), Pfizer. Consultant (Mayo): Janssen Research & Development, LLC, Mitsubishi Tanabe Pharma Corporation, Myriad Genetics, Neuralstem Inc., Sunovion, Supernus Pharmaceuticals, Teva Pharmaceuticals. CME/travel support: American Physician Institute, CME Outfitters. Financial interest/Mayo Clinic 2016: AssureRx. S.H.K. Grant/research support: Brain Canada, Bristol Meyer Squibb, CIHR, Janssen, Johnson & Johnson, Lundbeck, Ontario Brain Institute, Pfizer, Servier, St. Jude Medical, Sunovion. T.A.K. Grant/research support (through Stanford University): Sunovion Pharmaceuticals and Merck & Co., Inc.; consultant/advisory board bember: Allergan, Inc., Janssen Pharmaceuticals, Myriad Genetic Laboratories, Inc., and Sunovion Pharmaceuticals; lecture honoraria (not Speaker's Bureau payments): GlaxoSmithKline, and Sunovion Pharmaceuticals; royalties from American Psychiatric Publishing, Inc. Also, AstraZeneca Pharmaceuticals LP provided publication support to Parexel for preparation of a manuscript. Spouse employee and stockholder of Janssen Pharmaceuticals. R.W.L. Honoraria for speaking/advising/consulting, and/or received research funds: AstraZeneca, Brain Canada, Bristol Myers Squibb, Canadian Institutes of Health Research, Canadian Depression Research and Intervention Network, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Coast Capital Savings, Johnson and Johnson, Lundbeck, Lundbeck Institute, Pfizer, Servier, St. Jude Medical, Takeda University, Health Network Foundation, and Vancouver Coastal Health Research Institute. R.M. Investigator Janssen trials of esketamine; 'paid-for' ketamine clinic operated by Oxford Health NHS Foundation Trust - fees used to support the Trust. M.J.O. Consultant: Sunovion and Acadia Pharmaceuticals. Full-time employee of U.S. Department of Veterans Affairs. M.E.T. Advisory/Consultant: Alkermes, Allergan, AstraZeneca, Bristol-Myers Squibb Company, Cerecor inc., Eli Lilly & Co., Forest Laboratories, Gerson Lehrman Group, Fabre-Kramer Pharmaceuticals, Inc., GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, MedAvante Inc., Merck and Co. Inc. (formerly Schering Plough and Organon), Moksha8, Naurex Inc., Neuronetics Inc., Novartis, Ortho-McNeil Pharmaceuticals (Johnson & Johnson; Janssen), Otsuka, Pamlab, L.L.C. (Nestle), Pfizer (formerly Wyeth Ayerst Pharmaceuticals), Shire US Inc., Sunovion Pharmaceuticals Inc., Trius Therapeutical Inc. and Takeda. Grant support: Agency for Healthcare Research and Quality, Alkermes, AssureRx, Avanir, Forest Pharmaceuticals, Janssen, National Institute of Mental Health, and Otsuka Pharmaceuticals. Speakers Bureau: None since June, 2010. Equity Holdings: MedAvante, Inc. Royalties: American Psychiatric Foundation, Guilford Publications, Herald House, W.W. Norton & Company, Inc. Spouse's employment: Peloton Advantage, which does business with Pfizer. M.T. Full-time employee at Lilly 1997 to 2008. Honoraria/consulted: Abbott, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Johnson & Johnson, Allergan, Otsuka, Merck, Sunovion, Forest, Geodon Richter Plc, Roche, Elan, Alkermes, Lundbeck, Teva, Pamlab, Minerva, Wyeth and Wiley Publishing. Spouse was full time-employee at Lilly 1998-2013. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.
The Dunn Worry Questionnaire and the Paranoia Worries Questionnaire: new assessments of worry.
BACKGROUND: The cognitive process of worry, which keeps negative thoughts in mind and elaborates the content, contributes to the occurrence of many mental health disorders. Our principal aim was to develop a straightforward measure of general problematic worry suitable for research and clinical treatment. Our secondary aim was to develop a measure of problematic worry specifically concerning paranoid fears. METHODS: An item pool concerning worry in the past month was evaluated in 250 non-clinical individuals and 50 patients with psychosis in a worry treatment trial. Exploratory factor analysis and item response theory (IRT) informed the selection of scale items. IRT analyses were repeated with the scales administered to 273 non-clinical individuals, 79 patients with psychosis and 93 patients with social anxiety disorder. Other clinical measures were administered to assess concurrent validity. Test-retest reliability was assessed with 75 participants. Sensitivity to change was assessed with 43 patients with psychosis. RESULTS: A 10-item general worry scale (Dunn Worry Questionnaire; DWQ) and a five-item paranoia worry scale (Paranoia Worries Questionnaire; PWQ) were developed. All items were highly discriminative (DWQ a = 1.98-5.03; PWQ a = 4.10-10.7), indicating small increases in latent worry lead to a high probability of item endorsement. The DWQ was highly informative across a wide range of the worry distribution, whilst the PWQ had greatest precision at clinical levels of paranoia worry. The scales demonstrated excellent internal reliability, test-retest reliability, concurrent validity and sensitivity to change. CONCLUSIONS: The new measures of general problematic worry and worry about paranoid fears have excellent psychometric properties.
Short-term orchestral music training modulates hyperactivity and inhibitory control in school-age children: A longitudinal behavioural study
© 2019 Frontiers Media S.A. Survey studies have shown that participating in music groups produces several benefits, such as discipline, cooperation and responsibility. Accordingly, recent longitudinal studies showed that orchestral music training has a positive impact on inhibitory control in school-age children. However, most of these studies examined long periods of training not always feasible for all families and institutions and focused on children's measures ignoring the viewpoint of the teachers. Considering the crucial role of inhibitory control on hyperactivity, inattention and impulsivity, we wanted to explore if short orchestral music training would promote a reduction of these impulsive behaviors in children. This study involved 113 Italian children from 8 to 10 years of age. 55 of them attended 3 months of orchestral music training. The training included a 2-hour lesson per week at school and a final concert. The 58 children in the control group did not have any orchestral music training. All children were administered tests and questionnaires measuring inhibitory control and hyperactivity near the beginning and end of the 3-month training period. We also collected information regarding the levels of hyperactivity of the children as perceived by the teachers at both time points. Children in the music group showed a significant improvement in inhibitory control. Moreover, in the second measurement the control group showed an increase in self-reported hyperactivity that was not found in the group undergoing the music training program. This change was not noticed by the teachers, implying a discrepancy between self-reported and observed behavior at school. Our results suggest that even an intense and brief period of orchestral music training is sufficient to facilitate the development of inhibitory control by modulating the levels of self-reported hyperactivity. This research has implications for music pedagogy and education especially in children with high hyperactivity. Future investigations will test whether the findings can be extended to children diagnosed with ADHD.
Assuming ability of youth with autism: Synthesis of methods capturing the first-person perspectives of children and youth with disabilities.
Most research regarding youth with autism spectrum disorder has not focused on their first-person perspectives providing limited insight into methodologies best suited to eliciting their voices. We conducted a synthesis of methods previously used to obtain the first-person perspectives of youth with various disabilities, which may be applicable to youth with autism spectrum disorder. Two-hundred and eighty-four articles met the inclusion criteria of our scoping review. We identified six distinct primary methods (questionnaires, interviews, group discussion, narratives, diaries, and art) expressed through four communication output modalities (language, sign language and gestures, writing, and images). A group of parents who have children with autism spectrum disorder were then presented with a synthesis of results. This parent consultation was used to build on approaches identified in the literature. Parents identified barriers that may be encountered during participant engagement and provided insights on how best to conduct first-person research with youth with autism spectrum disorder. Based on our findings, we present a novel methodological framework to capture the perspectives of youth with various communication and cognitive abilities, while highlighting family, youth, and expert contributions.
Auditory verbal hallucinations in first-episode psychosis: a phenomenological investigation.
BACKGROUND: In dimensional understanding of psychosis, auditory verbal hallucinations (AVH) are unitary phenomena present on a continuum from non-clinical voice hearing to severe mental illness. There is mixed evidence for this approach and a relative absence of research into subjective experience of AVH in early psychosis. AIMS: To conduct primary research into the nature of subjective experience of AVH in first-episode psychosis. METHOD: A phenomenological study using diary and photo-elicitation qualitative techniques investigating the subjective experience of AVH in 25 young people with first-episode psychosis. RESULTS: AVH are characterised by: (a) entity, as though from a living being with complex social interchange; and (b) control, exerting authority with ability to influence. AVH are also received with passivity, often accompanied by sensation in other modalities. CONCLUSIONS: A modern detailed phenomenological investigation, without presupposition, gives results that echo known descriptive psychopathology. However, novel findings also emerge that may be features of AVH in psychosis not currently captured with standardised measures. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.
Insomnia in breast cancer: a prospective observational study.
STUDY OBJECTIVES: Insomnia in cancer patients is prevalent, persistent and confers risk for physical and psychological disorder. We must better understand how insomnia develops in cancer patients and explore the main contributors to its chronicity so that insomnia management protocols can be integrated more effectively within cancer care. This study monitors the etiology of insomnia in breast cancer patients and identifies risk factors for its persistence. METHODS: 173 females with newly diagnosed, non-metastatic breast cancer were tracked from diagnosis for 12-months. Participants completed monthly sleep assessments using the Insomnia Severity Index (ISI) and 3-monthly health-related quality-of-life assessments using the European Organisation for Research and Treatment of Cancer - Breast (EORTC QLQ-C30-BR23) scale. Clinical data on disease status and treatment regimens were also assessed. RESULTS: Prior to diagnosis, 25% of participants reported sleep disturbance, including 8% with insomnia syndrome (IS). Prevalence increased at cancer diagnosis to 46% (18% IS) and remained stable thereafter at around 50% (21% IS). We also explored sleep status transitions. The most common pattern was to remain a good sleeper (34%-49%) or to persist with insomnia (23%-46%). 77% of good sleepers developed insomnia during the 12-month period and 54% went into insomnia remission. Chemotherapy (odds ratio=0·08, 95% ci 0·02-0·29, p<·001) and pre-diagnosis ISI scores (odds ratio=1·13/unit increase in pre-diagnosis sleep score, 95% ci 1·05-1·21, p=·001) were identified as the main risk factors for persistent insomnia. CONCLUSIONS: These data advance our understanding of insomnia etiology in cancer patients and help identify those who should be prioritised for insomnia management protocols.
Implementing a digital clinical decision support tool for side effects of antipsychotics: a focus group study.
BACKGROUND: In medicine, algorithms can inform treatment decisions by combining the most up-to-date evidence about side effect profiles of medications, which are comparable in efficacy. Their use provides opportunities for improved shared clinician-patient decision-making when initiating therapy. We designed a decision support tool (DST) that incorporated the latest evidence regarding antipsychotic side effects. The tool allowed patients to select one side effect commonly associated with antipsychotics that they wished to avoid; the tool then provided a list of suggested medications and ones to avoid. OBJECTIVE: To explore qualitatively the acceptability and usefulness of the DST from the perspectives of patients and psychiatrists. METHODS: This qualitative study took place at a mental health and community hospital in Oxford, UK, in 2018. Four patients/carers and four psychiatrists were recruited to two focus groups to explore their perceptions of the tool. Data were thematically analysed. FINDINGS: Findings demonstrated a high degree of acceptability and potential usability of the DST for patients and psychiatrists. The main themes to emerge relating to the DST were 'prescribing preferences and practices', 'consideration and awareness of side effects', 'app content, layout and accessibility', 'influence on clinical practice' and 'role in decision-making'. CONCLUSIONS: A proof-of-concept clinical study will incorporate the recommendations produced from the findings into the tool's design. CLINICAL IMPLICATIONS: Digital DSTs provide opportunities for the most up-to-date information on medication side effects to be used as the basis for shared clinician-patient decision-making. This tool has the potential to improve adherence to psychiatric medication, with benefits to clinical outcomes and healthcare resourcing.
D-Cycloserine as Adjunct to Brief Computerised CBT for Spider Fear: Effects on Fear, Behaviour, and Cognitive Biases
Abstract In anxiety disorders, cognitive behavioural therapy (CBT) improves information-processing biases such as implicit fear evaluations and avoidance tendencies, which predicts treatment response, so they might constitute important treatment targets. This study investigated (i) whether information-processing biases changed following single-session computerised CBT for spider fear, and (ii) whether this effect could be augmented by administration of D-cycloserine (DCS). Spider-fearful individuals were randomized to receiving 250mg of DCS (n=21) or placebo (n=17) and spider fear was assessed using self-report, behavioural, and information-processing (Extrinsic Affective Simon Task & Approach Avoidance Task) measures. Linear mixed-effects analyses indicated improvements on self-report and behavioural spider fear following CBT, but not on cognitive bias measures. There was no evidence of an augmentation effect of DCS on any outcome. Cognitive biases at 1-day were not predictive of 1-month follow-up spider fear. These findings provide no evidence for information-processing biases relating to CBT response or augmentation with DCS.
Clusterin in Alzheimer's Disease: Mechanisms, Genetics, and Lessons From Other Pathologies.
Clusterin (CLU) or APOJ is a multifunctional glycoprotein that has been implicated in several physiological and pathological states, including Alzheimer's disease (AD). With a prominent extracellular chaperone function, additional roles have been discussed for clusterin, including lipid transport and immune modulation, and it is involved in pathways common to several diseases such as cell death and survival, oxidative stress, and proteotoxic stress. Although clusterin is normally a secreted protein, it has also been found intracellularly under certain stress conditions. Multiple hypotheses have been proposed regarding the origin of intracellular clusterin, including specific biogenic processes leading to alternative transcripts and protein isoforms, but these lines of research are incomplete and contradictory. Current consensus is that intracellular clusterin is most likely to have exited the secretory pathway at some point or to have re-entered the cell after secretion. Clusterin's relationship with amyloid beta (Aβ) has been of great interest to the AD field, including clusterin's apparent role in altering Aβ aggregation and/or clearance. Additionally, clusterin has been more recently identified as a mediator of Aβ toxicity, as evidenced by the neuroprotective effect of CLU knockdown and knockout in rodent and human iPSC-derived neurons. CLU is also the third most significant genetic risk factor for late onset AD and several variants have been identified in CLU. Although the exact contribution of these variants to altered AD risk is unclear, some have been linked to altered CLU expression at both mRNA and protein levels, altered cognitive and memory function, and altered brain structure. The apparent complexity of clusterin's biogenesis, the lack of clarity over the origin of the intracellular clusterin species, and the number of pathophysiological functions attributed to clusterin have all contributed to the challenge of understanding the role of clusterin in AD pathophysiology. Here, we highlight clusterin's relevance to AD by discussing the evidence linking clusterin to AD, as well as drawing parallels on how the role of clusterin in other diseases and pathways may help us understand its biological function(s) in association with AD.
A classical test theory evaluation of the Sleep Condition Indicator accounting for the ordinal nature of item response data.
BACKGROUND: Insomnia symptoms are common among young adults and affect about 5% to 26% of 19 to 34-year-olds. In addition, insomnia is associated with poor mental health and may affect daily performance. In research, as well as in clinical practice, sleep questionnaires are used to screen for and diagnose insomnia. However, most questionnaires are not developed according to current DSM-5 diagnostic criteria. An exception is the recently developed Sleep Condition Indicator (SCI), an eight-item scale screening for insomnia. AIM: The aim of this study was to perform a Classical Test Theory (CTT) based psychometric evaluation of the SCI in a sample of Swedish university students, by taking the ordinal nature of item level data into account. METHODS: The SCI was translated into Swedish and distributed online to undergraduate students at three Swedish universities, within programs of health, psychology, science or economy. Of 3673 invited students, 634 (mean age 26.9 years; SD = 7.4) completed the questionnaire that, in addition to the SCI, comprised other scales on sleep, stress, lifestyle and students' study environment. Data were analyzed according to CTT investigating data completeness, item homogeneity and unidimensionality. RESULTS: Polychoric based explorative factor analysis suggested unidimensionality of the SCI, and internal consistency was good (Cronbach's alpha, 0.91; ordinal alpha, 0.94). SCI scores correlated with the Insomnia Severity Index (-0.88) as well as with sleep quality (-0.85) and perceived stress (-0.50), supporting external construct validity. CONCLUSIONS: These observations support the integrity of the of the SCI. The SCI demonstrates sound CTT-based psychometric properties, supporting its use as an insomnia screening tool.
Specialised early intervention teams for first episode psychosis
Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To compare early intervention in psychosis (EIP) specialised teams to usual community mental health care for the treatment of people with first episode psychosis (FEP).
Effectiveness of universal programmes for the prevention of suicidal ideation, behaviour and mental ill health in medical students: a systematic review and meta-analysis.
QUESTION:A growing body of work suggests that medical students may be particularly at risk of mental ill health, suicidal ideation and behaviour, resulting in recent calls to develop interventions to prevent these outcomes. However, few reviews have synthesised the current evidence base regarding the effectiveness of these interventions and provided guidance to improve future intervention efforts. STUDY SELECTION AND ANALYSIS:The authors conducted a systematic review to identify studies of any design reporting the effectiveness of any universal intervention to address these outcomes in medical students. Embase, MEDLINE and PsycINFO databases were searched from their respective start dates until 1 December 2017. FINDINGS:Data from 39 studies were included. Most investigated the effectiveness of relatively brief interventions designed to reduce stress; most commonly using mindfulness-based or guided meditation approaches. Only one implemented an intervention specifically designed to address suicidal ideation; none investigated the effectiveness of an intervention specifically designed to address suicidal behaviour. Five investigated the effects of curriculum-level changes. Overall, there was limited evidence of an effect for these programmes at both the postintervention and longest follow-up assessment on depression, anxiety and stress. CONCLUSIONS:Relatively brief, individually focused, mindfulness-based interventions may be effective in reducing levels of anxiety, depression and stress in medical students in the short term. Effects on suicidal ideation and behaviour, however, remain to be determined. There has been a significant lack of attention on organisational-level stressors associated with medical education and training.
Chronic Fatigue & Fibromyalgia Syndromes
With four newly authored chapters and extensive revisions made to the remaining chapters, this third edition of The American Psychiatric Publishing Textbook of Psychosomatic Medicine and Consultation-Liaison Therapy has been thoroughly ...