John M. Kane

• Doctor of Medicine
• Professor at Feinstein Institute for Medical Research

Background Treatment of schizophrenia has traditionally aimed for symptomatic remission without addressing many daily problems patients face. Although no standard definition of functional recovery in patients with first-episode psychosis (FEP) and early-phase (EP) schizophrenia exists in the literature, most clinicians consider it a useful concept...

There is increasing interest in using computational speech and language analysis for the objective assessment of symptom severity in schizophrenia spectrum disorders (SSD), including negative symptom severity. However, the extent to which antipsychotic side effects influence speech markers of negative symptoms is unclear. This study investigated as...

Purpose/Background Clozapine was approved in the United States (US) using 1989 regulations and knowledge. After 30 years, many sections of the US package insert (PI) are outdated. Methods We comprehensively reviewed the literature to propose PI updates. We present the information in 2 articles. In Part I, we focus on basic pharmacology based on 40...

Purpose/Background This is the second part of a 2-part article that proposes improving the United States (US) clozapine package insert. Part II focuses on fatal outcomes and the 5 boxed warnings, 4 specifically for clozapine: severe neutropenia, seizure, orthostatic hypotension and myocarditis, and 1 for all antipsychotics (elderly with dementia)....

The Accelerating Medicines Partnership Schizophrenia (AMP® SCZ) program integrates lived experience into psychosis research, leveraging over three decades of foundational studies to improve research quality, promote community engagement, and ensure ethical implementation of precision psychiatry. Lived experience is embedded in the program’s governa...

The Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ) project assesses a large sample of individuals at clinical high-risk for developing psychosis (CHR) and community controls. Subjects are enrolled in 43 sites across 5 continents. The assessments include domains similar to those acquired in previous CHR studies along with novel domains...

Modern research management, particularly for publicly funded studies, assumes a data governance model in which grantees are considered stewards rather than owners of important data sets. Thus, there is an expectation that collected data are shared as widely as possible with the general research community. This presents problems in complex studies t...

Clinical ascertainment and clinical outcome are key features of any large multisite study. In the ProNET and PRESCIENT research networks, the Accelerating Medicines Partnership® Schizophrenia (AMP®SCZ) Clinical Ascertainment and Outcome Measures Team aimed to establish a harmonized clinical assessment protocol across these two research networks and...

Neuroimaging with MRI has been a frequent component of studies of individuals at clinical high risk (CHR) for developing psychosis, with goals of understanding potential brain regions and systems impacted in the CHR state and identifying prognostic or predictive biomarkers that can enhance our ability to forecast clinical outcomes. To date, most st...

Cognitive impairment occurs at higher rates in individuals at clinical high risk (CHR) for psychosis relative to healthy peers, and it contributes unique variance to multivariate prediction models of transition to psychosis. Such impairment is considered a core biomarker of schizophrenia. Thus, cognition is a key domain measured in the Accelerating...

Aims Both inflammation and smoking are known to affect clozapine metabolism. However, the impact of inflammation on clozapine metabolism in relation to smoking status is unclear. Therefore, we investigated correlations between C‐reactive protein (CRP) and clozapine levels in smokers and non‐smokers separately. Methods Patients were included retros...

Background The best pharmacological treatment practices for relapse prevention in patients with first-episode schizophrenia are unclear. We aimed to assess different treatment strategies used before and after the first relapse, and their associations with subsequent relapse risk. Methods In this population-based cohort study, we enrolled individua...

MRI quality control (QC) is challenging due to unbalanced and limited datasets, as well as subjective scoring, which hinder the development of reliable automated QC systems. To address these issues, we introduce an approach that pretrains a model on synthetically generated motion artifacts before applying transfer learning for QC classification. Th...

IntroductionIn RISE, TV46000 once monthly (q1m) or once every 2 months (q2m) significantly extended time to impending schizophrenia relapse. The current study (SHINE, NCT03893825) evaluated the long-term safety, tolerability, and effect of TV46000. Methods Patients completing RISE without relapse (rollover) or newly recruited (de novo) were eligibl...

IntroductionHealthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, including partial or nonadherence, may alleviate knowledge gaps and clarify the role of long-acting injectable antipsychotic agents (LAIs) in treating thi...

Background Long-acting injectable antipsychotics (LAIs) have demonstrated better rates of adherence among patients with schizophrenia than oral antipsychotics (OAs). While LAIs often cost more than OAs, better adherence can lead to cost offsets in other areas. Objective The purpose of this LAI Cost-Offset Value Calculator (LCVC) model is to provide...

IntroductionHealthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, such as unfamiliarity with prescribing information for long-acting injectable antipsychotics (LAIs), may assist clinicians when treating patients with sch...

Background Negative symptoms are a primary driver of poor outcomes in schizophrenia spectrum disorders (SSD), but there are no FDA-approved medications or FDA-cleared therapeutics targeting negative symptoms in schizophrenia. NST-SPARK is a novel digital therapeutic targeting negative symptoms in SSD. It is a smartphone application delivering recov...

Despite evidence of benefits beyond those of oral antipsychotics, long-acting injectable antipsychotics (LAIs) are underused in schizophrenia treatment. Underuse may be partially a result of misconceptions held by some healthcare professionals (HCPs) pertaining to LAIs. A panel of four experts convened between January 2022 and May 2022 to identify...

Introduction Long-acting injectable (LAI) antipsychotic medications and clozapine are effective yet underutilized medical therapies in early intervention services. The purpose of this study was to conduct a pre-implementation evaluation of contextual determinants of early intervention programs to implement innovations optimizing LAI antipsychotic a...

Background TV46000 is a long-acting subcutaneous antipsychotic (LASCA) formulation of risperidone approved for the treatment of schizophrenia in adults. Methods The RISE study (NCT03503318) compared TV-46000 once monthly (q1m) and once every 2 months (q2m) with placebo (1:1:1) in patients with schizophrenia who underwent stabilization on oral risp...

There is no multi-country/multi-language study testing a-priori multivariable associations between non-modifiable/modifiable factors and validated wellbeing/multidimensional mental health outcomes before/during the COVID-19 pandemic. Moreover, studies during COVID-19 pandemic generally do not report on representative/weighted non-probability sample...

Background and Hypotheses We sought to evaluate the ability of automated speech and language features to track fluctuations in the major psychosis symptoms domains: Thought Disorder, Negative Symptoms, and Positive Symptoms.Study Design Sixty-six participants with psychotic disorders were longitudinally assessed soon after inpatient admission, at d...

TV-46000 is a long-acting subcutaneous antipsychotic (LASCA) formulation of risperidone that is approved by the United States Food and Drug Administration for the treatment of schizophrenia in adults. In the phase 3, randomized, double-blind RIsperidone Subcutaneous Extended-release (RISE) study, TV-46000 once monthly (q1m) and once every 2 months...

There is increasing interest in using computational speech and language analysis for the objective assessment of symptom severity in schizophrenia spectrum disorders (SSD), including negative symptom severity. However, the extent to which antipsychotic side effects influence speech markers of negative symptoms is unclear. This study investigated as...

There is increasing interest in using computational speech and language analysis for the objective assessment of symptom severity in schizophrenia spectrum disorders (SSD), including negative symptom severity. However, the extent to which antipsychotic side effects influence speech markers of negative symptoms is unclear. This study investigated as...

BACKGROUND Digital health technologies are increasingly being integrated into mental health care. However, the adoption of these technologies can be influenced by patients' digital literacy and attitudes, which may vary based on sociodemographic factors. This variability necessitates a better understanding of patient digital literacy and attitudes...

Background Digital health technologies are increasingly being integrated into mental health care. However, the adoption of these technologies can be influenced by patients’ digital literacy and attitudes, which may vary based on sociodemographic factors. This variability necessitates a better understanding of patient digital literacy and attitudes...

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is gaining attention in pharmacovigilance, but its association with antipsychotics, other than clozapine, is still unclear. We conducted a case/non-case study with disproportionality analysis based on the World Health Organization (WHO) global spontaneous reporting database, Vig...

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of...

Background and Hypothesis Longer duration of untreated psychosis (DUP) predicts worse outcomes in First Episode Psychosis (FEP). Searching online represents one of the first proactive step toward treatment initiation for many, yet few studies have informed how best to support FEP youth as they engage in early online help-seeking steps to care. Stu...

Objective: The NIH has mandated equal representation of Black, Indigenous, and people of color (BIPOC) individuals in clinical research, but it is unclear whether such inclusion has been achieved in multisite research studies of individuals at clinical high risk for psychosis or with first-episode psychosis (FEP). An assessment of inclusion rates...

To bring biomarkers closer to clinical application, they should be generalizable, reliable, and maintain performance within the constraints of routine clinical conditions. The functional striatal abnormalities (FSA), is among the most advanced neuroimaging biomarkers in schizophrenia, trained to discriminate diagnosis, with post-hoc analyses indica...

International studies measuring wellbeing/multidimensional mental health before/ during the COVID-19 pandemic, including representative samples for >2 years, identifying risk groups and coping strategies are lacking. COH-FIT is an online, international, anonymous survey measuring changes in well-being (WHO-5) and a composite psychopathology P-score...

Duration of untreated psychosis (DUP) has been associated with poor mental health outcomes. We aimed to meta-analytically estimate the mean and median DUP worldwide, evaluating also the influence of several moderating factors. This PRISMA/MOOSE-compliant meta-analysis searched for non-overlapping individual studies from inception until 9/12/2022, r...

Objective: Patients' race and age have each been identified as risk factors for experiencing restraint events during psychiatric hospitalization. Restraint duration is also an important variable in determining disparities in treatment. To the authors' knowledge, no studies to date have examined the effect of the interaction of race and age on rest...

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Methods: The initial workshop is described in the companion report from Addin...

To bring biomarkers closer to clinical application, they should be generalizable, reliable, and maintain performance within the constraints of routine clinical conditions. The functional striatal abnormalities (FSA), is among the most advanced neuroimaging biomarkers in schizophrenia, trained to discriminate diagnosis, with post hoc analyses indica...

To bring biomarkers closer to clinical application, they should be generalizable, reliable, and maintain performance within the constraints of routine clinical conditions. The functional striatal abnormalities (FSA), is among the most advanced neuroimaging biomarkers in schizophrenia, trained to discriminate diagnosis, with post-hoc analyses indica...

We read with great interest the report by Inge Winter-van Rossum and colleagues comparing two long-acting injectable (LAI) antipsychotics with their oral equivalents in patients with early-phase schizophrenia.1 The inclusion of 511 participants in a pragmatic, open-label, randomised clinical trial using time to all-cause discontinuation as the main...

Abstract Background Schizophrenia is mostly a chronic disorder whose symptoms include psychosis, negative symptoms and cognitive dysfunction. Poor adherence is common and related relapse can impair outcomes. Long-acting injectable antipsychotics (LAIs) may promote treatment adherence and decrease the likelihood of relapse and rehospitalization. Usi...

Dr John M. Kane discusses cognitive impairments in schizophrenia with fellow expert Dr Philip D. Harvey and patient advocate and mental health clinician, Mr Carlos A. Larrauri, who was diagnosed with schizophrenia. The podcast aims to raise awareness of the unmet need to address cognitive impairments associated with schizophrenia (CIAS) as well as...

Dr John Kane discusses negative symptoms in schizophrenia alongside fellow expert, Dr William Carpenter, and Mr Matthew Racher, a Certified Recovery Peer Specialist and dedicated advocate for people living with schizophrenia, who is currently studying for his Master of Social Work (MSW) in Miami, Florida. In this podcast, the authors discuss challe...

Background: Early non-response is a well-established prognostic marker but evidence-based and consistent recommendations to manage it are limited. The aim of this systematic review and meta-analysis was to generate evidence-based strategies for the management of schizophrenia patients with early non-response to 2 weeks of antipsychotic treatment....

Tobacco smoking is highly prevalent among patients with serious mental illness (SMI), with known deleterious consequences. Smoking cessation is therefore a prioritary public health challenge in SMI. In recent years, several smoking cessation digital interventions have been developed for non-clinical populations. However, their impact in patients wi...

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Methods: The initial workshop is described in the companion report from Addingto...

Objective: Long-acting injectable antipsychotic agents (LAIs) are effective in schizophrenia relapse prevention but are often underutilized. This study aims to understand treatment patterns leading to a successful LAI implementation following schizophrenia diagnosis in a large dataset that included commercially insured patients in the United States...

Schizophrenia is among the top ten causes of years lost due to disability. Goals of treatment are evolving beyond remission of psychotic symptoms to include physical and mental functioning, quality of life, and long-term functional recovery. Evidence has shown long-acting injectables (LAIs) are beneficial for schizophrenia patients by increasing tr...

Functional recovery is a treatment goal that goes beyond symptomatic remission and encompasses multiple aspects of schizophrenia patients’ lives, including quality of life, physical, and mental functioning. There is evidence that long-acting injectable (LAI) treatments promote adherence and reduce rehospitalisation and functional decline, which cou...

Importance: Pathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS). Objective: We sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative im...

Objective: Patients with early-phase schizophrenia or bipolar I disorder (BD-I) are at greater risk for antipsychotic-associated weight gain. This 12-week, randomized, double-blind study conducted between June 2017 and December 2021 evaluated weight effects of combination olanzapine and samidorphan (OLZ/SAM) versus olanzapine in early-phase illness...

Background and hypothesis: There is limited evidence to guide the approaches to clozapine treatment. Accordingly, an international initiative was undertaken with the aim of developing consensus recommendations for the optimization of clozapine monotherapy. Study design: We conducted an online Delphi survey among members of the Treatment Response...

Purpose The COVID-19 pandemic substantially impacted care of patients with schizophrenia treated with long-acting injectable antipsychotics (LAIs). This study (OASIS-MAPS) examined how clinical sites adapted operations and used telepsychiatry to maintain standard of care for these patients during the pandemic. Methods Two online surveys (initial:...

Medication nonadherence in schizophrenia can have serious implications including relapses and hospitalization. Long-acting injectable (LAI) antipsychotics require fewer administrations, while ensuring sustained medication coverage. In this review, we summarize the expected real-world benefits of longer dosing intervals in the management of schizoph...

Background Schizophrenia is mostly a chronic disorder whose symptoms include psychosis, negative symptoms and cognitive dysfunction. Poor adherence is common and related relapse can impair outcomes. Long-acting injectable antipsychotics (LAIs) may promote treatment adherence and decrease the likelihood of relapse and rehospitalization. Using LAIs i...

Objective: Long-acting injectable antipsychotic agents (LAIs) have improved clinical effectiveness and adherence versus oral antipsychotic agents (OAs); however, a minority of individuals with schizophrenia are treated with LAIs compared with OAs. This cohort study aimed to evaluate predictors of initiation of atypical LAIs among patients with newl...

This study was designed to assess healthcare resource utilization (HCRU) and costs in patients with newly diagnosed schizophrenia based on timing and context of long-acting injectable antipsychotic agent (LAI) initiation. Using claims data, patients (aged 18-40 years) with first schizophrenia diagnosis January 2013-September 2019 (index date), no L...

Despite considerable progress in pharmacotherapy over the past seven decades, many mental disorders remain insufficiently treated. This situation is in part due to the limited knowledge of the pathophysiology of these disorders and the lack of biological markers to stratify and individualize patient selection, but also to a still restricted number...

Introduction: The clinical course of schizophrenia is often characterized by recurrent relapses. Blood inflammatory markers are altered in acute psychosis, and may be state markers for illness relapse in schizophrenia. Few studies have investigated longitudinal, intra-individual changes in inflammatory markers as a predictor of relapse. In the pre...

Evidence regarding effectiveness and safety of clozapine once- vs. multiple-daily dosing is limited. We compared demographic and clinical parameters between patients with once- vs. multiple-daily dosing in the Department of Psychiatry and Psychotherapy, University of Regensburg, Germany (AGATE dataset), and the Department of Psychiatry, Lausanne Un...

Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome,...

Background: Emraclidine is a novel, brain-penetrant, highly selective M4 receptor positive allosteric modulator in development for the treatment of schizophrenia. We aimed to evaluate the safety and tolerability of multiple ascending doses of emraclidine in patients with schizophrenia. Methods: We conducted a two-part, randomised, phase 1b trial...

Objective: Tardive dyskinesia (TD) is a movement disorder that can negatively affect health-related quality of life. However, the impact of TD is not necessarily dependent solely on the objective severity of TD movements. There is currently no easy-to-use, standardized, clinician-rated assessment of the impact of TD on functioning. The aim of this...

IntroductionEvidence is lacking on withdrawal syndrome related to individual antidepressants and relevant risk factors for severe reactions.Objective To ascertain whether antidepressants are associated with an increased reporting of withdrawal syndrome as compared with other medications, and to investigate risk factors for severe reactions.Methods...

Recent research has explored computational tools to manage workplace stress via personal sensing, a measurement paradigm in which behavioral data streams are collected from technologies including smartphones, wearables, and personal computers. As these tools develop, they invite inquiry into how they can be appropriately implemented towards improvi...

Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patient...

Introduction Treatment resistance constitutes the highest burden of disease within schizophrenia. We hypothesized that the synergistic activity of Lu AF35700 at dopamine D1 and D2 receptors might provide superior antipsychotic effects versus first-line antipsychotic therapy in patients with treatment resistant schizophrenia (TRS), with a benign tol...

Objective: Switching of antipsychotic medications, which are used for many psychiatric conditions, is common. However, reasons and clinical documentation of such switches have scarcely been studied. Methods: A systematic, retrospective review of prescription records and prescriber notes was conducted to characterize reasons for and types of antips...

Introduction Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome refers to a cluster of clinical symptoms/signs related to drug hypersensitivity. The main clinical features include fever, skin rash, eosinophilia, enlarged lymph nodes, atypical lymphocytosis, and involvement of at least one internal organ. Clozapine-related DRESS...

This continuing education supplement is jointly provided by Medical Education Resources and CMEology. The supplement is supported by an independent educational grant from Sunovion Pharmaceuticals Inc. It was edited and peer reviewed by the Journal of Clinical Psychopharmacology.After reviewing the learning objectives and reading the supplement, ple...

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional...