Ultra-treatment resistance

2018 ◽  
Author(s):  
Gary Remington ◽  
Ofer Agid ◽  
Hiroyoshi Takeuchi ◽  
Jimmy Lee ◽  
Araba Chintoh
Keyword(s):  
Substance Abuse ◽  
Conceptual Framework ◽  
Treatment Response ◽  
Clinical Application ◽  
Treatment Resistance ◽  
Confounding Factors ◽  
Treatment Resistant ◽  
Dynamic Nature ◽  
Case Based

Ultra-treatment resistance or ultra-resistant schizophrenia is defined as describing individuals who meet criteria for treatment-resistant schizophrenia and receive an adequate trial of clozapine in the absence of other confounding factors that might compromise response (e.g. substance abuse, antipsychotic non-adherence), but demonstrate a suboptimal response. Because the definition currently hinges on a trial of clozapine, ‘clozapine-resistant schizophrenia’ has also been proposed as a more precise descriptor. This chapter reviews issues specific to classifying this subpopulation, including existing criteria and challenges in their clinical application. It also underscores the importance of this conceptual framework in terms of better understanding schizophrenia’s heterogeneity and the opportunity to establish different pathophysiological subtypes, in this case based on treatment response. It reviews existing evidence specific to this sample, which at this point is limited as only recently have efforts begun to isolate these individuals for the purpose of investigation. Finally, it highlights the dynamic nature of this strategy, since gains in understanding will demand that the framework, terminology, and criteria be continuously revisited and revised.

Treatment response and resistance in schizophrenia: principles and definitions

2018 ◽  
Author(s):  
Robert McCutcheon ◽  
Christoph U. Correll ◽  
Oliver Howes ◽  
John Kane
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Treatment Response ◽  
Working Group ◽  
Treatment Resistance ◽  
Consensus Guidelines ◽  
Treatment Resistant

Clear, accepted definitions of treatment resistance and response are needed so that clinical trials of treatments can be compared, and evidence can be meaningfully interpreted to inform clinical practice. In this chapter, we review the definitions of treatment response and resistance used in clinical trials, highlighting the variability in definitions used across studies, as well as a number of problems with the definitions used, including mixing treatment-intolerant patients with treatment-resistant patients and limited evaluation of the adequacy of treatment in many cases. The chapter then summarizes the work undertaken by the Treatment Response and Resistance in Psychosis working group to produce consensus guidelines and benchmarks to address these issues. Also reviewed are the principles underlying the concept of resistance developed by the working group. Finally, the chapter discusses the implications of these findings for clinical practice.

A Comparison of Comorbid Patterns in Treatment-Resistant Unipolar and Bipolar Depression

1995 ◽  
Vol 40 (5) ◽  
pp. 270-274 ◽  
Author(s):  
Verinder Sharma ◽  
Dwight Mazmanian ◽  
Emmanuel Persad ◽  
Karen Kueneman
Keyword(s):  
Substance Abuse ◽  
Psychiatric Disorders ◽  
Bipolar Depression ◽  
Treatment Resistance ◽  
Unipolar Depression ◽  
Treatment Resistant ◽  
Entire Sample ◽  
Clinical Interviews ◽  
Axis I ◽  
Bipolar Patients

Objective To examine the occurrence of concomitant psychiatric disorders in patients with treatment-resistant unipolar and bipolar depression. Method Forty-nine patients participated as subjects. Twenty-four (49%) had unipolar depression and 25 (51%) had bipolar depression using DSM-III-R criteria. Structured clinical interviews were conducted with all patients. Chart reviews and interviews with family members were also carried out. Information relating to both current and lifetime diagnoses was obtained. Results Of the entire sample, 75.5% were found to have at least one other Axis I diagnosis and 46.9% had at least two additional Axis I diagnoses. The unipolar group had significantly more current comorbid diagnoses. When type of diagnoses was examined, unipolar patients had significantly more anxiety diagnoses at the time of the index episode, and over their entire lifetime. Bipolar patients had significantly more lifetime substance abuse diagnoses. Conclusions Axis I comorbidity appears to be differentially associated with treatment resistance in unipolar and bipolar depression.

MMPI Indicators of Treatment Response to Spinal Epidural Stimulation in Patients with Chronic Pain and Patients with Movement Disorders

1982 ◽  
Vol 51 (3_suppl) ◽  
pp. 1059-1064 ◽  
Author(s):  
Marvin A. Brandwin ◽  
Donald G. Kewman
Keyword(s):  
Chronic Pain ◽  
Treatment Response ◽  
Movement Disorders ◽  
Minnesota Multiphasic Personality Inventory ◽  
Treatment Resistance ◽  
Subjective Ratings ◽  
Treatment Resistant ◽  
Psychological Variables ◽  
Epidural Stimulation ◽  
Spinal Epidural

The usefulness of the Minnesota Multiphasic Personality Inventory (MMPI) for predicting treatment response to electrical spinal epidural stimulation was examined in 11 patients with chronic pain and 11 patients with movement disorders. The movement-disordered group had generally lower MMPI scores than the group with chronic pain and higher subjective ratings of improvement. However, physicians' ratings for the group as a whole showed that scores on Hs and Hy, while elevated, tended to be relatively lower for patients who were treatment resistant than for those rated as successes. Higher elevations on D were associated with treatment failure. The “conversion V” profile as an indicator of treatment resistance did not hold for this sample. The psychological implications of these findings are discussed. The results suggest that the MMPI has predictive value but the need for refinement of outcome measures and further clarification of psychological variables is evident.

Treatment Resistance: A Time-Based Approach For Early Identification in First Episode Samples

2018 ◽  
Author(s):  
Kara Dempster ◽  
Ross Norman ◽  
Lena Palaniyappan
Keyword(s):  
Early Intervention ◽  
Treatment Response ◽  
Intervention Program ◽  
Negative Symptoms ◽  
Treatment Resistance ◽  
First Episode ◽  
Symptom Improvement ◽  
Treatment Resistant ◽  
Early Intervention Program ◽  
First Episode Schizophrenia

Background: Although approximately 1/3 of individuals with schizophrenia are Treatment Resistant (TR), identifying these subjects prospectively for early intervention remains challenging. The Treatment Response and Resistance in Psychosis (TRIPP; Howes et al, 2017) working group recently published consensus guidelines defining lack of response as a <20% improvement in symptoms. However, it is unclear whether these criteria are sensitive in First Episode Schizophrenia (FES). Method: Patients experiencing a first episode of psychosis referred to the Prevention and Early Intervention Program for Psychosis (PEPP) in London, Canada were followed-up with longitudinal symptom assessments. We evaluated two improvement thresholds for ‘probable TR’ classifications; <20% (as per TRIPP) and <50% to identify subjects satisfying ‘probable TR’ based on positive, negative, and total symptom domains.Results: Using the criterion of <50% total, or <20% negative symptom improvement,resulted in ‘probable TR’ rates of 37% and 33% respectively, with notable overlap between the 2criteria (77% satisfying both). Using a 20% cut-off for positive and total symptomsresulted in very low rates of ‘probable TR’. Logistic regression analyses demonstrated that poorpremorbid functioning, longer duration of untreated illness, and limited treatment response atmonths one and two were significantly associated with probable TR (<50% totalsymptom improvement).Conclusions: Our results suggest that probable TR may be identified at 6 months after FESusing a time-based approach only by including negative symptoms (either alone, with a 20%improvement threshold, or in addition to positive symptoms, with a total 50%threshold) in the definition.

scholarly journals Frontostriatal Structural Connectivity and Striatal Glutamatergic Levels in Treatment-Resistant Schizophrenia: An Integrative Analysis of DTI and 1H-MRS

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Ryo Ochi ◽  
Ryosuke Tarumi ◽  
Yoshihiro Noda ◽  
Sakiko Tsugawa ◽  
Eric Plitman ◽  
...  
Keyword(s):  
Treatment Response ◽  
Structural Connectivity ◽  
Treatment Resistance ◽  
Antipsychotic Treatment ◽  
Treatment Resistant ◽  
First Line ◽  
1H Mrs ◽  
Dorsolateral Prefrontal ◽  
The Relationship ◽  
Glutamate System

Abstract Given that approximately one-third of patients with schizophrenia do not respond to antipsychotics, different neurobiological bases may underlie treatment resistance in schizophrenia. Previous studies showed that treatment response is associated with both frontostriatal connectivity and glutamatergic neurometabolite levels in the caudate in patients with schizophrenia, which leads to the hypothesis that the relationship between them may be altered, specifically in patients with treatment-resistant schizophrenia (TRS). Employing analyses of covariance and subsequent partial correlation analyses, we compared the relationship between glutamate+glutamine (Glx) levels in the caudate and fractional anisotropy (FA) values in the tract between the dorsolateral prefrontal cortex and caudate in 19 patients with TRS, 20 patients responsive to first-line antipsychotics (FL-Resp), and 19 healthy controls (HCs). TRS was defined by severe positive symptomatology despite first-line antipsychotic treatment. Patients with TRS had lower FA values in the bilateral frontostriatal tracts than patients with FL-Resp and HCs (P < .001), while no group differences were found in caudate Glx levels. There was a significant frontostriatal FA value-by-group interaction on caudate Glx levels (F = 7.37, P = .009). Frontostriatal FA values positively correlated with caudate Glx levels in HCs (r = −.55, P = .028), while they were negatively associated with caudate Glx levels in the TRS group (r = .53, P = .043). Furthermore, in the FL-Resp group, frontostriatal FA values did not significantly correlated with caudate Glx levels. The altered relationship between white matter integrity and the glutamate system in the frontostriatal circuit in the TRS group may reflect the pathophysiology underlying treatment response/resistance in schizophrenia.

scholarly journals Mapping Digital Religion: Exploring the Need for New Typologies

Religions ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 373
Author(s):  
Piotr Siuda
Keyword(s):  
Conceptual Framework ◽  
Religious Movements ◽  
New Religious Movements ◽  
Future Research ◽  
The Internet ◽  
Traditional Religion ◽  
Dynamic Nature ◽  
Visual Frame

Today, it is challenging to separate online and offline spaces and activities, and this is also true of digital religion as online and offline religious spaces become blended or blurred. With this background, the article explores the need for new typologies of what is religious on the Internet and proposes a conceptual framework for mapping digital religion. Four types of that which is religious on the Internet are presented based on influential classification by Helland. He introduced (1) religion online (sites that provide information without interactivity) and (2) online religion (interactivity and participation). Helland’s concept is developed by, among others, adding two types: (3) innovative religion (new religious movements, cults, etc.) and (4) traditional religion (e.g., Christianity or Islam). Each type is illustrated by selected examples and these are a result of a larger project. The examples are grouped into three areas: (1) religious influencers, (2) online rituals and (3) cyber-religions (parody religions). Additionally, the visual frame for mapping digital religion is presented including the examples mentioned. The presented framework attempts to improve Helland’s classification by considering a more dynamic nature of digital religion. The model is just one possible way for mapping digital religion and thus should be developed further. These and other future research threads are characterized.

scholarly journals Molecular and Functional Links between Neurodevelopmental Processes and Treatment-Induced Neuroendocrine Plasticity in Prostate Cancer Progression

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 692
Author(s):  
Roosa Kaarijärvi ◽  
Heidi Kaljunen ◽  
Kirsi Ketola
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Treatment Resistance ◽  
Research Field ◽  
Phenotypic Change ◽  
Prostate Cancer Progression ◽  
Castration Resistant Prostate Cancer ◽  
Treatment Resistant ◽  
Molecular Features ◽  
Neuroendocrine Prostate Cancer

Neuroendocrine plasticity and treatment-induced neuroendocrine phenotypes have recently been proposed as important resistance mechanisms underlying prostate cancer progression. Treatment-induced neuroendocrine prostate cancer (t-NEPC) is highly aggressive subtype of castration-resistant prostate cancer which develops for one fifth of patients under prolonged androgen deprivation. In recent years, understanding of molecular features and phenotypic changes in neuroendocrine plasticity has been grown. However, there are still fundamental questions to be answered in this emerging research field, for example, why and how do the prostate cancer treatment-resistant cells acquire neuron-like phenotype. The advantages of the phenotypic change and the role of tumor microenvironment in controlling cellular plasticity and in the emergence of treatment-resistant aggressive forms of prostate cancer is mostly unknown. Here, we discuss the molecular and functional links between neurodevelopmental processes and treatment-induced neuroendocrine plasticity in prostate cancer progression and treatment resistance. We provide an overview of the emergence of neurite-like cells in neuroendocrine prostate cancer cells and whether the reported t-NEPC pathways and proteins relate to neurodevelopmental processes like neurogenesis and axonogenesis during the development of treatment resistance. We also discuss emerging novel therapeutic targets modulating neuroendocrine plasticity.

Baseline Working Memory Predicted Response to Low-Dose Ketamine Infusion in Patients with Treatment-Resistant Depression

2021 ◽  
Author(s):  
Mu-Hong Chen ◽  
Wei-Chen Lin ◽  
Cheng-Ta Li ◽  
Shih-Jen Tsai ◽  
Hui-Ju Wu ◽  
...  
Keyword(s):  
Working Memory ◽  
Depressive Symptoms ◽  
Treatment Response ◽  
Low Dose ◽  
Memory Function ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Ketamine Infusion ◽  
Treatment Groups ◽  
Resistant Depression

Abstract Introduction Pretreatment neurocognitive function may predict the treatment response to low-dose ketamine infusion in patients with treatment-resistant depression (TRD). However, the association between working memory function at baseline and the antidepressant efficacy of ketamine infusion remains unclear. Methods A total of 71 patients with TRD were randomized to one of three treatment groups: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, or normal saline. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (HDRS) at baseline and after treatment. Cognitive function was evaluated using working memory and go-no-go tasks at baseline. Results A generalized linear model with adjustments for demographic characteristics, treatment groups, and total HDRS scores at baseline revealed only a significant effect of working memory function (correct responses and omissions) on the changes in depressive symptoms measured by HDRS at baseline (F=12.862, p<0.05). Correlation analysis further showed a negative relationship (r=0.519, p=0.027) between pretreatment working memory function and changes in HDRS scores in the 0.5 mg/kg ketamine group. Discussion An inverse relationship between pretreatment working memory function and treatment response to ketamine infusion may confirm that low-dose ketamine infusion is beneficial and should be reserved for patients with TRD.

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