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Treatment Resistance: A Time-Based Approach for Early Identification in First Episode Psychosis.

ABSTRACT: Although approximately 1/3 of individuals with schizophrenia are Treatment Resistant (TR), identifying these subjects prospectively remains challenging. The Treatment Response and Resistance in Psychosis working group defines <20% improvement as an indicator of TR, though its utility in First Episode Schizophrenia (FES) remains unknown. In a prospective cohort of FES (n = 129) followed up for 5 years, we evaluated two improvement thresholds for 'probable TR'; <20% and <50% based on positive, negative, and total symptoms. We ascertained (1) the ecological validity (i.e., the ability to identify an expected subgroup of 1/3rd of patients); (2) the predictive validity (i.e., ability to predict poor global functioning) and (3) the clinical utility (association with clozapine use at the 5th year). Using the criteria of a total symptom reduction of <50% or negative symptom reduction of <20% resulted in 'probable TR' rates of 37% and 33%, respectively. Using <20% positive or total symptoms criteria resulted in very low rates, indicating minimal utility in FES. <50% total symptom criterion best predicted the global functioning over 5 years. Clozapine use was only predicted by positive symptom criterion. Prospective characterization of TRS is possible at 6 months after FES through a time-based approach using a 50% threshold for symptom change in treatment-adherent patients.

SUBMITTER: Dempster K

PROVIDER: S-EPMC8400307 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVE:The premise of the National Institute of Mental Health Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) is to combine state-of-the-art pharmacologic and psychosocial treatments delivered by a well-trained, multidisciplinary team in order to significantly improve the functional outcome and quality of life for first-episode psychosis patients. The study is being conducted in non-academic (ie, real-world) treatment settings, using primarily extant reimbursement mechanisms. METHOD:We developed a treatment model and training program based on extensive literature review and expert consultation. Our primary aim is to compare the experimental intervention to "usual care" on quality of life. Secondary aims include comparisons on remission, recovery, and cost-effectiveness. Patients 15-40 years old with a first episode of schizophrenia, schizoaffective disorder, schizophreniform disorder, psychotic disorder not otherwise specified, or brief psychotic disorder according to DSM-IV and no more than 6 months of treatment with antipsychotic medications were eligible. Patients are followed for a minimum of 2 years, with major assessments conducted by blinded, centralized raters using live, 2-way video. We selected 34 clinical sites in 21 states and utilized cluster randomization to assign 17 sites to the experimental treatment and 17 to usual care. Enrollment began in July 2010 and ended in July 2012 with 404 subjects. The results of the trial will be published separately. The goal of the article is to present both the overall development of the intervention and the design of the clinical trial to evaluate its effectiveness. CONCLUSIONS:We believe that we have succeeded in both designing a multimodal treatment intervention that can be delivered in real-world clinical settings and implementing a controlled clinical trial that can provide the necessary outcome data to determine its impact on the trajectory of early phase schizophrenia. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT01321177.

Project description:Background:Though olfactory deficits are well-documented in schizophrenia, fewer studies have examined olfactory performance profiles across the psychosis spectrum. The current study examined odor identification, discrimination, and detection threshold performance in first-episode psychosis (FEP) patients diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, major depression with psychotic features, and other psychotic conditions. Method:FEP patients (n = 97) and healthy adults (n = 98) completed birhinal assessments of odor identification, discrimination, and detection threshold sensitivity for lyral and citralva. Participants also completed measures of anticipatory pleasure, anhedonia, and empathy. Differences in olfactory performances were assessed between FEP patients and controls and within FEP subgroups. Sex-stratified post hoc analyses were employed for a complete analysis of sex differences. Relationships between self-report measures and olfactory scores were also examined. Results:Individuals with psychosis had poorer scores across all olfactory measures when compared to the control group. Within the psychosis cohort, patients with schizophrenia-associated psychosis had poorer odor identification, discrimination, and citralva detection threshold scores relative to controls. In schizophrenia patients, greater olfactory disturbance was associated with increased negative symptomatology, greater self-reported anhedonia, and lower self-reported anticipatory pleasure. Patients with mood-associated psychosis performed comparable to controls though men and women in this cohort showed differential olfactory profiles. Conclusions:These findings indicate that olfactory deficits extend beyond measures of odor identification in FEP with greater deficits observed in schizophrenia-related subgroups of psychosis. Studies examining whether greater olfactory dysfunction confers greater risk for developing schizophrenia relative to other forms of psychosis are warranted.

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Treatment Resistance: A Time-Based Approach for Early Identification in First Episode Psychosis.

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