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"Psychotic Disorders -- therapy"
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Impact of integrated district level mental health care on clinical and social outcomes of people with severe mental illness in rural Ethiopia: an intervention cohort study
There is limited evidence of the safety and impact of task-shared care for people with severe mental illnesses (SMI; psychotic disorders and bipolar disorder) in low-income countries. The aim of this study was to evaluate the safety and impact of a district-level plan for task-shared mental health care on 6 and 12-month clinical and social outcomes of people with SMI in rural southern Ethiopia.
In the Programme for Improving Mental health carE, we conducted an intervention cohort study. Trained primary healthcare (PHC) workers assessed community referrals, diagnosed SMI and initiated treatment, with independent research diagnostic assessments by psychiatric nurses. Primary outcomes were symptom severity and disability. Secondary outcomes included discrimination and restraint.
Almost all (94.5%) PHC worker diagnoses of SMI were verified by psychiatric nurses. All prescribing was within recommended dose limits. A total of 245 (81.7%) people with SMI were re-assessed at 12 months. Minimally adequate treatment was received by 29.8%. All clinical and social outcomes improved significantly. The impact on disability (standardised mean difference 0.50; 95% confidence interval (CI) 0.35-0.65) was greater than impact on symptom severity (standardised mean difference 0.28; 95% CI 0.13-0.44). Being restrained in the previous 12 months reduced from 25.3 to 10.6%, and discrimination scores reduced significantly.
An integrated district level mental health care plan employing task-sharing safely addressed the large treatment gap for people with SMI in a rural, low-income country setting. Randomised controlled trials of differing models of task-shared care for people with SMI are warranted.
Journal Article
Timely N-Acetyl-Cysteine and Environmental Enrichment Rescue Oxidative Stress-Induced Parvalbumin Interneuron Impairments via MMP9/RAGE Pathway: A Translational Approach for Early Intervention in Psychosis
Abstract
Research in schizophrenia (SZ) emphasizes the need for new therapeutic approaches based on antioxidant/anti-inflammatory compounds and psycho-social therapy. A hallmark of SZ is a dysfunction of parvalbumin-expressing fast-spiking interneurons (PVI), which are essential for neuronal synchrony during sensory/cognitive processing. Oxidative stress and inflammation during early brain development, as observed in SZ, affect PVI maturation. We compared the efficacy of N-acetyl-cysteine (NAC) and/or environmental enrichment (EE) provided during juvenile and/or adolescent periods in rescuing PVI impairments induced by an additional oxidative insult during childhood in a transgenic mouse model with gluthation deficit (Gclm KO), relevant for SZ. We tested whether this rescue was promoted by the inhibition of MMP9/RAGE mechanism, both in the mouse model and in early psychosis (EP) patients, enrolled in a double-blind, randomized, placebo-controlled clinical trial of NAC supplementation for 6 months. We show that a sequential combination of NAC+EE applied after an early-life oxidative insult recovers integrity and function of PVI network in adult Gclm KO, via the inhibition of MMP9/RAGE. Six-month NAC treatment in EP patients reduces plasma sRAGE in association with increased prefrontal GABA, improvement of cognition and clinical symptoms, suggesting similar neuroprotective mechanisms. The sequential combination of NAC+EE reverses long-lasting effects of an early oxidative insult on PVI/perineuronal net (PNN) through the inhibition of MMP9/RAGE mechanism. In analogy, patients vulnerable to early-life insults could benefit from a combined pharmacological and psycho-social therapy.
Journal Article
Pharmacologic Augmentation of Computerized Auditory Training in Chronic Psychosis: Preliminary Findings From a Single-Site, Double-Blind Study
Abstract
Background
Computerized auditory training (AT) modestly improves symptoms, cognition, and functioning in schizophrenia. We assessed whether d-amphetamine (AMPH) or memantine (MEM) can enhance gains from 30-h of AT.
Methods
Antipsychotic-medicated individuals with chronic psychosis (n = 68; mean age 47.03y; M:F = 39:29) completed up to 30 AT sessions (2-3/week; n = 50 completed 30 sessions) in 3 groups: “AMPH group” (AMPH (5 mg po) 1-h before each AT session); “MEM group” (titrated to 10 mg MEM bid and maintained that dose throughout training); “PBO group” (PBO dosed identically to either AMPH or MEM). Primary (PANSS total, MCCB Composite, WHODAS) and secondary (PANSS positive, PANSS negative, YMRS, PHQ-9, PSYRATS) outcome measures were acquired at baseline, after 10, 20, and 30 AT sessions, and 12 weeks post-training. Pill identity (active/PBO) was blind to subjects and staff.
Results
Marginally significant between-group gains for AMPH vs PBO were detected for one of three primary outcomes (WHODAS, P =.050; but not PANSS total or MCCB Composite), and for 3 of 5 secondary clinical outcomes (PANSS positive, YMRS, PSYRATS, P’s≤.027–.049). Within-subject gains over time were detected for primary and secondary clinical measures for AMPH (P’s≤.014–.004) and MEM (P’s≤.02–.001) groups; some of these would not survive conservative correction for multiple comparisons. No measures detected symptom worsening; treatment satisfaction exceeded subjects’ expectations.
Conclusions
Results are mixed; drug-associated gains in several measures vs PBO suggest that these regimens may augment AT-induced functional and clinical improvement in psychosis patients, independent of changes in neurocognition. Assessment in larger samples seems warranted.
Journal Article
The Early Psychosis Intervention Center (EPICENTER): development and six-month outcomes of an American first-episode psychosis clinical service
Background
There is growing evidence that specialized clinical services targeted toward individuals early in the course of a psychotic illness may be effective in reducing both the clinical and economic burden associated with these illnesses. Unfortunately, the United States has lagged behind other countries in the delivery of specialized, multi-component care to individuals early in the course of a psychotic illness. A key factor contributing to this lag is the limited available data demonstrating the clinical benefits and cost-effectiveness of early intervention for psychosis among individuals served by the American mental health system. Thus, the goal of this study is to present clinical and cost outcome data with regard to a first-episode psychosis treatment center within the American mental health system: the Early Psychosis Intervention Center (EPICENTER).
Methods
Sixty-eight consecutively enrolled individuals with first-episode psychosis completed assessments of symptomatology, social functioning, educational/vocational functioning, cognitive functioning, substance use, and service utilization upon enrollment in EPICENTER and after 6 months of EPICENTER care. All participants were provided with access to a multi-component treatment package comprised of cognitive behavioral therapy, family psychoeducation, and metacognitive remediation.
Results
Over the first 6 months of EPICENTER care, participants experienced improvements in symptomatology, social functioning, educational/vocational functioning, cognitive functioning, and substance abuse. The average cost of care during the first 6 months of EPICENTER participation was lower than the average cost during the 6-months prior to joining EPICENTER. These savings occurred despite the additional costs associated with the receipt of EPICENTER care and were driven primarily by reductions in the utilization of inpatient psychiatric services and contacts with the legal system.
Conclusions
The results of our study suggest that multi-component interventions for first-episode psychosis provided in the US mental health system may be both clinically-beneficial and cost-effective. Although additional research is needed, these findings provide preliminary support for the growing delivery of specialized multi-component interventions for first-episode psychosis within the United States.
Trial registration
ClinicalTrials.gov Identifier:
NCT01570972
; Date of Trial Registration: November 7, 2011
Journal Article
Trial of Pimavanserin in Dementia-Related Psychosis
The serotonin-receptor modulator pimavanserin reduces psychosis in patients with Parkinson’s disease. In a randomized discontinuation trial involving patients with psychosis related to several types of dementia, the frequency of relapse over a period of 26 weeks was 13% with pimavanserin and 28% with placebo.
Journal Article