Effect of Sodium Benzoate vs Placebo Among Individuals With Early Psychosis: A Randomized Clinical Trial.

Importance: There is evidence that sodium benzoate (BZ) may be an effective adjunctive treatment for schizophrenia. The clinical efficacy of BZ has been investigated in chronic schizophrenia; however, the efficacy of this agent has not been studied in individuals with early psychosis. Objective: To examine the clinical efficacy of the adjunctive use of BZ for symptoms in people with early psychosis. Design, Setting, and Participants: Using a placebo-controlled double-masked parallel-group design, this randomized clinical trial was conducted from August 2015 to July 2018. Participants aged between 15 and 45 years experiencing early psychosis were enrolled from 5 major clinical sites in Queensland, Australia. Data analysis was conducted from October 2018 to February 2020. Interventions: Participants were randomized 1:1 (50 participants in each group) to receive 500 mg of sodium benzoate twice daily or placebo for 12 weeks. Main Outcomes and Measures: The primary efficacy outcome was the Positive and Negative Syndrome Scale (PANSS) total score at 12 weeks. The key secondary efficacy measures were (1) the Clinical Global Impression score, (2) the Hamilton Depression Rating Scale for depression, (3) functioning as assessed by the clinician-rated Global Assessment of Function, and (4) the Assessment of Quality of Life Scale. The PANSS subscale scores and impact on selected amino acid concentrations were also assessed. Results: The study comprised 100 participants with a mean (SD) age of 21.4 (4.1) years, of whom 73 (73%) were male individuals. The mean (SD) baseline PANSS score was 75.3 (15.4). We found no improvement in total PANSS score in the BZ group compared with the placebo group. The end result of least-squares mean difference (SE) for total PANSS was -1.2 (2.4) (P = .63). There were no differences in any subscales of the PANSS, any secondary measures, nor any amino acid concentrations. The dose of BZ was well tolerated without any clinically significant treatment-emergent adverse event differences between BZ and placebo groups. Conclusions and Relevance: In this randomized clinical trial, there was no evidence that adjunctive use of 500 mg of BZ twice daily is an effective treatment for individuals with early psychosis. Trial Registration: anzctr.org.au Identifier: ACTRN12615000187549.

Protocol update and statistical analysis plan for CADENCE-BZ: a randomized clinical trial to assess the efficacy of sodium benzoate as an adjunctive treatment in early psychosis.

BACKGROUND: CADENCE-BZ is a multi-centre, parallel-group, double-blind randomized controlled trial designed to examine the clinical efficacy and safety of an accessible food preservative, sodium benzoate, as an add-on treatment for patients with early psychosis. The original study protocol was published in 2017. Here, we describe the updated protocol along with the Statistical Analysis Plan (SAP) for the CADENCE-BZ trial prior to study completion. METHODS AND MATERIALS: Two important changes were made to the original protocol: (1) improvements to our statistical analysis plan permitted a reduction in sample size; and (2) a revision in the secondary outcomes with the intent of reducing redundancy and excluding those measures that were not appropriate as outcomes. CONCLUSIONS: We provide the updated SAP prior to the completion of the study with the intent of increasing the transparency of the data analyses for CADENCE-BZ. The final participants are currently completing the study and the results will be published in the near future. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12615000187549 ). Registered on 26th February 2015.

The prevalence and treatment outcomes of antineuronal antibody-positive patients admitted with first episode of psychosis.

BACKGROUND: Antineuronal antibodies are associated with psychosis, although their clinical significance in first episode of psychosis (FEP) is undetermined. AIMS: To examine all patients admitted for treatment of FEP for antineuronal antibodies and describe clinical presentations and treatment outcomes in those who were antibody positive. METHOD: Individuals admitted for FEP to six mental health units in Queensland, Australia, were prospectively tested for serum antineuronal antibodies. Antibody-positive patients were referred for neurological and immunological assessment and therapy. RESULTS: Of 113 consenting participants, six had antineuronal antibodies (anti-N-methyl-D-aspartate receptor antibodies [n = 4], voltage-gated potassium channel antibodies [n = 1] and antibodies against uncharacterised antigen [n = 1]). Five received immunotherapy, which prompted resolution of psychosis in four. CONCLUSIONS: A small subgroup of patients admitted to hospital with FEP have antineuronal antibodies detectable in serum and are responsive to immunotherapy. Early diagnosis and treatment is critical to optimise recovery. DECLARATION OF INTEREST: None.

The efficacy of sodium benzoate as an adjunctive treatment in early psychosis - CADENCE-BZ: study protocol for a randomized controlled trial.

BACKGROUND: Psychotic disorders affect up to 3% of the population and are often chronic and disabling. Innovation in the pharmacological treatment of psychosis has remained stagnant in recent decades. In order to improve outcomes for those with psychotic disorders, we present a protocol for the trial of a common food preservative, sodium benzoate, as an adjunctive treatment in early psychosis. METHODS: Persons experiencing early psychosis (n = 160) will be recruited through hospitals and community mental health services in Queensland, Australia. Patients will be randomized to receive either 12-week treatment with 1000 mg (500 mg twice daily (BD)) sodium benzoate or placebo. Patients will undergo fortnightly outcome assessments, in addition to weekly ongoing capacity to consent, drug compliance and safety assessments. The primary outcome measure is the Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcomes are Global Assessment of Function (GAF), Assessment of Quality of Life Scale (AQOL), the Activity and Participation Questionnaire (APQ6), International Physical Activity Questionnaires (IPAQ), Simple Physical Activity Questionnaire (SIMPAQ), Physical Activity Questionnaire, Clinical Global Impression (CGI), Hamilton Depression rating Scale-17 items (HDRS), Opiate Treatment Index (OTI) and the Patients' Global Impression of Improvement (PGI-I). As a tertiary objective, changes from baseline to endpoint in to serum markers related to D-alanine, L-alanine, D-serine, L-serine, glycine and glutamate will be investigated. DISCUSSION: Consumers and clinicians are keen to help develop better treatments for those with psychosis. This study, part of the wider Cadence clinical trials platform will examine if a safe and accessible food preservative can help optimize outcomes in those with psychosis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials registry (ANZCTR), ACTRN12615000187549 . Registered on 26 February 2015.

Delirium among children and adolescents in an urban sub-Saharan African setting.

OBJECTIVES: The purpose of this study is to describe the demographic and clinical profile, mortality rates, and effectiveness of a multifaceted treatment approach in hospitalized children and adolescents with delirium referred to psychiatry. METHODS: We report a series of 23 children and adolescents prospectively diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, delirium after referral to a consultation-liaison psychiatry service based in a large, regional, dedicated children's hospital in South Africa. RESULTS: Children and adolescents with delirium referred to psychiatrists appear to represent a subgroup of delirious patients with a high risk of mortality, an underrepresentation of hypoactive cases, and complex, multifactorial, and often uncertain etiologies. A significant minority of these cases may be managed without the use of psychotropic medications. Uncontrolled data provide supportive evidence for the moderate effectiveness of both haloperidol and risperidone in childhood delirium when explicit criteria guiding the use of antipsychotic medications are utilized. CONCLUSIONS: Delirium is an important and underresearched disorder in children and adolescents. Although the evidence base for the use of antipsychotic medications in childhood delirium remains relatively slim, tentative threshold criteria for the use of such medications are suggested by this study. Controlled studies comparing different antipsychotic medications with each other and with nonpharmacological strategies are urgently required.

Delirium in children and adolescents: A systematic review of the literature.

OBJECTIVES: The purpose of this study was to collate all works relating to delirium and probable delirium in children and adolescents published since 1980. METHODS: A systematic review of the literature in all languages published between 1980 and March 2009 was conducted. RESULTS: The literature is limited to small case series and case reports including a total of 217 children or adolescents with definite delirium and a further 136 children and adolescents with "probable delirium." These articles, in addition to unsystematic reviews, overviews, editorials, journal commentaries, and pertinent book chapters, are discussed in relation to prevalence, predisposing and precipitating factors, phenomenology, residual psychopathology, mortality, management, and prevention of delirium in childhood and adolescence. CONCLUSIONS: Delirium is an important but neglected disorder of childhood associated with significant morbidity and high mortality. Current clinical practice for management is based on slim empirical evidence.

Delirium in children with HIV/AIDS.

Delirium in children has received little attention from researchers until very recently, despite being a frequently encountered clinical problem, particularly in the context of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). In this article, we report 3 cases of severe hyperactive delirium occurring in children with advanced HIV/AIDS in the context of probable underlying HIV encephalopathy and complex drug-drug interactions. We also present a hypothesis in relation to HIV-associated delirium as a potential neuropsychiatric manifestation of the immune reconstitution inflammatory syndrome in children commenced on highly active antiretroviral therapy.

The diagnosis and treatment of delirium in children.

Delirium is commonly encountered in the setting of paediatric consultation-liaison psychiatry. However, it is commonly misdiagnosed as current operational diagnostic criteria may be difficult to apply in children. We present a practical approach to eliciting the signs and symptoms of delirium in children and a proposed treatment algorithm which elaborates a variety of environmental management strategies and includes explicit thresholds for the use of antipsychotic medications.