Dataset Information

Adjunctive nutrients in first-episode psychosis: A systematic review of efficacy, tolerability and neurobiological mechanisms.

ABSTRACT:

Aim

The effects of nutrient-based treatments, including adjunctive vitamin or antioxidant supplementation, have been explored extensively in long-term schizophrenia. However, no systematic evaluation of trials in "first-episode psychosis" (FEP) has been conducted, despite the potential benefits of using these treatments during the early stages of illness. Therefore, we aimed to review all studies examining efficacy, tolerability and the biological mechanisms of action, of nutrient supplementation in FEP.

Methods

A systematic review of electronic databases was conducted from inception to July 2017. All information on feasibility, clinical outcomes and mechanistic findings from nutrient supplementation clinical trials was extracted and systematically synthesized.

Results

Eleven studies with a total of 451 patients with FEP (from 8 independent randomized controlled trials) were eligible for inclusion. Six studies examined omega-3 fatty acids, with inconsistent effects on psychiatric symptoms. However, mechanistic studies found significant improvements in hippocampal neuronal health and brain glutathione. Antioxidants "n-acetyl cysteine" (n = 1) and vitamin C (n = 2) also improved oxidative status in FEP, which was associated with reduced psychiatric symptoms. No benefits were found for vitamin E (n = 1). Finally, one study trialling the amino acid taurine, showed significant improvements in positive symptoms and psychosocial functioning.

Conclusion

There is preliminary evidence that taurine improves outcomes in FEP, whereas effects of omega-3 and antioxidant vitamins/amino-acids are inconsistent; perhaps mainly benefitting patients with high levels of oxidative stress. Future studies should evaluate multifaceted dietary and supplementation interventions in FEP; targeting-specific nutritional deficits and the range of aberrant biological processes implicated in the disorder.

SUBMITTER: Firth J

PROVIDER: S-EPMC6175456 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

Adjunctive nutrients in first-episode psychosis: A systematic review of efficacy, tolerability and neurobiological mechanisms.

Firth Joseph J Rosenbaum Simon S Ward Philip B PB Curtis Jackie J Teasdale Scott B SB Yung Alison R AR Sarris Jerome J

Early intervention in psychiatry 20180321 5

<h4>Aim</h4>The effects of nutrient-based treatments, including adjunctive vitamin or antioxidant supplementation, have been explored extensively in long-term schizophrenia. However, no systematic evaluation of trials in "first-episode psychosis" (FEP) has been conducted, despite the potential benefits of using these treatments during the early stages of illness. Therefore, we aimed to review all studies examining efficacy, tolerability and the biological mechanisms of action, of nutrient supple ...[more]

PMID: 29561067

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Project description:BACKGROUND:First-episode psychosis (FEP) may lead to a progressive, potentially disabling and lifelong chronic illness; however, evidence suggests that the illness course can be improved if appropriate treatments are given at the early stages. Nonetheless, the efficacy of antipsychotic medications is suboptimal, particularly for negative and cognitive symptoms, and more efficacious and benign treatments are needed. Previous studies have shown that the antioxidant amino acid N-acetylcysteine (NAC) reduces negative symptoms and improves functioning in chronic schizophrenia and bipolar disorder. Research is scarce as to whether NAC is beneficial earlier in the course of illness. The primary aim of this study is to determine the efficacy of treatment with adjunctive NAC (2?g/day for 26?weeks) compared with placebo to improve psychiatric symptoms in young people experiencing FEP. Secondary aims are to explore the neurobiological mechanisms underpinning NAC and how they relate to various clinical and functional outcomes at 26- and 52-week follow-ups. METHODS/DESIGN:ENACT is a 26-week, randomised controlled trial of adjunctive NAC versus placebo, with a 26-week non-treatment follow-up period, for FEP. We will be recruiting 162 young people aged 15-25?years who have recently presented to, and are being treated at, the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia. The primary outcome is the Total Score on the Positive and Negative Syndrome Scale which will be administered at baseline, and weeks 4, 8, 12, 26 (primary endpoint), and 52 (end of study). Secondary outcomes include: symptomatology, functioning, quality of life, neurocognition, blood-derived measures of: inflammation, oxidative and nitrosative stress, and magnetic resonance spectroscopy measures of glutathione concentration. DISCUSSION:Targeted drug development for FEP to date has generally not involved the exploration of neuroprotective agents. This study has the potential to offer a new, safe, and efficacious treatment for people with FEP, leading to better treatment outcomes. Additionally, the neuroprotective dimension of this study may lead to a better long-term prognosis for people with FEP. It has the potential to uncover a novel treatment that targets the neurobiological mechanisms of FEP and, if successful, will be a major advance for psychiatry. TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry, ID: ACTRN12618000413224. Registered on 21 March 2018.

Project description:Because early treatment choice is critical in first-episode schizophrenia-spectrum disorders (FES), this meta-analysis compared efficacy and tolerability of individual second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs) in FES. We conducted systematic literature search (until 12 December 2010) and meta-analysis of acute, randomized trials with ?1 FGA vs. SGA comparison; patients in their first episode of psychosis and diagnosed with schizophrenia-spectrum disorders; available data for psychopathology change, treatment response, treatment discontinuation, adverse effects, or cognition. Across 13 trials (n = 2509), olanzapine (seven trials) and amisulpride (one trial) outperformed FGAs (haloperidol: 9/13 trials) in 9/13 and 8/13 efficacy outcomes, respectively, risperidone (eight trials) in 4/13, quetiapine (one trial) in 3/13 and clozapine (two trials) and ziprasidone (one trial) in 1/13, each. Compared to FGAs, extrapyramidal symptom (EPS)-related outcomes were less frequent with olanzapine, risperidone and clozapine, but weight gain was greater with clozapine, olanzapine and risperidone. Pooled SGAs were similar to FGAs regarding total psychopathology change, depression, treatment response and metabolic changes. SGAs significantly outperformed FGAs regarding lower treatment discontinuation, irrespective of cause, negative symptoms, global cognition and less EPS and akathisia, while SGAs increased weight more (p < 0.05-0.01). Results were not affected by FGA dose or publication bias, but industry-sponsored studies favoured SGAs more than federally funded studies. To summarize, in FES, olanzapine, amisulpride and, less so, risperidone and quetiapine showed superior efficacy, greater treatment persistence and less EPS than FGAs. However, weight increase with olanzapine, risperidone and clozapine and metabolic changes with olanzapine were greater. Additional FES studies including broader-based SGAs and FGAs are needed.

Project description:BackgroundThough 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.MethodFEP 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.ResultsIndividuals 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.ConclusionsThese 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.

Dataset Information

Adjunctive nutrients in first-episode psychosis: A systematic review of efficacy, tolerability and neurobiological mechanisms.

Aim

Methods

Results

Conclusion

Publications

Adjunctive nutrients in first-episode psychosis: A systematic review of efficacy, tolerability and neurobiological mechanisms.

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