The efficacy and mechanisms of action of N-acetylcysteine as an adjunct treatment for first episode psychosis.

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First episode psychosis (FEP) may lead to devastating, chronic illness. For many individuals with FEP, a progressive worsening of symptoms, decline in cognition, and associated reduction in quality of life is often observed. There is evidence to suggest that this illness progression can be diminished, and perhaps even averted, if appropriate treatments are given at the early stages of illness. N-acetyl cysteine (NAC) is a supplement form of an amino acid antioxidant found naturally in foods such as meat, fish and green leafy vegetables. NAC is currently used for treating some respiratory conditions and paracetamol overdose. NAC boosts the body’s antioxidant defences. There is evidence that the antioxidant defences are impaired in people who suffer from psychotic disorders. Antipsychotic medication is currently the best treatment for FEP; however, sometimes these medications are not effective at treating all of the symptoms of psychosis such as negative and cognitive symptoms. Several studies have shown a significant benefit for NAC in schizophrenia and bipolar disorder when it has been used in addition to antipsychotics; however, its benefits have not yet been determined for individuals with FEP. In this project we will test if NAC administered to young people who have experienced FEP can help to reduce some of the symptoms they experience. We will also investigate whether NAC can help to prevent this early psychotic experience from developing into a chronic disorder. Young people between the ages of 15 - 25 years admitted to the Early Psychosis Prevention and Intervention Centre for treatment of first episode of psychosis (N=162) will be randomised to 2000 mg daily NAC or placebo for 26 weeks, with a further 26-week non-treatment follow-up period, as an addition to treatment as usual (TAU). The primary outcome is reduction in global symptom severity. A range of symptomatic, functioning, quality of life, neuropsychological, neuroimaging and blood biomarkers of inflammation, oxidative and nitrostative stress measures will be included as secondary outcomes. Through this study, we will not only determine the clinical efficacy of NAC as an adjunct treatment for FEP, but potentially unlock some of the neurobiological mechanisms underpinning psychotic disorders.