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N-acetyl-cysteine in a double-blind randomized placebo-controlled trial: Towards biomarker guided treatment in early psychosis

Published online by Cambridge University Press:  23 March 2020

P. Conus ,
M. Fournier ,
L. Xin ,
P. Baumann ,
C. Ferrari ,
A. Cousins ,
L. Alameda ,
P. Golay ,
R. Jenni  and
M.S. Kashavan
...Show all authors
P. Conus
Affiliation:
Lausanne University, Psychiatry, Prilly, Switzerland
M. Fournier
Affiliation:
CNP, Psychiatry, Lausanne, Switzerland
L. Xin
Affiliation:
CNP, Psychiatry, Lausanne, Switzerland
P. Baumann
Affiliation:
PGE, Psychiatry, Lausanne, Switzerland
C. Ferrari
Affiliation:
CNP, Psychiatry, Lausanne, Switzerland
A. Cousins
Affiliation:
Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Department of Psychiatry, BostonMAUSA
L. Alameda
Affiliation:
CNP, Psychiatry, Lausanne, Switzerland
P. Golay
Affiliation:
PGE, Psychiatrie, Lausanne, Switzerland
R. Jenni
Affiliation:
CNP, Psychiatrie, Lausanne, Switzerland
M.S. Kashavan
Affiliation:
Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School Department of Psychiatry, BostonMAUSA
C.B. Eap
Affiliation:
CNP, Psychiatry, Lausanne, Switzerland
M. Cuenod
Affiliation:
CNP, Psychiatry, Lausanne, Switzerland
T. Buclin
Affiliation:
Division of clinical Pharmacology, CHUV, Lausanne, Switzerland
R. Gruetter
Affiliation:
Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
L. Seidman
Affiliation:
Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School Department of Psychiatry, BostonMAUSA
K.Q. Do
Affiliation:
CNP, Psychiatrie CHUV, Lausanne, Switzerland

Abstract

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Purpose

Recent evidence points to a critical role of redox dysregulation induced oxidative stress in the pathophysiology of early phases of schizophrenia. An add-on trial with n-acetyl-cysteine (NAC) led to a reduction in negative symptoms in chronic schizophrenia patients. Aim of this study was to explore impact of addition of NAC to standard treatment in early psychosis (EP) patients.

Methods

Double-blind, randomized, placebo-controlled trial of addition of NAC, 2700 mg daily, to antipsychotic treatment over 6 months. Monthly assessment of PANSS, GAF, SOFAS and antipsychotics treatment; quantification of brain glutathione levels (GSHmPFC) by 1H-magnetic-resonance-spectroscopy and of blood cells glutathione (GSHBC) and glutathione peroxidase activity (GPxBC) as marker of oxidation status at the beginning and end of treatment.

Results

Overall, 63 patients were included. Spectroscopy data showed that GSHmPFC increased by +23% in the NAC group, while it tended to decrease by −5% in the placebo group (P = 0.005). No significant difference between NAC and placebo was observed on global changes in negative symptoms, positive symptoms or functional outcome. However, in patients with high-baseline oxidation status (GPxBC>22.3U/gHb), subgroup explorations revealed an improvement of positive symptoms over time compared to patients with low-baseline GPx (P = 0.02).

Conclusions

While addition of NAC induced an increase of brain GSH, it had no impact on symptomatic and functional outcome in EP patients. However, in patients with high oxidation status, addition of NAC leads to significantly greater improvement in positive symptoms. Future studies on antioxidant interventions in EP should consider biomarker-guided treatment.

Disclosure of interest

The authors have not supplied their declaration of competing interest.

Type
e-Poster Viewing: Schizophrenia and other psychotic disorders
Information
European Psychiatry , Volume 41 , Issue S1: Abstract of the 25th European Congress of Psychiatry , April 2017 , pp. s806
Copyright
Copyright © European Psychiatric Association 2017
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