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Lancet Psychiatry. 2018 Nov;5(11):885-894. doi: 10.1016/S2215-0366(18)30345-6. Epub 2018 Oct 12.

The benefit of minocycline on negative symptoms of schizophrenia in patients with recent-onset psychosis (BeneMin): a randomised, double-blind, placebo-controlled trial.

Author information

1
Neuroscience and Psychiatry Unit, The University of Manchester, Manchester, UK; MAHSC, The University of Manchester, Manchester, UK; Greater Manchester Mental Health NHS Foundation Trust, Prestwich, Manchester, UK. Electronic address: bill.deakin@manchester.ac.uk.
2
Brain Mapping Unit, Department of Psychiatry, Herchel Smith Building for Brain and Mind Sciences, University of Cambridge, Cambridge, UK; Cambridgeshire & Peterborough NHS Foundation Trust, Cambridge, UK.
3
Centre for Psychiatry, Imperial College London, London, UK.
4
Neuroscience and Psychiatry Unit, The University of Manchester, Manchester, UK; Tropical Clinical Trials Unit, Liverpool School of Tropical Medicine, Liverpool, UK.
5
Division of Neuroscience and Experimental Psychology, The University of Manchester, Manchester, UK; Lancashire Care Early Intervention Service, Accrington, UK.
6
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
7
Division of Psychology and Mental Health, The University of Manchester, Manchester, UK; Greater Manchester Mental Health NHS Foundation Trust, Prestwich, Manchester, UK.
8
Division of Psychology and Mental Health, The University of Manchester, Manchester, UK.
9
Sobell Department of Motor Neurosciences and Movement Disorders, UCL Institute of Neurology, London, UK.
10
Neuroscience and Psychiatry Unit, The University of Manchester, Manchester, UK; Institute for Applied Clinical Sciences, Keele University, Guy Hilton Research Centre, Stoke-on-Trent, UK.
11
Institute for Mental Health, University of Birmingham, Birmingham, UK.
12
Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
13
MAHSC, The University of Manchester, Manchester, UK; Greater Manchester Mental Health NHS Foundation Trust, Prestwich, Manchester, UK.
14
Neurology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
15
Stress, Psychiatry and Immunology Lab & Perinatal Psychiatry, The Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.
16
Neuroscience and Psychiatry Unit, The University of Manchester, Manchester, UK.
17
Department for Neuroimaging, King's College London, London, UK.
18
Division of Population Health, Health Services Research and Primary Care, The University of Manchester, Manchester, UK.

Erratum in

Abstract

BACKGROUND:

The antibiotic minocycline has neuroprotective and anti-inflammatory properties that could prevent or reverse progressive neuropathic changes implicated in recent-onset schizophrenia. In the BeneMin study, we aimed to replicate the benefit of minocycline on negative symptoms reported in previous pilot studies, and to understand the mechanisms involved.

METHODS:

In this randomised, double-blind, placebo-controlled trial, we recruited people with a schizophrenia-spectrum disorder that had begun within the past 5 years with continuing positive symptoms from 12 National Health Service (NHS) trusts. Participants were randomly assigned according to an automated permuted blocks algorithm, stratified by pharmacy, to receive minocycline (200 mg per day for 2 weeks, then 300 mg per day for the remainder of the 12-month study period) or matching placebo, which were added to their continuing treatment. The primary clinical outcome was the negative symptom subscale score of the Positive and Negative Syndrome Scales (PANSS) across follow-ups at months 2, 6, 9, and 12. The primary biomarker outcomes were medial prefrontal grey-matter volume, dorsolateral prefrontal cortex activation during a working memory task, and plasma concentration of interleukin 6. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN49141214, and the EU Clinical Trials register (EudraCT) number is 2010-022463-35I.

FINDINGS:

Between April 16, 2013, and April 30, 2015, we recruited 207 people and randomly assigned them to receive minocycline (n=104) or placebo (n=103). Compared with placebo, the addition of minocycline had no effect on ratings of negative symptoms (treatment effect difference -0·19, 95% CI -1·23 to 0·85; p=0·73). The primary biomarker outcomes did not change over time and were not affected by minocycline. The groups did not differ in the rate of serious adverse events (n=11 in placebo group and n=18 in the minocycline group), which were mostly due to admissions for worsening psychiatric state (n=10 in the placebo group and n=15 in the minocycline group). The most common adverse events were gastrointestinal (n=12 in the placebo group, n=19 in the minocycline group), psychiatric (n=16 in placebo group, n=8 in minocycline group), nervous system (n=8 in the placebo group, n=12 in the minocycline group), and dermatological (n=10 in the placebo group, n=8 in the minocycline group).

INTERPRETATION:

Minocycline does not benefit negative or other symptoms of schizophrenia over and above adherence to routine clinical care in first-episode psychosis. There was no evidence of a persistent progressive neuropathic or inflammatory process underpinning negative symptoms. Further trials of minocycline in early psychosis are not warranted until there is clear evidence of an inflammatory process, such as microgliosis, against which minocycline has known efficacy.

FUNDING:

National Institute for Health Research Efficacy and Mechanism Evaluation (EME) programme, an MRC and NIHR partnership.

PMID:
30322824
PMCID:
PMC6206257
DOI:
10.1016/S2215-0366(18)30345-6
[Indexed for MEDLINE]
Free PMC Article

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