title: Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment.
abstract: The onset and early course of schizophrenia is associated with subtle loss of grey matter which may be responsible for the evolution and persistence of symptoms such as apathy, emotional blunting, and social withdrawal. Such 'negative' symptoms are unaffected by current antipsychotic therapies. There is evidence that the antibiotic minocycline has neuroprotective properties. We investigated whether the addition of minocycline to treatment as usual (TAU) for 1 year in early psychosis would reduce negative symptoms compared with placebo. In total, 144 participants within 5 years of first onset in Brazil and Pakistan were randomised to receive TAU plus placebo or minocycline. The primary outcome measures were the negative and positive syndrome ratings using the Positive and Negative Syndrome Scale. Some 94 patients completed the trial. The mean improvement in negative symptoms for the minocycline group was 9.2 and in the placebo group 4.7, an adjusted difference of 3.53 (s.e. 1.01) 95% CI: 1.55, 5.51; p < 0.001 in the intention-to-treat population. The effect was present in both countries. The addition of minocycline to TAU early in the course of schizophrenia predominantly improves negative symptoms. Whether this is mediated by neuroprotective, anti-inflammatory or others actions is under investigation.
authors.affiliation: University of Manchester, Manchester, UK. ibchaudhry@btinternet.com
authors.forename: Imran B
authors.initials: IB
authors.lastname: Chaudhry
authors.forename: Jaime
authors.initials: J
authors.lastname: Hallak
authors.forename: Nusrat
authors.initials: N
authors.lastname: Husain
authors.forename: Fareed
authors.initials: F
authors.lastname: Minhas
authors.forename: John
authors.initials: J
authors.lastname: Stirling
authors.forename: Paul
authors.initials: P
authors.lastname: Richardson
authors.forename: Serdar
authors.initials: S
authors.lastname: Dursun
authors.forename: Graham
authors.initials: G
authors.lastname: Dunn
authors.forename: Bill
authors.initials: B
authors.lastname: Deakin
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001938:Brazil; D003072:Cognition Disorders / Q000139:chemically induced / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008911:Minocycline / Q000009:adverse effects / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000517:prevention & control; D010154:Pakistan; D010352:Patient Dropouts; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D014150:Antipsychotic Agents; D018696:Neuroprotective Agents; D008911:Minocycline