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.

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

“…Of note, no study to date has focused primary outcomes on the above symptom constructs, although studies in schizophrenia, focusing on negative symptoms, have come the closest in this regard. For example, both a meta-analysis and two recent randomized clinical trials have demonstrated that minocycline (see caveats above) was superior to placebo on the PANSS negative subscale scores and the SANS, particularly the avolition measure (Chaudhry et al, 2012;Ghanizadeh et al, 2014;Oya et al, 2014).…”

Neuroinflammation in Schizophrenia Focused on the Pharmacological and Therapeutic Evidence

“…Similarly, a double blind, randomized placebo-controlled study by Levkovitz et al 142 demonstrated that the add-on treatment of minocycline has a beneficial effect on negative symptoms, cognitive functions and general outcomes in early phase patients with schizophrenia. In a recent randomized doubleblind placebo-controlled clinical trial, minocycline benefitted negative symptoms in early schizophrenia 143 . Despite of the above positive reports, a recent update of efficacy of anti-inflammatory agents to improve symptoms in patients with schizophrenia concluded that minocycline showed no significant effect on symptom severity 144 .…”

Update: Negativsymptome. Psychopathologie, Epidemiologie, Pathophysiologie und Behandlungsoptionen.

“…Der in Fallstudien sowie kleinen Gruppenstudien gefundene Effekt einer Verbesserung der Kognition in einzelnen Domänen konnte in grösseren Plazebo-kontrollierten Doppelblindstudien jedoch nicht nachgewiesen werden [82]. Weitere Substanzen mit initial vielversprechenden Befunden sind das tetrazyklische Antibiotikum Monocyclin, der Nikotinrezeptor-Agonist DMXB-A sowie Hemmer des Glycin-Transporters [83,84]. Diese Befunde konnten allerdings bisher nicht repliziert werden.…”