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Minocycline does not improve symptoms in recent-onset psychosis

Minocycline failed to reduce negative or other symptoms of schizophrenia in patients with first-episode psychosis, according to data published in The Lancet Psychiatry.

“Whether microglia are activated in an inflammatory state in schizophrenia has become a key research question,” Bill Deakin, PhD, professor of psychiatry at University of Manchester, England, and colleagues wrote. “Minocycline is widely used as a pharmacological inhibitor of microglial activation in experimental animal studies, and its possible efficacy in schizophrenia is a key test of microglial involvement in the disorder.”

The investigators conducted a randomized, double-blind, placebo-controlled trial to determine whether minocycline improved negative symptoms in recent-onset schizophrenia.

Participants with recent-onset schizophrenia (within the past 5 years) and continuing positive symptoms were randomly allocated to receive minocycline at 200 mg per day for 2 weeks, followed by 300 mg per day for the remainder of the 12-month study period (n = 104) or matching placebo (n = 103), along with their continuing treatment.

Researchers examined participants’ negative symptom subscale score via the Positive and Negative Syndrome Scales (PANSS) across follow-ups at 2, 6, 9 and 12 months. They also examined some biomarker outcomes, including medial prefrontal grey-matter volume, dorsolateral prefrontal cortex activation during a working memory task and plasma concentration of interleukin 6.

The researchers reported that minocycline had no effect on any clinical outcome variable in terms of direction, magnitude or statistical significance. Minocycline showed no effect on ratings of negative symptoms compared with placebo in patients with recent-onset psychosis (treatment effect difference = –0.19; 95% CI, –1.23 to 0.85). In addition, minocycline showed no effect on biomarker outcomes, according to the results.

The number of serious adverse events relating to minocycline and placebo did not differ significantly, Deakin and colleague found. In total, 11 in participants in the placebo group and 18 in the minocycline group experienced serious adverse events, which primarily occurred because of admissions for worsening psychiatric state. Gastrointestinal, psychiatric, nervous system and dermatological adverse events were the most commonly reported.

“There is no evidence from the ... study that minocycline treatment for up to 1 year has an effect on the progression or severity of negative symptoms of schizophrenia within the first 5 years of treatment onset,” Deakin and colleagues wrote. “Future studies should also carefully consider the stratification of recruitment and analysis plans, with sufficient numbers of patients included with evidence of an active inflammatory process.” – by Savannah Demko

Disclosures: Deakin reports grants from P1vital and grants and personal fees from Autifony. Please see the study for all other authors’ relevant financial disclosures.