Minocycline vs Routine Care for Clinical Symptom Improvement in Schizophrenia

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Minocycline has neuroprotective and anti-inflammatory effects that may be of value for several neurodegenerative disorders, including a possible neuropathic process in schizophrenia.
Minocycline has neuroprotective and anti-inflammatory effects that may be of value for several neurodegenerative disorders, including a possible neuropathic process in schizophrenia.

Treatment with minocycline did not improve negative symptoms or functional impairment over adherence to standard therapy and routine clinical care in patients recently diagnosed with schizophrenia, according to a study published in The Lancet Psychiatry.

The investigators of this double-blind, randomized, controlled study sought to understand the neuroprotective effects of minocycline in patients with recent-onset psychosis and to replicate the therapeutic benefits of minocycline on negative symptoms in a large sample.

Researchers recruited 207 individuals from 12 UK National Health Service trusts diagnosed with first-episode schizophrenia within the past 5 years who presented continuing positive symptoms. Participants were randomly assigned to receive minocycline 200 mg/day for the first 2 weeks, then 300 mg/day (n=104) or matched placebo (n=103) for the remainder of the 12-month study period in addition to continuing routine treatment. The primary outcome was the severity of negative symptoms and their change over time, assessed using the negative symptoms subscale in the Positive and Negative Syndrome Scales (PANSS) during follow-up at 2-, 6-, 9-, and 12-month time points. The positive symptom subscale and total PANSS score, along with functional measures, were secondary outcomes. Primary biomarker outcomes assessed medial prefrontal gray-matter volume, dorsolateral-prefrontal cortex response, and circulating interleukin 6 (IL-6) concentration.

Of 207 participants, 38% dropped out overall; primary outcome scores were available for 66% of the sample at 6 months and 61% of the sample at 12 months. Baseline measures were comparative among both groups. The mean total PANSS scores for both minocycline and placebo groups indicated mild to moderate symptom severity, and participants in both groups were assessed with moderately severe functional impairment. Compared with placebo, minocycline had no significant influence on negative symptom ratings at all follow-up time points. Although mean scores for negative, positive, and depressive symptoms improved in both groups during the study, the difference in treatment effect was minimal: -0.19 (95% CI, -1.23-0.85; P =.73). Biomarker outcomes did not change over time and were not significantly affected by treatment; circulating IL-6 levels and activation of the dorsolateral-prefrontal cortex were not affected. Researchers did not observe any significant difference in the rate of adverse events between the placebo group (67) and the minocycline group (60). The most common adverse events were gastrointestinal, psychiatric, nervous system, and dermatological; only 16 total patients experienced serious adverse events, and no deaths occurred during the study period.

Limitations of the study include a smaller sample of participants retained in the study over 12 months than expected and poor adherence to standard or routine treatments, which could have introduced bias in the results.

The study investigators conclude that treatment with minocycline up to 1 year does not improve symptoms or functional status of patients over routine clinical care within 5 years of a schizophrenia diagnosis. Further studies are needed to provide firmer biomarker evidence of inflammatory processes that minocycline could potentially target in patients with first-episode psychosis.

Disclosures: Multiple authors declare associations with the pharmaceutical industry. Please see original reference for a full list of authors' disclosures.

Reference                    

Deakin B, Suckling J, Barnes TRE, et al. The benefit of minocycline on negative symptoms of schizophrenia in patients with recent-onset psychosis (BeneMin): a randomized, double-blind, placebo-controlled trial [published online October 12, 2018]. Lancet Psychiatry. doi:10.1016/S2215-0366(18)30345-6

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