PARIS (FRONTLINE MEDICAL NEWS) – A report that adjunctive minocycline was found safe and effective for treatment of schizophrenia must be considered one of the year’s highlights in the field of psychosis, Pascal Steullet, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

The report came in the form of a meta-analysis conducted by investigators in China and Australia. This was the largest meta-analysis looking at the topic to date, and the only one to include a search of the Chinese language database, which provided three of the eight randomized, placebo-controlled clinical trials that were examined. Seven of the eight randomized trials were double-blind and deemed high quality by widely used criteria, including the Jadad scale and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, noted Dr. Steullet , a neuroscientist at the University of Lausanne (Switzerland).

The studies included 548 schizophrenia patients. The mean duration of the trials was 18.5 weeks, with the longest running 48 weeks. In five trials, minocycline or placebo was added to risperidone monotherapy.

The primary outcome was change in the PANSS (Positive and Negative Syndrome Scale) total psychopathology score, and the positive, negative, and general symptom subscale scores.

The biggest benefit was on PANSS negative symptoms. Minocycline brought significantly greater improvement in this domain than placebo, with a standard mean difference (SMD) of –0.69 and a P value of less than .00001 ( Eur Psychopharmacol. 2017 Jan;27[1]:8-18 ).

“That’s quite a good effect size,” Dr. Steullet commented.

The benefit on PANSS positive symptoms, while statistically significant, was far less robust, with an SMD of –0.22 in favor of minocycline.

The PANSS total psychopathology score favored minocycline with an SMD of –0.64, which Dr. Steullet again deemed “a quite significant effect size.” The PANSS general symptom score also showed a significant benefit in favor of minocycline, with an SMD of –0.45.

Among various secondary endpoints that were evaluated: A significant benefit was found favoring minocycline on the Clinical Global Impressions scale (SMD of –0.53) and the Abnormal Involuntary Movement Scale (SMD of –0.56). However, no differences were found between the minocycline and control groups on the Global Assessment of Functioning Scale , the Extrapyramidal Symptom Rating Scale , or the Calgary Depression Scale for Schizophrenia .

Although the average dose of minocycline prescribed in the eight trials was 171.9 mg/day, dosing strategies varied widely from trial to trial, and the investigators concluded that future studies are needed in order to pin down the optimal dosing and duration.

There was no increase in adverse drug reactions in the minocycline-treated group.

Neurocognitive function as assessed by the MATRICS Consensus Cognitive Battery showed no differences between the minocycline and placebo groups in working memory, problem solving, attention/vigilance, or other elements.

Proposed mechanisms of minocycline’s benefit as adjunctive therapy alongside antipsychotics for schizophrenia include the antimicrobial’s good CNS penetration and its anti-inflammatory effects, which could reduce neuroinflammation, dampen activated microglia, and enhance glutamate neurotransmitters.

The meta-analysis was supported by the University of Macau. Its authors reported having no financial conflicts of interest. Dr. Steullet, who was not involved in the work, also reported having no financial conflicts of interest.


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