Adjunctive minocycline for schizophrenia: A meta-analysis of randomized controlled trials

Xiang, Ying; Zheng, Wei; Wang, Shi Bin; Yang, Xin; Cai, Dong Bin; Ng, Chee H.; Ungvári, Gábor S.; Kelly, Deanna L.; Wang, Xu; Xiang, Yu‐Tao

doi:10.1016/j.euroneuro.2016.11.012

Cited by 71 publications

(53 citation statements)

References 39 publications

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“…In terms of the translatability of these finding, minocycline is currently under investigation as adjunctive therapy for Alzheimer's disease 68 , schizophrenia 69 and multiple sclerosis 70 with mixed results. While some studies report superiority over placebo, for instance in a metanalysis of adjunctive minocycline for schizophrenia 71 , others report little or no therapeutic benefit as well as issues of tolerability of a higher 400 mg dose 68 . Future work determining whether minocycline provides the same cognitive benefits to people with obesity as observed in these rodent studies, as well as investigations into long-term cognitive rescue, are warranted.…”

Section: Discussionmentioning

confidence: 99%

Minocycline-induced microbiome alterations predict cafeteria diet-induced spatial recognition memory impairments in rats

et al. 2020

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Diets rich in sugar and saturated fat are associated with cognitive impairments in both humans and rodents with several potential mechanisms proposed. To test the involvement of diet-induced pro-inflammatory signaling, we exposed rats to a high-fat, high-sugar cafeteria diet, and administered the anti-inflammatory antibiotic minocycline. In the first experiment minocycline was coadministered across the diet, then in a second, independent cohort it was introduced following 4 weeks of cafeteria diet. Cafeteria diet impaired novel place recognition memory throughout the study. Minocycline not only prevented impairment in spatial recognition memory but also reversed impairment established in rats following 4 weeks cafeteria diet. Further, minocycline normalized diet-induced increases in hippocampal pro-inflammatory gene expression. No effects of minocycline were seen on adiposity or dietary intake across the experiments. Cafeteria diet and minocycline treatment significantly altered microbiome composition. The relative abundance of Desulfovibrio_OTU31, uniquely enriched in vehicle-treated cafeteria-fed rats, negatively and significantly correlated with spatial recognition memory. We developed a statistical model that accurately predicts spatial recognition memory based on Desulfovibrio_OTU31 relative abundance and fat mass. Thus, our results show that minocycline prevents and reverses a dietary-induced diet impairment in spatial recognition memory, and that spatial recognition performance is best predicted by changes in body composition and Desulfovibrio_OTU31, rather than changes in pro-inflammatory gene expression.

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Section: Discussionmentioning

confidence: 99%

Minocycline-induced microbiome alterations predict cafeteria diet-induced spatial recognition memory impairments in rats

et al. 2020

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“…Yet, the immunomodulatory effect of minocycline has been successfully used in the treatment of the adverse events of immunotherapy in noncancer conditions 34 and treated psychosis that may be associated with immunotherapy. 35 However, minocycline or its metabolites could interact with the immune system and triggers severe autoimmune conditions, 36,37 thus, cancer patients on minocycline should be carefully monitored, 38 especially if they are receiving immunotherapy. Underlying genetics mechanism was also proposed as another explanation for the minocyclineinduced autoimmune phenomena.…”

Section: Discussionmentioning

confidence: 99%

Minocycline Reduces Chemoradiation-Related Symptom Burden in Patients with Non-Small Cell Lung Cancer: A Phase 2 Randomized Trial

Wang

Shi

Mendoza

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

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Using a low toxic agent that potentially with anti-inflammatory proprieties, minocycline, we conducted Phase II randomized placebo controlled trial and observed positive effect of reducing fatigue and other symptoms in patients undergoing CRT for NSCLC.Purpose: In patients with non-small cell lung cancer (NSCLC), concurrent chemoradiation therapy (CRT) exacerbates a cluster of difficult-to-manage symptoms, especially cancer-related fatigue. Minocycline is a readily available, low-cost antibiotic with antiinflammatory properties. We conducted a phase 2 randomized, doubleblinded, placebo-controlled trial to investigate the effect of minocycline in reducing CRT-symptom burden in NSCLC. Methods and Materials: Patients with NSCLC scheduled to receive CRT provided consent and were randomized to receive either minocycline (100 mg twice daily) or a matching placebo during 6 to 7 weeks of CRT. Patient-reported fatigue and other symptoms were assessed on MD Anderson Symptom Inventory weekly from the start of CRT for 12 weeks. The primary outcome was 12-week (AE2 days) area under the curve for symptom burden, which was compared between treatment groups. Results: Forty of 49 enrolled patients (80%) were evaluable (19 on minocycline and 21 on placebo). There were no grade 3 þ adverse events related to the study medication. Fatigue was significantly reduced in the minocycline group compared with placebo group during the 12-week trial period (area under the curve Z 31.2 AE 14.2 vs 45.0 AE 20.9, P Z .011), with a large effect size (Cohen's d Z 0.77). Pain (Cohen's d Z 0.54) and shortness of breath (Cohen's d Z 0.55) were also significantly reduced in the minocycline group (all P < .05).

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“…Additionally, minocycline was reported to improve cognitive symptomatology in some of the studies, but cognitive measures were not included in the analysis. A more recent meta-analysis with eight trials including a total of 548 participants with schizophrenia, found that minocycline was superior to placebo for PANSS total and all subscales, including the positive subscale, but was not superior to placebo when analyzed based on tests of cognitive function [55]. …”

Section: Treatmentsmentioning

confidence: 99%

“…Although these trials reported no serious side effects compared to placebo [55], it is critical to keep in mind the potential activation of autoimmune disorders such as lupus, thyroiditis, and hepatitis with minocycline administration [42]. …”

Section: Treatmentsmentioning

confidence: 99%

Targeting the Immune System With Pharmacotherapy in Schizophrenia

Melbourne

Feiner

Rosen

et al. 2017

Curr Treat Options Psych

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Adjunctive minocycline for schizophrenia: A meta-analysis of randomized controlled trials

Cited by 71 publications

References 39 publications

Minocycline-induced microbiome alterations predict cafeteria diet-induced spatial recognition memory impairments in rats

Minocycline-induced microbiome alterations predict cafeteria diet-induced spatial recognition memory impairments in rats

Minocycline Reduces Chemoradiation-Related Symptom Burden in Patients with Non-Small Cell Lung Cancer: A Phase 2 Randomized Trial

Targeting the Immune System With Pharmacotherapy in Schizophrenia

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