minocycline and Mental-Disorders

Minocycline is a broad-spectrum antibiotic, effective as a chronic treatment for recurrent bacterial infections. Beyond its antibiotic action, minocycline also has important anti-inflammatory, antioxidant and antiapoptotic properties. Its efficacy has therefore been evaluated in many neurodegenerative and psychiatric diseases that have an inflammatory basis. Our aim was to review preclinical and clinical studies performed in neurological and psychiatric diseases whose treatment involved the use of minocycline and thereby to discern the possible beneficial effect of minocycline in these disorders.. Completed and ongoing preclinical studies and clinical trials of minocycline for both neurodegenerative diseases and psychiatric disorders, published from January 1995 to January 2020, were identified through searching relevant databases (https://www.ncbi.nlm.nih.gov/pubmed/, https://clinicaltrials.gov/). A total of 74 preclinical studies and 44 clinical trials and open-label studies were selected.. The results of the nearly 20 years of research identified are diverse. While minocycline mostly proved to be effective in animal models, clinical results showed divergent outcomes, with positive results in some studies counterbalanced by a number of cases with no significant improvements. Specific data for each disease are further individually described in this review.. Despite minocycline demonstrating antioxidant and anti-inflammatory effects, discrepancies between preclinical and clinical data indicate that we should be cautious in analyzing the outcomes. Improving and standardizing protocols and refining animal models could help us to determine if minocycline really is a useful drug in the treatment of these pathologies.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Humans; Mental Disorders; Minocycline; Neurodegenerative Diseases

Pharmacological interventions to treat psychiatric illness have previously focused on modifying dysfunctional neurotransmitter systems to improve symptoms. However, imperfect understanding of the aetiology of these heterogeneous syndromes has been associated with poor treatment outcomes for many individuals. Growing evidence suggests that oxidative stress, inflammation, changes in glutamatergic pathways and neurotrophins play important roles in many psychiatric illnesses including mood disorders, schizophrenia and addiction. These novel insights into pathophysiology allow new treatment targets to be explored. Minocycline is an antibiotic that can modulate glutamate-induced excitotoxicity, and has antioxidant, anti-inflammatory and neuroprotective effects. Given that these mechanisms overlap with the newly understood pathophysiological pathways, minocycline has potential as an adjunctive treatment in psychiatry. To date there have been promising clinical indications that minocycline may be a useful treatment in psychiatry, albeit from small trials most of which were not placebo controlled. Case reports of individuals with schizophrenia, psychotic symptoms and bipolar depression have shown serendipitous benefits of minocycline treatment on psychiatric symptoms. Minocycline has been trialled in open-label or small randomized controlled trials in psychiatry. Results vary, with findings supporting use in schizophrenia, but showing less benefit for nicotine dependence and obsessive-compulsive disorder. Given the limited data from rigorous clinical trials, further research is required. However, taken together, the current evidence suggests minocycline may be a promising novel therapy in psychiatry.

Topics: Animals; Anti-Bacterial Agents; Drug Delivery Systems; Glutamic Acid; Humans; Inflammation; Mental Disorders; Minocycline; Nerve Growth Factors; Oxidative Stress

Due to the anti-inflammatory, antioxidant and anti-apoptotic properties of minocycline, clinical trials have evaluated the potential of this drug to treat several psychiatric and neurological disorders, including major depressive disorder, schizophrenia, bipolar disorder, stroke and amyotrophic lateral sclerosis. This protocol proposes a systematic review (and potential meta-analysis) that aims to identify and critically evaluate randomised controlled trials of minocycline for treating psychiatric and neurological disorders.. PubMed, Embase, Cochrane Central Register of Controlled Clinical Trials, PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL) will be used to identify randomised controlled trials that used minocycline to treat psychiatric and neurological disorders. Double-blind, randomised, controlled, clinical trials of participants aged 18 years or older and written in English will be included in the review. Data will be extracted by two independent reviewers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed and the Cochrane Collaboration's 'Risk of Bias' tool will be used to assess the risk of bias in all studies included in the systematic review. The Grading of Recommendations, Assessment, Development and Evaluation system will be used to access the overall quality of the level of evidence of the studies. If sufficient evidence is identified, a meta-analysis will be conducted using the standardised mean difference approach and reported with 95% CIs. Heterogeneity of evidence will be evaluated using the I. This systematic review will evaluate only published data; therefore, ethical approval is not required. The systematic review will be published in a peer-reviewed journal and presented at relevant research conferences.. CRD42020153292.

Topics: Amyotrophic Lateral Sclerosis; Anti-Inflammatory Agents; Antioxidants; Humans; Mental Disorders; Meta-Analysis as Topic; Minocycline; Systematic Reviews as Topic

Minocycline has neurological anti-inflammatory properties and has been hypothesised to have antipsychotic effects.. The aim of this study was to investigate, using routinely collected United Kingdom primary health care data, whether adolescent men and women are more or less likely to receive an urgent psychiatric referral during treatment for acne with minocycline compared with periods of non-treatment.. A self-controlled case series using United Kingdom Clinical Practice Research Datalink to calculate the incidence rate ratio of urgent psychiatric referrals for individuals, comparing periods during which minocycline was prescribed with unexposed periods, adjusted for age.. We found 167 individuals who were at the time exposed to minocycline for a mean of 99 days and who received an urgent psychiatric referral. There was no difference in psychiatric referral risk during periods of exposure compared with periods of non-exposure: incidence rate ratio first 6 weeks of exposure 1.96, 95% confidence interval 0.82-4.71, p=0.132; incidence rate ratio remaining exposure period=1.97, 95% confidence interval 0.86-4.47, p=0.107.. We found no evidence in support of a protective effect of minocycline against severe psychiatric symptoms in adolescence.

Topics: Acne Vulgaris; Adolescent; Anti-Bacterial Agents; Case-Control Studies; Female; Humans; Male; Mental Disorders; Minocycline; Referral and Consultation; United Kingdom

Animal studies suggest that the antibiotic and microglial activation inhibitor, minocycline, is likely to have a protective effect against the emergence of psychosis but evidence from human studies is lacking. The aim of this study is to examine the effects of exposure to minocycline during adolescence on the later incidence of severe mental illness (SMI).. A historical cohort study using electronic primary care data was conducted to assess the association between exposure to minocycline during adolescence and incidence of SMI. The Incidence Rate Ratio (IRR) was measured using Poisson regression adjusted for age, gender, time of exposure, socioeconomic deprivation status, calendar year and co-medications.. Early minocycline prescription ( n=13,248) did not affect the incidence of SMI compared with non-prescription of minocycline ( n=14,393), regardless of gender or whether or not the data were filtered according to a minimum exposure period (minimum period: IRR 0.96; 95% CI 0.68-1.36; p=0.821; no minimum period: IRR 1.08; 95% CI 0.83-1.42; p=0.566).. Exposure to minocycline for acne treatment during adolescence appears to have no effect on the incidence of SMI.

Topics: Acne Vulgaris; Adolescent; Anti-Bacterial Agents; Cohort Studies; Databases, Factual; Female; Humans; Incidence; Male; Mental Disorders; Minocycline; United Kingdom; Young Adult

Neuroinflammatory disturbances have been closely associated with depression and many other neuropsychiatric diseases. Although targeting neuroinflammatory mediators with centrally acting drugs has shown certain promise, its translation is faced with several challenges especially drug delivery and safety concerns. Here, we report that neuroinflammation-induced behavioral abnormality could be effectively attenuated with immunomodulatory agents that need not to gain brain penetration. In a rat model with intracerebral lipopolysaccharide (LPS) challenge, we validated that ginsenoside Rg1 (Rg1), a well-established anti-inflammatory agent, was unable to produce a direct action in the brain. Interestingly, peripherally restricted Rg1 could effectively attenuate the weight loss, anorexic- and depressive-like behavior as well as neurochemical disturbances associated with central LPS challenge. Biochemical assay of neuroimmune mediators in the periphery revealed that Rg1 could mitigate the deregulation of the hypothalamic-pituitary-adrenal axis and selectively blunt the increase in circulating interleukin-6 levels. Furthermore, these peripheral regulatory effects were accompanied by dampened microglial activation, mitigated expression of pro-inflammatory mediators and neurotoxic species in the central compartment. Taken together, our work suggested that targeting the peripheral immune system may serve as a novel therapeutic approach to neuroinflammation-induced neuropsychiatric disorders. Moreover, our findings provided the rationale for employing peripherally active agents like Rg1 to combat mental disturbances.

Topics: Analysis of Variance; Animals; Body Weight; Central Nervous System Agents; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Eating; Encephalitis; Enzyme-Linked Immunosorbent Assay; Food Preferences; Ginsenosides; Lipopolysaccharides; Male; Mental Disorders; Minocycline; Rats; Rats, Wistar; Serotonin

Topics: Depression; Drug Evaluation, Preclinical; Drug Repositioning; Humans; Mental Disorders; Minocycline; Molecular Targeted Therapy; Psychiatry; Schizophrenia; Warfarin