minocycline and Psychotic-Disorders

Studies have hypothesized that immunological abnormalities might contribute to schizophrenia, and basic science studies, as well as several clinical trials suggest that minocycline could be efficacious in ameliorating both positive and negative symptoms of schizophrenia. In this study we examined the effect of minocycline on schizophrenia in a large randomized controlled trial.. We performed a 16-week, multi-center, double-blind, randomized, placebo-controlled study on 200 subjects with schizophrenia or schizoaffective disorder randomized to receive either minocycline (200 mg/day, n = 100), or placebo (n = 100) as an add-on to anti-psychotic treatment. The primary outcome measure was the PANSS total score.. Mixed models for repeated measures showed no significant difference between minocycline and placebo for total PANSS (p = 0.862), PANSS subscales, CGI or BACS.. Minocycline did not improve symptoms or cognition in schizophrenia.

Topics: Adult; Anti-Bacterial Agents; Antipsychotic Agents; Cognition; Double-Blind Method; Female; Humans; Male; Middle Aged; Minocycline; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The antibiotic minocycline has neuroprotective and anti-inflammatory properties that could prevent or reverse progressive neuropathic changes implicated in recent-onset schizophrenia. In the BeneMin study, we aimed to replicate the benefit of minocycline on negative symptoms reported in previous pilot studies, and to understand the mechanisms involved.. In this randomised, double-blind, placebo-controlled trial, we recruited people with a schizophrenia-spectrum disorder that had begun within the past 5 years with continuing positive symptoms from 12 National Health Service (NHS) trusts. Participants were randomly assigned according to an automated permuted blocks algorithm, stratified by pharmacy, to receive minocycline (200 mg per day for 2 weeks, then 300 mg per day for the remainder of the 12-month study period) or matching placebo, which were added to their continuing treatment. The primary clinical outcome was the negative symptom subscale score of the Positive and Negative Syndrome Scales (PANSS) across follow-ups at months 2, 6, 9, and 12. The primary biomarker outcomes were medial prefrontal grey-matter volume, dorsolateral prefrontal cortex activation during a working memory task, and plasma concentration of interleukin 6. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN49141214, and the EU Clinical Trials register (EudraCT) number is 2010-022463-35I.. Between April 16, 2013, and April 30, 2015, we recruited 207 people and randomly assigned them to receive minocycline (n=104) or placebo (n=103). Compared with placebo, the addition of minocycline had no effect on ratings of negative symptoms (treatment effect difference -0·19, 95% CI -1·23 to 0·85; p=0·73). The primary biomarker outcomes did not change over time and were not affected by minocycline. The groups did not differ in the rate of serious adverse events (n=11 in placebo group and n=18 in the minocycline group), which were mostly due to admissions for worsening psychiatric state (n=10 in the placebo group and n=15 in the minocycline group). The most common adverse events were gastrointestinal (n=12 in the placebo group, n=19 in the minocycline group), psychiatric (n=16 in placebo group, n=8 in minocycline group), nervous system (n=8 in the placebo group, n=12 in the minocycline group), and dermatological (n=10 in the placebo group, n=8 in the minocycline group).. Minocycline does not benefit negative or other symptoms of schizophrenia over and above adherence to routine clinical care in first-episode psychosis. There was no evidence of a persistent progressive neuropathic or inflammatory process underpinning negative symptoms. Further trials of minocycline in early psychosis are not warranted until there is clear evidence of an inflammatory process, such as microgliosis, against which minocycline has known efficacy.. National Institute for Health Research Efficacy and Mechanism Evaluation (EME) programme, an MRC and NIHR partnership.

Topics: Adult; Anti-Bacterial Agents; Clinical Protocols; Double-Blind Method; Female; Humans; Male; Minocycline; Neuroprotective Agents; Psychotic Disorders

The at-risk mental state (ARMS) describes individuals at high risk of developing schizophrenia or psychosis. The use of antipsychotics in this population is not supported, because most individuals with ARMS are unlikely to develop psychosis. Anti-inflammatory treatments and polyunsaturated fatty acids (PUFAs) may have some beneficial effects in the treatment of ARMS. There have been no controlled clinical trials in which researchers have investigated the use of minocycline for ARMS and no trials involving PUFAs in combination with other proposed treatments. There is a need to find effective, tolerable and inexpensive interventions for individuals with ARMS that are available in high-, low- and middle-income countries.. A 6-month intervention study of minocycline and/or omega-3 fatty acids added to treatment as usual (TAU) in patients with ARMS will be conducted in Pakistan using a randomised, placebo-controlled, double-blind factorial design. A total of 320 consenting patients with capacity will be recruited from the community, general practitioner clinics and psychiatric units. Allowing for a 25% dropout rate, we will recruit 59 completing participants into each study arm, and in total 236 will complete the study. We will determine whether the addition of minocycline and/or omega-3 fatty acids to TAU attenuates the rate of transition from ARMS to first-episode psychosis and improves symptoms and/or level of functioning in ARMS. We will also investigate whether any candidate risk factors, such as negative symptoms, influence treatment response in the ARMS group. The primary efficacy endpoint is conversion to psychotic disorder at 12 months after study entry. Analysis will be done according to the intention to treat principle using analysis of variance, chi-square tests and adjusted ORs to assess between-group differences. Cox regression analysis will be used to evaluate potential between-group differences in time to onset of psychosis.. The outcomes of this trial will provide evidence of the potential benefits of minocycline and PUFAs in the treatment of ARMS. Both minocycline and PUFAs are inexpensive, are readily available in low-/middle-income countries such as Pakistan, and if proven, may be safe and effective for treating individuals with ARMS.. ClinicalTrials.gov, NCT02569307 . Registered on 3 October 2015.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Chi-Square Distribution; Clinical Protocols; Dietary Supplements; Double-Blind Method; Fatty Acids, Omega-3; Female; Humans; Intention to Treat Analysis; Male; Mental Health; Minocycline; Pakistan; Proportional Hazards Models; Psychotic Disorders; Research Design; Risk Assessment; Risk Factors; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Outcome; Young Adult

Negative symptoms of psychosis do not respond to the traditional therapy with first- or second-generation antipsychotics and are among main causes of a decrease in quality of life observed in individuals suffering from the disorder. Minocycline, a broad-spectrum tetracyclic antibiotic displaying neuroprotective properties has been suggested as a new potential therapy for negative symptoms. In the two previous clinical trials comparing minocycline and placebo, both added to the standard care, patients receiving minocycline showed increased reduction in negative symptoms. Three routes to neuroprotection by minocycline have been identified: neuroprotection against grey matter loss, anti-inflammatory action and stabilisation of glutamate receptors. However, it is not yet certain what the extent of the benefit of minocycline in psychosis is and what its mechanism is. We present a protocol for a multi-centre double-blind randomised placebo-controlled clinical trial entitled The Benefit of Minocycline on Negative Symptoms of Psychosis: Extent and Mechanism (BeneMin).. After providing informed consent, 226 participants in the early phase of psychosis will be randomised to receive either 100 mg modified-release capsules of minocycline or similar capsules with placebo for 12 months in addition to standard care. The participants will be tested for outcome variables before and after the intervention period. The extent of benefit will be tested via clinical outcome measures, namely the Positive and Negative Syndrome Scale score, social and cognitive functioning scores, antipsychotic medication dose equivalent and level of weight gain. The mechanism of action of minocycline will be tested via blood screening for circulating cytokines and magnetic resonance imaging with three-dimensional T1-weighted rapid gradient-echo, proton density T2-weighted dual echo and T2*-weighted gradient echo planar imaging with N-back task and resting state. Eight research centres in UK and 15 National Health Service Trusts and Health Boards will be involved in recruiting participants, performing the study and analysing the data.. The BeneMin trial can inform as to whether in minocycline we have found a new and effective therapy against negative symptoms of psychosis. The European Union Clinical Trial Register: EudraCT 2010-022463-35 with the registration finalised in July 2011. The recruitment in the trial started in January 2013 with the first patient recruited in March 2013.

Topics: Clinical Protocols; Double-Blind Method; Humans; Magnetic Resonance Imaging; Minocycline; Neuroprotective Agents; Outcome Assessment, Health Care; Psychotic Disorders

Approximately 25% of patients admitted to a hospital as a result of depression are actually suffering from psychotic depression. Psychotic symptoms can be present in patients with either unipolar depression or bipolar depression and can be difficult to treat. It was reported the second-generation tetracycline may exert potential antidepressant effects through its robust neuroprotective activities, which include neurogenesis, antioxidation, and anti-glutamate excitotoxicity, and may direct regulation of pro-inflammatory agents.. This was a 6-week, open-label study to evaluate the efficacy and safety of minocycline in combination with antidepressants in adult inpatients (n=25) diagnosed with major depression with psychotic features (psychotic depression) according to DSM-IV-TR. The primary endpoint was the change from baseline in the Hamilton Depression Rating Scale (HAM-D-21) score from baseline to week 6. Secondary endpoints were changes in the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression (CGI) Scale scores from baseline to week 6. Spontaneously reported adverse events were recorded.. The patients' average age was 46.9±10.2 years. Minocyline (150 mg/day) in combination with antidepressants (fulvoxamine, paroxetine, and sertraline) provided significant improvement in depression. Mean (± SD) HAM-D-21 was reduced to 6.7±1.9 at week 6 from a baseline value of 40.4±2.5. Significant improvement of psychotic symptoms (mean±SD) was indicated by the decrease in BPRS scores from baseline (63.3±8.7) to week 6 (4.6±2.4). No serious adverse events occurred.. These preliminary data suggest that minocycline in combination with antidepressants is effective and well tolerated in the treatment of unipolar psychotic depression. Further studies using larger, double-blind, parallel-group design are warranted to confirm these findings.

Topics: Adult; Antidepressive Agents; Depressive Disorder; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Minocycline; Psychotic Disorders; Treatment Outcome

Topics: Double-Blind Method; Humans; Minocycline; Psychotic Disorders; Schizophrenia

Topics: Double-Blind Method; Humans; Minocycline; Psychotic Disorders; Schizophrenia

In this study, we investigated whether minocycline, a second-generation tetracycline proposed as an add-on to antipsychotics in treatment-resistant schizophrenia (TRS), may affect the expression of Homer and Arc postsynaptic density (PSD) transcripts, implicated in synaptic regulation. Minocycline was administered alone or with haloperidol in rats exposed or not to ketamine, mimicking acute glutamatergic psychosis or naturalistic conditions, respectively. Arc expression was significantly reduced by minocycline compared with controls. Minocycline in combination with haloperidol also significantly reduced Arc expression compared with both controls and haloperidol alone. Moreover, haloperidol/minocycline combination significantly affected Arc expression in cortical regions, while haloperidol alone was ineffective on cortical gene expression. These results suggest that minocycline may strongly affect the expression of Arc as mediated by haloperidol, both in terms of quantitative levels and of topography of haloperidol-related expression. It is noteworthy that no significant pre-treatment effect was found, suggesting that pre-exposure to ketamine did not grossly affect gene expression. Minocycline was not found to significantly affect haloperidol-related Homer1a expression. No significant changes in Homer1b/c expression were observed. These results are consistent with previous observations that minocycline may modulate postsynaptic glutamatergic transmission, affecting distinct downstream pathways initiated by N-methyl-D-aspartate (NMDA) receptor modulation, i.e. Arc-mediated but not Homer1a-mediated pathways.

Topics: Animals; Antipsychotic Agents; Cerebral Cortex; Drug Resistance; Gene Expression; Haloperidol; Homer Scaffolding Proteins; Intracellular Signaling Peptides and Proteins; Ketamine; Male; Membrane Proteins; Minocycline; Nerve Tissue Proteins; Post-Synaptic Density; Psychotic Disorders; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Schizophrenia

A 26-year-old female developed a severe acneiform eruption on her face, chest and back soon after she started taking lithium carbonate for psychosis. Histopathological examination revealed it to be folliculitis, rather than true acne. The eruption continued for six months but was resolved three months after discontinuing the drug. It has not reappeared in the following 3 years.

Topics: Acne Keloid; Adult; Drug Eruptions; Facial Dermatoses; Female; Humans; Japan; Lithium Carbonate; Minocycline; Psychotic Disorders