Advertisement

Topics

Role of Minocycline in First Episode Psychosis

2014-08-27 03:21:38 | BioPortfolio

Summary

The purpose of this study is to determine whether the addition of minocycline or placebo to treatment as usual (TAU):

1. prevents the accumulation of negative symptoms and intellectual decline following a first episode of non-affective psychosis; and

2. whether minocycline stabilizes the efficacy of antipsychotics.

Description

Background:

There is increasing clinical, neuropsychological and imaging evidence that schizophrenia involves a progressive process at the time of the first episode and later in life. However, it is not clear which systems are affected nor in which parts of the brain. In two Stanley first episode cohorts at Manchester (Stirling et al, 2004,) and in a group of elderly patients with schizophrenia (Gabrovska-Johnson et al 2004), evidence of deterioration in visuo-spatial functions has been found. This implies a right-hemisphere pathology. Other evidence suggests that the initiation of schizophrenia may involve left-sided pathology (Lawrie et al 2002) so it could be that right hemisphere pathology may follow left and give rise to the deficits of chronic schizophrenia (Gabrovska-Johnson et al 2004). If so, early treatment with a neuroprotective agent might prevent the accumulation of deficit symptoms and cognitive impairment.

Minocycline is a tetracycline antibiotic with proven long-term high dose safety in humans, is routinely used to treat acne and rheumatoid arthritis demonstrating that it acts as a non-steroidal anti-inflammatory, as well as an antimicrobial drug. Minocycline, unlike tetracycline, crosses the blood-brain barrier. This and related compounds show neuroprotective properties in rat models of ischemic brain damage, in glutamate neurotoxicity in cell cultures and in a rat model of Huntington's disease in which it slowed progression (Chen et al, 2000; Yrjanheikki et al, 1999). Minocycline delays disease onset and extends survival in amyotrophic lateral sclerotic mice (Shan Zhu et al 2002).

Minocycline has various properties including inhibition of capsases, inhibition of microglial activation, reduced cyclooxygenase-2 expression and reduced prostaglandin E (2) formation. Furthermore, it inhibits the formation of inducible nitric oxide - a mechanism of glial activation. All these mechanisms have been implicated in schizophrenia. All these mechanisms have been implicated in schizophrenia.

Because of its broad spectrum of action, we consider minocycline is an important candidate molecule for the prevention of deterioration in schizophrenia. Based on the evidence so far we propose a randomised double blind placebo controlled study of minocycline added to treatment-as-usual (TAU) in first-episode psychosis.

Study Hypotheses:

- A neurodegenerative process, initially most marked in the left hemisphere, in late adolescence is responsible for the onset of schizophrenia in those at risk.

- Continuation of this process after onset and its extension to the right hemisphere causes accumulation of deficit symptoms and cognitive decline.

- Glutamate antagonism may enhance the antipsychotic effects of dopamine receptor blockade and prevent attenuation of efficacy with long-term treatment.

TREATMENT:

Minocycline is a widely available antibiotic given in doses of 50mg twice daily increasing to 200mgs per day. It has been used very widely and appears to be tolerated well. The study advisor, Dr. Serdar Dursun, has used doses of up to 200mg per day in the treatment of Huntington's disease (Denovan-Wright et al 2002).

It is widely available in Pakistan and Brazil and given in doses of 50mg twice daily increasing to 100mg twice daily (in total 200mg per day) (British National Formulary: BNF maximum dose 200mg per day). As per counselling recommendations in the British National Formulary: "minocycline medication should be swallowed whole with plenty of fluid while sitting or standing", to allow effective absorption. Patients will be counselled that 'the study medication should be swallowed whole with plenty of fluid while standing or sitting.'

Patients will be informed regarding reported side-effects as cited in the BNF these include; nausea, vomiting, diarrhoea, dysphagia, oesophageal irritation, anorexia, dizziness, tinnitus, vertigo, hypersensitivity reactions (rash, exfoliative dermatitis, urticaria, angioedema, anaphylaxis, pericarditis), headache, visual disturbances, hepatotoxicity, pancreatitis, antibiotic associated colitis, blood dyscrasias, exacerbation of systemic lupus erythematosus and myasthenia gravis, rarely photosensitivity, skin, teeth, conjunctiva, tears and sweat discoloration.

NUMBER OF PATIENTS:

Using data from the SOCRATES study, we are able to calculate that 40 patients per treatment arm will detect a group difference on the primary outcome measure, i.e, PANSS, giving a 85% chance of detecting a difference between treatment groups of 4 points. The power estimate is likely to be conservative as there are three treatment groups. The automated CSF measures will detect a 5% group difference with these sample sizes. A minimum of 52 completed patients will be necessary (26 completed patients per treatment group).

Study Advisors:

Prof Bill Deakin(design), Prof Serdar Dursun(scientific), Prof Shon Lewis (clinical), Dr John Stirling (cognition), Dr Paul Richardson (cognition), Prof Graham Dunn (analysis).

Study Design

Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Masking: Double-Blind, Primary Purpose: Treatment

Conditions

First Episode Psychosis

Intervention

Minocycline, Placebo

Location

Department of Neurology, Psychiatry and Psychological Medicine, University of San Paulo
San Paulo
Brazil

Status

Completed

Source

Stanley Medical Research Institute

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:21:38-0400

Clinical Trials [364 Associated Clinical Trials listed on BioPortfolio]

The Benefit of Minocycline on Negative Symptoms in Schizophrenia: Extent and Mechanisms

The purpose of this study is to investigate if minocycline limits the development of negative symptoms in early psychosis and to test via what mechanism of action this change occurs.

Reducing the Duration of Untreated Psychosis

The study examines the possible effect of a community campaign to decrease the duration of untreated psychosis in persons with their first episode of a psychotic disorder.

Minocycline and Tobacco Craving in Smokers With Schizophrenia

Craving for cigarettes is an important aspect that leads to challenges with smoking cessation. Persons with schizophrenia are more likely to smoke and to be heavier smokers than persons wi...

Tracking Service Use and Outcomes II:First Episode Psychosis and Psychotic Disorders Clinic

Main Research questions: 1. Who are the patients referred for treatment at the Psychotic Disorders Clinic? 2. What are the outcomes from treatment for first episode psychosis in mult...

Minocycline for the Treatment of Decreased Mental Function in HIV-Infected Adults

The purpose of this study is to determine the effectiveness of minocycline, an antibiotic, in lessening the decreased mental function sometimes caused by anti-HIV drugs.

PubMed Articles [1457 Associated PubMed Articles listed on BioPortfolio]

Increasing medication adherence and income assistance access for first-episode psychosis patients.

Assertive community treatment for first-episode psychosis programs have been shown to improve symptoms and reduce service use. There is little or no evidence on whether these programs can increase acc...

"Lanthanic Presentation" in First-Episode Psychosis Predicts Long Service Delay: The Challenge of Detecting Masked Psychosis.

Studies of pathways to care in first-episode psychosis have documented a substantial treatment delay occurring after patients enter mental health services. An initial presentation with neurotic rather...

The traumatic experience of first-episode psychosis: A systematic review and meta-analysis.

A psychotic episode may be sufficiently traumatic to induce symptoms of post-traumatic stress disorder (PTSD), which could impact outcomes in first-episode psychosis (FEP). The objectives of this syst...

Social network confidants, duration of untreated psychosis and cannabis use in people with first episode psychosis: An exploratory study.

Reduced social network (SN) might be associated with a longer duration of untreated psychosis (DUP) in people with first episode psychosis (FEP). We aimed at exploring the specific role of SN confidan...

Social functioning in individuals with first episode psychosis: One-year follow-up study.

Improvement in social functioning is important for recovery in first episode psychosis (FEP).

Medical and Biotech [MESH] Definitions

An episode of MYOCARDIAL ISCHEMIA that generally lasts longer than a transient anginal episode but that does not usually result in MYOCARDIAL INFARCTION.

A TETRACYCLINE analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant STAPHYLOCOCCUS infections.

Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.

An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.

Reactions to an event or set of events which are considered to be of pathological degree, that have not developed into a neurosis, psychosis, or personality disorder with fixed patterns.

More From BioPortfolio on "Role of Minocycline in First Episode Psychosis"

Quick Search
Advertisement
 

Relevant Topics

Psychiatry
Psychiatry is the study of mental disorders and their diagnosis, management and prevention.  Conditions include schizophrenia, severe depression and panic disorders among others. There are pharmaceutical treatments as well as other therapies to help...

Alzheimer's Disease
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase  'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...

Schizophrenia
Schizophrenia is a common  serious long-term mental health condition that affects 5 in 1000 in the UK. It causes a range of different psychological symptoms; hallucinations, delusions, muddled thoughts based on the hallucinations or delusions and ch...


Searches Linking to this Trial