Multisite Double-Blind Randomised Controlled Study Of Estradiol Plus Antipsychotic Versus Placebo Plus Antipsychotic In The Treatment Of Psychotic Symptoms In Women With Schizophrenia: A Definitive Estrogen Patch Trial (Adept)
Investigators
Professor Jayashri Kulkarni
Professor Michael Berk
Associate Professor Saji Damodaran
Mr Anthony de Castella
Dr Caroline Gurvich
Background
In recent times, gender differences in schizophrenia have received some attention, in particular from an epidemiological and psychopathological perspective. Hormonal studies have been utilised to investigate underlying neuroendocrine disturbances in schizophrenia, but information from these studies has not been used in the development of new gender specific treatment strategies. Overall the treatment of schizophrenia has remained gender-blind. The main gender differences observed in schizophrenia that have international consensus include the later age of onset in women; better response to antipsychotics in women; and more treatment resistant negative symptoms in men. Women have also demonstrated vulnerability to psychotic episodes during menopause, the post-partum period and at low estrogen phases of the menstrual cycle.
Our previous clinical trials in patients with schizophrenia, using estrogen as an adjunctive treatment, have indicated that the estrogen adjunct group showed dramatic earlier improvement, with significant reduction in positive psychotic symptoms by day 3 of treatment. This suggests that estradiol may act as a catalyst for treatment and could prove to be an important adjunctive treatment in the therapy of schizophrenia.
Aims and Hypotheses
The current research aims to conduct an 8 week, three-arm, double-blind, randomized, placebo-controlled, trial across three sites, to investigate the 'estrogen-protection' hypothesis in women with schizophrenia. The study objectives include (a) replicating previous research, thereby providing 'proof of concept' for the potential use of estradiol as a treatment in women with schizophrenia; (b) investigating the effect of an increased dose of estradiol (200mcg transdermal); and, (c) investigating the duration of the "antipsychotic effect" of estradiol. Participants will be assessed on psychopathology and cognitive measures.
Current Status
The project will begin recruitment in August 2006.
THE DIAGNOSIS, BIOMARKER IDENTIFICATION AND MEASUREMENT OF DRUG EFFICACY FOR NEUROLOGICAL AND MENTAL DISORDERS
Investigators
Professor Jayashri Kulkarni
Mr Brian Lithgow
Associate Professor Paul Fitzgerald
Mr Anthony de Castella
Caroline Gurvich
Background
For many neurological and psychiatric conditions, diagnosis is based on qualitative measures. Currently, there are no quantitative techniques for diagnosing many conditions including Parkinson's disease, schizophrenia, major depression. Similarly, quantitative techniques to measure the efficacy of drugs applied to these conditions are also lacking. Therefore, this research seeks to discover, identify and statistically differentiate healthy and neuropathological response biomarkers for these disorders using advanced signal analysis and improved prediction processing with data derived from electrovestibulography.
Electrovestibulography is a variant of brainstem audio evoked response where the recording electrode is rested against the tympanic membrane. Following stimulation of the vestibular system (i.e. a voluntary or involuntary head tilt) a vestibular response is measured. The neural activity output is depicted as a recording signal that can be decomposed to determine the origin of the signal (i.e. muscle artefact; eye movement; vestibular response stemming from the semi-circular canals and otolithic organse). Hence, abnormalities can be distinctive and representative of particular neuronal activity.
Pilot studies have indicated that electovestibulography techniques can provide unique signals for individuals with Meniere's disease, Benign Paroxysmal Positional Vertigo (BPPV), depression and Parkinson's disease. Moreover, electrovestibulography techniques have proved useful in differentiating levels of l-dopa medication in individuals with Parkinson's disease and SSRI's in individuals with depression. It is hypothesised that similar techniques may also be able to differentiate individuals with schizophrenia.
All participants will complete a series of tasks at the Alfred Hospital or Monash University over an approximately four hour period. These include electrovestibulography recordings, an audiogram, frontal brain asymmetry measures (using EEG) as well as a series of questionnaires to screen for depression and cognitive decline and assess symptom severity, fatigue, attention and concentration.
Aims and Hypotheses
The current research aims to compare output of electrovestibulography between Parkinson's disease, schizophrenia, major depressive disorder and age-matched healthy controls in order to determine whether profiles can provide unique biomarkers for different patient populations. In addition, using advanced signal analysis and improved prediction processing, it will be explored whether changes in medication levels can be detected with electrovestibulography. The impact of fatigue levels on output of electrovestibulography will also be measured.
Current Status
The project will begin recruitment in September 2006.
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