Jayashri Kulkarni

Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders.

Objectives: This guideline provides recommendations for the clinical management of schizophrenia and related disorders for health professionals working in Australia and New Zealand. It aims to encourage all clinicians to adopt best practice principles. The recommendations represent the consensus of a group of Australian and New Zealand experts in the management of schizophrenia and related disorders. This guideline includes the management of ultra-high risk syndromes, first-episode psychoses and prolonged psychoses, including psychoses associated with substance use. It takes a holistic approach, addressing all aspects of the care of people with schizophrenia and related disorders, not only correct diagnosis and symptom relief but also optimal recovery of social function. Methods: The writing group planned the scope and individual members drafted sections according to their area of interest and expertise, with reference to existing systematic reviews and informal literature reviews undertaken for this guideline. In addition, experts in specific areas contributed to the relevant sections. All members of the writing group reviewed the entire document. The writing group also considered relevant international clinical practice guidelines. Evidence-based recommendations were formulated when the writing group judged that there was sufficient evidence on a topic. Where evidence was weak or lacking, consensus-based recommendations were formulated. Consensus-based recommendations are based on the consensus of a group of experts in the field and are informed by their agreement as a group, according to their collective clinical and research knowledge and experience. Key considerations were selected and reviewed by the writing group. To encourage wide community participation, the Royal Australian and New Zealand College of Psychiatrists invited review by its committees and members, an expert advisory committee and key stakeholders including professional bodies and special interest groups. Results: The clinical practice guideline for the management of schizophrenia and related disorders reflects an increasing emphasis on early intervention, physical health, psychosocial treatments, cultural considerations and improving vocational outcomes. The guideline uses a clinical staging model as a framework for recommendations regarding assessment, treatment and ongoing care. This guideline also refers its readers to selected published guidelines or statements directly relevant to Australian and New Zealand practice. Conclusions: This clinical practice guideline for the management of schizophrenia and related disorders aims to improve care for people with these disorders living in Australia and New Zealand. It advocates a respectful, collaborative approach; optimal evidence-based treatment; and consideration of the specific needs of those in adverse circumstances or facing additional challenges.

Reliability and validity of a new Medication Adherence Rating Scale (MARS) for the psychoses

Medication compliance is one of the foremost problems affecting neuroleptic efficacy in psychiatric patients. To date, compliancy has most commonly been assessed with the Drug Attitude Inventory (DAI) developed by Hogan et al. (Hogan, T.P., Awad, A.G., Eastwood, R., 1983. A self-report scale predictive of drug compliance in schizophrenics: reliability and discriminative validity. Psychol. Med. 13, 177-183). The present study identified several deficiencies in the DAI. Using the partial credit version of the Item Response Theory measurement model, the DAI was refined with the aim of greater validity and clinical utility. The new inventory was administered to 66 patients, the majority of whom were diagnosed with schizophrenia. When available, lithium levels and carer ratings of compliance were also recorded and used to verify compliancy. The new inventory appears to be a valid and reliable measure of compliancy for psychoactive medications.

Estrogen - a potential treatment for schizophrenia.

Estrogen has been shown in animal studies to modulate both the dopamine and serotonin neurotransmitter systems - the main neurotransmitters implicated in the pathogenesis of schizophrenia. A double blind, 28 day, placebo-controlled study was conducted with three groups of women of child-bearing age (N=12 in each group) who received standardized antipsychotic medication plus 50mcg transdermal estradiol or 100mcg transdermal estradiol or transdermal placebo. Analyses show that women receiving 100mcg of estradiol made greater improvements in the symptoms of schizophrenia than both the 50mcg estradiol and placebo groups. Women receiving 50mcg estradiol had more improvement in their symptoms compared with the placebo group. The 100mcg estradiol group had significantly lower mean lutenizing hormone (LH) and higher mean prolactin levels across the study period compared with both the 50mcg and placebo groups. The addition of 100mcg adjunctive transdermal estrogen significantly enhanced the treatment of acute, severe psychotic symptoms in women with schizophrenia. The differential response of adding 50mcg versus 100mcg estradiol on the types of symptom affected may be related to the estrogen effect on LH and prolactin. The positive impact of estrogen treatment on psychotic symptoms by a direct effect on dopamine and serotonin systems or via an indirect prolactin-mediated effect may be very useful in the overall treatment of women with schizophrenia.

Gender differences in schizophrenia and first-episode psychosis: a comprehensive literature review

Recent studies have begun to look at gender differences in schizophrenia and first-episode psychosis in an attempt to explain the heterogeneity of the illness. However, a number of uncertainties remain. This paper tries to summarize the most important findings in gender differences in schizophrenia and first-psychosis episodes. Several studies indicate that the incidence of schizophrenia is higher in men. Most of the studies found the age of onset to be earlier in men than in women. Findings on symptoms are less conclusive, with some authors suggesting that men suffer more negative symptoms while women have more affective symptoms. Premorbid functioning and social functioning seem to be better in females than males. However, cognitive functioning remains an issue, with lack of consensus on differences in neuropsychological profile between women and men. Substance abuse is more common in men than women with schizophrenia and first-episode psychosis. In terms of the disease course, women have better remission and lower relapse rates. Lastly, there is no evidence of specific gender differences in familial risk and obstetric complications. Overall, gender differences have been found in a number of variables, and further study in this area could help provide useful information with a view to improving our care of these patients.

An analysis of functional neuroimaging studies of dorsolateral prefrontal cortical activity in depression.

Repetitive transcranial magnetic stimulation (rTMS) is currently undergoing active investigation for use in the treatment of major depression. Recent research has indicated that current methods used to localize the site of stimulation in dorsolateral prefrontal cortex (DLPFC) are significantly inaccurate. However, little information is available on which to base a choice of stimulation site. The aim of the current study was to systematically examine imaging studies in depression to attempt to identify whether there is a pattern of imaging results that suggests an optimal site of stimulation localization. We analysed all imaging studies published prior to 2005 that examined patients with major depression. Studies reporting activation in DLPFC were identified. The DLPFC regions identified in these studies were analysed using the Talairach and Rajkowska-Goldman-Rakic coordinate systems. In addition, we conducted a quantitative meta-analysis of resting studies and studies of serotonin reuptake inhibitor antidepressant treatment. There was considerable heterogeneity in the results between studies. Changes in Brodmann area 9 were relatively consistently identified in resting, cognitive activation and treatment studies included in the meta-analysis. However, there was little consistency in the direction of these changes or the hemisphere in which they were identified. At this stage, the results of imaging studies published to date have limited capacity to inform the choice of optimal prefrontal cortical region for the use in rTMS treatment studies.

Estrogen in Severe Mental Illness: A Potential New Treatment Approach

CONTEXT Accumulating evidence suggests that estrogens may have therapeutic effects in severe mental illnesses, including schizophrenia, via neuromodulatory and neuroprotective activity. OBJECTIVE To compare the efficacy of adjunctive transdermal estradiol with that of adjunctive placebo in the treatment of acute psychotic symptoms. DESIGN Randomized, double-blind study. SETTING Patients were recruited from inpatient acute hospital wards and outpatient clinics of 2 metropolitan Melbourne general hospitals. PARTICIPANTS One hundred two women of childbearing age with schizophrenia. All participants were in an acute or chronic phase of their illness; 73 participants were outpatients and the rest were inpatients. Intervention Patients were randomized to receive 100 microg of transdermal estradiol (n = 56) or transdermal placebo (n = 46) for 28 days. MAIN OUTCOME MEASURES Psychopathological symptoms were assessed weekly with the Positive and Negative Syndrome Scale. RESULTS The addition of 100 microg of transdermal estradiol significantly reduced positive (P < .05) and general psychopathological (P < .05) symptoms during the 28-day trial period compared with women receiving antipsychotic medication alone. CONCLUSION Estradiol appears to be a useful treatment for women with schizophrenia and may provide a new adjunctive therapeutic option for severe mental illness. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00206570.

A Randomized Trial of rTMS Targeted with MRI Based Neuro-Navigation in Treatment-Resistant Depression

The aim of this study is to investigate whether repetitive transcranial magnetic stimulation (rTMS) targeted to a specific site in the dorsolateral prefrontal cortex (DLPFC), with a neuro-navigational method based on structural MRI, would be more effective than rTMS applied using the standard localization technique. Fifty-one patients with treatment-resistant depression were randomized to receive a 3-week course (with a potential 1-week extension) of high-frequency (10 Hz) left-sided rTMS. Thirty trains (5 s duration) were applied daily 5 days per week at 100% of the resting motor threshold. Treatment was targeted with either the standard 5 cm technique (n=27) or using a neuro-navigational approach (n=24). This involved localizing the scalp location that corresponds to a specific site at the junction of Brodmann areas 46 and 9 in the DLPFC based on each individual subjects MRI scan. There was an overall significant reduction in the Montgomery–Asberg Depression Rating Scale scores over the course of the trial, and a better outcome in the targeted group compared with the standard localization group at 4 weeks (p=0.02). Significant differences were also found on secondary outcome variables. The use of neuro-navigational methods to target a specific DLPFC site appears to enhance response to rTMS treatment in depression. Further research is required to confirm this in larger samples, or to establish whether an alternate method based on surface anatomy, including measurement from motor cortex, can be substituted for the standard 5 cm method.

A clinical trial of the effects of estrogen in acutely psychotic women.

This study was a preliminary open clinical trial aimed at exploring the hypothesis that estrogen may provide protection against schizophrenia in women. Eleven women with acute psychotic symptoms, as scored on the BPRS, SAPS and SANS, had 0.02 mg estradiol added to neuroleptic treatment for eight weeks. Their response was compared to seven women with similar symptom severity receiving neuroleptic treatment alone. Both groups had baseline hormonal assays of estrogen, progesterone, LH and FSH and underwent regular psychopathology ratings during the eight weeks. The group receiving the estradiol adjunct showed more rapid improvement in psychotic symptoms compared with the group receiving neuroleptics only. This difference was not sustained for the entirety of the trial. Both groups reached similar levels of recovery by the eighth week. These results suggest that estradiol may have antipsychotic properties and/or act as a catalyst for neuroleptic responsiveness in women with schizophrenia.

Intensity-dependent effects of 1 Hz rTMS on human corticospinal excitability

OBJECTIVES This study explored whether the effects of repetitive transcranial magnetic stimulation (rTMS) on corticospinal excitability are dependent on the stimulation intensity and examined the effect of rTMS on inhibitory function. METHODS Nine normal volunteers received 15min of 1Hz rTMS at 85 and 115% of the resting motor threshold (RMT). Cortical excitability was measured before and after rTMS. RESULTS rTMS at both intensities produced an increase in the RMT but only 115% stimulation reduced the size of motor evoked potentials (MEPs). rTMS had no effects on the cortical silent period or cortical inhibition measured with paired pulse TMS. CONCLUSIONS The effects of 1Hz rTMS on motor cortex excitability are partially dependent on stimulus intensity and the effects of rTMS on motor thresholds and MEP size may differ.

Subject and observer-rated quality of life in schizophrenia

Objective: We aimed to explore the relationship between objectively rated quality of life and subjective measures of social functioning and life satisfaction.