Association of symptom severity and cerebrospinal fluid alterations in recent onset psychosis in schizophrenia-spectrum disorders - An individual patient data meta-analysis.

Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorders(SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta-analysis, investigating the association of BCB disruption and cerebrospinal fluid (CSF) alterations with symptom severity in first-episode psychosis (FEP) and recent onset psychotic disorder (ROP) individuals, with a focus on sex-related differences. Data was collected from PubMed and EMBASE databases. FEP, ROP and high-risk syndromes for psychosis IPD were included if routine basic CSF-diagnostics were reported. Risk of bias of the included studies was evaluated. Random-effects meta-analyses and mixed-effects linear regression models were employed to assess the impact of BCB alterations on symptom severity. Published (6 studies) and unpublished IPD from n = 531 individuals was included in the analyses. CSF was altered in 38.8 % of individuals. No significant differences in symptom severity were found between individuals with and without CSF alterations (SMD = -0.17, 95 %CI -0.55-0.22, p = 0.341). However, males with elevated CSF/serum albumin ratios or any CSF alteration had significantly higher positive symptom scores than those without alterations (SMD = 0.34, 95 %CI 0.05-0.64, p = 0.037 and SMD = 0.29, 95 %CI 0.17-0.41p = 0.005, respectively). Mixed-effects and simple regression models showed no association (p > 0.1) between CSF parameters and symptomatic outcomes. No interaction between sex and CSF parameters was found (p > 0.1). BCB disruption appears highly prevalent in early psychosis and could be involved in positive symptoms severity in males, indicating potential difficult-to-treat states. This work highlights the need for considering BCB breakdownand sex-related differences in SSDs clinical trials and treatment strategies.

Making meaning of multimorbidity and severe mental illness: A viewpoint.

People living with severe mental illness, such as schizophrenia and bipolar affective disorder, frequently experience poorer physical health compared to those without mental illness. This issue has hitherto been approached through the disease-centred construct of comorbidity, where subsequent conditions are viewed as secondary to an 'index condition'. In contrast, this Viewpoint sets out to explain why multimorbidity, a patient-centred concept that instead refers to the coexistence of multiple chronic illnesses, is a more versatile and robust framework for tackling the issue of poor physical health in people with severe mental illness. In establishing this argument, this Viewpoint has sought to address three key areas. First, this article will discuss the epidemiology of both physical and psychiatric multimorbidity, with respect to how they manifest at greater frequency and at younger ages in people with severe mental illness. Second, the profound consequences of this multimorbidity burden will be explored, with respect to the 'three D's' of death (premature mortality), disability (functional impacts) and deficit (health-economic impacts). Finally, the utility of multimorbidity as a framework will be illustrated through a proposal for a three-dimensional multimorbidity construct composed of (1) quantity, (2) severity and (3) duration of an individual's chronic illnesses. Consequently, this Viewpoint aims to capture why it is necessary for modern psychiatry to grasp the concept of multimorbidity to facilitate holistic healthcare for people living with severe mental illness.

Experiences of individuals presenting to the emergency department for mental health reasons: A systematic mixed studies review.

OBJECTIVE: Emergency departments the world over have seen substantial increases in the number of individuals presenting for mental health reasons. However, we have a limited understanding of their experiences of care. The aim of this review was to systematically examine and synthesise literature relating to the experiences of individuals presenting to emergency department for mental health reasons. METHODS: We followed Pluye and Hong's seven-step approach to conducting a systematic mixed studies review. Studies were included if they investigated adult mental health experiences in emergency department from the users' perspective. Studies describing proxy, carer/family or care provider experiences were excluded. RESULTS: Sixteen studies were included. Thematic synthesis identified three themes and associated subthemes. Theme 1 - ED staff can make-or-break and ED experience - comprised: Feeling understood and heard; Engaging in judgement-free interactions; Receiving therapeutic support; Being actively and passively invalidated for presenting to the ED; and Once a psych patient, always a psych patient. Theme 2 - Being in the ED environment is counter-therapeutic - comprised: Waiting for an 'extremely' long time; and Lacking privacy. Theme 3 was Having nowhere else to go. CONCLUSIONS: The experiences described by individuals presenting to emergency department for mental health reasons were mostly poor. The results illustrate a need for increased mental health education and training for all emergency department staff. Employment of specialist and lived experience workers should also be prioritised to support more therapeutic relationships and emergency department environments. In addition, greater investment in mental health systems is required to manage the current crisis and ensure future sustainability.

The effectiveness and tolerability of pharmacotherapy for psychosis in 22q11.2 Deletion Syndrome: A systematic review.

OBJECTIVE: The 22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion in humans with over 180 phenotypic expressions. Approximately 30-40% of affected individuals will develop psychosis and 25% meet the criteria for schizophrenia. Despite this, pharmacotherapy for managing psychosis in 22q11.2DS is poorly understood and 22q11.2DS psychosis is frequently labelled as treatment resistant. The objectives of this paper are to evaluate the effectiveness and tolerability of pharmacotherapy for 22q11.2DS psychosis and evaluate the evidence for treatment resistance. METHOD: A systematic search was performed using CINAHL, The Cochrane Library (Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials and Cochrane Clinical Answers), EMBASE, PsycINFO, PubMed, Scopus and Web of Science Core Collection from inception to December 2022. It yielded 39 case reports, 6 case series and 1 retrospective study which met the inclusion criteria. RESULTS: Based on the current literature, individuals with 22q11.2DS psychosis experience a greater rate of medical co-morbidities such as cardiac arrhythmias, seizures and movement disorders, which complicate pharmacotherapy. Poor tolerability rather than poor clinical response motivates the switching of antipsychotics, which may explain the labelling of treatment resistance in the literature. CONCLUSION: There are insufficient data to recommend a single antipsychotic for 22q11.2DS psychosis. Nonetheless, with proactive management of co-morbidities, antipsychotic medication in 22q11.2DS psychosis is an effective treatment commonly resulting in improvement in quality of life.

Achieving gender equity in academic psychiatry - barriers to involvement and solutions for success.

OBJECTIVE: Women face considerable barriers in pursuing careers in academic psychiatry. METHODS: A group of Australian and New Zealand academic women psychiatrists convened in September 2022 to identify and propose solutions to increase opportunities for women in academic psychiatry. RESULTS: Limiting factors were identified in pathways to academia including financial support, engagement and coordination between academia and clinical services, and flexible working conditions. Gender biases and the risk of burnout were additional and fundamental barriers. Potential solutions include offering advanced training certificates to enable trainees to commence a PhD and Fellowship contemporaneously; improved financial support; expanding opportunities for research involvement; establishing mentoring opportunities and communities of practice; and strategies to enhance safety at work and redress gender bias and imbalance in academia. CONCLUSIONS: Support for women in research careers will decrease gender disparity in academic psychiatry and may decrease problematic gender bias in research. Fellows and trainees, the RANZCP, universities, research institutes, governments, industry and health services should collaborate to develop and implement policies supporting changes in working conditions and training. Facilitating the entry and retention of women to careers in academic psychiatry requires mentoring and development of a community of practice to provide and enable support, role modelling, and inspiration.

A systematic review of modified electroconvulsive therapy (ECT) to treat delirium.

BACKGROUND: Delirium is costly for patients, carers, and healthcare systems. In addition, non-pharmacological and pharmacological management of delirium is challenging. Electroconvulsive therapy (ECT) has been proposed and used as an anecdotal treatment of delirium in clinical practice. However, the efficacy and safety of this approach are not well understood. OBJECTIVE: To synthesise and review the evidence relating to the safety and efficacy of ECT as a treatment for delirium. METHODS: A systematic review was completed according to PRISMA guidelines using the PubMed, CINAHL, Cochrane Library, and PsycINFO databases. Studies were eligible for inclusion if modified ECT was used to treat delirium symptoms. ECT for delirium in people with neuroleptic malignant syndrome, catatonia, or confusional states associated with acute primary psychiatric conditions were excluded. All included records were first ranked using the hierarchy of evidence-based medicine; quality was then assessed using the Joanna Briggs critical appraisal checklists. Pooled data across the cases identified were analysed using descriptive statistics. RESULTS: Of 1226 records screened, 10 studies met inclusion criteria: six case reports, three case series, and one quasi-experimental study. The literature base was of mixed quality. A single quasi-experimental study was assessed to be of 'fair' quality, the remainder of the case series and case reports were rated as 'poor' to 'fair' quality. A total of only 40 individual people with delirium who were treated with ECT were identified. In 33/40 cases, the aetiology of delirium was substance withdrawal. The number of ECT treatments administered ranged from 1 to 13. ECT was reported to positively contribute towards treatment of delirium in all cases, although objective measures of improvement were reported in only 6/13 patient cases from case reports and case series (46%). The singular quasi-experimental study reported a statistically significant decrease in duration of delirium, time spent in physical restraint, and in benzodiazepine requirement when ECT was used as an adjunct in benzodiazepine withdrawal delirium. When adverse events were described these included mild confusion and memory deficits; all were reported as time limited and reversible. Considerable limitations in the quality of the evidence base were identified, including the risk of selection, publication and reporting bias. Much data reporting on safety and efficacy of ECT in delirium was missing. CONCLUSION: There is insufficient literature to support modified ECT as a clinical treatment for delirium. The few studies identified were generally of weak evidence lacking important data on safety and objective outcome measures, and not including populations with broad delirium aetiologies. Further research using more robust methodologies and broader populations (age, aetiology) of people with delirium treated with ECT is needed.

Anti-glutamic acid decarboxylase antibody screening in first-episode psychosis.

OBJECTIVE: The Royal Australian and New Zealand College of Psychiatrists recommends screening for a range of antibodies in first-episode psychosis, including anti-glutamic acid decarboxylase antibodies. Glutamic acid decarboxylase antibody-associated encephalitis occurs with high antibody titres and may cause cognitive dysfunction, seizures and psychiatric symptoms. However, glutamic acid decarboxylase antibodies are more frequently found in lower titre in association with other autoimmune disorders (such as diabetes mellitus type 1) and in healthy individuals. The utility of testing unselected populations of consumers with psychosis is unclear. The psychiatric manifestations of this disorder are also poorly described. METHODS: First, systematic review of cohort and case-control studies that tested for IgG glutamic acid decarboxylase antibodies in psychiatric populations was conducted. Random-effects meta-analysis of odds ratio for antibody positivity in cases with psychosis and controls assessed prevalence. Second, literature review of all published cases and case series of glutamic acid decarboxylase antibody-associated limbic encephalitis was assessed for frequency and description of psychotic symptoms. RESULTS: There were 17 studies, in which 2754 individuals with psychotic disorders were tested for glutamic acid decarboxylase IgG antibodies. Thirty-one consumers with psychosis (0.7%) had positive glutamic acid decarboxylase antibodies compared to 24 controls (1.0%), all at low titre and not fulfilling diagnostic criteria for autoimmune encephalitis. Meta-analysis found no significant difference in rates of glutamic acid decarboxylase antibody positivity (odds ratio = 1.8, 95% confidence interval: [0.90, 3.63]). Literature review found 321 cases of glutamic acid decarboxylase antibody-associated limbic encephalitis, with psychosis in 15 (4.3%) cases. Clinical screening would have identified all cases that presented to psychiatric services. CONCLUSION: Glutamic acid decarboxylase antibodies were uncommon in consumers with psychosis, with no significant difference in prevalence from controls and no cases of encephalitis identified. In cases with established glutamic acid decarboxylase antibody-associated limbic encephalitis, psychotic symptoms were uncommon and identifiable by clinical assessment. Targeted antibody testing guidelines should be further considered.

Frailty and Treatment-Resistant Schizophrenia: A Retrospective Cohort Study.

Frailty, a state of reduced physiological reserve, has not been studied in consumers with treatment-resistant schizophrenia, despite known elevated rates of comorbidity and psychosocial impairment. This study applies a frailty index to the electronic medical records of 78 adults with treatment-resistant schizophrenia, aged 18-64 years, to determine the prevalence and characteristics of frailty (defined as a frailty index score > 0.21). The mean frailty index score was 0.24 (SD = 0.091, range = 0.061-0.54), with 52.6% of the population categorised as frail (40.0% in those aged 18-39 years). Frailty was positively correlated with age and psychiatric illness severity. This study provides novel evidence that individuals with treatment-resistant schizophrenia have a high rate of frailty and become frail at a younger age. Routine frailty assessments could be used to trigger the delivery of appropriate interventions, which have the potential to improve life expectancy and quality of life.

A guide to support trainee's success in the psychotherapy written case submission.

OBJECTIVE: Many trainees find the Psychotherapy Written Case (PWC) requirement of the Royal Australian and New Zealand College of Psychiatrists training program challenging. The skills developed and assessed through this experience are critical to the competencies expected of a psychiatrist. However, the process of psychodynamic psychotherapy is often dramatically different from the expectations associated with early clinical placements in acute psychiatric settings. To support trainees in achieving success in the PWC, a guide to the written report was developed based on a review of existing resources and various stakeholder perspectives. CONCLUSIONS: The submission should reflect a training case rather than an idealised or fictionalised story attempting to demonstrate the therapist's competence. The PWC submission must meet the requirements of a general psychiatric report and provide a considered reflection on the experience of the novice therapist.

Formulation in psychiatry - a guide to developing competence.

OBJECTIVE: This paper highlights the importance of psychiatric formulation and provides guidance to those learning the art of formulation. To achieve this, we explore the guidance on formulation that has been previously published in Australasian Psychiatry, identify the key components of psychiatric formulation, and outline an approach to comprehensive formulation in routine clinical practice. CONCLUSION: Formulation is the foundation of good psychiatric practice but presents a considerable challenge to the novice practitioner. Understanding the ingredients of formulation and a method for meaningfully putting these together will guide deliberate practice to learn the art of psychiatric formulation.

Rates of treatment-resistant schizophrenia from first-episode cohorts: systematic review and meta-analysis.

BACKGROUND: Treatment-resistant schizophrenia (TRS) is associated with high levels of functional impairment, healthcare usage and societal costs. Cross-sectional studies may overestimate TRS rates because of selection bias. AIMS: We aimed to quantify TRS rates by using first-episode cohorts to improve resource allocation and clozapine access. METHOD: We undertook a systematic review of TRS rates among people with first-episode psychosis and schizophrenia, with a minimum follow-up of 8 weeks. We searched PubMed, PsycINFO, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews, and meta-analysed TRS rates from included studies. RESULTS: Twelve studies were included, totalling 11 958 participants; six studies were of high quality. The rate of TRS was 22.8% (95% CI 19.1-27.0%, P < 0.001) among all first-episode cohorts and 24.4% (95% CI 19.5-30.0%, P < 0.001) among first-episode schizophrenia cohorts. Subgroup sensitivity analyses by location of recruitment, TRS definition, study quality, time of data collection and retrospective versus prospective data collection did not lead to statistically significant differences in heterogeneity. In a meta-regression, duration of follow-up and percentage drop-out did not significantly affect the overall TRS rate. Men were 1.57 times more likely to develop TRS than women (95% CI 1.11-2.21, P = 0.010). CONCLUSIONS: Almost a quarter of people with first-episode psychosis or schizophrenia will develop TRS in the early stages of treatment. When including people with schizophrenia who relapse despite initial response and continuous treatment, rates of TRS may be as high as a third. These high rates of TRS highlight the need for improved access to clozapine and psychosocial supports.

Treatment strategies for clozapine-induced nocturnal enuresis and urinary incontinence: a systematic review.

BACKGROUND: Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug reactions, including nocturnal enuresis and urinary incontinence. This side effect can be burdensome and lead to medication nonadherence and psychotic relapse. Evidence to guide treatment of clozapine-induced nocturnal enuresis and urinary incontinence is sparse. We therefore aimed to synthesize the evidence base to guide management for clinicians, patients, and their carers. METHODS: We systematically searched PubMed, Embase, PsycInfo, CINAHL, and the Cochrane Trial Registry databases from inception to May 2021 for publications on management of clozapine-induced nocturnal enuresis and urinary incontinence using a PROSPERO preregistered search strategy. RESULTS: We identified 22 case reports and case series describing 74 patients. Interventions included clozapine dose reduction, nonpharmacological treatment, and pharmacological treatments. Among pharmacological treatments, desmopressin, oxybutynin, trihexyphenidyl, tolterodine, imipramine, amitriptyline, ephedrine, pseudoephedrine, aripiprazole, and verapamil were associated with complete resolution of nocturnal enuresis and urinary incontinence. Balancing evidence for effectiveness against risk of adverse effects, we developed a management framework for clozapine-induced nocturnal enuresis and urinary incontinence. CONCLUSIONS: Following assessment of urological, psychiatric, pharmacological, and common comorbid medical issues, first-line treatments should be nonpharmacological, including bathroom alarms, voiding before bedtime, and nocturnal fluid restriction. If these interventions do not provide adequate relief, aripiprazole should be trialed. Desmopressin may be considered for severe refractory cases, but monitoring for hyponatremia is essential.

Analysing triggers for anti-NMDA-receptor encephalitis including herpes simplex virus encephalitis and ovarian teratoma: results from the Queensland Autoimmune Encephalitis cohort.

BACKGROUND: Anti-N-methyl-D-aspartate-receptor (anti-NMDA-R) encephalitis is a complex autoimmune neuropsychiatric syndrome. Although initially associated with ovarian teratoma, subsequent studies have demonstrated that anti-NMDA-R encephalitis may occur without an identifiable cause or be triggered by viral infection of the central nervous system such as herpes simplex virus encephalitis (HSVE). AIM: To present details from a Queensland cohort analysing triggering events in patients with anti-NMDA-R encephalitis in an Australian context. METHODOLOGY: The authors identified patients with anti-NMDA-R encephalitis diagnosed and managed through public hospitals in Queensland, Australia, between 2010 and the end of 2019. Data collected included demographics, clinical presentation, investigation results, management and outcome measurements. RESULTS: Thirty-one cases of anti-NMDA-R encephalitis were included in the study. Three cases of anti-NMDA-R encephalitis were triggered by prior HSVE, five cases were associated with ovarian teratoma and 23 cases had no identifiable trigger. There were an additional three cases in which anti-NMDA receptor antibodies were present in the context of other disease states but where the patient did not develop anti-NMDA-R encephalitis. Cases triggered by HSVE or associated with ovarian teratoma experienced a more severe disease course compared to cases with no identifiable trigger. All groups responded to immunosuppressive or immunomodulatory therapy. Analysis of clinical characteristics revealed a complex heterogeneous syndrome with some variability between groups. CONCLUSION: In this cohort, the number of cases of anti-NMDA-R encephalitis triggered by HSVE is comparable to those triggered by ovarian teratoma. However, the majority of cases of anti-NMDA-R encephalitis had no identifiable trigger or associated disease process.

Tardive Seizures After Electroconvulsive Therapy.

OBJECTIVES: Seizures that occur spontaneously after termination of an electroconvulsive therapy (ECT) seizure are termed tardive seizures. They are thought to be a rare complication of ECT, influenced by risk factors that affect seizure threshold. However, there has been limited review of tardive seizures with modified ECT. We aimed to review the literature to provide clinical guidance for the use of ECT after tardive seizures. METHODS: PubMed, EMBASE, PsycInfo, and CINAHL databases were searched from inception to May 2021 to identify cases of modified ECT, with evidence of a seizure occurring within 7 days of a terminated ECT seizure. Data for demographic, medical, pharmacological, anesthetic, and ECT variables as well as management strategies were collected. RESULTS: There have been 39 episodes of modified ECT-related tardive seizures published over a period of 40 years. In 97.4% of cases, there was at least 1 identified potential risk factor for seizures, including use of a seizure-lowering medication and/or preexisting neurological injury. Major complications were uncommon (<15% of cases); however, 1 fetal death and 1 subsequent suicide were reported. No case was diagnosed with epilepsy, although around 20% continued on antiepileptic medications. More than half of the included patients were retrialed on ECT, with only 15% developing further tardive seizures. CONCLUSIONS: Seizures that occurred spontaneously after the termination of an ECT seizure are a rare complication of modified ECT. Recommencing ECT after a tardive seizure may occur after review of modifiable seizure risk factors and with consideration of antiepileptic medication and extended post-ECT monitoring.

Enhancing the quality of supervision: description and initial outcomes of a blended-learning approach to RANZCP supervisor accreditation.

OBJECTIVE: Evaluation of a blended learning adaptation of the accreditation process for supervisors in the Royal Australian and New Zealand College of Psychiatrists' (RANZCP) Competency-Based Fellowship Program. METHOD: The adaption of the accreditation process is described, and a mixed-methods approach was taken in its evaluation. Descriptive statistics are presented for participant responses to and engagement with interactive workshop elements. The Wilcoxon signed ranks test was applied to examine the change in participants' confidence in their understanding of the expectations of a supervisor at the commencement and conclusion of the workshop. Free text evaluative responses were subject to qualitative content analysis. RESULTS: Most participants expressed a preference for the blended learning workshop format and indicated that live polling improved the learning experience. Additionally, participants expressed greater confidence in their understanding of the expectations of the supervisor role following workshop completion. CONCLUSIONS: The blended learning approach to supervisor training was preferred by participants and may provide a model to be adopted by other training committees and institutions.

Outcomes of a co-located approach for metabolic health care for people with schizophrenia.

OBJECTIVE: Metabolic syndrome is highly prevalent among people with schizophrenia. This study aims to assess the impact on metabolic and attendance outcomes of a co-located, dedicated, endocrinologist-led metabolic clinic in a stand-alone public community mental health service. METHODS: Demographic and metabolic data on the first 48 consecutive referrals over a 12-month period were retrospectively collected and analysed. Attendance rates at the co-located clinic were compared to the general hospital obesity and diabetes clinics. RESULTS: Clinic attendees had significant reductions in triglycerides and total cholesterol, but not mean weight, BMI, waist circumference, blood pressure or HbA1c. Attendance rates were significantly higher in the co-located clinic compared to the general hospital obesity and diabetes clinics for both initial consult (80.0% vs 51.2%, p < 0.001) and review appointment (64.3% vs 47.6%, p < 0.001). CONCLUSION: The co-location of a specialist metabolic clinic within a mental health service resulted in enhanced engagement and improvement of metabolic health in people with schizophrenia.

Psychiatric management of anti-NMDAR encephalitis: a cohort analysis.

BACKGROUND: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an immune-mediated disorder which requires multi-disciplinary treatment including immunomodulation therapy. First presentation is most commonly to psychiatric services and continuing psychiatric care is required to treat disabling symptoms, such as behaviour disturbance, psychosis and catatonia. There is minimal available evidence to guide symptomatic treatment and concern for increased sensitivity to antipsychotics complicates traditional approaches. METHODS: All cases of cerebrospinal fluid positive anti-NMDAR encephalitis tested in Queensland, Australia were identified. Demographic, clinical and therapeutic data were collected and reviewed by two independent clinicians. Pre-specified variables reflecting possible treatment side effects were compared. RESULTS: The majority of the 30 cases (83%) had early psychiatric symptoms and were treated with antipsychotics (67%), average daily olanzapine equivalence dose of 11.5 mg, prior to immunomodulation therapy. Although there was an 88% reduction in cases with aggression, there was little improvement in psychosis, affective symptoms or catatonia with antipsychotics alone. In the cases with psychiatric symptoms, there was no significant difference in the rate of occurrence of neurological and autonomic symptoms between cases prescribed and not prescribed antipsychotics. CONCLUSIONS: Psychiatric input is imperative for both acute and longer-term management of anti-NMDAR encephalitis. Primary symptomatic treatment should remain immunotherapy and surgery. Antipsychotic medications have particular value in managing agitation and aggression. Potential side effects from antipsychotic treatment are difficult to differentiate from progression of anti-NMDAR encephalitis but there was no evidence in this cohort of increased antipsychotic sensitivity. Treatment with psychotropic medication should be individualised and adjusted during the course of the illness.

Clozapine levels as a predictor for therapeutic response: A systematic review and meta-analysis.

OBJECTIVES: Clozapine levels may be a more useful predictor of therapeutic response than the dose, given the variability in clozapine metabolism between individuals. We therefore systematically reviewed and meta-analysed the impact of clozapine levels on response and/or relapse to provide guidance on optimal clozapine levels. METHODS: We systematically searched PubMed, PsycInfo and Embase for studies exploring clozapine levels and response and/or relapse. Our primary meta-analysis was rates of response above and below clozapine level thresholds of 350 ng/ml and 600 ng/ml. Secondary analyses were undertaken of mean clozapine levels, dose and concentration/dose (C/D) ratio and response and/or relapse. A meta-regression by study duration was conducted. RESULTS: Twenty studies met inclusion criteria. Clozapine levels above 350 ng/ml were associated with statistically significantly higher rates of response (OR 2.27 95% CI 1.40-3.67, p < 0.001), but not above 600 ng/ml (OR 1.40 95% CI 0.85-2.31, p = 0.19). Higher mean clozapine levels were associated with better rates of response (SMD 0.24, 95% CI 0.00-0.49, p = 0.05), and lower rates of relapse (SMD -0.72, 95% CI -1.26 to -0.19, p = 0.008). By contrast, neither clozapine dose nor C/D ratio was associated with differing rates of response. Similarly, study duration did not affect outcome. CONCLUSIONS: Our findings are in keeping with current guidelines that recommend targeting clozapine levels above 350 ng/ml before augmentation is considered. As some clozapine associated ADRs are dose dependent, levels above 600 ng/ml may have an unfavourable risk-benefit ratio.

The Patient Experience of Recovery Following Anti-NMDA Receptor Encephalitis: A Qualitative Content Analysis.

OBJECTIVE: The authors examined patients' perceptions of the factors affecting their recovery from anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, which is a rare, severe immune-mediated neurological disorder. METHODS: Seven patients completed semistructured interviews exploring their experience of recovery. Participants were interviewed between 7 and 41 months after the initiation of treatment. Interviews were transcribed and subjected to qualitative content analysis. RESULTS: Facilitators of recovery included the presence of a support system and treatment-related factors. Barriers to recovery included perceived psychiatric stigma, insufficient illness education, and lifestyle disruptions to accommodate ongoing treatment. Adverse physical, psychological, and neurocognitive sequelae of anti-NMDAR encephalitis continued to affect participants' daily functioning. Most participants described strategies to manage neurocognitive deficits, fatigue, and anxiety. CONCLUSIONS: Anti-NMDAR encephalitis contributes to persistent burden on patients, their families, and health services after the resolution of acute symptoms. Physical, psychological, and cognitive changes contribute to long-term disease morbidity. To optimize recovery and reduce disability, further attention must be directed toward illness education, reducing stigma, and role disruption. Longer-term disability support may benefit those who do not fully recover.

Voltage-gated potassium channel blanket testing in first-episode psychosis: Diagnostic nihilism?

OBJECTIVE: Voltage-gated potassium channel antibodies are implicated in limbic encephalitis and currently included in first-episode psychosis organic screening guidelines. Individuals with high-positive voltage-gated potassium channel titres most commonly present with neurological symptoms as well as sleep, cognitive, behaviour, psychosis and mood disturbance. The significance of low-positive voltage-gated potassium channel antibody titres in psychiatric patients is unclear and has not been previously examined. We aim to describe a statewide cohort of psychiatric patients with low- and high-positive voltage-gated potassium channel titres and explore if this finding influenced clinical management and patient outcomes. METHODS: A retrospective review of all voltage-gated potassium channel antibodies testing performed in public psychiatric services in Queensland, Australia, with comparison of the clinical presentation and long-term outcomes of low- and high-positive voltage-gated potassium channel titre cases. Specific antigen targets (leucine-rich glioma-inactivated protein 1 and contactin-associated protein 2 antibodies) were also assessed. RESULTS: The overall prevalence of voltage-gated potassium channel antibody positivity in Queensland, public, psychiatric service testing was 0.3% (14/4098), with 12 cases of low-positive voltage-gated potassium channel titre, 2 cases of high-positive (leucine-rich glioma-inactivated protein 1 antibody positive) cases and a voltage-gated potassium channel negative contactin-associated protein 2 antibody positive case. No low-positive case developed neurological abnormalities or had abnormal paraclinical investigations. In comparison, both high-positive voltage-gated potassium channel/leucine-rich glioma-inactivated protein 1 cases and the contactin-associated protein 2 antibody positive case rapidly developed neurological symptoms, had abnormal paraclinical testing and improved only with immunotherapy. There was no later development of encephalitic symptoms in the low-positive cases over an average of 1067 days follow-up. CONCLUSION: Voltage-gated potassium channel antibody-associated limbic encephalitis was rare, and always associated with high antibody titres. Low-positive titres were not associated with the development of encephalitis over a long period of follow-up. The value of universal voltage-gated potassium channel antibody screening is unclear, and further prospective studies in first-episode psychosis populations are required.