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The European Clozapine Task Force is a group of psychiatrists and pharmacologists practicing in 18 countries under European Medicines Agency (EMA) regulation, who are deeply concerned about the underuse of clozapine in European countries. Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia, a large proportion of them do not have access to this treatment. Concerns about clozapine-induced agranulocytosis and stringent blood monitoring rules are major barriers to clozapine prescribing and use. There is a growing body of evidence that the incidence of clozapine-induced agranulocytosis is very low after the first year of treatment. Maintaining lifelong monthly blood monitoring after this period contributes to unjustified discontinuation of clozapine. We leverage recent and replicated evidence on the long-term safety of clozapine to call for the revision and updating of the EMA’s blood monitoring rules, thus aiming to overcome this major barrier to clozapine prescribing and use. We believe the time has come for relaxing the rules without increasing the risks for people using clozapine in Europe.
This study aimed to evaluate the proportion of Irish medical students exposed to ‘badmouthing’ of different specialities and to ascertain: the degree of criticism of specialities based on the seniority of clinical or academic members of staff; if ‘badmouthing’ influenced student career choice in psychiatry; and attitudes of medical students towards psychiatry as a speciality and career choice.
Methods:
Medical students in three Irish universities were invited to complete an online survey to determine the frequency and effect of non-constructive criticism on choice of medical specialty. The online questionnaire was distributed to Royal College of Surgeons in Ireland (RCSI), University of Galway (UoG) and University College Dublin (UCD) in the academic year 2020–2021.
Results:
General practice (69%), surgery (65%) and psychiatry (50%) were the most criticised specialties. Criticism was most likely to be heard from medical students. 46% of students reported reconsidering a career in psychiatry due to criticism from junior doctors. There was a positive perception of psychiatry with 27% of respondents considering psychiatry as a first-choice specialty.
Conclusions:
Criticism of psychiatry by doctors, academics and student peers negatively influences students’ career choice, which could be contributing to recruitment difficulties in psychiatry.
Clozapine dose assessment in treatment-refractory schizophrenia is complicated. There is a narrow margin between an effective and a potentially toxic dose and wide inter-individual variation in clozapine metabolic capacity. Moreover, factors such as changes in smoking habit, infection/inflammation, co-prescription of certain drugs, notably fluvoxamine, and age alter the dose requirement within individuals. Therapeutic drug monitoring (TDM) of plasma clozapine and N-desmethylclozapine (norclozapine) can help assess adherence, guide dosage and guard against toxicity. This article gives an overview of clozapine pharmacokinetics and factors affecting clozapine dose requirements. It then outlines the procedures and processes of clozapine TDM, from taking the blood sample for laboratory assay or point-of-contact (finger-prick) testing (POCT) to interpreting and acting on the results.
Chronic mania is variably defined but classically recognized as the presence of manic symptoms for more than 2 years without remission. The reported incidence ranges between 6–15% among all patients with bipolar disorders. Although it has been described in psychiatry literature for a long time, it has not yet found a place in current nosological systems
Methods
We present a 32-year-old single and unemployed man who is supported by his family and living with a sudden-onset, continuous illness of 12 years’ duration characterized by a resistant and markedly euphoric and expansive mood with grandiose delusions. Other features such as distractibility, pressured speech, racing thoughts and psychomotor disturbance remain significant but vary and are more responsive to medical interventions. Psychotic symptoms are largely confined to mood-congruent delusions, grandiose and religious, and are reported to have followed the mood disturbance from early on. There is no history of substance use, past psychiatric or medical illness, or head trauma and no evidence of a neurological cause on workup. This gentleman has been treated with a range of mood stabilizers and antipsychotics and two courses of ECT over the years. In the recent years, he has been on a combination of Clozapine, Valproate, and Pregabalin with relatively favorable but inadequate response and limited functional improvement.
Results
Chronic mania lasting for 12 years, in the absence of an organic cause, despite the use of a wide gamut of modern psychotropics, alone and in combination with ECT, and with adequate compliance is an exceptionally rare entity. It poses manifold challenges both in terms of diagnostic considerations and therapeutic approaches. The overlap of symptoms of mania, schizophrenia, and schizoaffective disorders along with chronicity adds a particular layer of complexity. The hallmark of chronic mania is euphoric and expansive mood along with grandiose delusions and the presentation is relatively less centered on sleep disturbance, hypersexuality, and psychomotor agitation as compared to an acute manic episode. It is distinguished from schizophrenia spectrum disorders as it lacks flat or inappropriate affect, incongruent delusions and disorganized thought. Course of illness, prior mood episodes and family history are important in differentiating from a schizoaffective pattern of disease.
Conclusion
Unremitting mania of this duration is unique in its psychiatric morbidity and devastating in its impact on the individual in terms of psychosocial functioning, quality of life, physical health and safety. It also brings unprecedented stress on the family and other support systems.
Lithium is a gold standard maintenance treatment in bipolar affective disorder. It has a narrow therapeutic range, and at higher serum lithium levels there is a risk of adverse effects and toxicity. There are three patterns of lithium intoxication: acute, acute-on-chronic and chronic. We describe risk factors for lithium intoxication, mechanisms of toxicity and clinical symptoms seen in lithium intoxication. We describe both the acute and chronic effects of lithium toxicity. Lithium intoxication may be life-threatening and associated with longer-term sequelae. The management of lithium intoxication involves determining the type of intoxication. We discuss treatment strategies aimed at reducing absorption and increasing elimination of lithium. We discuss clinical indications for extracorporeal methods such as dialysis, which are used to limit the time and degree of exposure of the central nervous system to toxic lithium concentrations. Haemodialysis is the most rapid method of eliminating lithium from the body, but careful monitoring is required. Preventive strategies to mitigate the risk for lithium intoxication are discussed.
This observational study aims to describe the course of the admission and clinical characteristics of admissions to the PICUs in the Phoenix Care Centre, Dublin, Ireland. The authors hypothesised that the length of stay (LOS) would be shorter in male patients as compared to females.
Method
This retrospective cohort study was carried out at the Phoenix Care Centre Dublin, Ireland. Informed consent was not sought as this was a retrospective chart study involving anonymised clinical data which was collected as part of routine clinical care and no items of information were reported that would enable the identification of any subject. We described primary outcomes using frequencies, percentages, mean and standard deviations, median and interquartile ranges (IQR). Between groups comparisons were made using x2 tests for categorical variables; t-tests, ANOVA tests, or Kruskal-Wallis tests, for continuous variables; All analyses were two-tailed, and a P-value ≤ 0.05 was considered statistically significant
Result
Over the study period from Jan 2014 to Jan 2017 inclusive, there were 96 admission episodes to the PICU. The mean age of admitted cases was 37.1 (SD = 11.3) years (range 18–63 years). The mean length of stay (LOS) was 59.3 (SD = 61.0) days (median 39.5 days). All patients were admitted under the Mental Health Act legislation. We identified assault as the primary risk factor for pre-admission 62% (n = 62) to the PICU. Antipsychotic polypharmacy was used in 61% (n = 55) of the admission. The mean daily antipsychotic dosage was 139.4 % (SD = 65.1) of BNF maximum daily dose. A diagnosis of acute psychotic disorder (B= -1.027, p = 0.003, 95% CI: –1.691 to –0.363) was associated with reduced LOS in PICU. Majority of admissions 43% (n = 39) had a diagnosis of schizophrenia, followed by Bipolar affective disorder BPAD 21% (n = 21), schizoaffective disorder 18% (n = 18), and acute psychotic disorder 9% (n = 9).
Conclusion
Psychiatric Intensive Care Unit is an essential service for the severely ill psychiatric patients and is a progressively developing sub-speciality. An important finding from our study describes the cohort of patients admitted being predominantly male, younger-aged, single, with a diagnosis of schizophrenia, legally detained, and from an Irish background. The primary indication for a referral is the risk of assault, showing the need for the intensive and secure treatment model that a PICU can provide.
There is an increasing prevalence of mental disorders in Malaysia, with a growing need to improve access to timely and efficient mental healthcare to address this burden. This review outlines the current legislative framework and the challenges of delivering mental healthcare and treating mental disorders in Malaysia.
We sought to assess the effectiveness of clozapine augmentation with Electroconvulsive therapy (ECT) (C+ECT) in patients with clozapine-resistant schizophrenia.
Methods:
We conducted a retrospective review of electronic health records to identify patients treated with C+ECT. We determined the response to C+ECT and the rate of rehospitalisation over the year following treatment with C+ECT.
Results:
Forty-two patients were treated with C+ECT over a 10-year period. The mean age of the patients at initiation of ECT was 46.3 (SD = 8.2) years (range 27–62 years). The mean number of ECTs given was 10.6 (SD = 5.3) (range 3–25) with the majority receiving twice weekly ECT. Seventy-six per cent of patients (n = 32) showed a Clinical Global Impression-Improvement (CGI-I) score of ≤3 (at least minimally improved) following C+ECT. The mean number of ECT treatments was 10.6 (SD = 5.3) (range 3–25) with the majority receiving twice weekly ECT. Sixty-four per cent of patients experienced no adverse events. Response to C+ECT was not associated with gender, age, duration of illness or duration of clozapine treatment. Seventy-five per cent of responders remained out of hospital over the course of 1-year follow-up, while 70% of those with no response to C+ECT were not admitted to hospital. Three patients received maintenance ECT, one of whom was rehospitalised.
Conclusion:
This study lends support to emerging evidence for the effectiveness of C+ECT in clozapine-resistant schizophrenia. These results are consistent with the results of a meta-analysis and the only randomised controlled trial (RCT) of this intervention. Further RCTs are required before this treatment can be confidently recommended.
The first episode of psychosis is a critical period in the emergence of cardiometabolic risk.
Aims
We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis.
Method
This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months.
Results
Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol).
Conclusions
Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.
Reducing hospitalisation and length of stay (LOS) in hospital following first episode psychosis (FEP) is important, yet reliable measures of these outcomes and their moderators are lacking. We conducted a systematic review and meta-analysis to investigate the proportion of FEP cases who were hospitalised after their first contact with services and the LOS in a hospital during follow-up.
Methods
Studies were identified from a systematic search across major electronic databases from inception to October 2017. Random effects meta-analyses and meta-regression analyses were conducted.
Results
81 longitudinal studies encompassing data for 23 280 FEP patients with an average follow-up length of 7 years were included. 55% (95% CI 50.3–60.5%) of FEP cases were hospitalised at least once during follow-up with the pooled average LOS of 116.7 days (95% CI 95.1–138.3). Older age of illness onset and being in a stable relationship were associated with a lower proportion of people who were hospitalised. While the proportion of hospitalised patients has not decreased over time, LOS has, with the sharpest reduction in the latest time period. The proportion of patients hospitalised during follow-up was highest in Australia and New Zealand (78.4%) compared to Europe (58.1%) and North America (48.0%); and lowest in Asia (32.5%). Black ethnicity and longer duration of untreated psychosis were associated with longer LOS; while less severe psychotic symptoms at baseline were associated with shorter LOS.
Conclusion
One in two FEP cases required hospitalisation at least once during a 7-year follow-up with an average length of hospitalisation of 4 months during this period. LOS has declined over time, particularly in those countries in which it was previously longest.
Evidence from preclinical and clinical studies supports a role for vitamin D deficiency in many mental disorders. In this review, we discuss the role of vitamin D in the aetiology and treatment of schizophrenia and depression and their physical health comorbidities. Although observational studies support a potential association between vitamin D and schizophrenia and depression, sufficient high-quality evidence from clinical trials does not yet exist to establish a place for vitamin D supplementation in optimising clinical response or promoting physical health. Completed randomised controlled trials are needed to provide insights into the efficacy and safety of vitamin D in the management of mental disorders.
LEARNING OBJECTIVES
After reading this article you will be able to:
• outline the epidemiology of vitamin D deficiency in schizophrenia
• describe the associations of vitamin D with schizophrenia and depression
• know how to assess, and consider treatment for, vitamin D deficiency.
DECLARATION OF INTEREST
F.G. has received support or honoraria for CME, advisory work and lectures from Bristol-Myers Squibb, Janssen, Lundbeck, Otsuka, Roche and Sunovion, and has a family member with professional links to Lilly and GSK, including shares. She is in part funded by the National Institute for Health Research's (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London and the South London Collaboration for Leadership in Applied Health Research & Care Funding scheme, and by the Maudsley Charity. The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
National information on mental health services in the Philippines indicates that there are substantial gaps and inconsistencies in the delivery of mental healthcare. The recently enacted Mental Health Act legislation provides a platform for the delivery of comprehensive and integrated mental health services. However, there remain many challenges in the provision of accessible and affordable mental healthcare.
The first mental health act legislation in the history of the Philippines has been officially signed into law and was enacted as the Republic Act no. 11036 on 21 June 2018. It provides a rights-based mental health bill and a comprehensive framework for the implementation of optimal mental healthcare in the Philippines. We review the principles and provisions of the Mental Health Act of 2017 and the implications for mental healthcare in the Philippines.
We aimed to examine clinical and risk outcomes at follow-up, and reoffending and readmission rates, for a sample of 50 admissions to a female medium secure unit (MSU). Demographic, clinical risk assessment (HCR-20 and HoNOS-Secure) and quality of life data were collected using validated measures for all admissions to a female MSU ward in London, UK, between April 2008 and November 2014.
Results
All clinical and risk assessment scale scores had improved at follow-up. Quality of life compared favourably to community samples and was good for physical, social and environmental factors and acceptable for psychological health. Twenty-six per cent had at least one readmission, while 17.5% reoffended in the period studied. A longer duration of admission and use of restrictions on discharge was associated with reduced reoffending, but not readmission.
Clinical implications
Admission is associated with improvement on clinical risk assessment at follow-up. Longer hospital admissions and use of restrictions on discharge may be necessary to prevent reoffending in this group.
A case is presented of a 30-year-old female with treatment-resistant schizoaffective disorder who was referred to a tertiary-level specialist psychosis service. We describe the history of clozapine trials and associated episodes of agranulocytosis and neutropenia, followed by the successfully tolerated third clozapine re-challenge within our service.
Remission and recovery rates for people with first-episode psychosis (FEP) remain uncertain.
Aims
To assess pooled prevalence rates of remission and recovery in FEP and to investigate potential moderators.
Method
We conducted a systematic review and meta-analysis to assess pooled prevalence rates of remission and recovery in FEP in longitudinal studies with more than 1 year of follow-up data, and conducted meta-regression analyses to investigate potential moderators.
Results
Seventy-nine studies were included representing 19072 patients with FEP. The pooled rate of remission among 12301 individuals with FEP was 58% (60 studies, mean follow-up 5.5 years). Higher remission rates were moderated by studies from more recent years. The pooled prevalence of recovery among 9642 individuals with FEP was 38% (35 studies, mean follow-up 7.2 years). Recovery rates were higher in North America than in other regions.
Conclusions
Remission and recovery rates in FEP may be more favourable than previously thought. We observed stability of recovery rates after the first 2 years, suggesting that a progressive deteriorating course of illness is not typical. Although remission rates have improved over time recovery rates have not, raising questions about the effectiveness of services in achieving improved recovery.
There has been much recent excitement about the possibility that some cases of psychosis may be wholly due to brain-reactive antibodies, with antibodies to N-methyl-D-aspartate receptor (NMDAR) and the voltage-gated potassium channel (VGKC)-complex reported in a few patients with first-episode psychosis (FEP).
Methods
Participants were recruited from psychiatric services in South London, UK, from 2009 to 2011 as part of the Genetics and Psychosis study. We conducted a case–control study to examine NMDAR and VGKC-complex antibody levels and rates of antibody positivity in 96 patients presenting with FEP and 98 controls matched for age and sex. Leucine-rich glioma inactiviated-1 (LGI1) and contactin-associated protein (CASPR) antibodies were also measured. Notably, patients with suspicion of organic disease were excluded.
Results
VGKC-complex antibodies were found in both cases (n = 3) and controls (n = 2). NMDAR antibody positivity was seen in one case and one control. Either LGI1-Abs or CASPR2-Abs were found in three cases and three controls. Neuronal antibody staining, consistent with the above results or indicating potential novel antigens, was overall positive in four patients but also in six controls. Overall, antibody positivity was at low levels only and not higher in cases than in controls.
Conclusions
This case–control study of the prevalence of antibodies in FEP does not provide evidence to support the hypothesis that FEP is associated with an immune-mediated process in a subgroup of patients. Nevertheless, as other bio-clinical factors may influence the effect of such antibodies in a given individual, and patients with organic neurological disease may be misdiagnosed as FEP, the field requires more research to put these findings in context.
The traditional approach to selecting antipsychotic medication involves little more than trial and error. Recent advances in genetics and molecular science offer the hope of a ‘personalised medicine’ approach to antipsychotic development and prescribing in schizophrenia. Personalised medicine is the practice of tailoring medical treatment to the individual characteristics of each patient. In schizophrenia, this will involve the identification of more homogeneous subsets of patients through the application of genetics, epigenetics, proteomics and metabolomics, neuroimaging and other biomarkers, and the use of these findings to stratify patients according to their response to treatment. In this article, we focus on the emerging evidence in pharmacogenetics and biomarkers for assessing individual response and tolerability of antipsychotic medication in schizophrenia.