Treatment-resistant Psychosis Research Articles

Electroconvulsive Therapy in Forensic Psychiatry: A Systematic Review.

Patients with schizophrenia are the largest population in forensic hospitals, and treatment-resistant psychosis is associated with length of stay. For patients with severe and treatment-resistant psychotic disorders, electroconvulsive therapy (ECT) is a potentially effective treatment. Data regarding the use of ECT in forensic psychiatry are scarce. This systematic review aims to provide an overview of the use of ECT in forensic psychiatry. Three databases (PubMed, Web of Science, and PsycINFO) were searched for publications since 1980. Peer-reviewed articles describing patients who underwent ECT treatment in the context of forensic psychiatry were included when a treatment outcome was reported. We identified 5 case reports and 1 case series comprising 13 patients treated with ECT in forensic settings. The quality of evidence was poor accompanied by a considerable risk of bias. Patients were diagnosed with schizophrenia spectrum disorders (n = 10) or depression with psychotic features (n = 3). Eleven patients (84.6%) were described as responders in terms of symptom improvement associated with a reduction of aggressive behavior and improved functioning. At least 3 patients were able to return to community settings. Despite the very limited evidence base, our review suggests that patients in forensic hospitals may benefit from ECT, but more systematic and higher-quality evidence is urgently needed. In addition to prospective, controlled observational studies, a qualitative view focusing on patients' perspectives in this specific setting is of particular importance.

Electroconvulsive Therapy in Forensic Psychiatry: A Systematic Review.

Patients with schizophrenia are the largest population in forensic hospitals, and treatment-resistant psychosis is associated with length of stay. For patients with severe and treatment-resistant psychotic disorders, electroconvulsive therapy (ECT) is a potentially effective treatment. Data regarding the use of ECT in forensic psychiatry are scarce. This systematic review aims to provide an overview of the use of ECT in forensic psychiatry. Three databases (PubMed, Web of Science, and PsycINFO) were searched for publications since 1980. Peer-reviewed articles describing patients who underwent ECT treatment in the context of forensic psychiatry were included when a treatment outcome was reported. We identified 5 case reports and 1 case series comprising 13 patients treated with ECT in forensic settings. The quality of evidence was poor accompanied by a considerable risk of bias. Patients were diagnosed with schizophrenia spectrum disorders (n = 10) or depression with psychotic features (n = 3). Eleven patients (84.6%) were described as responders in terms of symptom improvement associated with a reduction of aggressive behavior and improved functioning. At least 3 patients were able to return to community settings. Despite the very limited evidence base, our review suggests that patients in forensic hospitals may benefit from ECT, but more systematic and higher-quality evidence is urgently needed. In addition to prospective, controlled observational studies, a qualitative view focusing on patients' perspectives in this specific setting is of particular importance.

Identifying and managing treatment resistance early with the integration of a clozapine clinic within an early intervention for psychosis service.

Despite being the most effective antipsychotic medication for treatment-resistant psychosis, clozapine is often under-utilized with long delays to initiation. This study aimed to determine whether the integration of a clozapine clinic within an early intervention for psychosis service resulted in a change in the rate and time to initiation of clozapine, the number of trials of different antipsychotic medications prior to clozapine, community initiation and discontinuation rates. A clozapine clinic was established in the Early Psychosis Prevention and Intervention Centre in Melbourne. This was a pre- and post-evaluation study design. The 'clozapine clinic' cohort included those who commenced on clozapine from 01 January 2016 to 30 June 2018. Prior to the clozapine clinic, 24 young people commenced clozapine over the 30-month period compared to 36 in the clozapine clinic cohort (RR = 1.30, 95% CI: 0.75-2.28, p = .32). In the pre-clozapine clinic cohort, 4.6% of all those with a first episode of psychosis were commenced on clozapine compared to 6% in the clozapine clinic cohort. Prior to the clozapine clinic, the median time to the commencement of clozapine was 72 weeks (IQR: 38, 87), compared to 53.5 weeks (IQR: 38, 81.5) in the clozapine clinic (Z = -0.86, p = .393). The mean number of different antipsychotic medications prior to commencing clozapine remained stable at 3.2 (SD ± 1.1) in both cohorts (t = -0.20, p = .841). There was a lower rate of discontinuation in the clozapine clinic (43.5% vs. 14.7%, HR = 0.30, 95% CI: 0.09-0.98, p = .046). While this study was underpowered and there are limitations to the naturalistic study design, the findings lend support to the integration of a clozapine clinic within early intervention for psychosis services.

Efficacy of clozapine versus standard treatment in adult individuals with intellectual disability and treatment-resistant psychosis (CLOZAID): study protocol of a multicenter randomized clinical trial.

Intellectual disability (ID) affects approximately 1% of the worldwide population and individuals with ID have a higher comorbidity with mental illness, and specifically psychotic disorders. Unfortunately, among individuals with ID, limited research has been conducted since ID individuals are usually excluded from mental illness epidemiological studies and clinical trials. Here we perform a clinical trial to investigate the effectiveness of clozapine in the treatment of resistant psychosis in individuals with ID. The article highlights the complexity of diagnosing and treating psychopathological alterations associated with ID and advocates for more rigorous research in this field. A Phase IIB, open-label, randomized, multicenter clinical trial (NCT04529226) is currently ongoing to assess the efficacy of oral clozapine in individuals diagnosed with ID and suffering from treatment-resistant psychosis. We aim to recruit one-hundred and fourteen individuals (N=114) with ID and resistant psychosis, who will be randomized to TAU (treatment as usual) and treatment-with-clozapine conditions. As secondary outcomes, changes in other clinical scales (PANSS and SANS) and the improvement in functionality, assessed through changes in the Euro-QoL-5D-5L were assessed. The main outcome variables will be analyzed using generalized linear mixed models (GLMM), assessing the effects of status variable (TAU vs. Clozapine), time, and the interaction between them. The treatment of resistant psychosis among ID individuals must be directed by empirically supported research. CLOZAID clinical trial may provide relevant information about clinical guidelines to optimally treat adults with ID and treatment-resistant psychosis and the benefits and risks of an early use of clozapine in this underrepresented population in clinical trials. Clinicaltrials.gov: NCT04529226. EudraCT: 2020-000091-37.

The Use of Clozapine in Children and Adolescents With Treatment-Resistant Psychosis

The Use of Clozapine in Children and Adolescents With Treatment-Resistant Psychosis

Developing prediction models for symptom severity around the time of discharge from a tertiary-care program for treatment-resistant psychosis.

Antipsychotics are the only therapeutic class indicated in the symptomatic management of psychotic disorders. However, individuals diagnosed with schizophrenia or schizoaffective disorder may not always benefit from these first-line agents. This refractoriness to conventional treatment can be difficult to address in most clinical settings. Therefore, a referral to a tertiary-care program that is better able to deliver specialized care in excess of the needs of most individuals may be necessary. The average outcome following a period of treatment at these programs tends to be one of improvement. Nonetheless, accurate prognostication of individual-level responses may be useful in identifying those who are unlikely to improve despite receiving specialized care. Thus, the main objective of this study was to predict symptom severity around the time of discharge from the Refractory Psychosis Program in British Columbia, Canada using only clinicodemographic information and prescription drug data available at the time of admission. To this end, a different boosted beta regression model was trained to predict the total score on each of the five factors of the Positive and Negative Syndrome Scale (PANSS) using a data set composed of 320 hospital admissions. Internal validation of these prediction models was then accomplished by nested cross-validation. Insofar as it is possible to make comparisons of model performance across different outcomes, the correlation between predictions and observations tended to be higher for the negative and disorganized factors than the positive, excited, and depressed factors on internal validation. Past scores had the greatest effect on the prediction of future scores across all 5 factors. The results of this study serve as a proof of concept for the prediction of symptom severity using this specific approach.

What are the barriers and facilitators of clozapine use in early psychosis? A survey of UK early intervention clinicians

Clozapine is the most effective medication for treatment-resistant psychosis, but evidence points to substantial underuse, especially within early intervention psychosis (EIP) services. We explored clinicians’ views on perceived barriers and facilitators to offering patients clozapine within EIP services. A cross-sectional survey was distributed electronically to clinicians practising in EIP services across England. A mixed methods approach was used to assess barriers to clozapine, and attitudes and opinions concerning clozapine underutilisation. Based on the barriers identified in the literature, clinicians were asked to rate each one (scale:1-7) based on importance, with a higher score indicating higher importance. Clinicians were also asked open-ended questions on barriers to clozapine and how access can be improved in EIP services. Quantitative data were analysed using descriptive and inferential statistics, and qualitative responses were analysed thematically. One hundred and nineteen EIP clinicians from 35 services in England completed the survey. In total, 37% (n = 45) of clinicians perceived that clozapine was under-prescribed in their EIP service. The most important barrier to utilising clozapine were patient concerns with side effects, followed by monitoring requirements and clinician concerns with side effects. Thematic analysis identified 17 perceived barriers, which were grouped into three major themes: administrative (5 subthemes), clinician-related (6 subthemes), and patient-related (6 subthemes). Perceived facilitators to improving clozapine use were greater training, improved resources, and optimised monitoring. The main barriers to clozapine in EIP services, as identified by clinicians, are patient concerns regarding side effects and monitoring requirements. Identified facilitators for improved clozapine use include clinician training, improved resources, guidelines, and point-of-care testing.

Clozapine use at a specialised psychiatric hospital in Johannesburg.

Clozapine is the gold standard medication for treatment-resistant psychosis, with robust evidence supporting its efficacy in multiple symptom domains. However, clozapine's side effect profile contributes to its underutilisation and discontinuation. This study aimed to explore the magnitude of clozapine use and describe factors that impact on its effective use among in-patients. Tara Hospital, a specialised psychiatric hospital in Johannesburg. This was a retrospective, cross-sectional file review of clozapine-treated patients admitted over the 2-year study period. Data variables included: demographics, clinical information, discharge prescription, clozapine-related side effects and details of clozapine discontinuation, where applicable. A cohort of 33.2% of patients from Tara's biological wards received a trial of clozapine. Participants experienced anti-cholinergic clozapine-related side effects that included weight gain (79.5%), tachycardia (35.2%) and constipation (35.2%). Clozapine was discontinued in 13.7% of participants, and no life-threatening side effects or deaths occurred. Significantly more use of flupenthixol decanoate (64.3% vs. 30.7%; p = 0.0322) and anticholinergics (35.7% vs. 11.4%; p = 0.0474) occurred in the clozapine-discontinued group. Polypharmacy rates were high for psychiatric and non-psychiatric medications. One-third of patients received clozapine trials, most of whom continued at discharge. Although side effects occurred frequently, life-threatening side effects did not. Clozapine monitoring protocols, side effect rating scales, pre-emptive management of side effects, lifestyle interventions and clinician education may improve outcomes of clozapine use. The use of plasma clozapine levels may be beneficial. This study expands our limited knowledge regarding current clozapine prescribing trends in South Africa.

IVIG for Treatment-Resistant Psychosis For a Child with Turner Syndrome

AbstractPsychosis is defined as the presence of false beliefs or false perceptions. In children some causes of psychosis include psychiatric diagnosis such as schizophrenia and autism. However, it may also be secondary to medical conditions like various forms of encephalitis. Studies have shown that IVIG has been efficacious in the treatment of psychosis in the setting of autoimmune encephalitis.A 9-year-old girl with a past medical history of Turner Syndrome, developmental delay, epilepsy, growth hormone deficiency, metabolic bone disease, and autism (ASD) presented with auditory and visual hallucinations that began June 2020. She began with her hearing voices that repeated the word “dead” and told her that she would not live. The hallucination later took the form of a man that would mock her, laugh about her parents dying, and tell her to kill them. The patient had associated symptoms of insomnia, anxiety, sadness, and increased anger. On her initial admission, CSF studies including culture and gram strain were unremarkable. NMDA, VHKC, and GAD65 antibodies were negative. At this time the hallucinations were thought to be due to ASD and she was prescribed Risperdal 0.25mg twice a day. Unfortunately, this did not improve her symptoms and from the time period of June 2020 to May 2021 she subsequently underwent trials of Risperdal, Zyprexa, Invega, Abilify, Thorazine, Haldol, and Clozaril. However, the symptoms persisted. Zoloft was prescribed, which was efficacious for anger and dysphoria. Trazodone, melatonin, and Remeron were tried for the treatment of insomnia, but did not cause enough improvement to continue the medications. Due to progression of command hallucinations with “the man” instructing her to hurt others, the patient was admitted July 2021 for administration of IVIG. Repeat CSF studies and brain MRI were unremarkable. From July 29, 2021 to August 1, 2021 she received three doses of IVIG which resulted in improvement of psychosis. Prior to administration, she was seeing “the man” throughout the day every single day, was sleeping only 3–4 hours a night, and having nightmares everyday. On evaluation 2 weeks after IVIG, she was only seeing “the man” 1–2 time a day, sleeping 6–8 hours a night, having nightmares 1–2 times a week, and her mood had improved.This case illustrates the potential use of IVIG for the treatment of treatment-resistant psychosis. Although the cause of this patient’s symptoms remains unclear, there were clear benefits from the administration of IVIG that were not seen with trials of antipsychotics.FundingNo Funding

Treatment resistant psychosis in children and adolescents and clozapine: Nuances.

With proliferation in research on high-risk psychosis spectrum diseases, it is crucial to distinguish a prodrome or psychosis-like episode in children and adolescents from true psychosis. The limited role of psychopharmacology in such circumstances is well-documented, underlining the difficulties in diagnosing treatment resistance. To add to the confusion is emerging data on the head-to-head comparison trials for treatment-resistant and treatment-refractory schizophrenia. Clozapine, the gold-standard drug for resistant schizophrenia and other psychotic psychopathology, lacks FDA or manufacturer guidelines for use in the pediatric population. Possibly due to developmental pharmacokinetic (PK) considerations, clozapine-related side effects are more commonly seen in children than adults. Despite evidence of an increased risk for seizures and hematological problems in children, clozapine is widely used off-label. Clozapine reduces the severity of resistant childhood schizophrenia, aggression, suicidality, and severe non-psychotic illness. There is inconsistent prescribing, administration, and monitoring of clozapine, and limited database evidence-backed guidelines. Despite the overwhelming efficacy, problems remain regarding unambiguous indications of use and risk-benefits assessments. This article reviews the nuances in the diagnosis of treatment resistance psychosis in childhood and adolescents and its management, in particular highlighting the evidence base for clozapine in this population group.

Clozapine-induced Cardiomyopathy: A Case Report

The diagnosis and treatment of new-onset systolic dysfunction can be challenging, particularly in patients presenting with cardiogenic shock. We present a case of a young African-American man who was admitted for cardiogenic shock following an admission a month earlier for treatment-resistant psychosis. He was diagnosed with medication-induced cardiomyopathy, which resolved with a remarkable recovery of his systolic function after discontinuation of the culprit medication, clozapine.

Childhood Trauma in Clozapine-Resistant Schizophrenia: Prevalence, and Relationship With Symptoms

Abstract Background and Hypothesis The role of early adversity and trauma is increasingly recognized in psychosis but treatments for trauma and its consequences are lacking. Psychological treatments need to understand the prevalence of these experiences, the relationship with specific symptoms and identify potentially tractable processes that may be targeted in therapy. It was hypothesized that greater adversity, and specifically abuse rather than neglect, would be associated with positive symptoms and specifically hallucinations. In addition, negative beliefs would mediate the relationship with positive symptoms. Study Design 292 Patients with treatment resistant psychosis completed measures of early adversity as well as current symptoms of psychosis. Study Results Early adversity in the form of abuse and neglect were common in one-third of the sample. Adversity was associated with higher levels of psychotic symptoms generally, and more so with positive rather than negative symptoms. Abuse rather than neglect was associated with positive but not with negative symptoms. Abuse rather than neglect was associated with hallucinations but not delusions. Abuse and neglect were related to negative beliefs about the self and negative beliefs about others. Mediation demonstrated a general relationship with adversity, negative-self, and other views and overall psychotic symptoms but not in relation to the specific experience of abuse and hallucinations. Females were more likely to be abused, but not neglected, than males. Conclusions Whilst most relationships were modest, they supported previous work indicating that adversity contributes to people with psychosis experiencing distressing symptoms especially hallucinations. Treatments need to address and target adversity.

Effects of clozapine treatment on the improvement of substance use disorders other than nicotine in individuals with schizophrenia spectrum disorders: A systematic review and meta-analysis.

Antipsychotic medications are the mainstay of treatment for schizophrenia and are associated with a reduction in psychiatric hospitalization and overall mortality. Some evidence suggest that antipsychotic medications might have a varying effect on the improvement of comorbid substance use disorders (SUDs), with clozapine showing more favorable outcomes. We systematically reviewed all available evidence on effects of clozapine on the improvement of SUDs other than nicotine. Electronic searches of MEDLINE, Embase, PsycINFO, and CINHAL were conducted up to March 1, 2022. Studies of any methodological design involving two concepts: (1) clozapine and (2) SUD terms (excluding nicotine) were included. For SUD outcomes with three or more comparative studies with available raw data meta-analysis was performed. SUD outcomes not meeting criteria for meta-analysis were described qualitatively. Risk of bias was examined using "Downs and Black," and "Q-Coh" instruments. The majority of individuals in the included 31 studies were male and of European ancestry. Abstinence was the most common outcome. Most of the studies were of low-to-moderate quality, and none of the studies met all the quality criteria. Pooled findings from four observational studies in samples of patients with predominantly comorbid alcohol use disorder showed that clozapine treatment is associated with significantly higher odds of remaining abstinent. In addition clozapine was associated with decreased odds of psychiatric hospitalization in all but one observational study. Our systematic review and meta-analysis builds upon previous reviews, and it suggests the association of clozapine treatment with significantly higher odds of remaining abstinent from substance use and decreased likelihood of psychiatric hospitalization, compared with continuing treatment with other antipsychotic medications. Still, the validity of this association needs greater exploration and providing recommendations for the utility of clozapine in individuals without treatment-resistant psychosis and comorbid SUDs would be premature.

Increased Prevalence of Rare Copy Number Variants in Treatment-Resistant Psychosis.

It remains unknown why ~30% of patients with psychotic disorders fail to respond to treatment. Previous genomic investigations of treatment-resistant psychosis have been inconclusive, but some evidence suggests a possible link between rare disease-associated copy number variants (CNVs) and worse clinical outcomes in schizophrenia. Here, we identified schizophrenia-associated CNVs in patients with treatment-resistant psychotic symptoms and then compared the prevalence of these CNVs to previously published schizophrenia cases not selected for treatment resistance. CNVs were identified using chromosomal microarray (CMA) and whole exome sequencing (WES) in 509 patients with treatment-resistant psychosis (a lack of clinical response to ≥3 adequate antipsychotic medication trials over at least 5 years of psychiatric hospitalization). Prevalence of schizophrenia-associated CNVs in this sample was compared to that in a previously published large schizophrenia cohort study. Integrating CMA and WES data, we identified 47 cases (9.2%) with at least one CNV of known or possible neuropsychiatric risk. 4.7% (n = 24) carried a known neurodevelopmental risk CNV. The prevalence of well-replicated schizophrenia-associated CNVs was 4.1%, with duplications of the 16p11.2 and 15q11.2-q13.1 regions, and deletions of the 22q11.2 chromosomal region as the most frequent CNVs. Pairwise loci-based analysis identified duplications of 15q11.2-q13.1 to be independently associated with treatment resistance. These findings suggest that CNVs may uniquely impact clinical phenotypes beyond increasing risk for schizophrenia and may potentially serve as biological entry points for studying treatment resistance. Further investigation will be necessary to elucidate the spectrum of phenotypic characteristics observed in adult psychiatric patients with disease-associated CNVs.

Underuse of recommended treatments among people living with treatment-resistant psychosis.

BackgroundInternational guidelines recommend that individuals with treatment-resistant psychosis must be treated with clozapine. ECT has also been reported to improve symptom profiles. Identification of clozapine and/or ECT use in real-world practice enables understanding of the extent to which this evidence-base is implemented.SettingStatewide public health tertiary referral service, the Tertiary Referral Service for Psychosis (TRSP), NSW, Australia.ObjectivesTo (i) describe clinical characteristics of individuals with treatment-resistant psychosis and to detail the proportion who had received a trial of clozapine or ECT at any point during their illness course; (ii) describe the characteristics of the treatment trials in both those currently on clozapine and those previously on clozapine; (iii) document reasons in relevant individuals why clozapine had never been used.MethodsAll TRSP clients who met the criteria for treatment resistance (TR) were included. A detailed casenote review was conducted to examine whether clozapine and/or ECT had ever been prescribed. Characteristics of clozapine and ECT trials were documented. Tertiary service treatment recommendations are described.FindingsThirty-six of 48 individuals had TR. They had marked clinical and functional impairment. A minority were currently receiving clozapine (n = 14/36). Most had received a clozapine trial at some point (n = 32/36). Most experienced persistent clinical symptoms while on clozapine (n = 29/32). Clozapine plasma levels were very rarely reported (4/32). Augmentation and antipsychotic polypharmacy were common among those currently on clozapine. The median clozapine trial duration was 4.0 (IQR: 3.0–20.3) months in individuals previously prescribed clozapine. Reasons for clozapine discontinuation included intolerable side effects (n = 10/18) and poor adherence (n = 7/18). One-quarter of TR individuals had trialed ECT (n = 9/36). Tertiary service recommendations included routine plasma monitoring to optimize dose among people currently on clozapine; clozapine retrial in those previously treated; and clozapine initiation for those who had never received clozapine. ECT was recommended to augment clozapine and as an alternative where clozapine trial/retrial was not feasible.ConclusionAmong people with TR referred to a tertiary service, clozapine and ECT were underutilized. Clozapine trials are typically terminated without an adequate trial. Strategies to optimize the use of clozapine therapy and ECT in clinical settings are needed to increase the therapeutic effectiveness of evidence-based therapies for treatment-resistant psychosis.

Subjective cognitive functioning, depressive symptoms, and objective cognitive functioning in people with treatment-resistant psychosis

ABSTRACT Introduction: Relationships between subjective cognitive functioning (SCF), objective cognitive functioning (OCF), and depressive symptoms are poorly understood in treatment-resistant psychosis (TRP). This study (a) compares SCF in TRP using positively and negatively worded scales, (b) assess these scales’ accuracy, and (c) explores the association between these scales and depressive symptoms. We hypothesised that both SCF scales would be highly correlated, minimally associated with OCF, and similarly associated with depressive symptoms. Methods: Archival clinical data from 52 TRP inpatients was utilised. OCF composite scores were derived from a broad neuropsychological battery. SCF was assessed using the norm-referenced PROMIS 2.0 Cognitive Abilities (positively worded) and Concerns (negatively worded) subscales. A depressive symptom score was derived from the Positive and Negative Syndrome Scale. Results: SCF ratings were higher in patients than OCF. There was a small but significant correlation between PROMIS subscales (r = .30). Neither PROMIS subscale was associated with OCF (r = −.11, r = .01). Depressive symptoms were correlated with the positively (r = −.29) but not negatively worded scale (r = −.13). Conclusion: Individuals with TRP inaccurately rate their cognitive functioning and tend to overestimate their ability. Positively and negatively worded SCF scales associate variably with depressive symptoms, indicating they may not be used interchangeably in TRP.

Relaxation of the criteria for entry to the UK Clozapine Central Non-Rechallenge Database: a modelling study

Clozapine is uniquely effective in treatment-resistant psychosis. In the UK, patients must discontinue clozapine indefinitely if they are placed on the Central Non-Rechallenge Database (CNRD) after their haematological parameters fall below particular thresholds. Under exceptional circumstances, patients can be rechallenged on clozapine under an off-licence agreement. In the USA in 2015, restrictive practice was discontinued to allow greater flexibility for clozapine maintenance. The absolute neutrophil count leading to treatment interruption was lowered from less than 1·5 × 109/L to less than 1·0 × 109/L and platelet and white cell count monitoring were ceased. We aimed to investigate the implications of a similar policy change on clozapine use in the UK. This was a modelling study of all patients registered on the UK CNRD. First, we determined the proportion of patients placed on the database in the UK who would have had to discontinue clozapine treatment under the US Food and Drug Administration (FDA) criteria. Second, we compared the haematological characteristics of patients who did or did not meet FDA criteria for discontinuing clozapine, including the time to registration from clozapine initiation and the proportion of cases of severe neutropenia at registration. Third, we investigated the success rates of clozapine re-challenge for patients that had been placed on the CNRD. Successful rechallenge was defined as no recurrence of CNRD registration. Between May 2, 2002 and March 1, 2021, 3731 patients were placed on the CNRD, with a mean age of 47 years (SD 15), including 1420 (38%) women and 2311 (62%) men, of whom 3089 (83%) were White, 360 (10%) were Black, 190 (5%) were Asian, and 92 (2%) were classified as other. 566 (15%) of 3731 patients met the equivalent criteria for clozapine discontinuation under the FDA guidelines. The median time to CNRD registration from clozapine initiation was 1·6 years (IQR 0·2-4·9). Data for 519 rechallenged patients were examined; 419 (81%) were successful. Clozapine rechallenge success rates were broadly similar between individuals who did not meet the US CNRD registration criteria (36 [78%] of 46) and those who did meet the criteria (383 [81%] of 473). Implementing the revised FDA monitoring criteria in the UK would substantially reduce clozapine discontinuation for haematological reasons, which would greatly improve the mental health outcomes of these patients without having a major effect on their physical health. None.

Rehabilitation or Stagnation? a Six Month Mirror-Image Study Reviewing the Effectiveness of an Inpatient Rehabilitation Unit

AimsThe Tony Hillis Unit (THU) is a locked rehabilitation unit for men aged 18–65 years with Treatment Resistant Psychosis, with or without mild personality disorders; drug and alcohol misuse; and challenging behaviour. The multi-disciplinary team including psychiatrists, psychologists, nurses, occupational therapists and specialist pharmacists offer service-users a holistic, personalised and pragmatic management plan to facilitate an improvement in their level of functioning. This service evaluation aimed to review the effectiveness of our intervention as a unit as defined by functional outcome at six months pre- and post- admission.MethodsA retrospective, mirror-image study design was used to collect data. Data were obtained from South London & Maudsley's Electronic Patient Journey System (ePJS) records. All patients discharged from THU over a two-year period, from May 2019 to May 2021, were considered in the study (n = 25 patients). Two service users died during the evaluation period and were excluded. A further service user was excluded as he had an admission length less than 28 days. Variables recorded included patient demographics and the presence of biopsychosocial interventions at THU including Clozapine initiation, engagement in weekly 1:1 occupational therapy (OT) and 1:1 psychology sessions. The functional status at six months pre-admission and post-discharge was defined by placement type, graded in terms of level of support; 1 = Psychiatric Intensive Care Unit, 2 = Acute ward, 3 = Rehabilitation service/Prison, 4 = Care home, 5 = Supported accommodation and 6 = Independent living. The change in patient acuity pre- and post- THU was compared using Wilcoxon-signed rank test.Results23 service users were included in this evaluation. The average admission length was 365 days, and average age at admission was 38 years. The difference in patient acuity before and after THU intervention was statistically significant (P < 0.005), with an overall reduction in level of placement support required. The most common placement prior to admission was an acute ward, compared to a rehabilitation service six months after discharge. 60% of patients (n = 13) were newly initiated or re-titrated on Clozapine during their admission, with a further 4 patients already on Clozapine. 82% of patients engaged with 1:1 weekly OT and 72% engaged with 1:1 weekly psychology sessions.ConclusionThis study demonstrates the effectiveness of our role as a locked rehabilitation unit. It outlines some of the key biopsychosocial interventions likely contributing to this, including initiation of Clozapine.

Beyond “Evidence-Based Medicine” in “Detained Patients"

AimsTreatments without robust evidence are not recommended. However, some patients detained in secure hospitals might need novel approaches such as: off-license use of medication, use of psychological (rather than their biological) effects of drugs. In addition, some detained patients may request for unconventional treatments they believe in. In community and capacitous patients, the clinician's role is advisory and the burden is on the patient to make the final decision and access such treatments privately. However, in a detained patient (with or without capacity), it may fall on the Responsible Clinician (RC) to deny or facilitate access to such interventions. Currently, there is no guidance for such circumstances. We have presented three real cases followed by proposing a flowchart to guide RCs.MethodsCase 1 (2019–2020): X with mild Learning Disability (LD) and mixed personality disorder detained under Section 3 with no leave to community. X asked for Hypericum which has been helpful with her headaches in the past. X had capacity to make that decision.Case 2 (1996–97): Y with mild LD and aggressive behaviours responding instantly to any injection. Y lacked capacity so injections of distilled water was tried in his best interest, with equal positive effect. The question was about using distilled water as rapid tranquilisation with no side effects.Case 3 (2020–21): Z with a treatment-resistant psychosis who has been unwell for months and detained in four different PICUs. Z's father requested N Acetyl Cysteine which had historical calming and sedative effects for Z.ResultsThe main issue in case 1 is the conflict between the patient's Human Rights and RC's Duty of care. Here the patient could be potentially deprived of their right to make an ‘unwise decision’ should the RC bar her access to a treatment which lacks evidence but is privately available to public. This can be construed as an infringement of Article 8 of Human Rights.The issue in case 2 and 3 is rather different. Here the conflict is between the RC's duty of care to provide evidence-based treatments and the patient's “best interest” which seems to be an intervention without robust evidence.ConclusionWe have developed a flowchart to help RCs by navigating amongst several competing/ conflicting legal and ethical concepts such as: Patient's wish/Human rights, Patient's capacity, Bolam test, “Medical Treatment” Under Section 63, 62 or 58 of Mental Health Act 1983, Best interest, Second Opinion (SOAD) and advice from court.

Clozapine for treatment resistance in early psychosis: a survey of UK clinicians' training, knowledge and confidence.

Clozapine is the only medication licenced for patients with psychosis that is resistant to conventional antipsychotic treatment. However, despite its effectiveness, it remains widely underutilised. One contributory factor for this may be clinicians' lack of confidence around the management of clozapine. We conducted a survey of clinicians working in Early Intervention in Psychosis (EIP) services to determine their training needs for clozapine management in EIP services. An electronic survey was made available to all clinicians working in EIP services in England. The survey assessed confidence and training needs regarding managing clozapine in patients with treatment-resistant psychosis. Quantitative data were analysed using total mean scores and the Mann-Whitney U test. In all, 192 (27%) of approximately 700 clinicians from 35 EIP services completed the survey. Approximately half (54%) had not received training on treatment with clozapine. Experience of training was higher in prescribers than non-prescribers, and among medical than non-medical clinicians. Previous training was associated with significantly higher confidence in offering clozapine and managing treatment-resistant psychosis (p < 0.001). Confidence levels with managing treatment-resistant psychosis and clozapine were relatively high (mean = 4 out of 5, SD = 1). Respondents were most confident about monitoring mental health response to treatment (mean = 5, SD = 1). Participants were least confident about how to discontinue clozapine treatment safely (mean = 3, SD = 1). Most clinicians working in EIP have not received training on the use of clozapine. This may account, in part, for the underutilisation of clozapine in EIP services. The provision of training in the identification of treatment-resistant psychosis and the use of clozapine will likely improve the detection and management of treatment resistance in the early phase of psychosis.