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Compulsory community treatment orders (CTOs) are controversial because they enforce psychiatric treatment of patients in the community. It is important to know which patients benefit from compulsory treatment to better inform CTO use.
To examine the effect of a range of diagnoses on outcomes associated with CTOs to determine whether there are specific outcome signatures for CTOs according to diagnosis.
New Zealand's Ministry of Health databases provided demographic, service use and medication-dispensing data for all individuals placed on a CTO between 2009 and 2018. We used a hierarchical approach to categorise individuals according to diagnosis. Admission rates, admission days per year, community care and medication dispensing were analysed according to diagnosis and CTO status.
In total, 14 726 patients were placed on a CTO over the 10-year period between 1 January 2009 and 31 December 2018. For psychotic disorders, CTOs were associated with reduced admission frequency and duration. However, the opposite occurred for dementia disorders, bipolar disorders, major depressive disorder and personality disorders. Higher rates of medications, including depot antipsychotic medications, were dispensed on CTOs for all diagnostic groups.
CTOs were associated with reduced admission frequency and admission days per year for patients with psychotic disorders, whereas the opposite occurred for other diagnostic groups. Rather than seeking to establish whether CTOs are effective, we suggest that there are specific outcome signatures associated with CTOs for different disorders and knowledge of these can improve understanding and clinical practice in this area.
Discontinuation of antipsychotic medication may be linked to high risk of relapse, hospitalization and mortality. This study investigated the use and discontinuation of antipsychotics in individuals with first-episode schizophrenia in relation to cohabitation, living with children, employment, hospital admission and death.
Danish registers were used to establish a nationwide cohort of individuals ⩾18 years with schizophrenia included at the time of diagnosis in1995–2013. Exposure was antipsychotic medication calculated using defined daily dose and redeemed prescriptions year 2–5. Outcomes year 5–6 were analysed using binary logistic, negative binomial and Cox proportional hazard regression.
Among 21 351, 9.3% took antipsychotics continuously year 2–5, 38.6% took no antipsychotics, 3.4% sustained discontinuation and 48.7% discontinued and resumed treatment. At follow-up year 6, living with children or employment was significantly higher in individuals with sustained discontinuation (OR 1.98, 95% CI 1.53–2.56 and OR 2.60, 95% CI 1.91–3.54), non-sustained discontinuation (OR 1.25, 95% CI 1.05–1.48 and 2.04, 95% CI 1.64–2.53) and no antipsychotics (OR 2.00, 95% CI 1.69–2.38 and 5.64, 95% CI 4.56–6.97) compared to continuous users. Individuals with non-sustained discontinuation had more psychiatric hospital admissions (IRR 1.27, 95% CI 1.10–1.47) and longer admissions (IRR 1.68, 95% CI 1.30–2.16) year 5–6 compared to continuous users. Mortality during year 5–6 did not differ between groups.
Most individuals with first-episode schizophrenia discontinued or took no antipsychotics the first years after diagnosis and had better functional outcomes. Non-sustained discontinuers had more, and longer admissions compared to continuous users. However, associations found could be either cause or effect.
The antipsychotic clozapine is known to have immune-modulating effects. Clozapine treatment has been reported to be associated with increased risk of COVID-19 infection. However, it remains unclear whether this is because of increased testing of this patient group, who are closely monitored. We linked anonymised health records from mental health services in Cambridgeshire (UK), for patients taking antipsychotic medication, with data from the local COVID-19 testing hub. Patients receiving clozapine were more likely to be tested for COVID-19, but not to test positive. Increased testing in patients receiving clozapine suggests prudent judgement by clinicians, considering the overall health vulnerabilities of this group.
Psychopharmacological interventions for the management of the neuro-behavioral manifestations of PWS that have been described throughout the book are the main focus of this particular chapter. A majority of patients with PWS are on one or more psychiatric medications by the time they reach adulthood. Patients with PWS are uniquely vulnerable to psychiatric illness and require a thorough assessment and diagnosis in order to receive appropriate treatment. This chapter outlines the main classes of medication that have been or, in our opinion, ought to be utilized in patients with PWS. We specifically address their common indications, side effects, and dosage recommendations, among other characteristics. Additionally, the complex phenomenon of drug–drug interactions is discussed in some detail, due to the high incidence of “polypharmacy” in PWS. We recognize that a significant portion of caregiver burden is attributable to neuro-behavioral symptoms and endeavor to provide the information necessary to guide providers in addressing that.
This chapter describes the phenomenon of psychosis and how it presents in patients with PWS. Characteristics of psychosis, including delusions, hallucinations, disorganized thinking, abnormal motor behavior, or negative symptoms are described. Although the classical presentation of schizophrenia, schizophreniform, and other schizoid disorders is uncommon in PWS, there are other less-recognized psychotic presentations that are explained in the text. Delirium, despite not being considered a psychotic disorder, is important to recognize due to its association with medications patients with PWS are prescribed. Cycloid psychosis is another phenomenon that, although not formally recognized in the DSM-5, is frequently seen in PWS. The sudden onset and cycling between normalcy and psychosis makes it difficult to diagnose for providers who are unfamiliar with it. We emphasize the need for immediate medical attention and treatment in the case of suspected psychosis. Some commonly used strategies for management are discussed. Continued monitoring by mental healthcare providers and need for maintenance treatment is discussed.
Overweight and obesity are twice as likely to develop in people living with severe mental illness (SMI), compared with those without. Many factors contribute to this, such as reduced physical activity and the use of certain medications that induce weight gain. Obesity contributes to the premature mortality seen in people living with SMI, as it is one of the fundamental risk factors for cardiovascular disease and diabetes. Bariatric surgery is an effective treatment option, although patients living with SMI might face stigma when being considered for surgical intervention. This article proposes a discussion around obesity and bariatric surgery in patients living with SMI. It will also reflect on the challenges faced by healthcare professionals and patients living with SMI and obesity, when considering appropriate treatments for weight loss. The paper utilises a fictional case, informed by contributions from a lived experience author, to explore bariatric surgery in people living with SMI.
Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics in individuals at clinical high-risk for psychosis (CHR-P) is associated with a higher risk of an imminent transition to psychosis. Despite their tolerability profile and potential beneficial effects, baseline exposure to antidepressants (AD) in CHR-P has surprisingly received far less attention as a potential risk modulator for transition to psychosis. The current systematic review and meta-analysis were performed to fix such a knowledge gap.
Systematic scrutiny of Medline and Cochrane library, performed up to 1 August 2021, searching for English-language studies on CHR-P reporting numeric data about the sample, the transition outcome at a predefined follow-up time and raw data on AD baseline exposure in relation to such outcome.
Of 1942 identified records, 16 studies were included in the systematic review and meta-analysis. 26% of the participants were already exposed to AD at baseline; at the end of the follow-up 13.5% (95% CI 10.2–17.1%) of them (n = 448) transitioned to psychosis against 21.0% (18.9 to 23.3%) of non-AD exposed CHR-P (n = 1371). CHR-P participants who were already under AD treatment at baseline had a lower risk of transition than non-AD exposed CHR-P. The RR was 0.71 (95% CI 0.56–0.90) in the fixed-effects model (z = −2.79; p = 0.005), and 0.78 (0.58–1.05) in the random-effects model (z = −1.77; p = 0.096; tau-squared = 0.059). There was no relevant heterogeneity (Cochran's Q = 18.45; df = 15; p = 0.239; I2 = 18.7%).
Ongoing AD exposure at inception in CHR-P is associated to a reduced risk of transition to psychosis at follow up.
Sedation is one of the most common adverse effects of clozapine. Although tolerance develops to some extent, a significant proportion of patients continue to experience sedation and associated negative consequences on their quality of life. Sedation is also one of the most common reasons for the discontinuation of clozapine and it is therefore important to proactively manage it. This article provides brief guidance for clinicians.
The high risk of psychosis among migrants is often attributed to social stressors in the host country. We examined whether the relative risk of psychosis among migrants is low on arrival and increases thereafter.
In this cohort study, first-generation immigrants to the Netherlands, aged 10 years and older (N = 1 281 678), were matched by birth year and sex to 2 542 313 native-born Dutch controls. The first occurrence of psychosis after arrival was established using data on dispensing of antipsychotic medication (APM) (during 2006–2017) and on insurance claims for treatment of psychosis (2011–2016). The Incidence Rate Ratios (IRRs) for migrants compared to controls were estimated by year since arrival.
The IRR of APM was 0.22 (95% CI 0.21–0.24) in the year of arrival (‘year 1’) and increased gradually to 1.39 (1.19–1.62) after 10 or more years. The IRR of an insurance claim increased from 0.57 (0.51–0.62) to 1.87 (1.38–2.55) in year 5. Among migrants from sub-Saharan Africa, the IRR of an insurance claim was already high in year 1 [2.46 (1.95–3.11)], especially when aged 10–20 years at arrival [6.09 (2.93–12.64)]. Among migrants from other non-Western countries, the IRR was already significantly increased in year 2 [1.28 (1.03–1.59)].
The relative risk of psychosis among migrants was generally low at arrival and increased thereafter. The increased IRRs in the early years after arrival among those from non-Western countries indicate that for these groups certain risk factors are already relevant shortly after arrival.
Antipsychotics are widely used in the treatment of major depressive disorder (MDD), but there has been no comprehensive meta-analytic assessment that examined their use as monotherapy and adjunctive therapy.
A systematic review and a meta-analysis were conducted on randomized placebo-controlled trials (RCTs) that reported on the efficacy and safety/tolerability of antipsychotics for the treatment of adults with MDD. Data of both monotherapy and adjunctive antipsychotic use were extracted, but analyzed separately using a random-effects model. Co-primary outcomes were study-defined-treatment response and intolerability-related discontinuation. We also illustrated the risk/benefit balance of antipsychotics for MDD, using two-dimensional graphs representing the primary efficacy and safety/tolerability outcome. Secondary outcomes included psychopathology, remission, all-cause-discontinuation, inefficacy-related discontinuation, and adverse events.
Forty-five RCTs with 12 724 patients were included in the analysis. In monotherapy (studies = 13, n = 4375), amisulpride [1.99 (1.55–2.55)], sulpiride [1.50 (1.03–2.17)], and quetiapine [1.48 (1.23–1.78)] were significantly superior to placebo regarding treatment response. However, intolerability-related discontinuations were significantly higher compared to placebo with amisulpride and quetiapine. In adjunctive therapy (studies = 32, n = 8349), ziprasidone [1.80 (1.07–3.04)], risperidone [1.59 (1.19–2.14)], aripiprazole [1.54 (1.35–1.76)], brexpiprazole [1.41 (1.21–1.66)], cariprazine [1.27 (1.07–1.52)], and quetiapine [1.23 (1.08–1.41)] were significantly superior to placebo regarding treatment response. However, of these antipsychotics that were superior to placebo, only risperidone was equivalent to placebo regarding discontinuation due to intolerability, while the other antipsychotics were inferior.
Results suggest that there are significant differences regarding the risk/benefit ratio among antipsychotics for MDD, which should inform clinical care.
Antipsychotic polypharmacy (APP) occurs commonly but it is unclear whether it is associated with an increased risk of adverse drug reactions (ADRs). Electronic health records (EHRs) offer an opportunity to examine APP using real-world data. In this study, we use EHR data to identify periods when patients were prescribed 2 + antipsychotics and compare these with periods of antipsychotic monotherapy. To determine the relationship between APP and subsequent instances of ADRs: QT interval prolongation, hyperprolactinaemia, and increased body weight [body mass index (BMI) ⩾ 25].
We extracted anonymised EHR data. Patients aged 16 + receiving antipsychotic medication at Camden & Islington NHS Foundation Trust between 1 January 2008 and 31 December 2018 were included. Multilevel mixed-effects logistic regression models were used to elucidate the relationship between APP and the subsequent presence of QT interval prolongation, hyperprolactinaemia, and/or increased BMI following a period of APP within 7, 30, or 180 days respectively.
We identified 35 409 observations of antipsychotic prescribing among 13 391 patients. Compared with antipsychotic monotherapy, APP was associated with a subsequent increased risk of hyperprolactinaemia (adjusted odds ratio 2.46; 95% CI 1.87–3.24) and of registering a BMI > 25 (adjusted odds ratio 1.75; 95% CI 1.33–2.31) in the period following the APP prescribing.
Our observations suggest that APP should be carefully managed with attention to hyperprolactinaemia and obesity.
Negative psychotic symptoms are among the most disabling features of schizophrenia, and are strongly associated with relatively poor clinical and functional outcomes. However, there are no effective treatments for negative symptoms, and this represents a major unmet clinical need. Recent research has shown that negative symptoms are already present in many patients at illness onset. There is evidence that cariprazine may improve negative symptoms in patients with chronic schizophrenia. However, its utility in treating negative symptoms in the early stage of the disorder is unclear. Here, we report six cases of patients with first-episode psychosis who were treated with cariprazine.
There is a distinction between very late onset schizophrenia like disorders and shcizophrenia that develops in early life and persists to old age. Assessment, pharmacological and psychosocial management are addressed.
In the UK, the incidence of schizophrenia appears highest in Black Caribbean and Black African communities (four- to six-fold that of the White British population). The incidence of psychosis in other minority ethnic groups is also raised, but to a lesser magnitude. Although there are numerous environmental confounding factors, the data stresses the importance of optimising treatment in high-risk (minority) groups. Antipsychotic nonadherence is the most common reason for schizophrenia relapse, and is associated with increased rates of relapse, readmission to hospital and suicide. This article examines available literature to discover how culture can affect antipsychotic nonadherence, and considers culture-based solutions that could enhance antipsychotic adherence. Acknowledging the importance of the therapeutic alliance and sociocultural aspects in antipsychotic adherence, I argue that current cultural competence training provided to clinicians is inadequate. Organisational- and system-level approaches are required to reduce oppressive practise and promote culturally competent, person-centred care.
It has been postulated that neurotrophin dysregulation leads to disorganisation in neuronal networks, which results in schizophrenia. The current study sets out to evaluate if the finding of lower brain-derived neurotrophic factor (BDNF) levels in schizophrenia patients could be confirmed in an independent cohort and to investigate if the BDNF levels can be altered with different treatment modalities such as electroconvulsive therapy (ECT) and/or antipsychotic pharmacotherapy (PT).
A total of 54 male patients with schizophrenia and 35 healthy controls were included in the study. Schizophrenia patients were subdivided into two groups as the ones who underwent ECT + PT and only PT. Clinical and sociodemographic data questionnaire, Positive and Negative Syndrome Scale (PANSS) and blood sample collection for BDNF assessment were applied to all patients (on first and last days of admissions) and healthy participants (on the day of the interview). Then, clinical parameters and blood sample outcomes were statistically analysed.
Mean BDNF levels of healthy individuals were significantly higher than mean pre- and post-treatment BDNF levels in both PT only and ECT + PT groups. While serum BDNF levels did not increase after ECT + PT, there was a trend level increase in the PT only group. There was no significant correlation between the changes in serum BDNF levels with total PANSS scores in either group after treatment.
We could confirm previously suggested data of lower serum BDNF levels in schizophrenia patients compared to healthy population but we could not find significant increase in serum BDNF levels with ECT + PT or only PT as some previous studies suggested.
Aripiprazole augmentation is proven effective for antidepressant-refractory depression, but its licensed dose range is wide and optimal dosage remains unclear.
To find the optimal dosage of aripiprazole augmentation.
Multiple electronic databases were searched (from inception to 16 February 2021) to identify all assessor-masked randomised controlled trials evaluating aripiprazole augmentation therapy in adults (≥18 years old, both genders) with major depressive disorder showing inadequate response to at least one antidepressant treatment. A random-effects, one-stage dose–effect meta-analysis with restricted cubic splines was conducted. Outcomes were efficacy (treatment response: ≥50% reduction in depression severity), tolerability (drop-out due to adverse effects) and acceptability (drop-out for any reason) after 8 weeks of treatment (range 4–12 weeks).
Ten studies met the inclusion criteria. All were individually randomised, placebo-controlled, multi-centre, parallel studies including 2625 participants in total. The maximum target dose–efficacy curve showed an increase up to doses between 2 mg (odds ratio OR = 1.46, 95% CI 1.15–1.85) and 5 mg (OR = 1.93, 95% CI 1.33–2.81), and then a non-increasing trend through the higher licensed doses up to 20 mg (OR = 1.90, 95% CI 1.52–2.37). Tolerability showed a similar trend with greater uncertainty. Acceptability showed no significant difference through the examined dose range. Certainty of evidence was low to moderate.
Low-dose aripiprazole as augmentation treatment might achieve the optimal balance between efficacy, tolerability and acceptability in the acute treatment of antidepressant-refractory depression. However, the small number of included studies and the overall moderate to high risk of bias seriously compromise the reliability of the results. Further research is required to investigate the benefits of low versus high dose.
Rates of prescriptions of antidepressants and suicide are inversely correlated at an epidemiological level. Less attention has been paid to relationships between other drugs used in mental health and suicide rates. Here we tested relationships between prescriptions of anxiolytics and antipsychotics and suicide rates in Scotland.
Suicide rates were inversely correlated with prescriptions of antidepressants and antipsychotics over 14 years (2004–2018), and positively with prescriptions of anxiolytics.
This illustrates the role of medications used in mental health in suicide prevention, and highlights the importance of identifying causal mechanisms that link anxiolytics with suicide.
Despite policy pressure and concerns regarding the use of antipsychotics and benzodiazepines, many care home residents with dementia are prescribed psychotropic medication, often off licence. This is the first large study to report psychotropic prescribing and ‘as required’ administration patterns in English care homes.
To explore the prevalence and associates of psychotropic prescription in care home residents with dementia and compare the results with national guidance.
We collected data in a longitudinal cohort study of residents with diagnosed or probable dementia in 86 care homes in England in 2014–2016. We reported the prevalence of psychotropic (antipsychotics, anxiolytics/hypnotics, antidepressants) prescriptions and drug receipt. We explored the associations between resident factors (sociodemographic, agitation [Cohen–Mansfield Agitation Inventory], dementia severity [Clinical Dementia Rating]) and care home factors (type, ownership, size, dementia registration/specialism, quality rating) in prescription and ‘as required’ administration, using multilevel regression models.
We analysed data from 1425 residents. At baseline, 822 residents (57.7%, 95% CI: 55.1–60.2) were prescribed a psychotropic drug, 310 residents (21.8% 95% CI: 19.7–24.0) were prescribed an anxiolytic/hypnotic, 232 (94.3%, 95% CI: 90.6–96.6) were prescribed one antipsychotic and 14 (5.7%, 95% CI: 3.4–9.4) were prescribed two antipsychotics. The median prescription duration during the study was 1 year. Residents with clinically significant agitation were prescribed more antipsychotics (odds ratio [OR] = 2.00, 95% CI: 1.64–2.45) and anxiolytics/hypnotics (OR = 2.81, 95% CI: 2.31–3.40).
Antipsychotics and anxiolytics/hypnotics are more commonly prescribed for people with dementia in care homes than in the community, and prescribing may not reflect guidelines. Policies which advocate reduced use of psychotropics should better support psychosocial interventions.
Aripiprazole, brexpiprazole and cariprazine are partial dopamine (and serotonin) agonists developed as novel antipsychotics. This article discusses their pharmacology, evidence on their licensed and off-licence uses (including psychosis, mania, bipolar depression, Tourette syndrome and autism spectrum disorder) and side-effects. In schizophrenia, they have a low risk of Parkinsonism or hyperprolactinaemia, cause modest increases in body weight and are of moderate efficacy.