Contemporary data relating to antipsychotic prescribing in UK primary care for patients diagnosed with severe mental illness (SMI) are lacking.

To describe contemporary patterns of antipsychotic prescribing in UK primary care for patients diagnosed with SMI.

Cohort study of patients with an SMI diagnosis (i.e. schizophrenia, bipolar disorder, other non-organic psychoses) first recorded in primary care between 2000 and 2017 derived from Clinical Practice Research Datalink. Patients were considered exposed to antipsychotics if prescribed at least one antipsychotic in primary care between 2000 and 2019. We compared characteristics of patients prescribed and not prescribed antipsychotics; calculated annual prevalence rates for antipsychotic prescribing; and computed average daily antipsychotic doses stratified by patient characteristics.

Of 309 378 patients first diagnosed with an SMI in primary care between 2000 and 2017, 212,618 (68.7%) were prescribed an antipsychotic between 2000 and 2019. Antipsychotic prescribing prevalence was 426 (95% CI, 420–433) per 1000 patients in the year 2000, reaching a peak of 550 (547–553) in 2016, decreasing to 470 (468–473) in 2019. The proportion prescribed antipsychotics was higher among patients diagnosed with schizophrenia (81.0%) than with bipolar disorder (64.6%) and other non-organic psychoses (65.7%). Olanzapine, quetiapine, risperidone and aripiprazole accounted for 78.8% of all antipsychotic prescriptions. Higher mean olanzapine equivalent total daily doses were prescribed to patients with the following characteristics: schizophrenia diagnosis, ethnic minority status, male gender, younger age and greater relative deprivation.

Antipsychotic prescribing is dominated by olanzapine, quetiapine, risperidone and aripiprazole. We identified potential disparities in both the receipt and prescribed doses of antipsychotics across subgroups. To inform efforts to optimise prescribing and ensure equity of care, further research is needed to understand why certain groups are prescribed higher doses and are more likely to be treated with long-acting injectable antipsychotics compared with others.

The association between heatwave and heat-related outcomes in people with mental health conditions with and without psychotropics was unclear.

We identified people with severe mental illness (SMI) and depression, respectively, using Japanese claim data of Ibaraki prefecture during 1/1/2014–31/12/2021. We conducted self-controlled case series to estimate the incidence rate ratio (IRR) of heat-related illness, myocardial infarction and delirium, respectively, during 5-day pre-heatwave, heatwave, and 5-day post-heatwave periods v. all other periods (baseline) within an individual, stratified by periods prescribed psychotropics and periods not prescribed psychotropics, respectively.

Among people with SMI, heatwave was associated with an increased rate of heat-related illness v. baseline, with no evidence of a difference in the IRRs between those prescribed v. not prescribed antipsychotics (IRR: 1.48 [95% CI 1.40–1.56]; 1.45 [95% CI 1.35–1.56] respectively, p interaction: 0.53). Among people with depression, heatwave was similarly associated with heat-related illness, with no evidence of a difference in the IRRs between those prescribed v. not prescribed antidepressants (IRR: 1.54 [95% CI 1.46–1.64]; 1.64 [95% CI 1.57–1.71] respectively, p interaction: 0.33). Smaller increased rates of heat-related illness were also observed in pre- and post-heatwave periods, v. baseline in both cohorts. There was weak evidence of an increased risk of MI and delirium associated with heatwave v. baseline.

We showed an increased risk of heat-related illness, myocardial infarction and delirium associated with heatwave in people with mental health conditions regardless of whether being prescribed psychotropics. Risks of heat-related illness, myocardial infarction and delirium associated with heatwave might not be factors to influence decisions about the routine use of psychotropics.

The lifetime prevalence of suicide is around 5% in patients with schizophrenia. Non-adherence to antipsychotic medication is an important risk factor, but prospective studies investigating joint effects of antipsychotic drugs, antidepressants, and benzodiazepines on suicidality are scarce. We aimed to investigate how use and non-use of psychotropic medications are associated with suicidality in schizophrenia.

An open cohort study followed all patients consecutively admitted to a psychiatric acute unit during a 10-year period with a diagnosis of schizophrenia (n = 696). Cox multiple regression analyses were conducted with use of antipsychotics, antidepressants, and benzodiazepines as time-dependent variables. Adjustments were made for age, gender, depressive mood, agitated behavior, and use of alcohol and illicit substances.

A total of 32 (4.6%) suicide events were registered during follow-up. Of these, 9 (28%) were completed suicides and 23 (72%) were attempted suicides. A total of 59 (8.5%) patients were readmitted with suicidal plans during the follow-up. Compared to non-use, use of antipsychotics was associated with 70% lower risk of attempted or completed suicide (adjusted hazard ratio [AHR] = 0.30, p < 0.01, CI 0.14–0.65) and 69% reduced risk of readmission with suicidal plans (AHR = 0.31, p < 0.01, CI 0.18–0.55). Use of prescribed benzodiazepines was associated with 126% increased risk of readmission with suicidal plans (AHR = 2.26, p = 0.01, CI 1.24–4.13).

Adherence to antipsychotic medication is strongly associated with reduced suicidal risk in schizophrenia. The use of prescribed benzodiazepines was identified as a significant risk factor for being readmitted with suicidal plans.

Early worsening of plasma lipid levels (EWL; ≥5% change after 1 month) induced by at-risk psychotropic treatments predicts considerable exacerbation of plasma lipid levels and/or dyslipidaemia development in the longer term.

We aimed to determine which clinical and genetic risk factors could predict EWL.

Predictive values of baseline clinical characteristics and dyslipidaemia-associated single nucleotide polymorphisms (SNPs) on EWL were evaluated in a discovery sample (n = 177) and replicated in two samples from the same cohort (PsyMetab; n1 = 176; n2 = 86).

Low baseline levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides, and high baseline levels of high-density lipoprotein cholesterol (HDL-C), were risk factors for early increase in total cholesterol (P = 0.002), LDL-C (P = 0.02) and triglycerides (P = 0.0006), and early decrease in HDL-C (P = 0.04). Adding genetic parameters (n = 17, 18, 19 and 16 SNPs for total cholesterol, LDL-C, HDL-C and triglycerides, respectively) improved areas under the curve for early worsening of total cholesterol (from 0.66 to 0.91), LDL-C (from 0.62 to 0.87), triglycerides (from 0.73 to 0.92) and HDL-C (from 0.69 to 0.89) (P ≤ 0.00003 in discovery sample). The additive value of genetics to predict early worsening of LDL-C levels was confirmed in two replication samples (P ≤ 0.004). In the combined sample (n ≥ 203), adding genetics improved the prediction of new-onset dyslipidaemia for total cholesterol, LDL-C and HDL-C (P ≤ 0.04).

Clinical and genetic factors contributed to the prediction of EWL and new-onset dyslipidaemia in three samples of patients who started at-risk psychotropic treatments. Future larger studies should be conducted to refine SNP estimates to be integrated into clinically applicable predictive models.

There is a high incidence of serious mental illness (SMI) and antipsychotic use in the respiratory high dependence unit (HDU) compared with the general population. However, there is a paucity of data in the extant literature evaluating the relationships between respiratory failure and antipsychotics.

To investigate the relationship between antipsychotics and respiratory failure in people admitted to a respiratory HDU, and to gain a better understanding of the potential impact of antipsychotic medications on respiratory outcomes.

Medical, demographic and clinical outcome data were collected for a consecutive sample of 638 individuals admitted to a respiratory HDU between the dates 1 January 2018 and 29 May 2021 at a large quaternary hospital.

Multivariate models controlling for confounders found that antipsychotic medications increased risk of admission for type 2 respiratory failure and chronic obstructive pulmonary disease exacerbation without hypercapnia by 3.7 and 11.45 times, respectively. For people admitted with type 2 respiratory failure, antipsychotic use increased the risk of requiring non-invasive ventilation by 4.9 times. Those prescribed an antipsychotic were more likely to be readmitted within 30 days. Over 30% of individuals were prescribed antipsychotics for an unlicensed indication.

Poor respiratory outcomes may be a previously unknown adverse drug reaction of antipsychotics. Modifications to clinical care and clinical pathways for those with SMI prescribed antipsychotic medications, including optimising their chronic health and deprescribing where appropriate, should be prioritised.

One of the ‘critical goals’ for psychiatric liaison services is reducing hospitalisation. Psychotropic medication is a treatment for psychosis, although research determining the efficacy of early medication administration is lacking.

To determine whether commencing psychotropic medication within 2 days of psychiatric liaison input in the accident and emergency (A&E) department is correlated with length of in-patient psychiatric admissions for patients with psychosis.

We gathered data on patients presenting to A&E sites covered by South London and Maudsley (SLaM) National Health Service Trust, who were subsequently admitted to and discharged from SLaM psychiatric in-patient wards with discharge diagnosis of psychosis between 2015 and 2020. The analysis set comprised 228 patients waiting in the A&E department under psychiatric liaison care for ≥2 days, of which 140 were started on medication within those 2 days (group A) and 88 were not (group B). Group A was divided into A1 (patients restarted on previous psychotropic medication taken within 1 week) and A2 (others, including those new to psychotropic medication or with past usage).

Although Kaplan–Meier survival curves with log-rank tests demonstrated no statistically significant difference of in-patient admission duration between groups A and B or groups B1 and B2, further analysis revealed that subgroup A1 had statistically significant shorter admissions than group B (P = 0.05).

Restarting patients with psychosis on medication they were taking within the week before A&E department attendance, within 2 days of arrival at the A&E department, is associated with statistically significant shorter admissions. The limitation is a relatively small sample size.

Breast cancer is a major global health issue, especially among women. Previous research has indicated a possible association between psychiatric conditions, particularly schizophrenia, and an increased risk of breast cancer. However, the specific risk of breast cancer in women with schizophrenia, compared with those with other psychiatric disorders and the general population, remains controversial and needs further clarification.

To estimate the risk of breast cancer among people with schizophrenia compared with people with other psychiatric disorders and people in the general population.

We utilised medical claims data of women aged 18 to 80 years in the Korean National Health Information Database from 2007 to 2018. Individuals with schizophrenia were defined as women with ICD-10 codes F20 or F25 (n = 224 612). The control groups were defined as women with other psychiatric disorders (n = 224 612) and women in the general Korean population (n = 449 224). Cases and controls were matched by index date and age, in a 1:1:2 ratio. We estimated the hazard of breast cancer using the Cox proportional hazards model, adjusting for insurance premiums and medical comorbidities. Among the people with schizophrenia, we used the landmark method to estimate the association between duration of antipsychotic medication use and the incidence of breast cancer.

In multivariable Cox regression models, the hazard rate of breast cancer was 1.26 times higher in the people with schizophrenia than in the general population (95% CI: 1.20–1.32). In comparison with the psychiatric patient group, the hazard ratio was 1.17 (95% CI: 1.11–1.28). Among women with schizophrenia, the hazard of breast cancer was greater among those who took antipsychotic medications for 1 year or more compared with those who took antipsychotics for less than 6 months.

Women with schizophrenia have an elevated risk of breast cancer, and long-term use of antipsychotics is associated with an increased risk of breast cancer.

While antipsychotic medication reduces the risk of relapse for patients with schizophrenia, high prevalence of adverse effects results in low adherence. Lower doses of antipsychotics have been associated with increased level of function but also with increased risk of relapse. This study presents findings from a specialized deprescribing clinic. In addition, we aim to identify clinical predictors for relapse.

Patients diagnosed with schizophrenia were referred to the clinic, which offers a six-month guided tapering program. Antipsychotic dose was reduced by 10% every four weeks. Patients were monitored closely for symptom progression or decrease in level of function, with defined cut-offs prompting a pause in or cessation of dose reduction.

After 12 months, the antipsychotic dose was reduced from 404 (±320 mg) to 255 (±236 mg) chlorpromazine equivalent. Of the 88 patients included, 22 (27%) experienced relapse during the six-month tapering period, while 29 (37%) experienced relapse at the 12-month follow-up visit and nine patients were antipsychotic free. Patients who remained stable experienced a slightly increased level of functioning and markedly fewer side effects (p < 0.001). Following relapse, patients were clinically stabilized and showed an improved attitude toward antipsychotic medication. The predictive models were weak.

We show that most patients undergoing guided antipsychotic tapering remained stable after one year and improved in level of function, while most patients who relapsed were quickly stabilized. Our inability to create strong predictive models could be due to limitations in the study design, warranting future studies exploring tapering of antipsychotics in patients with schizophrenia.

Despite proven effectiveness in refractory schizophrenia, clozapine remains underutilised, and it is important to understand potential reasons for this. This study’s aim was to examine in a National sample of Consultant Psychiatrists their knowledge of, attitudes and perceived barriers to clozapine use.

A novel questionnaire was designed and distributed by email to 275 Consultant Psychiatrists in Republic of Ireland.

Twenty-eight percent (n = 77) completed the survey, with 55% of respondents practicing for 15 or more years. Clinicians expressed confidence in managing clozapine treatment and side effects and were well aware of clozapine’s clinical effectiveness and guideline-based use. A majority indicated insufficient experience managing rechallenge and half expressed insufficient experience managing adverse events. Perceived patient factors were highlighted as barriers with 69% of respondents reporting patients’ concern about effectiveness and 50% regarding tolerability. Sixty-four percent (n = 40) indicated that a specialised/tertiary clozapine service would facilitate initiation, with 57% (n = 36) reporting less frequent blood monitoring would aid clozapine prescribing. A majority identified that access to dedicated staff (81%, n = 51) and dedicated day hospital services (84%, n = 53) would facilitate community initiation.

Consultants are familiar with clozapine use and related guidelines. Dedicated staff and facilities for clozapine use is one identified structural change to enhance clozapine prescribing in Ireland. Tertiary service or clinical advice service would assist in clozapine rechallenge cases or in managing significant adverse events. More structured patient education regarding clozapine effectiveness and professional development programmes focused on managing side effects and rechallenge may promote clozapine use.

We need to better understand the risk factors and predictors of medication-related weight gain to improve metabolic health of individuals with schizophrenia. This study explores how trajectories of antipsychotic medication (AP) use impact body weight early in the course of schizophrenia.

We recruited 92 participants with first-episode psychosis (FEP, n = 92) during their first psychiatric hospitalization. We prospectively collected weight, body mass index (BMI), metabolic markers, and exact daily medication exposure during 6-week hospitalization. We quantified the trajectory of AP medication changes and AP polypharmacy using a novel approach based on meta-analytical ranking of medications and tested it as a predictor of weight gain together with traditional risk factors.

Most people started treatment with risperidone (n = 57), followed by olanzapine (n = 29). Then, 48% of individuals remained on their first prescribed medication, while 33% of people remained on monotherapy. Almost half of the individuals (39/92) experienced escalation of medications, mostly switch to AP polypharmacy (90%). Only baseline BMI was a predictor of BMI change. Individuals in the top tercile of weight gain, compared to those in the bottom tercile, showed lower follow-up symptoms, a trend for longer prehospitalization antipsychotic treatment, and greater exposure to metabolically problematic medications.

Early in the course of illness, during inpatient treatment, baseline BMI is the strongest and earliest predictor of weight gain on APs and is a better predictor than type of medication, polypharmacy, or medication switches. Baseline BMI predicted weight change over a period of weeks, when other traditional predictors demonstrated a much smaller effect.

Clozapine is the most effective medication for treatment-resistant psychoses, but the balance of benefits and risks is understudied in real-world settings.

To examine the relative re-hospitalisation rates for mental health relapse and adverse events associated with clozapine and other antipsychotics in adult and child/youth cohorts.

Data were obtained from the Canadian Institute of Health Information for adults (n = 45 616) and children/youth (n = 1476) initially hospitalised for mental health conditions in British Columbia, Manitoba and Saskatchewan from 2008 to 2018. Patient demographics and hospitalisations were linked with antipsychotic prescriptions dispensed following the initial visit. Recurrent events survival analysis for relapse and adverse events were created and compared between clozapine and other antipsychotics.

In adults, clozapine was associated with a 14% lower relapse rate versus other drugs (adjusted hazard ratio: 0.86, 95% CI: 0.83–0.90) over the 10-year follow-up. In the first 21 months, the relapse rate was higher for clozapine but then reversed. Over 1000 person-months, clozapine-treated adults could be expected to have 38 relapse hospitalisations compared with 45 for other drugs. In children/youth, clozapine had a 38% lower relapse rate compared with other antipsychotic medications (adjusted hazard ratio: 0.62, 95% CI: 0.49–0.78) over the follow-up period. This equates to 29 hospitalisations for clozapine and 48 for other drugs over 1000 person-months. In adults, clozapine had a higher risk for adverse events (hazard ratio: 1.34, 95% CI: 1.18–1.54) over the entire follow-up compared with other antipsychotics. This equates to 1.77 and 1.30 hospitalisations over 1000 person-months for clozapine and other drugs, respectively.

Clozapine was associated with lower relapse overall, but this was accompanied by higher adverse events for adults. For children/youth, clozapine was associated with lower relapse all throughout and had no difference in adverse events compared with other antipsychotics.

Clozapine is the most effective antipsychotic for treatment-resistant psychosis. However, clozapine is underutilised in part because of potential agranulocytosis. Accumulating evidence indicates that below-threshold haematological readings in isolation are not diagnostic of life-threatening clozapine-induced agranulocytosis (CIA).

To examine the prevalence and timing of CIA using different diagnostic criteria and to explore demographic differences of CIA in patients registered on the UK Central Non-Rechallenge Database (CNRD).

We analysed data of all patients registered on the UK Clozaril® Patient Monitoring Service Central Non-Rechallenge Database (at least one absolute neutrophil count (ANC) < 1.5 × 109/L and/or white blood cell count < 3.0 × 109/L) between May 2000 and February 2021. We calculated prevalence rates of agranulocytosis using threshold-based and pattern-based criteria, stratified by demographic factors (gender, age and ethnicity). Differences in epidemiology based on rechallenge status and clozapine indication were explored. The proportion of patients who recorded agranulocytosis from a normal ANC was explored.

Of the 3029 patients registered on the CNRD with 283 726 blood measurements, 593 (19.6%) were determined to have threshold-based agranulocytosis and 348 (11.4%) pattern-based agranulocytosis. In the total sample (75 533), the prevalence of threshold-based agranulocytosis and pattern-based agranulocytosis was 0.8% and 0.5%, respectively. The median time to threshold-based agranulocytosis was 32 weeks (IQR 184) and 15 (IQR 170) weeks for pattern-based agranulocytosis. Among age groups, the prevalence of pattern-based agranulocytosis and threshold-based agranulocytosis was highest in the >48 age group. Prevalence rates were greatest for White (18%) and male individuals (13%), and lowest for Black individuals (0.1%). The proportion of people who were determined to have pattern-based agranulocytosis without passing through neutropenia was 70%.

Threshold-based definition of agranulocytosis may over-diagnose CIA. Monitoring schemes should take into consideration neutrophil patterns to correctly identify clinically relevant CIA. In marked contrast to previous studies, CIA occurred least in Black individuals and most in White individuals.

Exposure to second-generation antipsychotics (SGAs) carries a risk of type 2 diabetes, but questions remain about the diabetogenic effects of SGAs.

To assess the diabetes risk associated with two frequently used SGAs.

This was a retrospective cohort study of adults with schizophrenia, bipolar I disorder or severe major depressive disorder (MDD) exposed during 2008–2013 to continuous monotherapy with aripiprazole or olanzapine for up to 24 months, with no pre-period exposure to other antipsychotics. Newly diagnosed type 2 diabetes was quantified with targeted minimum loss-based estimation; risk was summarised as the restricted mean survival time (RMST), the average number of diabetes-free months. Sensitivity analyses were used to evaluate potential confounding by indication.

Aripiprazole-treated patients had fewer diabetes-free months compared with olanzapine-treated patients. RMSTs were longer in olanzapine-treated patients, by 0.25 months [95% CI: 0.14, 0.36], 0.16 months [0.02, 0.31] and 0.22 months [0.01, 0.44] among patients with schizophrenia, bipolar I disorder and severe MDD, respectively. Although some sensitivity analyses suggest a risk of unobserved confounding, E-values indicate that this risk is not severe.

Using robust methods and accounting for exposure duration effects, we found a slightly higher risk of type 2 diabetes associated with aripiprazole compared with olanzapine monotherapy regardless of diagnosis. If this result was subject to unmeasured selection despite our methods, it would suggest clinician success in identifying olanzapine candidates with low diabetes risk. Confirmatory research is needed, but this insight suggests a potentially larger role for olanzapine in the treatment of well-selected patients, particularly for those with schizophrenia, given the drug's effectiveness advantage among them.

Patients prescribed clozapine are increasingly living into old age. However, there is a lack of studies to guide prescribing in this age group. We sought to identify all clozapine patients in Hertfordshire Partnership NHS Foundation Trust over a 5-year period and review side-effect burden and co-prescribing in all patients aged over 65 years.

We identified 69 patients. The majority (61%) were stable in terms of mental state; 94% of cases had experienced a side-effect within the past year, with constipation occurring most commonly (65% of cases).

Our findings reveal a significant side-effect burden, particularly in relation to constipation. Clozapine-induced gastrointestinal hypomotility (CIGH) can be fatal; however, increasing age has not been a recognised risk factor for constipation in clozapine patients to date. This raises questions about increasing risk to physical health as patients age and adds to concerns about the lack of monitoring for CIGH.