Naomi Launders

Background: People diagnosed with severe mental illnesses (SMI) including bipolar disorder, schizophrenia and psychosis are disproportionately exposed to adverse social determinants of health, contributing to premature morbidity and mortality. Social prescribing aims to address social risk factors for poor health by linking patients in primary care to community activities. However, whether people with SMI access social prescribing through primary care remains unexplored. Aims: To describe prevalence of, and sociodemographic characteristics associated with, social prescribing consultations in patients with SMI in primary care. Methods: Using the UK Clinical Practice Research Datalink, we identified patients aged 18+ with a diagnosis of SMI between 2004-2019. We calculated the percentage of patients with SMI who received a social prescribing consultation between 2019-2023 and used logistic regression to examine associations between sociodemographic, health-related factors and social prescribing consultations and refusals. We used fixed effects analysis to determine whether a new diagnosis of SMI made between 2019-2023 was associated with an increased odds of receiving a social prescribing consultation. Results: Among 112,334 patients with SMI, 0.8% received a social prescribing consultation in 2019 increasing to 9.5% in 2023. Between 2020-2023, older age (OR=1.18-2.34), being female (OR=1.16-1.31) and living in more deprived areas (OR=1.14-1.49) were associated with higher odds of receiving a social prescribing consultation amongst patients with SMI. Across all years, patients with SMI and depression (OR=1.32-1.92), diabetes (OR=1.19-1.35) or obesity (OR=1.17-1.54) also had increased odds. In 140,514 patients with time-varying SMI status, a new diagnosis of SMI was associated with higher odds of receiving a social prescribing consultation (OR=1.39, 95% CI 1.26-1.53). Conclusion: Since 2019, social prescribing consultations among patients with SMI in primary care have increased and are reaching those in areas of higher deprivation and with greater health needs. Strategies to remove barriers to consultations among younger adults and males are still needed.

Background: Dihydropyridine calcium channel blockers have been implicated in both symptom improvement and exacerbation in pre-existing severe mental illness (SMI). We aimed to test the hypothesis that blood-brain barrier penetrant dihydropyridines (DHPs) reduce rates of mental health hospitalisation and self-harm compared to non-penetrant DHPs. Methods: We used English electronic health records (Clinical Practice Research Datalink) to conduct a target trial emulation study in people with schizophrenia, bipolar disorder or other psychosis. We compared admissions for mental health and self-harm in those prescribed blood-brain barrier penetrant (intervention) and non-penetrant DHPs (control). Our primary endpoint was a 12-month intention-to-treat analysis using covariate adjustment. We additionally completed overlap weighting, per-protocol analyses and negative outcome controls. Results: We included 918 people prescribed blood-brain barrier penetrant DHPs and 3384 prescribed amlodipine (control). In the primary covariate-adjusted intention-to-treat analysis, there was no clear evidence of a difference in rates of combined mental health admissions and self-harm events (adjusted hazard ratio (HR): 1.22; 95% confidence interval (CI): 0.78–1.91 at 12 months). In a pre-specified sensitivity analysis using overlap weighting, self-harm event rates were elevated in the intervention group at 12 months (HR: 2.10; 95% CI: 1.13–3.94); however, the equivalent covariate-adjusted estimate showed no clear difference (HR: 1.81; 95% CI: 0.52–6.26). Conclusion: In people with SMI, blood-brain barrier penetrant DHPs were not associated with reduced mental health hospitalisations or self-harm events compared to those treated with amlodipine, though estimates were imprecise. This active comparator design cannot distinguish between absence of effect or equivalent benefit of both drug classes. There are peripheral pathways through which DHPs may impact psychiatric symptoms and these require further exploration.

Background: Bipolar disorder is an episodic mental illness, often requiring complex pharmacological management. Lithium is a first-line treatment, while antidepressant monotherapy can precipitate mania symptoms in some patients. Aims: To (a) describe patterns of antidepressant, antipsychotic and mood stabiliser prescribing in the 12-month periods before and after first-recorded bipolar diagnosis; (b) describe treatment trajectories in the year post-diagnosis; and (c) investigate associations between sociodemographic and treatment-related characteristics of (i) antidepressant monotherapy and (ii) lithium prescription post-diagnosis. Method: A longitudinal cohort study of patients with a first-recorded diagnosis of bipolar disorder between 2000 and 2022 derived from Clinical Practice Research Datalink. Prescriptions for antidepressants, antipsychotics and mood stabilisers were examined in the 12 months before and after diagnosis. Logistic regression models tested associations between sociodemographic and treatment-related characteristics and prescribing outcomes. A web application ( https://dop-mhds.shinyapps.io/bpd-prescribing-uk-shiny/ ) was developed to visualise treatment trajectories over the year following diagnosis. Results: We included 40 965 patients with a first-recorded diagnosis of bipolar disorder between 2000 and 2022 (median age at diagnosis 43 years, 60.9% female, 11.1% ethnic minority). Of these, 32 460 (79.2%) were prescribed a relevant medication in the year prior to diagnosis compared with 37 208 (90.8%) in the year after. Antidepressant monotherapy was the most common pre-diagnosis treatment (48.4%), but was also prescribed to 28.9% during at least 1 month in the year after diagnosis. Antipsychotic monotherapy was the most common post-diagnosis treatment (36.0%). Lithium was prescribed to 18.5% within 1 year of diagnosis, with 4.0% receiving it as first-line monotherapy. Almost half (46.0%) switched medication at least once within 1 year. Males, ethnic minorities and patients residing in the most deprived areas had lower odds of receiving either lithium or antidepressant monotherapy. Conclusions: Prescribing patterns for bipolar disorder in the UK are highly variable and often outside of guideline recommendations, with persistent use of antidepressant monotherapy and potential under-utilisation of lithium.

Initiating aripiprazole as antipsychotic monotherapy rather than olanzapine, quetiapine, or risperidone, might prevent/delay major adverse cardiovascular events (MACEs) over the long-term in people diagnosed with severe mental illness. Using Clinical Practice Research Datalink data, we emulated a trial of aripiprazole versus olanzapine, quetiapine, and risperidone in 20,404 patients 2005–2014. Primary outcome was five-year MACE risk (composite of hospitalisation for acute myocardial infarction or stroke and cardiovascular death). Here we show that patients initiating aripiprazole had a similar five-year MACE risk as those initiating olanzapine (risk ratio: 1.03, 95% CI, 0.78-1.32), quetiapine (1.02, 95% CI, 0.72-1.32), and risperidone (0.88, 95% CI, 0.67-1.17). Risk was lower among patients initiating and continuing aripiprazole versus risperidone (0.58, 95% CI, 0.39-0.84). For patients at clinical equipoise, antipsychotic selection does not appear to significantly impact risk of the most severe, long-term cardiovascular events. However, further research is needed to replicate our finding of increased risk with continued risperidone use versus aripiprazole.

Background: Evidence regarding the efficacy of adjunct statins to treat severe mental illness (SMI) is mixed. The varying pharmacokinetic properties of statins mean that specific statin-antipsychotic combinations might improve psychiatric symptoms. Objective: To test whether some statin-antipsychotic/mood stabiliser combinations result in psychiatric symptom improvement in patients with SMI, while others do not, using target trial emulation in observational data. Methods: We identified patients with SMI (schizophrenia, bipolar disorder, ‘other’ psychoses) prescribed antipsychotics/mood stabilisers and statins from 2000 to 2019 in English linked primary care records (Clinical Practice Research Datalink). We defined hypothetical randomised trials and observational emulations: (1) blood-brain barrier (BBB)-penetrant (simvastatin) versus non-penetrant (atorvastatin/pravastatin/rosuvastatin) statins; (2A) P-glycoprotein inhibitors (simvastatin/atorvastatin) versus non-inhibitors (pravastatin) in patients prescribed aripiprazole/risperidone/olanzapine (P-glycoprotein affinity); (2B) high (aripiprazole/risperidone/olanzapine) versus low (quetiapine) P-glycoprotein affinity antipsychotics in patients prescribed P-glycoprotein-inhibiting statins. Findings: We found no reduction in our primary outcomes (12-month psychiatric admissions) in trial 1 (HR 1.07, 95% CI 0.88 to 1.31); trial 2A (HR 0.77, 95% CI 0.28 to 2.15); or trial 2B (HR 0.93, 95% CI 0.79 to 1.09). In trial 2B, we observed lower self-harm events (HR 0.60, 95% CI 0.38 to 0.97) in per-protocol analysis and lower psychiatric admissions in the ‘other’ psychoses subgroup (HR 0.53, 95% CI 0.34 to 0.85). Conclusions: BBB penetrance appears unlikely to be the mechanism by which statins improve SMI symptoms. Interaction with P-glycoprotein may have some effect. Further mechanistic and clinical research is needed to understand statin-antipsychotic interactions and the role of interaction with P-glycoprotein. Clinical implications: There is currently not enough evidence to guide the prescription of statins for psychiatric symptom improvement in patients with SMI. If there is an effect of statins, it may be through specific statin-antipsychotic combinations.

Background: A higher prevalence of neurological conditions has been found in schizophrenia, bipolar disorder and other psychotic illnesses compared to the general population. We aimed to understand the cumulative prevalence of 15 neurological conditions in people with severe mental illness (SMI) from 5 years before to 5 years after their SMI diagnosis. Methods: We identified patients with SMI, aged 18–100 years from 1 Jan 2000 to 31 Dec 2018, from the UK Clinical Practice Research Datalink. Each SMI patient was matched 1:4 to individuals without SMI. The cumulative prevalence of 15 neurological conditions was recorded at 5, 3 and 1 years prior to SMI diagnosis; at SMI diagnosis; and 1, 3 and 5 years after SMI diagnosis. Prevalences were compared with logistic regression. Results: We identified 68 789 patients with SMI and 274 827 comparators. Of 15 neurological conditions, 13 (multiple sclerosis, cerebrovascular disease, dementia, ataxic disorders, epilepsy, Parkinson’s disease, other parkinsonism, paralysis, other movement disorders, cerebrospinal fluid disorders, cerebral palsy, disorders of nerve root, plexus or peripheral nerves and autonomic disorders) were more prevalent in SMI compared with comparators at the time of SMI diagnosis. Dementia (OR: 4.22; 95% CI 3.88 to 4.58), epilepsy (OR: 3.01; 95% CI 2.83 to 3.19) and Parkinson’s disease (OR: 3.97; 95% CI 3.45 to 4.57) were particularly elevated at 5 years post-SMI diagnosis. Conclusions: Many neurological conditions have higher prevalence in the SMI cohort compared with those without SMI. The different prevalence patterns observed in our study highlight the need to establish the causal pathways between specific SMI and neurological disease diagnoses.

Background: Research on mortality and admissions for physical health problems across eating disorder diagnoses in representative settings is scarce. Inequalities in these outcomes across a range of sociodemographic characteristics have rarely been investigated. Aims: We investigated whether people with eating disorders had greater all-cause mortality and physical health-related in-patient admissions compared with those without eating disorders, and whether associations varied by sex, ethnicity, deprivation, age and calendar year at diagnosis. Method: Using primary care Clinical Research Practice Datalink linked to Hospital Episode Statistics, we matched people with an incident eating disorder diagnosis (any, anorexia nervosa, bulimia nervosa, eating disorders not otherwise specified, generic eating disorder or a referral code) from primary care Read codes to four people without eating disorders (1:4 matching) on year of birth, sex, primary care practice, year of registration and index date. We used univariable and multivariable Cox (mortality) and Poisson (admissions) models, and fitted interactions to investigate whether associations varied by sociodemographic characteristics. Results: We included 58 735 people (90.1% female, 91.6% White). People with any eating disorders had higher all-cause mortality (hazard ratio: 2.15, 95% CI: 1.73–2.67). Anorexia nervosa had the highest mortality (hazard ratio: 3.49, 95% CI: 2.43–5.01). People with any eating disorders had higher rates of planned (incidence rate ratio (IRR): 1.80, 95% CI: 1.4–1.87) and emergency admissions for physical health problems (IRR: 2.35. 95% CI: 2.35–2.46) and emergency admissions for injuries, accidents and substance misuse (IRR: 5.26, 95% CI: 5.24–5.29). Mortality and admission rate ratios were greater in males. Conclusions: People with eating disorders have high rates of mortality and physical health-related admissions. Observed inequalities call for an understanding of why such inequalities exist. These findings highlight the need for prompt and effective treatment for eating disorders, and for improved guidance on primary care management of people with eating disorders.

Background: Physical health checks in primary care for people with severe mental illness ((SMI) defined as schizophrenia, bipolar disorders and non-organic psychosis) aim to reduce health inequalities. Patients who decline or are deemed unsuitable for screening are removed from the denominator used to calculate incentivisation, termed exception reporting. Aims: To describe the prevalence of, and patient characteristics associated with, exception reporting in patients with SMI. Method: We identified adult patients with SMI from the UK Clinical Practice Research Datalink (CPRD), registered with a general practice between 2004 and 2018. We calculated the annual prevalence of exception reporting and investigated patient characteristics associated with exception reporting, using logistic regression. Results: Of 193 850 patients with SMI, 27.7% were exception reported from physical health checks at least once. Exception reporting owing to non-response or declining screening increased over the study period. Patients of Asian or Black ethnicity (Asian: odds ratio 0.72, 95% CI 0.65–0.80; Black: odds ratio 0.86, 95% CI 0.76–0.97; compared with White) and women (odds ratio 0.90, 95% CI 0.88–0.92) had a reduced odds of being exception reported, whereas patients diagnosed with ‘other psychoses’ (odds ratio 1.19, 95% CI 1.15–1.23; compared with bipolar disorder) had increased odds. Younger patients and those diagnosed with schizophrenia were more likely to be exception reported owing to informed dissent. Conclusions: Exception reporting was common in people with SMI. Interventions are required to improve accessibility and uptake of physical health checks to improve physical health in people with SMI.

Background: Metformin is a pharmacological candidate to mitigate second-generation antipsychotic (SGA)-induced weight gain in patients diagnosed with severe mental illnesses (SMI). Objective: To determine the incidence, prevalence and demographic patterns of metformin co-prescription among patients diagnosed with SMI initiating SGAs. To estimate the impact of metformin co-prescription on weight over 2 years post-SGA initiation. Methods: A cohort study of patients diagnosed with SMI initiating aripiprazole, olanzapine, quetiapine or risperidone in 2005–2019 using primary care data from Clinical Practice Research Datalink. We estimated cumulative incidence and period prevalences of co-prescription and explored prescribing differences by demographic and clinical factors. We compared weight change among patients prescribed an SGA-only versus an SGA plus metformin, accounting for confounders using linear regression. Findings: Among 26 537 patients initiating SGAs, 4652 were ever prescribed metformin and 21 885 were not. The two-year incidence of first metformin prescription was 3.3%. The SGA plus metformin group were more ethnically diverse, had greater social deprivation, more comorbidities and higher baseline weight (mean 90.4 vs 76.8 kg). By 2 years post-SGA initiation, mean weight in the SGA-only group had changed by +4.16% (95% CI −1.26 to +9.58) compared with −0.65% (95% CI −4.26 to +2.96) in the SGA plus metformin group. After confounder adjustment, the 2-year mean difference in weight with metformin co-prescription was −1.48 kg (95% CI −4.03 to 1.07) among females and −1.84 kg (95% CI −4.67 to 0.98) among males. Conclusion: Metformin is infrequently co-prescribed, despite apparent efficacy and guidelines. Clinical implications: Primary and secondary care collaboration should be strengthened and barriers to co-prescribing addressed.