Antidepressant treatment and mortality in people with comorbid depression and type 2 diabetes: UK electronic health record study.

BACKGROUND: Depression is associated with higher rates of premature mortality in people with physical comorbidities, such as type 2 diabetes. Conceptually, the successful treatment of depression in people with type 2 diabetes could prevent premature mortality. AIMS: To investigate the association between antidepressant prescribing and the rates of all-cause and cause-specific (endocrine, cardiovascular, respiratory, cancer, unnatural) mortality in individuals with comorbid depression and type 2 diabetes. METHOD: Using UK primary care records between years 2000 and 2018, we completed a nested case-control study in a cohort of people with comorbid depression and type 2 diabetes who were starting oral antidiabetic treatment for the first time. We used incident density sampling to identify cases who died and matched controls who remained alive after the same number of days observation. We estimated incidence rate ratios for the association between antidepressant prescribing and mortality, adjusting for demographic characteristics, comorbidities, medication use and health behaviours. RESULTS: We included 5222 cases with a recorded date of death, and 18 675 controls, observed for a median of 7 years. Increased rates of all-cause mortality were associated with any antidepressant prescribing during the observation period (incidence rate ratio 2.77, 95% CI 2.48-3.10). These results were consistent across all causes of mortality that we investigated. CONCLUSIONS: Antidepressant prescribing was highly associated with higher rates of mortality. However, we suspect that this is not a direct causal effect, but that antidepressant treatment is a marker of more severe and unsuccessfully treated depression.

Incidence of mental health diagnoses during the COVID-19 pandemic: a multinational network study.

AIMS: Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic. METHODS: By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions. RESULTS: A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021. CONCLUSIONS: Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.

Ethnic differences in depression and anxiety among adults with atopic eczema: Population-based matched cohort studies within UK primary care.

BACKGROUND: Evidence demonstrates that individuals with atopic eczema (eczema) have increased depression and anxiety; however, the role of ethnicity in these associations is poorly understood. We aimed to investigate whether associations between eczema and depression or anxiety differed between adults from white and minority ethnic groups in the UK. METHODS: We used UK Clinical Practice Research Datalink GOLD to conduct matched cohort studies of adults (≥18 years) with ethnicity recorded in primary care electronic health records (April 2006-January 2020). We matched (age, sex, practice) adults with eczema to up to five adults without. We used stratified Cox regression with an interaction between eczema and ethnicity, to estimate hazard ratios (HRs) for associations between eczema and incident depression and anxiety in individuals from white ethnic groups and a pooled minority ethnic group (adults from Black, South Asian, Mixed and Other groups). RESULTS: We identified separate cohorts for depression (215,073 with eczema matched to 646,539 without) and anxiety (242,598 with eczema matched to 774,113 without). After adjusting for matching variables and potential confounders (age, sex, practice, deprivation, calendar period), we found strong evidence (p < 0.01) of ethnic differences in associations between eczema and depression (minority ethnic groups: HR = 1.33, 95% CI = 1.22,1.45; white ethnic groups: HR = 1.15, 95% CI = 1.12,1.17) and anxiety (minority ethnic groups: HR = 1.41, 95% CI = 1.28,1.55; white ethnic groups: HR = 1.17, 95% CI = 1.14,1.19). CONCLUSIONS: Adults with eczema from minority ethnic groups appear to be at increased depression and anxiety risk compared with their white counterparts. Culturally adapted mental health promotion and prevention strategies should be considered in individuals with eczema from minority ethnic groups.

The association between antidepressant treatment and rates of insulin initiation in comorbid depression and type 2 diabetes: A UK electronic health record nested case-control study.

AIMS: To investigate the association between antidepressant prescribing and the rate of insulin initiation in type 2 diabetes. METHODS: Using UK primary care records we completed a nested-case control study in a individuals with comorbid depression and type 2 diabetes. Cases were defined as individuals initiating insulin, controls were individuals remaining on oral antidiabetic medication. We used conditional logistic regression to estimate incident rate ratios (IRR) and the 95% confidence intervals (CI) for the association between antidepressant prescribing and initiating insulin. We adjusted for demographic characteristics, comorbidities, health service and previous medication use. RESULTS: We included 11,862 cases who initiated insulin, and 43,452 controls. Increased rates of insulin initiation were associated with any antidepressant prescription (IRR 3.78, 95% CI 3.53-4.04), longer (24+ months) durations of antidepressant treatment (IRR 5.61, 95% CI 5.23-6.03), and higher numbers (3+) of different antidepressant agents prescribed (IRR 5.72, 95% CI 5.25-6.24). There was no difference between recent and non-recent antidepressant prescriptions, or between different antidepressant agents. CONCLUSIONS: Antidepressant prescribing was highly associated with the initiation of insulin therapy. However, this may not indicate a direct causal effect of the antidepressant medication itself, and may be a marker of more severe depression influencing diabetic control.

Anxiety and Depression in People with Eczema or Psoriasis: A Comparison of Associations in UK Biobank and Linked Primary Care Data.

Introduction: Previous research has shown associations between eczema and psoriasis and anxiety and depression. We investigated whether associations are consistent across different settings of ascertainment for depression and anxiety, including interview and survey responses from UK Biobank (a large longitudinal cohort recruiting individuals aged 40-69 years between 2006-2010), and linked primary care data, with the aim of drawing more reliable conclusions through triangulation. Methods: In cross-sectional studies, we estimated associations between eczema or psoriasis and anxiety or depression, defining anxiety or depression as 1) self-reported previous diagnosis at UK Biobank recruitment interview; 2) PHQ-9/GAD-7 score indicating depression or anxiety from a UK Biobank mental health follow-up survey in 2016; and 3) diagnosis in linked primary care electronic health record data. Results: We analysed 230,047 people with linked Biobank and primary care data. We found poor agreement between the data sources for eczema, psoriasis, anxiety, and depression. Eg, 9474 had a previous eczema diagnosis in primary care data, 4069 self-reported previous eczema diagnosis at the UK biobank interview, and 1536 had eczema in both data sources (for depression 40,455; 13,320; and 9588 respectively). Having eczema or psoriasis (recorded in primary care or baseline interview) was associated with higher odds of anxiety and depression. Eg, the adjusted odds ratio for depression comparing those with eczema to those without was greater than 1 when defining the outcome from 1) the recruitment interview (1.36, 95% confidence interval 1.27-1.45); 2) the follow-up survey (1.24, 1.09-1.39), and 3) primary care records (1.56, 1.50-1.62). Discussion: Our findings support increased prevalence of mental illness in people with psoriasis and eczema across multiple data sources, which should be considered in planning of mental health services. However, we found poor agreement in disease ascertainment between settings, with implications for data interpretation in electronic health records.

Gabapentinoid consumption in 65 countries and regions from 2008 to 2018: a longitudinal trend study.

Recent studies raised concerns about the increasing use of gabapentinoids in different countries. With their potential for misuse and addiction, understanding the global consumption of gabapentinoids will offer us a platform to examine the need for any interventional policies. This longitudinal trend study utilised pharmaceutical sales data from 65 countries and regions across the world to evaluate the global trends in gabapentinoid consumption between 2008-2018. The multinational average annual percentage change of gabapentinoid consumption was +17.20%, increased from 4.17 defined daily dose per ten thousand inhabitants per day (DDD/TID) in 2008 to 18.26 DDD/TID in 2018. High-income countries had the highest pooled gabapentinoid consumption rate (39.92 DDD/TID) in 2018, which was more than six times higher than the lower-middle income countries (6.11 DDD/TID). The study shows that despite differences in healthcare system and culture, a consistent increase in gabapentinoid consumption is observed worldwide, with high-income countries remaining the largest consumers.

Ethnic differences in the indirect effects of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: a population-based, observational cohort study using the OpenSAFELY platform.

Background: The COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England. Methods: In this population-based, observational cohort study we used primary care electronic health record data with linkage to hospital episode statistics data and mortality data within OpenSAFELY, a data analytics platform created, with approval of NHS England, to address urgent COVID-19 research questions. We included adults aged 18 years and over registered with a TPP practice between March 1, 2018, and April 30, 2022. We excluded those with missing age, sex, geographic region, or Index of Multiple Deprivation. We grouped ethnicity (exposure), into five categories: White, Asian, Black, Other, and Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (blood pressure and Hba1c measurements, chronic obstructive pulmonary disease and asthma annual reviews) before and after March 23, 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to diabetes, cardiovascular disease, respiratory disease, and mental health before and after March 23, 2020. Findings: Of 33,510,937 registered with a GP as of 1st January 2020, 19,064,019 were adults, alive and registered for at least 3 months, 3,010,751 met the exclusion criteria and 1,122,912 were missing ethnicity. This resulted in 14,930,356 adults with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to the White ethnic group (Pre-pandemic hazard ratio (HR): 0.50, 95% confidence interval (CI) 0.41, 0.60, Pandemic HR: 0.75, 95% CI: 0.65, 0.87). There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in those of White ethnicity (heart failure risk difference: 5.4). Relatively, ethnic differences narrowed for heart failure admission in those of Asian (Pre-pandemic HR 1.56, 95% CI 1.49, 1.64, Pandemic HR 1.24, 95% CI 1.19, 1.29) and Black ethnicity (Pre-pandemic HR 1.41, 95% CI: 1.30, 1.53, Pandemic HR: 1.16, 95% CI 1.09, 1.25) compared with White ethnicity. For other outcomes the pandemic had minimal impact on ethnic differences. Interpretation: Our study suggests that ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes. Funding: LSHTM COVID-19 Response Grant (DONAT15912).

Real-time air pollution and bipolar disorder symptoms: remote-monitored cross-sectional study.

Air pollution is associated with unipolar depression and other mental health problems. We assessed the real-time association between localised mean air quality index and the severity of depression and mania symptoms in people with bipolar disorder. We found that as air quality worsened, symptoms of depression increased. We found no association between air quality and mania symptoms.

Association between the mood stabilizing treatment of bipolar disorder and risk of suicide attempts: A self-controlled case series study.

Bipolar disorder (BPD) is associated with high rates of suicide attempts but the anti-suicidal effect of mood stabilizing agents remains unclear. This study aimed to examine the association between mood stabilizing agents (lithium, valproate, lamotrigine, carbamazepine or antipsychotics) and risk of suicide attempts in patients with BPD using self-controlled case series study design. Among 14,087 patients with BPD who received mood stabilizing agents from 2001 to 2020 in Hong Kong, 1316 patients had at least one suicide attempts during the observation period. An increased risk of suicide attempts was observed 14 days before treatment initiation compared to non-exposed period. Following treatment initiation, an increased risk with smaller magnitude was found with the use of mood stabilizing agents. A lower risk was observed with lithium and antiepileptics while the risk remained attenuated with decreasing magnitude with antipsychotics. During 30-day post-treatment period, the risk was elevated. Therefore, this study suggests that use of mood stabilizing agents is not causally associated with an increased risk of suicide attempts. Indeed, there are potential protective effects of lithium and antiepileptics against suicide attempts. Assiduous monitoring of symptoms relapse and warning signs of suicide should be part of the management plan and discussed between clinicians, caregivers and patients.

Vaccine effectiveness of BNT162b2 and CoronaVac against SARS-CoV-2 omicron infection and related hospital admission among people with substance use disorder in Hong Kong: a matched case-control study.

BACKGROUND: People with substance use disorder have a high risk of SARS-CoV-2 infection and subsequent poor outcomes. Few studies have evaluated COVID-19 vaccine effectiveness among people with substance use disorder. We aimed to estimate the vaccine effectiveness of BNT162b2 (Fosun-BioNTech) and CoronaVac (Sinovac) against SARS-CoV-2 omicron (B.1.1.529) infection and related hospital admission in this population. METHODS: We did a matched case-control study using electronic health databases in Hong Kong. Individuals diagnosed with substance use disorder between Jan 1, 2016, and Jan 1, 2022, were identified. People aged 18 years and older with SARS-CoV-2 infection from Jan 1 to May 31, 2022, and people with COVID-19-related hospital admission from Feb 16 to May 31, 2022, were included as cases and were matched by age, sex, and previous clinical history with controls from all individuals diagnosed with substance use disorder who attended the Hospital Authority health services: up to three controls for SARS-CoV-2 infection and up to ten controls for hospital admission. Conditional logistical regression was used to evaluate the association between vaccination status (ie, one, two, or three doses of BNT162b2 or CoronaVac) and the risk of SARS-CoV-2 infection and COVID-19-related hospital admission, adjusted for baseline comorbidities and medication use. FINDINGS: Among 57 674 individuals with substance use disorder, 9523 people with SARS-CoV-2 infections (mean age 61·00 years, SD 14·90; 8075 [84·8%] males and 1448 [15·2%] females) were identified and matched to 28 217 controls (mean age 60·99 years, 14·67; 24 006 [85·1%] males and 4211 [14·9%] females), and 843 people with COVID-19-related hospital admissions (mean age 70·48 years, SD 14·68; 754 [89·4%] males and 89 [10·6%] females) were identified and matched to 7459 controls (mean age 70·24 years, 13·87; 6837 [91·7%] males and 622 [8·3%] females). Data on ethnicity were not available. We observed significant vaccine effectiveness against SARS-CoV-2 infection for two-dose BNT162b2 vaccination (20·7%, 95% CI 14·0-27·0, p<0·0001) and three-dose vaccination (all BNT162b2 41·5%, 34·4-47·8, p<0·0001; all CoronaVac 13·6%, 5·4-21·0, p=0·0015; BNT162b2 booster after two-dose CoronaVac 31·3%, 19·8-41·1, p<0·0001), but not for one dose of either vaccine or two doses of CoronaVac. Significant vaccine effectiveness against COVID-19-related hospital admission was detected after one dose of BNT162b2 vaccination (35·7%, 3·8-57·1, p=0·032), two-dose vaccination (both BNT162b2 73·3%, 64·3 to 80·0, p<0·0001; both CoronaVac 59·9%, 50·2-67·7, p<0·0001), and three-dose vaccination (all BNT162b2 86·3%, 75·6-92·3, p<0·0001; all CoronaVac 73·5% 61·0-81·9, p<0·0001; BNT162b2 booster after two-dose CoronaVac 83·7%, 64·6-92·5, p<0·0001), but not after one dose of CoronaVac. INTERPRETATION: For both BNT162b2 and CoronaVac, two-dose or three-dose vaccination was protective against COVID-19-related hospital admission and the booster dose provided protection against SARS-CoV-2 infection among people with substance use disorder. Our findings confirm the importance of booster doses in this population during the period dominated by the omicron variant. FUNDING: Health Bureau, the Government of the Hong Kong Special Administrative Region.

Polypharmacy and antidepressant acceptability in comorbid depression and type 2 diabetes: a cohort study using UK primary care data.

BACKGROUND: Polypharmacy may increase the risk of drug interactions, side effects, and poor adherence; however, the impact of polypharmacy on antidepressant acceptability in individuals with type 2 diabetes (T2DM) is unknown. AIM: To investigate the association between number of prescribed medications and early antidepressant discontinuation in adults with T2DM. DESIGN AND SETTING: Cohort study using UK primary care data from the Clinical Practice Research Datalink between 1 January 2000 and 31 December 2018. METHOD: Cox regression with penalised B-splines was used to describe the association between the number of concurrently prescribed medications at the time of starting antidepressant treatment and each of the outcomes. RESULTS: A total of 73 808 individuals with comorbid depression and T2DM starting antidepressant treatment for the first time were identified. A median of 7 concurrent medications were prescribed. Within 32 weeks, 44.26% (n = 32 665) of participants discontinued antidepressant treatment altogether, and 11.75% (n = 8672) of participants switched antidepressant agents. An inverse relationship between the number of concurrent medications and discontinuing antidepressant treatment altogether was found. The median of 7 concurrent medications was associated with a 65.06% decrease in early antidepressant discontinuation; hazard ratio 0.45, 95% confidence interval = 0.37 to 0.55. No evidence of an association between the number of concurrent medications and switching antidepressant agents was found. CONCLUSION: Early discontinuation of antidepressants is common in adults with T2DM; however, individuals with higher levels of concurrent polypharmacy may be more adherent to treatment. These are likely to represent individuals with worse physical or mental health. Individuals with lower levels of concurrent polypharmacy may benefit from adherence support.

Long-term stability in obsessive thoughts and compulsive behavior in the general population: a longitudinal study in Sweden.

OBJECTIVE: Obsessive thoughts and compulsive behavior and their related disorder Obsessive-Compulsive Disorder (OCD) commonly occur in the general population. Clinical populations indicate a high level of stability, although there are few longitudinal studies in the general population. The recommended drug treatments are SSRIs/TCAs. However, there are few long-term follow up studies. The goal of this study was to 1) examine the occurrence and stability of obsessions, compulsions, and OCD in a longitudinal population-based survey, 2) investigate the use of SSRI and TCA and the potential effect on symptoms. METHODS: A ten-year longitudinal general population in Stockholm was used (2000 and 2010, n = 5650) Obsessional washing, checking, intrusive unpleasant thoughts and the level of suffering due to these symptoms were measured by self-report. Information on use of SSRIs and TCAs by these individuals was obtained from registers. Stability was examined using contingency tables and multinomial logistic regression. RESULTS: At baseline, 2.1, 11.7 and 11.9% reported obsessional washing, checking and intrusive thoughts. A total of 5% reported considerable suffering from these (i.e. OCD). Based on psychiatric interview only 0.4% had OCD. Ten years later a quarter of OCD cases were still classified as having OCD, one quarter reported any obsessive or compulsive symptom and half were classified as symptom-free. Treatment receipt was low and controlling for medication did not change the stability. CONCLUSION: Obsessive thoughts and compulsive behavior are common and stable. While this group is potentially undertreated, there is no indication that those treated display a different pattern of recovery.

Severe Mental Illness Among Adults with Atopic Eczema or Psoriasis: Population-Based Matched Cohort Studies within UK Primary Care.

Background: Existing research exploring associations between atopic eczema (AE) or psoriasis, and severe mental illness (SMI - ie, schizophrenia, bipolar disorder, other psychoses) is limited, with longitudinal evidence particularly scarce. Therefore, temporal directions of associations are unclear. We aimed to investigate associations between AE or psoriasis and incident SMI among adults. Methods: We conducted matched cohort studies using primary care electronic health records (January 1997 to January 2020) from the UK Clinical Practice Research Datalink GOLD. We identified two cohorts: 1) adults (≥18 years) with and without AE and 2) adults with and without psoriasis. We matched (on age, sex, general practice) adults with AE or psoriasis with up to five adults without. We used Cox regression, stratified by matched set, to estimate hazard ratios (HRs) comparing incident SMI among adults with and without AE or psoriasis. Results: We identified 1,023,232 adults with AE and 4,908,059 without, and 363,210 with psoriasis and 1,801,875 without. After adjusting for matching variables (age, sex, general practice) and potential confounders (deprivation, calendar period) both AE and psoriasis were associated with at least a 17% increased hazard of SMI (AE: HR=1.17,95% CI=1.12-1.22; psoriasis: HR=1.26,95% CI=1.18-1.35). After additionally adjusting for potential mediators (comorbidity burden, harmful alcohol use, smoking status, body mass index, and, in AE only, sleep problems and high-dose glucocorticoids), associations with SMI did not persist for AE (HR=0.98,95% CI=0.93-1.04), and were attenuated for psoriasis (HR=1.14,95% CI=1.05-1.23). Conclusion: Our findings suggest adults with AE or psoriasis are at increased risk of SMI compared to matched comparators. After adjusting for potential mediators, associations with SMI did not persist for AE, and were attenuated for psoriasis, suggesting that the increased risk may be explained by mediating factors (eg, sleep problems). Our research highlights the importance of monitoring mental health in adults with AE or psoriasis.

Factors associated with depression, anxiety and severe mental illness among adults with atopic eczema or psoriasis: a systematic review and meta-analysis.

BACKGROUND: Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness; however, the factors associated with mental illness are unclear. OBJECTIVES: To synthesize and evaluate all available evidence on factors associated with depression, anxiety and severe mental illness (SMI) among adults with AE or psoriasis. METHODS: We searched electronic databases, grey literature databases and clinical trial registries from inception to February 2022 for studies of adults with AE or psoriasis. Eligible studies included randomized controlled trials (RCTs), cohort, cross-sectional or case-control studies where effect estimates of factors associated with depression, anxiety or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesized results narratively, and if at least two studies were sufficiently homogeneous, we pooled effect estimates in a random effects meta-analysis. RESULTS: We included 21 studies (11 observational, 10 RCTs). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety - one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest that female sex and psoriatic arthritis were associated with depression [female sex: odds ratio (OR) 1.62, 95% confidence interval (CI) 1.09-2.40, 95% prediction intervals (PIs) 0.62-4.23, I2 = 24.90%, τ2 = 0.05; psoriatic arthritis: OR 2.26, 95% CI 1.56-3.25, 95% PI 0.21-24.23, I2 = 0.00%, τ2 = 0.00] and anxiety (female sex: OR 2.59, 95% CI 1.32-5.07, 95% PI 0.00-3956.27, I2 = 61.90%, τ2 = 0.22; psoriatic arthritis: OR 1.98, 95% CI 1.33-2.94, I2 = 0.00%, τ2 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR 1.14, 95% CI 1.05-1.25, I2 0.00%, τ2 = 0.00), but not depression. Evidence from RCTs suggested that adults with AE or psoriasis given placebo had higher depression and anxiety scores compared with comparators given targeted treatment (e.g. biologic agents). CONCLUSIONS: Our review highlights limited existing research on factors associated with depression, anxiety and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested that AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared with skin disease treated with targeted therapy; however, follow-up was limited. Therefore, long-term effects on mental health are unclear.

Investigating the association between schizophrenia and distance visual acuity: Mendelian randomisation study.

BACKGROUND: Increased rates of visual impairment are observed in people with schizophrenia. AIMS: We assessed whether genetically predicted poor distance acuity is causally associated with schizophrenia, and whether genetically predicted schizophrenia is causally associated with poorer visual acuity. METHOD: We used bidirectional, two-sample Mendelian randomisation to assess the effect of poor distance acuity on schizophrenia risk, poorer visual acuity on schizophrenia risk and schizophrenia on visual acuity, in European and East Asian ancestry samples ranging from approximately 14 000 to 500 000 participants. Genetic instrumental variables were obtained from the largest available summary statistics: for schizophrenia, from the Psychiatric Genomics Consortium; for visual acuity, from the UK Biobank; and for poor distance acuity, from a meta-analysis of case-control samples. We used the inverse variance-weighted method and sensitivity analyses to test validity of results. RESULTS: We found little evidence that poor distance acuity was causally associated with schizophrenia (odds ratio 1.00, 95% CI 0.91-1.10). Genetically predicted schizophrenia was associated with poorer visual acuity (mean difference in logMAR score: 0.024, 95% CI 0.014-0.033) in European ancestry samples, with a similar but less precise effect that in smaller East Asian ancestry samples (mean difference: 0.186, 95% CI -0.008 to 0.379). CONCLUSIONS: Genetic evidence supports schizophrenia being a causal risk factor for poorer visual acuity, but not the converse. This highlights the importance of visual care for people with psychosis and refutes previous hypotheses that visual impairment is a potential target for prevention of schizophrenia.

Association between visual impairment and psychosis: A longitudinal study and nested case-control study of adults.

BACKGROUND: Theories propose that visual impairment might increase the risk of psychosis, and vice versa. We aimed to investigate the relationship between visual impairment and psychosis in the UK Biobank cohort. STUDY DESIGN: In a nested case control study of ~116,000 adults, we tested whether a Schizophrenia Spectrum Disorder (SSD) diagnosis as exposure was associated with visual impairment. We also tested longitudinally whether poorer visual acuity, and thinner retinal structures on Optical Coherence Tomography (OCT) scans in 2009 were associated with psychotic experiences in 2016. We adjusted for age, sex, depression and anxiety symptoms; and socioeconomic variables and vascular risk factors where appropriate. We compared complete case with multiple imputation models, designed to reduce bias potentially introduced by missing data. RESULTS: People with visual impairment had greater odds of SSD than controls in multiply imputed data (Adjusted Odds Ratio [AOR] 1.42, 95 % Confidence Interval [CI] 1.05-1.93, p = 0.021). We also found evidence that poorer visual acuity was associated with psychotic experiences during follow-up (AOR per 0.1 point worse visual acuity score 1.06, 95 % CI 1.01-1.11, p = 0.020; and 1.04, 95 % CI 1.00-1.08, p = 0.037 in right and left eye respectively). In complete case data (15 % of this cohort) we found no clear association, although confidence intervals included the multiple imputation effect estimates. OCT measures were not associated with psychotic experiences. CONCLUSIONS: Our findings highlight the importance of eye care for people with psychotic illnesses. We could not conclude whether visual impairment is a likely causal risk factor for psychosis.

Association between polypharmacy and depression relapse in individuals with comorbid depression and type 2 diabetes: a UK electronic health record study.

BACKGROUND: Individuals with physical comorbidities and polypharmacy may be at higher risk of depression relapse, however, they are not included in the 'high risk of relapse' group for whom longer antidepressant treatment durations are recommended. AIMS: In individuals with comorbid depression and type 2 diabetes (T2DM), we aimed to investigate the association and interaction between depression relapse and (a) polypharmacy, (b) previous duration of antidepressant treatment. METHOD: This was a cohort study using primary care data from the UK Clinical Practice Research Datalink (CPRD) from years 2000 to 2018. We used Cox regression models with penalised B-splines to describe the association between restarting antidepressants and our two exposures. RESULTS: We identified 48 001 individuals with comorbid depression and T2DM, who started and discontinued antidepressant treatment during follow-up. Within 1 year of antidepressant discontinuation, 35% of participants restarted treatment indicating depression relapse. As polypharmacy increased, the rate of restarting antidepressants increased until a maximum of 18 concurrent medications, where individuals were more than twice as likely to restart antidepressants (hazard ratio (HR) = 2.15, 95% CI 1.32-3.51). As the duration of previous antidepressant treatment increased, the rate of restarting antidepressants increased - individuals with a previous duration of ≥25 months were more than twice as likely to restart antidepressants than those who previously discontinued in <7 months (HR = 2.36, 95% CI 2.25-2.48). We found no interaction between polypharmacy and previous antidepressant duration. CONCLUSIONS: Polypharmacy and longer durations of previous antidepressant treatment may be associated with depression relapse following the discontinuation of antidepressant treatment.

Association between the pharmacological treatment of bipolar disorder and risk of traumatic injuries: a self-controlled case series study.

BACKGROUND: Patients with bipolar disorder (BPD) are prone to engage in risk-taking behaviours and self-harm, contributing to higher risk of traumatic injuries requiring medical attention at the emergency room (ER).We hypothesize that pharmacological treatment of BPD could reduce the risk of traumatic injuries by alleviating symptoms but evidence remains unclear. This study aimed to examine the association between pharmacological treatment and the risk of ER admissions due to traumatic injuries. METHODS: Individuals with BPD who received mood stabilizers and/or antipsychotics were identified using a population-based electronic healthcare records database in Hong Kong (2001-2019). A self-controlled case series design was applied to control for time-invariant confounders. RESULTS: A total of 5040 out of 14 021 adults with BPD who received pharmacological treatment and had incident ER admissions due to traumatic injuries from 2001 to 2019 were included. An increased risk of traumatic injuries was found 30 days before treatment [incidence rate ratio (IRR) 4.44 (3.71-5.31), p < 0.0001]. After treatment initiation, the risk remained increased with a smaller magnitude, before returning to baseline [IRR 0.97 (0.88-1.06), p = 0.50] during maintenance treatment. The direct comparison of the risk during treatment to that before and after treatment showed a significant decrease. After treatment cessation, the risk was increased [IRR 1.34 (1.09-1.66), p = 0.006]. CONCLUSIONS: This study supports the hypothesis that pharmacological treatment of BPD was associated with a lower risk of ER admissions due to traumatic injuries but an increased risk after treatment cessation. Close monitoring of symptoms relapse is recommended to clinicians and patients if treatment cessation is warranted.