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.

The effect of immigration policy reform on mental health in people from minoritised ethnic groups in England: an interrupted time series analysis of longitudinal data from the UK Household Longitudinal Study cohort.

BACKGROUND: In 2012, the UK Government announced a series of immigration policy reforms known as the hostile environment policy, culminating in the Windrush scandal. We aimed to investigate the effect of the hostile environment policy on mental health for people from minoritised ethnic backgrounds. We hypothesised that people from Black Caribbean backgrounds would have worse mental health relative to people from White ethnic backgrounds after the Immigration Act 2014 and the Windrush scandal media coverage in 2017, since they were particularly targeted. METHODS: Using data from the UK Household Longitudinal Study, we performed a Bayesian interrupted time series analysis, accounting for fixed effects of confounders (sex, age, urbanicity, relationship status, number of children, education, physical or mental health impairment, housing, deprivation, employment, place of birth, income, and time), and random effects for residual temporal and spatial variation. We measured mental ill health using a widely used, self-administered questionnaire on psychological distress, the 12-item General Health Questionnaire (GHQ-12). We compared mean differences (MDs) and 95% credible intervals (CrIs) in mental ill health among people from minoritised ethnic groups (Black Caribbean, Black African, Indian, Bangladeshi, and Pakistani) relative to people of White ethnicity during three time periods: before the Immigration Act 2014, after the Immigration Act 2014, and after the start of the Windrush scandal media coverage in 2017. FINDINGS: We included 58 087 participants with a mean age of 45·0 years (SD 34·6; range 16-106), including 31 168 (53·6%) female and 26 919 (46·3%) male participants. The cohort consisted of individuals from the following ethnic backgrounds: 2519 (4·3%) Black African, 2197 (3·8%) Black Caribbean, 3153 (5·4%) Indian, 1584 (2·7%) Bangladeshi, 2801 (4·8%) Pakistani, and 45 833 (78·9%) White. People from Black Caribbean backgrounds had worse mental health than people of White ethnicity after the Immigration Act 2014 (MD in GHQ-12 score 0·67 [95% CrI 0·06-1·28]) and after the 2017 media coverage (1·28 [0·34-2·21]). For Black Caribbean participants born outside of the UK, mental health worsened after the Immigration Act 2014 (1·25 [0·11-2·38]), and for those born in the UK, mental health worsened after the 2017 media coverage (2·00 [0·84-3·15]). We did not observe effects in other minoritised ethnic groups. INTERPRETATION: Our finding that the hostile environment policy worsened the mental health of people from Black Caribbean backgrounds in the UK suggests that sufficient, appropriate mental health and social welfare support should be provided to those affected. Impact assessments of new policies on minority mental health should be embedded in all policy making. FUNDING: Wellcome Trust.

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.

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.

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.

Prevalence and characteristics of antidepressant prescribing in adults with comorbid depression and type 2 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Treatment guidelines do not provide specific recommendations for antidepressant prescribing in people with type 2 diabetes mellitus (T2DM). It is important to understand the prevalence of antidepressant prescribing and associated patient characteristics, to recognise safety issues or inequalities related to treatment access. METHODS AND RESULTS: Seven databases were searched using terms related to depression, T2DM and antidepressant medication. From 14,389 reports retrieved, 9 met inclusion criteria. The prevalence of antidepressant prescribing varied considerably between studies from 18% to 87%. Where meta-analyses were possible, the pooled odds ratio for receiving an antidepressant were 1.52 (95% confidence intervals (CIs) 1.28 - 1.82) in women compared to men, 0.53 (95% CIs 0.23-1.20%) in Black and Ethnic Minorities compared to White ethnicity and 1.29 (95% CIs 0.92-1.80) in insulin users compared to individuals with non-insulin controlled T2DM. CONCLUSIONS: Antidepressant prescribing is more common in women with T2DM compared to men, however, the difference is less than in the general population. Insulin users, representing individuals with more advanced T2DM, were as likely to be prescribed antidepressants as those who did not use insulin. There is a gap in the literature concerning which antidepressant agents are being prescribed, and alongside which concurrent medications and comorbidities.