ADHD Pharmacotherapy and Mortality in Individuals With ADHD.

Importance: Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risks of adverse health outcomes including premature death, but it is unclear whether ADHD pharmacotherapy influences the mortality risk. Objective: To investigate whether initiation of ADHD pharmacotherapy was associated with reduced mortality risk in individuals with ADHD. Design, Setting, and Participants: In an observational nationwide cohort study in Sweden applying the target trial emulation framework, we identified individuals aged 6 through 64 years with an incident diagnosis of ADHD from 2007 through 2018 and no ADHD medication dispensation prior to diagnosis. Follow-up started from ADHD diagnosis until death, emigration, 2 years after ADHD diagnosis, or December 31, 2020, whichever came first. Exposures: ADHD medication initiation was defined as dispensing of medication within 3 months of diagnosis. Main Outcomes and Measures: We assessed all-cause mortality within 2 years of ADHD diagnosis, as well as natural-cause (eg, physical conditions) and unnatural-cause mortality (eg, unintentional injuries, suicide, and accidental poisonings). Results: Of 148 578 individuals with ADHD (61 356 females [41.3%]), 84 204 (56.7%) initiated ADHD medication. The median age at diagnosis was 17.4 years (IQR, 11.6-29.1 years). The 2-year mortality risk was lower in the initiation treatment strategy group (39.1 per 10 000 individuals) than in the noninitiation treatment strategy group (48.1 per 10 000 individuals), with a risk difference of -8.9 per 10 000 individuals (95% CI, -17.3 to -0.6). ADHD medication initiation was associated with significantly lower rate of all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.70 to 0.88) and unnatural-cause mortality (2-year mortality risk, 25.9 per 10 000 individuals vs 33.3 per 10 000 individuals; risk difference, -7.4 per 10 000 individuals; 95% CI, -14.2 to -0.5; HR, 0.75; 95% CI, 0.66 to 0.86), but not natural-cause mortality (2-year mortality risk, 13.1 per 10 000 individuals vs 14.7 per 10 000 individuals; risk difference, -1.6 per 10 000 individuals; 95% CI, -6.4 to 3.2; HR, 0.86; 95% CI, 0.71 to 1.05). Conclusions and Relevance: Among individuals diagnosed with ADHD, medication initiation was associated with significantly lower all-cause mortality, particularly for death due to unnatural causes.

Association between incident depression and clinical outcomes in patients with chronic kidney disease.

Background: Depression is highly prevalent and related to increased morbidity and mortality in patients on dialysis, but less is known among patients with earlier stages of CKD. This study investigated the associations between depression and clinical outcomes in patients with CKD not receiving dialysis. Methods: We identified 157 398 adults with CKD stages 3-5 not previously diagnosed with depression from the Stockholm CREAtinine Measurements (SCREAM) project. The primary outcomes included hospitalization, CKD progression (>40% decline in eGFR, initiation of kidney replacement therapy, or death due to CKD), major adverse cardiovascular events (MACE; myocardial infarction, stroke, or cardiovascular death), and all-cause mortality. Survival analyses were used to estimate the associations between incident depression and adverse health outcomes, adjusting for socio-demographics, kidney disease severity, healthcare utilization, comorbidities, and concurrent use of medications. Results: During a median follow-up of 5.1 (interquartile range: 2.3-8.5) years, 12 712 (8.1%) patients received an incident diagnosis of depression. A total of 634 471 hospitalizations (4 600 935 hospitalized days), 42 866 MACEs, and 66 635 deaths were recorded, and 9795 individuals met the criteria for CKD progression. In the multivariable-adjusted analyses, incident depression was associated with an elevated rate of hospitalized days [rate ratio: 1.77, 95% confidence interval (CI): 1.71-1.83], as well as an increased rate of CKD progression [hazard ratio (HR): 1.38, 95% CI: 1.28-1.48], MACE (HR: 1.22, 95% CI: 1.18-1.27), and all-cause mortality (HR: 1.41, 95% CI: 1.37-1.45). The association with CKD progression was more evident after one year of depression diagnosis (HR: 1.47, 95% CI: 1.36-1.59). Results were robust across a range of sensitivity analyses. Conclusion: Among patients with nondialysis-dependent CKD stages 3-5, incident depression is associated with poor prognosis, including hospitalization, CKD progression, MACE, and all-cause mortality.

Comparative Safety of Antidepressants in Adults with CKD.

BACKGROUND: Depression is prevalent in patients with CKD and is related to poor prognosis. Despite the widespread use of antidepressants in the CKD population, their safety remains unclear. METHODS: We identified adults with CKD stages G3-5 (eGFR <60 ml/min per 1.73 m2 not treated with dialysis) and incident depression diagnosis during 2007-2019 from the Stockholm Creatinine Measurements project. Using the target trial emulation framework, we compared the following treatment strategies: (1) initiating versus not initiating antidepressants, (2) initiating mirtazapine versus selective serotonin reuptake inhibitors (SSRIs), and (3) initiating SSRIs with a lower dose versus a standard dose. RESULTS: Of 7798 eligible individuals, 5743 (74%) initiated antidepressant treatment. Compared with noninitiation, initiation of antidepressants was associated with higher hazards of short-term outcomes, including hip fracture (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.88 to 1.74) and upper gastrointestinal bleeding (HR, 1.38; 95% CI, 0.82 to 2.31), although not statistically significant. Initiation of antidepressants was not associated with long-term outcomes, including all-cause mortality, major adverse cardiovascular event, CKD progression, and suicidal behavior. Compared with SSRIs, initiation of mirtazapine was associated with a lower hazard of upper gastrointestinal bleeding (HR, 0.52; 95% CI, 0.29 to 0.96), but a higher hazard of mortality (HR, 1.11; 95% CI, 1.00 to 1.22). Compared with the standard dose, initiation of SSRIs with a lower dose was associated with nonstatistically significantly lower hazards of upper gastrointestinal bleeding (HR, 0.68; 95% CI, 0.35 to 1.34) and CKD progression (HR, 0.80; 95% CI, 0.63 to 1.02), but a higher hazard of cardiac arrest (HR, 2.34; 95% CI, 1.02 to 5.40). CONCLUSIONS: Antidepressant treatment was associated with short-term adverse outcomes but not long-term outcomes in people with CKD and depression.

Effect of selective serotonin reuptake inhibitor treatment following diagnosis of depression on suicidal behaviour risk: a target trial emulation.

There is concern regarding the impact of selective serotonin reuptake inhibitors (SSRIs) on suicidal behaviour. Using the target trial framework, we investigated the effect on suicidal behaviour of SSRI treatment following a depression diagnosis. We identified 162,267 individuals receiving a depression diagnosis aged 6-59 years during 2006-2018 in Stockholm County, Sweden, after at least 1 year without antidepressant dispensation. Individuals who initiated an SSRI within 28 days of the diagnosis were assigned as SSRI initiators, others as non-initiators. Intention-to-treat and per-protocol effects were estimated; for the latter, individuals were censored when they ceased adhering to their assigned treatment strategy. We applied inverse probability weighting (IPW) to account for baseline confounding in the intention-to-treat analysis, and additionally for treatment non-adherence and time-varying confounding in the per-protocol analysis. The suicidal behaviour risk difference (RD), and risk ratio (RR) between SSRI initiators and non-initiators were estimated at 12 weeks. In the overall cohort, we found an increased risk of suicidal behaviour among SSRI initiators (intention-to-treat RR = 1.50, 95% CI = 1.25, 1.80; per-protocol RR = 1.69, 95% CI = 1.20, 2.36). In age strata, we only found evidence of an increased risk among individuals under age 25, with the greatest risk among 6-17-year-olds (intention-to-treat RR = 2.90, 95% CI = 1.72, 4.91; per-protocol RR = 3.34, 95% CI = 1.59, 7.00). Our finding of an increased suicidal behaviour risk among individuals under age 25 reflects evidence from RCTs. We found no evidence of an effect in the high-risk group of individuals with past suicidal behaviour. Further studies with information on a wider array of confounders are called for.

Kidney function and prescribed dose in middle-aged and older patients starting selective serotonin reuptake inhibitors.

PURPOSE: To avoid adverse drug reactions, dose reductions are recommended when prescribing selective serotonin reuptake inhibitors (SSRIs) to patients with impaired kidney function. The extent of this practice in routine clinical care is however unknown. We aimed to evaluate the starting and maintenance SSRI doses prescribed to patients stratified by levels of kidney function in real-world practice. METHODS: Using data from the Stockholm CREAtinine Measurements (SCREAM) project, we identified 101 409 new users of antidepressants (including 52 286 SSRI users) in the region of Stockholm during 2006-2019, who were ≥50 years of age and had a recent creatinine test taken in order to estimate glomerular filtration rate (eGFR). SSRI dose reduction was defined as a prescribed SSRI dose of ≤0.5 defined daily doses, according to current recommendations. We examined the associations between eGFR and reductions in initial dose and maintenance dose of SSRIs using logistic regression models. RESULTS: Overall, reductions in initial and maintenance dose were observed among 54.1% and 34.1% of new SSRI users. Nevertheless, about 40% of individuals with an eGFR <30 ml/min/1.73 m2 were prescribed an SSRI without dose reduction. After adjusting for age and other covariates, lower eGFR was associated with moderately higher odds of dose reduction, for both initial and maintenance dose. Compared to individuals with an eGFR of 90-104 ml/min/1.73 m2 , the adjusted odds ratios for those with an eGFR <30 ml/min/1.73 m2 were 1.18 (95% CI: 1.03, 1.36) for initial dose reduction, and 1.49 (1.29, 1.72) for maintenance dose reduction. Stratified analyses showed stronger associations between lower eGFR and SSRI dose reduction among individuals aged 50-64 years and in those receiving prescriptions from psychiatric care. CONCLUSIONS: Lower kidney function was moderately associated with a reduced SSRI dose, independently of age. Prescribing SSRIs to middle-aged and older patients should not only consider patients' age but also their kidney function.

Adherence to a healthy lifestyle and all-cause and cause-specific mortality in Chinese adults: a 10-year prospective study of 0.5 million people.

BACKGROUND: Adherence to a healthy lifestyle is associated with substantially lower risks of mortality from all causes, cardiovascular diseases, and cancer in white populations. However, little is known about the health benefits among non-white populations. Also, no previous studies have focused on respiratory disease mortality in both white and non-white populations. We assessed the relationships between a combination of healthy lifestyle factors and multiple death outcomes in Chinese adults. METHODS: This study included 487,198 adults aged 30-79 years from the China Kadoorie Biobank without heart disease, stroke, and cancer at study enrolment. We defined five healthy lifestyle factors as never smoking or smoking cessation not due to illness; non-daily drinking or moderate alcohol drinking; median or higher level of physical activity; a diet rich in vegetables, fruits, legumes and fish, and limited in red meat; a body mass index of 18.5 to 27.9 kg/m2 and a waist circumference < 90 cm (men)/85 cm (women). Cox regression was used to produce adjusted hazard ratios (HRs) relating these healthy lifestyle factors to all-cause and cause-specific mortality. RESULTS: During a median follow-up of 10.2 years (IQR 9.2-11.1), we documented 37,845 deaths. After multivariable adjustment, the number of healthy lifestyle factors exhibited almost inverse linear relationships with the risks of all-cause and cause-specific mortality. Compared with participants without any healthy factors, the hazard ratio of participants with five healthy factors was 0.32 [95% confidence interval (CI): 0.28, 0.37] for all-cause mortality. The corresponding HRs in specific cause of death were 0.42 (95% CI: 0.26, 0.67) for ischaemic heart disease, 0.21 (95% CI: 0.09, 0.49) for ischaemic stroke, 0.37 (95% CI: 0.22, 0.60) for haemorrhage stroke, 0.36 (95% CI: 0.29, 0.45) for cancer, 0.26 (95% CI: 0.14, 0.48) for respiratory diseases, and 0.29 (95% CI: 0.22, 0.39) for other causes. Theoretically, 38.5% (95% CI: 33.0, 43.8%) of all-cause mortality was attributable to nonadherence to a healthy lifestyle, and the proportions of preventable deaths through lifestyle modification ranged from 26.9 to 47.9% for cause-specific mortality. CONCLUSIONS: Adherence to a healthy lifestyle was associated with substantially lower risks of all-cause, cardiovascular, respiratory, and cancer mortality in Chinese adults. Promotion of a healthy lifestyle may considerably reduce the burden of non-communicable diseases in China.

Habitual Tea Consumption and Risk of Fracture in 0.5 Million Chinese Adults: A Prospective Cohort Study.

BACKGROUND: Tea consumption may have favorable effects on risk of fracture. However, little is known about such association in Chinese adults. The aim of this study was to examine the association between tea consumption and risk of hospitalized fracture in Chinese adults. METHODS: The present study included 453,625 participants from the China Kadoorie Biobank (CKB). Tea consumption was self-reported at baseline. Hospitalized fractures were ascertained through linkage with local health insurance claim databases. THE RESULTS: During a median of 10.1 years of follow-up, we documented 12,130 cases of first-time any fracture hospitalizations, including 1376 cases of hip fracture. Compared with never tea consumers, daily tea consumption was associated with lower risk of any fracture (hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.83, 0.93). Statistically significant reduced risk of hip fracture was shown among daily consumers who most commonly drank green tea (HR: 0.80; 95% CI: 0.65, 0.97) and those who had drunk tea for more than 30 years (HR: 0.68; 95% CI: 0.52, 0.87). Our conclusions: Habitual tea consumption was associated with moderately decreased risk of any fracture hospitalizations. Participants with decades of tea consumption and those who preferred green tea were also associated with lower risk of hip fracture.