Sedative drug prescription patterns in Danish adults from 2002 through 2021. A register-based cohort study.

OBJECTIVE: Pharmacological treatment strategies for insomnia seem to vary, and there is lack of knowledge about how sedative drugs are used in a real-world setting. We investigated changes in sedative drug prescription patterns in Danish adults who initiated treatment between 2002 and 2016. METHODS: All adults with a first-time purchase of a sedative drug registered in the Danish National Prescription Register from 2002 through 2016 were followed for five years between 2002 and 2021 for subsequent prescriptions of sedative drugs, death, or emigration. Sedative drugs were classified into anxiolytic benzodiazepines (N05BA), hypnotic benzodiazepines (N05CD), Z-drugs (N05CF), melatonin (N05CH01), promethazine (R06AD), and low-dose quetiapine (N05AH04). Analyses were stratified on time: 2002-2006, 2007-2011, and 2012-2016. RESULTS: A total of 842,880 individuals purchased their first sedative drug between 2002 and 2016. Most of them (40.0%) initiated treatment between 2002 and 2006, whereas 29.2% initiated treatment in 2012-2016. In 2002-2006, anxiolytic benzodiazepines (46.4%), Z-drugs (42.8%), and hypnotic benzodiazepines (5.4%) were the most common first treatment. This pattern changed over time with a gradual increase in the use of melatonin, promethazine, and low-dose quetiapine, which in 2011-2016 accounted for 27% of all first treatments. During the five years from first prescription, around 27% shifted to a different sedative drug. This percentage increased slightly over time, but over time the first shift to another drug class was most often to a Z-drug or anxiolytic benzodiazepine. Few individuals (5.8%) had more than one shift and the third choice seemed randomly distributed across all other drug classes. CONCLUSION: Sedative drug prescriptions are distributed on different drug classes, with Z-drugs and anxiolytic benzodiazepines as the most frequent first treatment, and second choice in case of shift.

Long-Term Use of Benzodiazepines and Benzodiazepine-Related Drugs: A Register-Based Danish Cohort Study on Determinants and Risk of Dose Escalation.

OBJECTIVE: The authors investigated the frequency and determinants of long-term use and risk of dose escalation of benzodiazepines and benzodiazepine-related drugs (benzodiazepine receptor agonists, or BZRAs). METHODS: All adults ages 20-80 years living in Denmark on January 1, 2000 (N=4,297,045) were followed for redeemed prescriptions of BZRAs in the Danish National Prescription Registry from January 1, 2000, to December 31, 2020. For each drug class, we calculated long-term use for more than 1 or 7 years, and dose escalation measured as increase in dose to a level above the recommended level. Associations were examined using logistic regression. RESULTS: The authors identified 950,767 incident BZRA users, of whom 15% and 3% became long-term users for more than 1 or 7 years, respectively. These percentages were highest for individuals who initiated Z-drugs (17.8% and 4%). Among the 5% of BZRA users who had at least 3 years of continuous use, there was no indication of dose escalation, as the median dose remained relatively stable. However, 7% (N=3,545) of BZRA users escalated to doses above the recommended level. Psychiatric comorbidity, especially substance use disorder, was associated with higher risk of long-term use and dose escalation. CONCLUSIONS: A limited portion of the population that received BZRA prescriptions were classified as continuous users, and only a small proportion of this group escalated to doses higher than those recommended in clinical guidelines. Thus, this study does not, under the current regulations, support the belief that BZRA use frequently results in long-term use or dose escalation.

Use of hypnotic-sedative medication and risk of falls and fractures in adults: A self-controlled case series study.

OBJECTIVE: To evaluate the risk of falls and fractures in users of benzodiazepines, Z-drugs, or melatonin. METHODS: We followed 699,335 adults with a purchase of benzodiazepines, Z-drugs, or melatonin in the Danish National Prescription Registry between 2003 and 2016 for falls and fractures in the Danish National Patient Registry between 2000 and 2018. A self-controlled case-series analysis and conditional Poisson regression were used to derive incidence rate ratios (IRR) of falls and fractures during six predefined periods. RESULTS: In total 62,105 and 36,808 adults, respectively, experienced a fall or fracture. For older adults, the risk of falls was highest during the 3-month pre-treatment period (IRRmen+70 , 4.22 (95% confidence interval, 3.53-5.05), IRRwomen + 70 , 3.03 (2.59-3.55)) compared to the baseline (>1 year before initiation). The risk continued to be higher in the later treatment periods. Contrarily, in men and women aged 40-69 years, the risk was only higher in the 3-month pre-treatment period. The incidence of falls among young men and women was slightly lower after initiation of sedating medication (treatment period, IRRmen15-39 , 0.66 (0.50-0.86), IRRwomen15-39 , 0.65 (0.51-0.83)). Analyses with fractures as outcome yielded similar results. CONCLUSIONS: Although falls and fractures occur more often in persons using sedative-hypnotic medication, the higher risk of falls and fractures in the pre-treatment period relative to the period directly after treatment, suggests that this association is better explained by other factors that elicited the prescription of this medication rather than the adverse effects of the sedative-hypnotic medication.

Is urban regeneration associated with antidepressants or sedative medication users: a registry-based natural experiment.

BACKGROUND: Area deprivation is associated with adverse mental health outcomes. In Denmark, urban regeneration is being used to dissolve concentrated socio-economic area deprivation and ethnic segregation. However, evidence on how urban regeneration affects mental health of residents is ambiguous partly due to methodological challenges. This study investigates if urban regeneration affects users of antidepressant and sedative medication among residents in an exposed and control social housing area in Denmark. METHODS: Using a longitudinal quasi-experimental design we measured users of antidepressant and sedative medication in one area undergoing urban regeneration compared with a control area. We measured prevalent and incident users from 2015 to 2020 among non-Western and Western women and men and used logistic regression to measure annual change in users over time. Analyses are adjusted for a covariate propensity score estimated using baseline socio-demographic characteristics and general practitioner contacts. RESULTS: Urban regeneration did not affect the proportion of prevalent nor incident users of antidepressant and sedative medication. However, levels were high in both areas compared with the national average. Descriptive levels of prevalent and incident users were generally lower among residents in the exposed area compared with the control area for most years and stratified groups confirmed by the logistic regression analyses. CONCLUSION: Urban regeneration was not associated with users of antidepressant or sedative medication. We found lower levels of antidepressant and sedative medication users in the exposed area compared with the control area. More studies are needed to investigate the underlying reasons for these findings, and whether they could be related to underuse.

Sedative drug-use in Denmark, 2000 to 2019: a nationwide drug utilization study.

AIM: To describe trends in and characteristics of sedative drug use from 2000 through 2019 in relation to the introduction of central regulations and new drugs. METHODS: In this descriptive study, we used individual prescription data on the entire Danish population from the Danish National Prescription Registry to calculate yearly incidence and prevalence of use of benzodiazepines, benzodiazepine-related drugs (Z-drugs), melatonin, olanzapine, low-dose quetiapine, mianserin/mirtazapine, pregabalin, and promethazine from 2000 through 2019. From the Danish National Patient Registry, we obtained data on drug users' psychiatric and somatic comorbidity. RESULTS: The use of benzodiazepines and Z-drugs declined gradually from 2000 through 2019, whereas the newer alternatives, melatonin, low-dose quetiapine, pregabalin and promethazine, increased in use, while the use of olanzapine and mianserin/mirtazapine was relatively stable. This development was seen in both men and women and across all age groups except for hypnotic benzodiazepines which showed a steep increase in the oldest age group from 2010. For all sedative drugs depression, anxiety, alcohol and misuse disorder, pain and cancer were the most prevalent comorbidities. During our study period, the number of individuals without any of the selected diagnoses increased. CONCLUSION: In Denmark different central regulations have influenced prescription practice toward more restrictive use of Z-drugs and benzodiazepines, except for hypnotic benzodiazepine prescriptions increased after the introduction of special palliative care. An increase in use of newer sedative drugs, however, indicates that the regulations do not remove the need for sedative drugs in the population.

Diabetes, sleep disorders and risk of depression - A Danish register-based cohort study.

AIMS: We examined the influence of comorbid sleep disorder on the association between type 2 diabetes (T2D) and risk of incident depression. METHODS: The study population (N = 232,489) was based on all individuals registered aged ≥40 years with a T2D diagnosis between January 1, 2000 to December 31, 2012 in the Danish National Diabetes Register and a matched reference population. The risk of incident depression (diagnosis or anti-depressant medication) following T2D and possible effect modification of comorbid sleep disorder was estimated using adjusted Cox proportional hazards regression. Sleep disorder was defined as a diagnosis of insomnia, hypersomnia or sleep-wake schedule disorders or use of sleep medication (z-drugs or melatonin) in the Danish National Patient Registry or the Danish National Prescription Registry. RESULTS: At study entry, 15.3 % of the participants had a sleep disorder. During follow-up, 2.6 % were diagnosed with depression and 32.1 % received antidepressant medication. The unadjusted hazard ratio (HR) for depression was 1.54 (95%CI 1.52-1.56) for patients with diabetes, which attenuated to 1.50 (1.48-1.52) after adjustment for sleep disorders, which further attenuated to 1.27 (1.26-1.29) in the model further adjusted for psychiatric and somatic comorbidities. The analyses of T2D and sleep disorder as independent and combined variables compared with none of the conditions on risk of depression, showed a HR of 1.27 (95 % CI 1.19-1.35) for T2D without sleep disorder, 1.46 (95 % CI 1.33-1.59) for sleep disorders without T2D, and 1.49 (95%CI 1.37-1.63) for both conditions. CONCLUSIONS: T2D and sleep disorders were independently associated with subsequent risk of depression and individuals with both conditions experienced the greatest relative risk. Sleep disorders neither explained nor amplified the relation between diabetes and depression.

Use of GLP-1 receptor agonists and subsequent risk of alcohol-related events. A nationwide register-based cohort and self-controlled case series study.

Animal studies have related glucagon-like peptide 1 receptor agonists (GLP-1) to lower alcohol intake. We examined whether GLP-1 was associated with risk of alcohol-related events in a nationwide cohort study and a self-controlled case series analysis including all new users of GLP1 (n = 38 454) and dipeptidyl peptidase 4 inhibitors (DPP4) (n = 49 222) in Denmark 2009-2017. They were followed for hospital contacts with alcohol use disorder or purchase of drugs for treatment of alcohol dependence in nationwide registers from 2009 to 2018. Associations were examined using Cox proportional hazard and conditional Poisson regression. During follow-up of median 4.1 years, 649 (0.7%) of participants were registered with an alcohol-related event. Initiation of GLP-1 treatment was associated with lower risk of an alcohol-related event (Hazard ratio = 0.46 (95%CI: 0.24-0.86) compared with initiation of DPP4 during the first 3 months of follow-up. Self-controlled analysis showed the highest risk of alcohol-related events in the 3-month pretreatment period (incidence rate ratio [IRR] = 1.25 (1.00-1.58)), whereas the risk was lowest in the first 3-month treatment period (IRR = 0.74 (0.56-0.97). In conclusion, compared with DPP4 users, individuals who start treatment with GLP-1 had lower incidence of alcohol-related events both in cohort and self-controlled analyses. Thus, there might be a transient preventive effect of GLP1 on alcohol-related events the first months after treatment initiation.

Diabetes, antidiabetic medications and risk of depression - A population-based cohort and nested case-control study.

OBJECTIVE: Diabetes type 2 is associated with depression, but the impact of antidiabetic drugs is not clear. The objective was to analyze the association between diabetes type 2, antidiabetic drugs, and depression. METHODS: This register-based study included 116.699 patients with diabetes type 2 diagnosed from 2000 to 2012 and an age, gender, and municipality matched reference group of 116.008 individuals without diabetes. All participants were followed for a diagnosis of depression or prescription of antidepressant medication. Based on this, a case-control study was nested within the cohort, using risk set sampling. Antidiabetic medication was categorized into insulin, metformin, sulfonylureas and glinides combined, glitazones, dipeptidyl peptidase 4 (DPP4) inhibitors, glucagon-like peptide 1 (GLP1) analogs, sodium-glucose transport protein 2 (SGLT2) inhibitors and acarbose. The association between diabetes and depression was analyzed using Cox proportional hazards regression, whereas conditional logistic regression was used to analyze the association between use of antidiabetic drugs and depression. RESULTS: Patients with diabetes had higher risk of depression compared to individuals without diabetes (hazard ratio 1.14 (95% confidence interval 1.14-1.15)). Low doses of metformin, DPP4 inhibitors, GLP1 analogs, and SGLT2 inhibitors were associated with lower risk of depression in patients with diabetes compared to non-users, with the lowest risk for sodium-glucose transport protein 2 inhibitor users (odds ratio 0.55 (0.44-0.70)). Use of insulin, sulfonylurea and high doses of metformin were associated with higher risk of depression. CONCLUSION: Patients with diabetes had increased risk of depression. However, users of specific antidiabetic drugs had lower risk of depression compared to non-users.

Depression in adulthood and risk of dementia later in life: A Danish register-based cohort study of 595,828 men.

BACKGROUND: Associations between depression and dementia could express a causal relationship, reverse causality or be explained by health-related factors. This study explores the association of depression and indicators of depression severity with subsequent risk of dementia while ensuring temporality and adjusting for important health-related factors. METHOD: 595,828 men from the Danish Conscription Database born in 1939-59 with register-based information on lifetime depression and covariates at age 55 years were followed in nationwide registers to identify dementia cases until 2016. Associations were analyzed using Cox proportional hazard regression models with adjustment for intelligence, education level, body mass index, and comorbidities. RESULTS: The dementia incidence per 1000 person-years was 1.2 cases for men without prior depression and 2.1 and 3.6 cases for men who had depression identified by antidepressants and hospitalization, respectively. Compared to no prior depression, depression identified by antidepressant medication was associated with 1.94 times [95% confidence interval (CI) 1.81;2.07] higher hazard of dementia and depression identified by hospitalization with depression was associated with 2.18 [95% CI: 1.95;2.45] higher hazard of dementia. Long-term course of depression identified by antidepressant prescriptions (>20 prescriptions), was associated with 40% 95% CI: 1.23;1.59 higher hazard of dementia compared to having ≤10 prescriptions. LIMITATIONS: This study is restricted to men and dementia cases until age 57-77 years. CONCLUSION: Men with depression before late midlife are subject to a higher risk of dementia later in life. Clinicians should be aware of dementia symptoms in patients with a long history of depression to initiate early treatment.

Body mass index and height in young adult men in relation to subsequent risk of mood disorder.

Adolescence represents an important period in brain and mental development, which raises the question of whether measures of body size at entry into adult life influence the risk of developing mood disorders. We examined the association of BMI and height in a cohort of young men with risk of mood disorders throughout life. The study included 630,807 Danish men born 1939-1959 and 1983-1997 with measures of height and weight at conscription board examinations. Psychiatrist's diagnosis of mood disorders was obtained from national patient registries from 1969 to 2016. The associations of BMI and height with mood disorders were estimated by Cox proportional hazard regression analyses adjusting for education, cognitive ability, migration status drug and alcohol misuse. During a mean follow-up of 26.3 years, 2,608 (0.6%) and 19,690 (3.1%) men were diagnosed with bipolar disorder and depression, respectively. We found an inverse linear association of BMI with risk of bipolar disorder, whereas the association of BMI with depression was curve-linear with a decline in risk until BMI around 25 kg/m2, and an almost constant risk across the BMI range above 25 kg/m2. Height was not associated with bipolar disorder or depression. Comparison of brothers, assumed to share family factors of possible influence on the risk of mood disorders, showed similar results although with wider confidence intervals. BMI in the lower range at men's entry into adulthood is inversely associated with risk of bipolar disorder and depression throughout adult life, whereas height is not related.

An analysis of the relative and absolute incidence of somatic morbidity in patients with affective disorders-A nationwide cohort study.

BACKGROUND: Patients with affective disorder seem to experience higher risks of several somatic diseases, but no studies have provided estimates of both absolute and relative risks for these diseases in the same population. METHODS: A prospective cohort of all patients age ≥18 years old with a hospital contact with affective disorder between 1997-2014 (n=246,282) and a random sample from the background population (n=167,562) was followed for hospitalizations with cardiovascular disease, diabetes, cancers, chronic obstructive pulmonary disease (COPD), asthma, inflammatory bowel disease, hip fracture, psoriasis, migraine, or dementia. Adjusted absolute and relative risk estimates were calculated using multivariable adjusted Aalen's additive and Cox proportional hazard regression models. RESULTS: After adjustments, the absolute risk difference was 130.6 (95% confidence interval [CI] 125.5-135.7) additional cases per 10,000 person-years among affective disorder patients compared to the reference population. The corresponding hazard ratio for any somatic disease was 1.50 (95% CI 1.48-1.52). The strongest associations were found for dementia, hip fracture, COPD, and stroke on both the relative and absolute scale. The patients did not have higher risk of cancers except for lung cancer and brain tumors. Risk estimates tended to be slightly higher for individuals with depression or other affective disorder compared to bipolar disorder. LIMITATIONS: Limitations include use of register-based data, risk of reverse causation and Berkson's bias. CONCLUSIONS: Patients with affective disorder have both higher absolute and relative risk of most somatic diseases except for cancers. Further identification of the shared mechanisms will facilitate the development of targeted interventions.

Use of register- and survey-based measures of anxiety in a population-based Danish cohort.

OBJECTIVE: We explored the comparability of anxiety measures from register- and survey-based data including analyses of prevalence and associations with selected psychiatric and somatic diseases. METHODS: We measured anxiety using Danish registers (hospital diagnosis and anxiolytic drug prescriptions), self-reports, symptom checklist (SCL) scores, and a clinical interview in 7493 adults with mean age 52 (SD 13.3) years who participated in a health survey between 2012 and 2015. We estimated the prevalence of anxiety, agreement between different measures and performed quantitative bias analysis. RESULTS: The lifetime prevalence of hospital diagnosed anxiety, anxiolytic drug prescriptions, and self-reported anxiety were 4.4%, 6.2%, and 5.1%, respectively, after adjusting for selective participation. The agreement between the different anxiety measures was low. Thus, 25% with an anxiety diagnosis and 20% with anxiolytic drug prescriptions also had a high SCL score. Anxiolytic drugs were the only measure significantly associated with higher odds of heart disease. Hospital diagnosis and self-reported anxiety were associated with depression with odds ratio (OR) above 15, whereas anxiolytic drug prescriptions were less strongly associated (OR = 2.2(95% confidence interval: 1.26-3.91)). The risk estimates attenuated considerably when correcting for measurement error, whereas the ORs became slightly higher when the selective participation in the survey was accounted for. CONCLUSION: Anxiety diagnosed in hospitals and self-reported anxiety showed low level of agreement but provide comparable results regarding frequency measures and associations with disease outcomes.

The familial and genetic contribution to the association between depression and cardiovascular disease: a twin cohort study.

Depression and cardiovascular disease (ischemic heart disease and stroke) are associated in a bidirectional manner. Their relatively high heritability has led to the hypothesis that this co-occurrence is related to shared familial and genetic factors; this study aims to test this hypothesis. We included 23,498 monozygotic and 39,540 same-sex dizygotic twins from the Danish Twin Registry followed from January 1977 until December 2011 in nationwide Danish registries. We used survival analyses accounting for censoring and competing risk of death to estimate cumulative incidence, casewise concordance, relative recurrence risk, and heritability of the co-occurrence of depression and cardiovascular disease by age using monozygotic and same-sex dizygotic twin pairs. The casewise concordance of ischemic heart disease or stroke in twins whose co-twin was diagnosed with depression was at all ages similar for the monozygotic and dizygotic twin pairs and to the cumulative incidence of ischemic heart disease or stroke, respectively, in the entire twin population. A similar pattern was seen in analyses of depression risk given the co-twin being diagnosed with ischemic heart disease or stroke. Relative recurrence risk and heritability estimates were also of modest size and with confidence intervals including unity. Results were similar after stratification by gender as well as when redefining depression to include the use of antidepressant medication from 1995. Our findings do not support that co-occurrence between depression and cardiovascular disease is explainable by shared genetic factors, nor did we find strong evidence of a familial effect.

An attempt to explain the bidirectional association between ischaemic heart disease, stroke and depression: a cohort and meta-analytic approach.

BACKGROUND: Depression and cardiovascular diseases (CVDs) are common diseases and associated in a bidirectional manner. AIMS: To examine whether a bidirectional association between CVD and depression could be explained by shared risk factors, misclassification of disease measures or non-response. METHOD: A total of 10 population-based cohorts including 93 076 men and women (mean age 54.4 years, s.d. = 9.2) and an additional 10 510 men (mean age 51.2 years, s.d. = 0.3) were followed for subsequent depression, ischaemic heart disease (IHD) and stroke in the Danish National Patient Registry from health examinations between 1982 and 2015 and until end of follow-up in 2017-2018. Exposures were physicians' diagnoses of IHD, stroke, depression or self-reported chest pain, depression, use of antidepressant medication and the Major Depression Inventory at the time of study entry in the Metropolit study. Associations were analysed using Cox proportional hazard regression with disease as time-dependent variables. RESULTS: IHD and stroke were associated with subsequent depression (hazard ratio (HR) for IHD: 1.79, 95% CI 1.43-2.23 and HR for stroke: 2.62, 95% CI 2.09-3.29) and the associations were present in both men and women. Adjustment for the shared risk factors socioeconomic status, lifestyle, body mass index, statin use and serum lipids did not change the risk estimates. Furthermore, depression was associated with higher risk of subsequent IHD (HR = 1.63, 95% CI 1.36-1.95) and stroke (HR = 1.94, 95% CI 1.63-2.30). The associations were also present when the analyses were based on self-reported disease measures or restricted to include non-responders. CONCLUSIONS: The bidirectional association between CVD and depression was not explained by shared risk factors, misclassification or non-response.

Antidiabetic medication and risk of dementia in patients with type 2 diabetes: a nested case-control study.

OBJECTIVE: Diabetes is a risk factor for dementia, but whether antidiabetic medication decreases the risk is unclear. We examined the association between antidiabetic medication and dementia. DESIGN: We performed a nested case-control study within a cohort of all 176 250 patients registered with type 2 diabetes in the Danish National Diabetes Register between 1995 and 2012. This population was followed for dementia diagnosis or anti-dementia medication use until May 2018. Using risk-set sampling, each dementia case (n = 11 619) was matched on follow-up time and calender year of dementia with four controls randomly selected among cohort members without dementia (n = 46 476). Ever use and mean daily defined dose of antidiabetic medication was categorized in types (insulin, metformin, sulfonylurea and glinides combined, glitazone, dipeptidyl peptidase 4 (DPP4) inhibitors, glucagon-like peptide 1 (GLP1) analogs, sodium-glucose transport protein 2 (SGLT2) inhibitors and acarbose). METHODS: Conditional logistic regression models were fitted to calculate odds ratios (ORs) for dementia associated with antidiabetic medication use, adjusting for potential confounders. RESULTS: Use of metformin, DPP4 inhibitors, GLP1 analogs, and SGLT2 inhibitors were associated with lower odds of dementia after multible adjustments (ORs of 0.94 (95% confidence interval (CI): 0.89-0.99), 0.80 (95% CI 0.74-0.88), 0.58 (95% CI: 0.50-0.67), and 0.58 (95% CI: 0.42-0.81), respectively), with a gradual decrease in odds of dementia for each increase in daily defined dose. Analyses of the most frequent treatment regimes did not show any synergistic effects of combined treatment. CONCLUSION: Use of metformin, DPP4 inhibitors, GLP1 analogs and SGLT2 inhibitors was associated with lower risk of dementia in patients with diabetes.

Migraine and risk of stroke and acute coronary syndrome in two case-control studies in the Danish population.

INTRODUCTION: Migraine has consistently been associated with increased risk of ischemic stroke, while the evidence for a relation with other types of stroke or coronary outcomes is limited. We examined the association between migraine and stroke and acute coronary syndrome (ACS) subtypes and the influence of potential confounding factors. METHODS: All first-time hospital contacts for stroke (n=155,216) or ACS (n=97,799) were identified in Danish National Patient Registers and matched with 2 control groups of the background population. A hospital diagnosis of migraine and use of migraine medication were the main exposures and associations (odds ratios [OR]) were estimated using multiple logistic regression. Confounding was also addressed by including use of general headache medication as a negative control exposure. RESULTS: The diagnosis of migraine was associated with increased odds of both stroke (ORcrude, age <50 years: 4.80 [95% CI: 3.75-6.21]; ORcrude, age ≥50 years:1.91 [95% CI: 1.67-2.19]) and ACS (ORcrude:1.88 [95% CI: 1.53-2.32]), while the ORs for the associations between migraine medication and stroke and ACS were lower. Patients with a diagnosis of migraine or redeemed migraine medication had increased ORs of all stroke subtypes (ischemic, hemorrhagic stroke and transient ischemic attacks). The diagnosis of migraine was also associated with both angina and myocardial infarction (ST-elevation Myocardial Infarction [STEMI], non-STEMI and unspecified) with the highest OR for angina. These associations were not fully explained by adjustment for confounding co-variables or when compared with the negative control exposure that were assumed to be influenced by similar confounding factors, but no shared pathogenesis. CONCLUSION: Hospital-diagnosed migraine was associated with all stroke and ACS subtypes, with ischemic stroke and angina having the highest odds. Confounding did not explain the associations.

Anti-inflammatory treatment and risk of depression in 91,842 patients with acute coronary syndrome and 91,860 individuals without acute coronary syndrome in Denmark.

BACKGROUND: We examined if treatment with acetylsalicylic acid (ASA), non-steroid anti-inflammatory drugs (NSAID), or statins after acute coronary syndrome (ACS) are associated with decreased risk of depression. METHOD: This register-based cohort study included all individuals with a first-time hospital admissions with an ACS diagnosis registered between January 2001 to December 2009 (N=91,842) and a comparable reference population without ACS (N=91,860). Information of ASA, NSAID, and statin use were retrieved from a national prescription register. The study population was followed for hospitalization with depression or receiving prescription of antidepressant medication for up to one year after ACS or study entry (early depression) or one to twelve years after ACS or study entry (late depression). RESULTS: ASA use after ACS was associated with decreased risk of early depression with hazard ratios (HR) of 0.89 (95% confidence interval 0.85-0.93) but not with late depression 0.96 (0.90-1.01). The corresponding HRs for statin were 0.90 (0.86-0.94) and 0.86 (0.82-0.90). In the non-ACS population, statin use was not associated with neither early nor late depression (HRs 1.04 (0.96-1.12) and 1.00 (0.95-1.06)), while ASA was associated with increased risk of late (HR 1.09 (1.04-1.14)) but not early depression (HR 1.03 (0.97-1.09)). In both populations, NSAID use was associated with increased risk of late but not early depression. CONCLUSION: Use of ASA or statins were associated with decreased risk of depression in ACS patients but not in individuals without ACS, while use of NSAID was associated with increased risk of late depression in both populations.

Anti-inflammatory treatment and risk for depression after first-time stroke in a cohort of 147 487 Danish patients.

BACKGROUND: Depression is a common complication after stroke, and inflammation may be a pathophysiological mechanism. This study examines whether anti-inflammatory treatment with acetylsalicylic acid (ASA), nonsteroid anti-inflammatory drugs (NSAIDs) or statins influence the risk of depression after stroke. METHODS: A register-based cohort including all patients admitted to hospital with a first-time stroke from Jan. 1, 2001, through Dec. 31, 2011, and a nonstroke population with a similar age and sex distribution was followed for depression until Dec. 31, 2014. Depression was defined as having a hospital contact with depression or having filled prescriptions for antidepressant medication. The associations between redeemed prescriptions of ASA, NSAIDs or statins with early- (≤ 1 year after stroke or study entry) and late-onset (> 1 year after stroke or study entry) depression were analyzed using Cox proportional hazard regression. RESULTS: We identified 147 487 patients with first-time stroke and 160 235 individuals without stroke for inclusion in our study. Redeemed prescriptions of ASA, NSAIDs or statins after stroke decreased the risk for early-onset depression, especially in patients with ischemic or severe stroke. Patients who received a combination of anti-inflammatory treatments had the lowest risk for early-onset depression. On the other hand, use of ASA or NSAIDs 1 year after stroke increased the risk for late-onset depression, whereas statin use was associated with a tendency toward a decreased risk. LIMITATIONS: The study used prescription of antidepressant medication as a proxy measure for depression and did not include anti-inflammatory drugs bought over the counter. CONCLUSION: Anti-inflammatory treatment is associated with a lower risk for depression shortly after stroke but a higher risk for late depression. This suggests that inflammation contributes differently to the development of depression after stroke depending on the time of onset.

Personalized medicine in psychiatry.

BACKGROUND: Personalized medicine is a model in which a patient's unique clinical, genetic, and environmental characteristics are the basis for treatment and prevention. Aim, method, and results: This review aims to describe the current tools, phenomenological features, clinical risk factors, and biomarkers used to provide personalized medicine. Furthermore, this study describes the target areas in which they can be applied including diagnostics, treatment selection and response, assessment of risk of side-effects, and prevention. DISCUSSION AND CONCLUSION: Personalized medicine in psychiatry is challenged by the current taxonomy, where the diagnostic categories are broad and great biological heterogeneity exists within each category. There is, thus, a gap between the current advanced research prospects and clinical practice, and the current taxonomy is, thus, a poor basis for biological research. The discussion proposes possible solutions to narrow this gap and to move psychiatric research forward towards personalized medicine.