Ida Kim Wium-Andersen

Incidence of Depression After Stroke, and Associated Risk Factors and Mortality Outcomes, in a Large Cohort of Danish Patients

Importance More than 30 million people live with a stroke diagnosis worldwide. Depression after stroke is frequent, and greater knowledge of associated risk factors and outcomes is needed to understand the etiology and implications of this disabling complication. Objectives To examine whether the incidence of and risk factors for depression differ between patients with stroke and a reference population without stroke and to assess how depression influences mortality. Design, Setting, and Participants Register-based cohort study in Denmark. Participants were all individuals 15 years or older with a first-time hospitalization for stroke between January 1, 2001, and December 31, 2011 (n = 157 243), and a reference population (n = 160 236) matched on age, sex, and municipality. The data were analyzed between January and March 2016. Main Outcomes and Measures The incidence of depression and mortality outcomes of depression (defined by hospital discharge diagnoses or antidepressant medication use) were examined using Cox proportional hazards regression analyses. Results In total, 34 346 patients (25.4%) with stroke and 11 330 (7.8%) in the reference population experienced depression within 2 years after study entry. Compared with the reference population, patients with stroke had a higher incidence of depression during the first 3 months after hospitalization (hazard ratio for stroke vs the reference population, 8.99; 95% CI, 8.61-9.39), which declined during the second year of follow-up (hazard ratio for stroke vs the reference population, 1.93; 95% CI, 1.85-2.08). Significant risk factors for depression for patients with stroke and the reference population included older age, female sex, single cohabitation status, basic educational attainment, diabetes, high level of somatic comorbidity, history of depression, and stroke severity (in patients with stroke). The associations were strongest for the reference population. In both populations, depressed individuals, especially those with new onset, had increased all-cause mortality (hazard ratio for new-onset depression, 1.89 [95% CI, 1.83-1.95] for patients with stroke and 3.75 [95% CI, 3.51-4.00] for the reference population) after adjustment for confounders. Similar patterns were found for natural and unnatural causes of death. In most models, the depression-related relative mortality was approximately twice as high in the reference population vs the stroke population. Conclusions and Relevance Depression is common in patients with stroke during the first year after diagnosis, and those with prior depression or severe stroke are especially at risk. Because a large number of deaths can be attributable to depression after stroke, clinicians should be aware of this risk.

A new perspective on the anti-suicide effects with ketamine treatment: a procognitive effect

Abstract Available evidence indicates that a single, low-dose administration of ketamine is a robust, rapid-onset intervention capable of mitigating depressive symptoms in adults with treatment-resistant mood disorders. Additional evidence also suggests that ketamine may offer antisuicide effects. Herein, we propose that the antidepressant effects reported with ketamine administration are mediated, in part, by targeting neural circuits that subserve cognitive processing relevant to executive function and cognitive emotional processing. Empirical support for the conceptual framework of the cognitive domain as a critical target of ketamines action is the additional observation that pretreatment cognitive function predicts treatment outcomes with ketamine administration. The proposal that beneficial effects on cognitive function may be, in some individuals, the proximate mechanism mitigating symptom relief in mood disorders exists alongside the well-established deleterious effect of ketamine on cognitive function. During the past 5 years, there have been several reviews and meta-analyses concluding that ketamine has possible clinical benefits in refractory mood disorders. We introduce the conceptual framework that ketamines salutary effects, notably in suicidality, may in part be via procognitive mechanisms.

Depression After First Hospital Admission for Acute Coronary Syndrome: A Study of Time of Onset and Impact on Survival

We examined incidence of depression after acute coronary syndrome (ACS) and whether the timing of depression onset influenced survival. All first-time hospitalizations for ACS (n = 97,793) identified in the Danish Patient Registry during 2001-2009 and a reference population were followed for depression and mortality via linkage to patient, prescription, and cause-of-death registries until the end of 2012. Incidence of depression (as defined by hospital discharge or antidepressant medication use) and the relationship between depression and mortality were examined using time-to-event models. In total, 19,520 (20.0%) ACS patients experienced depression within 2 years after the event. The adjusted rate ratio for depression in ACS patients compared with the reference population was 1.28 (95% confidence interval (CI): 1.25, 1.30). During 12 years of follow-up, 39,523 (40.4%) ACS patients and 27,931 (28.6%) of the reference population died. ACS patients with recurrent (hazard ratio (HR) = 1.62, 95% CI: 1.57, 1.67) or new-onset (HR = 1.66, 95% CI: 1.60, 1.72) depression had higher mortality rates than patients with no depression. In the reference population, the corresponding relative estimates for recurrent (HR =1.98, 95% CI: 1.92, 2.05) and new-onset (HR = 2.42, 95% CI: 2.31, 2.54) depression were stronger. Depression is common in ACS patients and is associated with increased mortality independently of time of onset, but here the excess mortality associated with depression seemed to be lower in ACS patients than in the reference population.

Time trend in depression diagnoses among acute coronary syndrome patients and a reference population from 2001 to 2009 in Denmark

Abstract Introduction In the last decade a range of recommendations to increase awareness of depression in acute coronary syndrome patients have been published. To test the impact of those recommendations we examine and compare recent time trends in depression among acute coronary syndrome patients and a reference population. Methods 87 218 patients registered with acute coronary syndrome from 2001–2009 in Denmark and a match reference population were followed through hospital registries and medication prescriptions for early (≤30 days), intermediate (31 days to 6 months) and later (6 months to 2 years) depression in the acute coronary syndrome population and overall depression in the reference population. Cox regression models were used to compare hazard ratios (HRs) for depression over calendar years. Results During the study period, 11.0% and 6.2% were diagnosed with depression in the acute coronary syndrome population and in the reference population, respectively. For the acute coronary syndrome population, the adjusted HRs increased for early (HR (95% CI) 1.04 (1.01–1.06)) and intermediate depression (HR (95% CI) 1.01 (1.00–1.03)), whereas the adjusted HRs did not change for later depression (HR (95% CI) 0.99 (0.98–1.00)). For the reference population the adjusted HRs for depression increased through the study period (HR (95% CI) 1.01 (1.01–1.03)). Conclusion Increase in diagnoses of depressions within 6 months of acute coronary syndrome may be explained by increased focus on depression in this patient group in combination with increased awareness of depression in the general population.

Anti-inflammatory treatment and risk for depression

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 anti-depressant 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.

Anhedonia and cognitive function in adults with MDD: results from the International Mood Disorders Collaborative Project

BACKGROUND Cognitive dysfunction is common in major depressive disorder (MDD) and a critical determinant of health outcome. Anhedonia is a criterion item toward the diagnosis of a major depressive episode (MDE) and a well-characterized domain in MDD. We sought to determine the extent to which variability in self-reported cognitive function correlates with anhedonia. METHOD A post hoc analysis was conducted using data from (N=369) participants with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR)-defined diagnosis of MDD who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. The IMDCP is a collaborative research platform at the Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, Canada, and the Cleveland Clinic, Cleveland, Ohio. Measures of cognitive function, anhedonia, and depression severity were analyzed using linear regression equations. RESULTS A total of 369 adults with DSM-IV-TR-defined MDD were included in this analysis. Self-rated cognitive impairment [ie, as measured by the Adult ADHD Self-Report Scale (ASRS)] was significantly correlated with a proxy measure of anhedonia (r=0.131, p=0.012). Moreover, total depression symptom severity, as measured by the total Montgomery-Åsberg Depression Rating Scale (MADRS) score, was also significantly correlated with self-rated measures of cognitive dysfunction (r=0.147, p=0.005). The association between anhedonia and self-rated cognitive dysfunction remained significant after adjusting for illness severity (r=0.162, p=0.007). CONCLUSIONS These preliminary results provide empirical data for the testable hypothesis that anhedonia and self-reported cognitive function in MDD are correlated yet dissociable domains. The foregoing observation supports the hypothesis of overlapping yet discrete neurobiological substrates for these domains.

The Impact of Comorbid Depression on Educational Inequality in Survival after Acute Coronary Syndrome in a Cohort of 83 062 Patients and a Matched Reference Population

Background Patients with low socioeconomic position have higher rates of mortality after diagnosis of acute coronary syndrome (ACS), but little is known about the mechanisms behind this social inequality. The aim of the present study was to examine whether any educational inequality in survival after ACS was influenced by comorbid conditions including depression. Methods From 2001 to 2009 all first-time ACS patients were identified in the Danish National Patient Registry. This cohort of 83 062 ACS patients and a matched reference population were followed for incident depression and mortality until December 2012 by linkage to person, patients and prescription registries. Educational status was defined at study entry and the impact of potential confounders and mediators (age, gender, cohabitation status, somatic comorbidity and depression) on the relation between education and mortality were identified by drawing a directed acyclic graph and analysed using multiple Cox regression analyses. Findings During follow-up, 29 583(35.6%) of ACS patients and 19 105(22.9%) of the reference population died. Cox regression analyses showed an increased mortality in the lowest educated compared to those with high education in both ACS patients and the reference population. Adjustment for previous and incident depression or other covariables only attenuated the relations slightly. This pattern of associations was seen for mortality after 30 days, 1 year and during total follow-up. Conclusion In this study the relative excess mortality rate in lower educated ACS patients was comparable with the excess risk associated with low education in the background population. This educational inequality in survival remained after adjustment for somatic comorbidity and depression.

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.