Andrew A Nierenberg's research while affiliated with Aarhus University Hospital and other places

Publications (721)

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Introduction Osteoporosis, a systemic skeletal disorder associated with substantial morbidity and mortality, has been suggested to be particularly common among individuals with bipolar disorder. Lithium, a mood-stabilizer used as first-line treatment for bipolar disorder, may have bone-protecting properties. Objectives We aimed to subject both of...
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Objective: This study compared the impact of 3 eicosapentaenoic acid (EPA) doses versus placebo on inflammatory biomarkers and depressive symptoms. Methods: Sixty-one unmedicated adults (75% female; 45.5 ± 13.8 years) with DSM-5 major depressive disorder (MDD), body mass index > 25 kg/m2, and plasma high-sensitivity C-reactive protein (hs-CRP) ≥ 3...
Preprint
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Objectives We tested the hypothesis that after initial improvement with intravenous ketamine in patients with bipolar disorder (BD) with severe depression and acute suicidal thinking or behavior, a fixed-dose combination of oral D-cycloserine (DCS) and lurasidone (NRX-101) can maintain improvement more effectively lurasidone alone. Methods This wa...
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Prior work demonstrates a relationship between suicidal behavior and mood disorders, as well as between suicidal behavior and cardiovascular risk. When cardiovascular risk and mood disorders co-occur, people with these comorbid conditions tend to experience worse outcomes than people with only one of these conditions. As such, given the relevance o...
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Background Only a limited number of patients with major depressive disorder (MDD) respond to a first course of antidepressant medication (ADM). We investigated the feasibility of creating a baseline model to determine which of these would be among patients beginning ADM treatment in the US Veterans Health Administration (VHA). Methods A 2018–2020...
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The use of randomized clinical trials, in particular placebo-controlled trials, for drug approval, is the subject of long-standing debate in the scientific community and beyond. This study offers consensus recommendations from clinical and academic experts to guide the selection of clinical trial design in psychiatry. Forty-one highly cited clinica...
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Background Major depressive disorder (MDD) is a leading cause of disease morbidity. Combined treatment with antidepressant medication (ADM) plus psychotherapy yields a much higher MDD remission rate than ADM only. But 77% of US MDD patients are nonetheless treated with ADM only despite strong patient preferences for psychotherapy. This mismatch is...
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Patient‐reported helpfulness of treatment is an important indicator of quality in patient‐centered care. We examined its pathways and predictors among respondents to household surveys who reported ever receiving treatment for major depression, generalized anxiety disorder, social phobia, specific phobia, post‐traumatic stress disorder, bipolar diso...
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Objectives Societal restrictions imposed to prevent transmission of COVID-19 may challenge circadian-driven lifestyle behaviours, particularly amongst those vulnerable to mood disorders. The overarching aim of the present study was to investigate the hypothesis that, in the routine-disrupted environment of the COVID-19, amongst a sample of people l...
Preprint
Background Mental disorders, including major depressive disorder (MDD), are a leading cause of non-fatal burden of disease globally. Current conventional treatments for depression have significant limitations, and there have been few new treatments in decades. The microbiota-gut-brain- axis is now recognised as playing a role in mental and brain he...
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Objective To examine the association between antibiotic and acid suppressant prescriptions in the first two years and subsequent childhood psychiatric disorder treatment. Study design A retrospective cohort study of children born from October 2001 to September 2012 into the Military Health System (MHS), enrolled in TRICARE past two years of age an...
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The Frontal Systems Behavior Scale (FrSBe) is a self-report measure that assesses difficulties with cognitive and emotional control such as apathetic behavior, lack of inhibitory control, and executive dysfunction. Previous neuroimaging studies highlight the involvement of the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and dorsola...
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Importance: Osteoporosis, a systemic skeletal disorder associated with substantial morbidity and mortality, may be particularly common among individuals with bipolar disorder. Lithium, a first-line mood-stabilizing treatment for bipolar disorder, may have bone-protecting properties. Objective: To evaluate if treatment with lithium is associated...
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Background Individuals with bipolar disorder experience cognitive and affective processing deficits that often persist beyond the remission of acute mood symptoms. One possible biological mechanism for these deficits involves the potential effects of chronic low-grade peripheral inflammation on brain function. Peripheral inflammation has been assoc...
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Background: Childhood trauma affects the course of mood disorders. Researchers are now considering childhood trauma as an influential factor in the treatment of mood disorders. However, the role of childhood trauma in the treatment of bipolar disorder remains understudied. Methods: The effect of childhood trauma on treatment outcomes was evaluat...
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Background Individuals experiencing socioeconomic deprivation consistently demonstrate poorer physical and mental health. Income alone is inadequate as a measure of socioeconomic status (SES); a better measure for assessing the deprivation status of individuals is needed. Methods The New Zealand Index of Socioeconomic Deprivation for Individuals,...
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Objectives: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD. Methods:...
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Bipolar disorder (BD) is a complex and dynamic condition with a typical onset in late adolescence or early adulthood followed by an episodic course with intervening periods of subthreshold symptoms or euthymia. It is complicated by the accumulation of comorbid medical and psychiatric disorders. The etiology of BD remains unknown and no reliable bio...
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Objective Patients with bipolar disorder treated with lithium often require additional antipsychotics or anticonvulsants. However, the comparative effectiveness and safety of these agents as add-on to lithium has not been studied. Methods This secondary analysis combined two similar 24-week trials on outpatients with bipolar disorder randomized to...
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Background Fewer than half of patients with major depressive disorder (MDD) respond to psychotherapy. Pre-emptively informing patients of their likelihood of responding could be useful as part of a patient-centered treatment decision-support plan. Methods This prospective observational study examined a national sample of 807 patients beginning psy...
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Background Mindfulness can improve overall well-being by training individuals to focus on the present moment without judging their thoughts. However, it is unknown how much mindfulness practice and training are necessary to improve well-being. Objective The primary aim of this study was to determine whether a standard 8-session web-based mindfulne...
Preprint
BACKGROUND Mindfulness can improve overall well-being by training individuals to focus on the present moment without judging their thoughts. However, it is unknown how much mindfulness practice and training are necessary to improve well-being. OBJECTIVE The purpose of this study was to compare standard with brief mindfulness training to improve ov...
Article
Using network analysis, we estimated the structure of relations among manic and depressive symptoms, respectively, in 486 patients (59% women; age: M = 37, SD = 12.1) with bipolar disorder prior to their entering a clinical trial. We computed three types of networks: (a) Gaussian graphical models (GGMs) depicting regularized partial correlations, (...
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Background Patients with bipolar disorder have higher rates of cardiometabolic comorbidities and mortality. Although guidelines emphasize the importance of cardiovascular monitoring, few studies characterized the cardiometabolic risk profile during treatment and their relation to symptomatology and treatment response. Methods We analyzed data from...
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S Background Suicide is among the leading cause of death in children and adolescents. There are well-known risk factors of suicide, including childhood abuse, family conflicts, social adversity, and psychopathology. While suicide risk is also known to be heritable, few studies have investigated genetic risk in younger individuals. Methods Using p...
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Bipolar disorder (BD) is associated with higher rates of sedentarism, metabolic syndrome, obesity and early onset cardiovascular disease leading to premature mortality. Moreover, BD is often associated with disability and deficits in general functioning associated with residual subsyndromal depressive symptoms and persistent neurocognitive impairme...
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Individuals with bipolar disorder (BP) show abnormalities in the default mode network (DMN), a brain network active at rest and during self-referential cognition. In healthy individuals, the DMN is anti-correlated (strongly negatively correlated) with the task positive network (TPN), a brain network that is active during attention demanding tasks....
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Bipolar Disorder (BD) involves altered neural affective processing, but studies comparing BD patients to controls have yielded inconsistent results. This might relate to substantial variability in the nature and severity of mood symptoms among individuals with BD. Hence, we dimensionally examined the relationship between depressive and manic sympto...
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Engage diverse stakeholders and share narratives of those with lived experience Establish shared language, mission, and infrastructure to build trust Cultivate diverse partnerships to build bridges between fragmented systems Build stakeholder capacity to take action and track progress toward defined goals Create targeted dissemination strategies an...
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Depression is a disabling, highly prevalent, frequently chronic, and difficult-to-treat disorder with an immense cognitive, social, and economic burden. Given that many of the advances in other non-communicable disorders like cancer have been in prevention rather than treatment, the prevention of depression is currently an unmet public health prior...
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Cigarette smoking is prevalent among individuals with mood disorders, and particularly among those with bipolar disorder1. Given that depression and smoking independently predict poor cardiovascular health over time, understanding the characteristics of smokers with depression who engage in interventions to improve their cardiovascular health (e.g....
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Social distancing/lockdown policies during the coronavirus (COVID-19) pandemic may alter social rhythms of people through imposition of restrictions on normal daily activities. This may in turn challenge circadian function, particularly in people with mood disorders. Although objective data describing the relationship between circadian disturbances...
Chapter
The current global crisis in mental health has seen psychiatry assume an increasingly integral role in healthcare. This comprehensive and accessible textbook provides an evidence-based foundation in psychiatry for medical students and serves as an excellent refresher for all mental health professionals. Written by medical school faculty and experts...
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Background We aimed to study the probability of bipolar depression response at 24 weeks given initial non-response. Methods We combined two multi-site, 24-week trials including similar populations following the same evidence-based guidelines randomizing patients to lithium or quetiapine. Additional mood-stabilizing treatment was possible if clinic...
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Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) treat dyslipidaemia and cardiovascular disease by inhibiting cholesterol biosynthesis. They also have immunomodulatory and anti-inflammatory properties. Beyond cardiovascular disease, cholesterol and inflammation appear to be components of the pathogenesis and pathophysiology of n...
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Bipolar disorder often follows a set progression best described in stages where advanced stages are associated with poorer outcomes. Bipolar disorder is also often characterized by a predominance of episode polarity, where some individuals experience more depressive episodes (termed predominant depressive polarity) while others experience more hypo...
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Patient-reported outcome measures (PROMs) are self-rated scales and indices developed to improve the detection of the patients’ subjective experience. Given that a considerable number of PROMs are available, it is important to evaluate their validity and usefulness in a specific research or clinical setting. Published guidelines, based on psychomet...
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Background : Physical activity can mitigate the risk of cardiovascular diseases, but the presence of mood disorders makes it challenging to follow or develop a regular exercise habit. We conducted an online comparative effectiveness study (Healthy Hearts Healthy Minds) to evaluate whether an online psychosocial intervention adjunctive to an activit...
Preprint
Full-text available
Background: Major Depressive Disorder (MDD) is a leading cause of disease morbidity. Combined treatment with antidepressant medication (ADM) plus psychotherapy yields a much higher MDD remission rate than ADM-only. But 77% of US MDD patients are nonetheless treated with ADM-only despite strong patient preferences for psychotherapy. This mismatch is...
Article
Background Although randomized trials show that social phobia treatments can be effective, it is unclear whether patients experience treatment as helpful in clinical practice. We investigated this issue by assessing perceived treatment helpfulness for specific phobia in a cross-national epidemiological survey. Methods Cross-sectional population-ba...
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Objective: Self-management of bipolar disorder (BD) is an important component of treatment. Methods: We developed a patient-centered computational software system based on concepts from nonlinear systems (chaos) theory with mobile access to assist in managing BD known as KIOS. KIOS tracks interacting symptoms to determine theprecise state of a B...
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Patients taking dopamine-blocking agents such as antipsychotics are at risk for developing tardive dyskinesia. In this webcast, Drs McEvoy and Nierenberg discuss symptoms of tardive dyskinesia, how to observe patients (whether in person or via telemedicine), and how to educate patients and families about TD.
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Objective: We investigated the feasibility and acceptability of a brief sleep intervention and sleep monitoring device in bipolar disorder (BD), as well as the intervention's effectiveness in reducing suicidal ideation through improved sleep quality and duration. Methods: Participants (N=13) with BD received 4 sessions of cognitive-behavioral th...
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Background In real-world pragmatic administrative databases, patient reported remission is often missing. Objective We evaluate if, in administrative data, five features of antidepressant use patterns can replace patient-reported symptom remission. Method We re-examined data from Sequence Treatment Alternatives to Relieve Depression (STAR*D) stud...
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Clinical practice guidelines for bipolar disorder should lead to better treatment outcomes by providing evidence‐based and easy to use recommendations for clinicians regarding diagnosis and treatment. When formulating clinical guidelines, experts and taskforces face a dilemma of including evidence‐based recommendations versus consensus‐based recomm...
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Background Adjunctive antidepressants are frequently used for bipolar depression but their clinical efficacy has been studied in few trials and little is known about how co‐occurring manic symptoms affect treatment response. Methods Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (N = 482) and Lithium Treatment Moderate‐Do...
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Objectives To examine patterns and predictors of perceived treatment helpfulness for mania/hypomania and associated depression in the WHO World Mental Health Surveys. Methods Face‐to‐face interviews with community samples across 15 countries found n=2,178 who received lifetime mania/hypomania treatment and n=624 with lifetime mania/hypomania who r...
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Background Eicosapentaenoic acid (EPA) supplementation is an effective treatment option in major depressive disorder (MDD) associated with chronic low-grade inflammation. EPA is the precursor of specialized pro-resolving lipid mediators (SPMs) termed resolvins (Rv), that serve important roles in the resolution of inflammation. The objective of this...
Article
Tardive dyskinesia (TD) is a serious and potentially irreversible movement disorder that occurs in 20%-50% of patients taking antipsychotic drugs. TD is also associated with several other classes of medications, including antidepressants, antihistamines, decongestants, mood stabilizers, and stimulants. As more people are prescribed medications that...
Article
Bipolar disorders are a complex group of severe and chronic disorders that includes bipolar I disorder, defined by the presence of a syndromal, manic episode, and bipolar II disorder, defined by the presence of a syndromal, hypomanic episode and a major depressive episode. Bipolar disorders substantially reduce psychosocial functioning and are asso...
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Background : Psychotic symptoms during bipolar depressive episodes, especially in outpatients, are under recognized and studied by clinicians and researchers. We examined the relationship between psychotic symptoms during a depressive episode and suicidal ideation in bipolar patients. Methods : Participants (N=351) were adult, depressed, outpatien...
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Objective: In this study, we aimed to determine clinical correlates of false positive assignment (FPA) on commonly used bipolar screening questionnaires. Methods: A retrospective chart review was conducted to a total of 3885 psychiatric outpatients. After excluding patients who have bipolar spectrum illnesses, patients who were assigned as havin...
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The intestinal microbiome has been identified as a key modifier for a variety of health conditions. Fecal Microbiota Transplantation (FMT) has emerged as a fast, safe, and effective means by which to modify the intestinal microbiome and potentially treat a variety of health conditions. Despite extensive research of FMT for CDI, there is a lack of c...
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Many patients who are at risk for tardive dyskinesia fear that they might develop the involuntary neurological movement disorder, yet it is possible for clinicians to convey a realistic assessment of the benefits and risks of medications that might induce TD. Clinicians need to be aware of the importance of communicating reasonable risk in a way th...
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Importance: Medicare has historically imposed higher beneficiary coinsurance for behavioral health services than for medical and surgical care but gradually introduced parity between 2009 and 2014. Although Medicare insures many people with serious mental illness (SMI), there is limited information on the impact of coinsurance parity in this popul...
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Objectives The aim was to describe the pre‐diagnostic and post‐diagnostic psychopharmacological treatment of bipolar disorder over the past two decades. Methods We identified all 16,288 individuals aged ≥18 years, who received their first diagnosis of bipolar disorder at a psychiatric hospital in Denmark between 1997 and 2014. For each calendar ye...
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Objectives The immunomodulatory effects of eicosapentaenoic acid (EPA) support it as an effective treatment for major depressive disorder (MDD) associated with chronic inflammation. Increased production of specialized pro-resolving mediators (SPM) during EPA supplementation may help reduce inflammation. We compared the effects of different EPA dose...
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Introduction Although clinical practice guidelines (CPG) identify first, second‐ and third‐line mood stabilizer (MS) treatments, they rarely define clinical response to prophylaxis or the core issues to be considered. This project aimed to develop a template for describing how clinical response may be classified and a framework to assist decision‐m...
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Objective: Pharmacological options for treating bipolar disorder have increased over the past 20 years, with several second-generation antipsychotics receiving regulatory approval in the 1990s. The authors describe trends in use of pharmacological agents in the outpatient management of bipolar disorder. Methods: Using nationally representative d...
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Background: While bipolar disorder (BD) and posttraumatic stress disorder (PTSD) frequently co-occur and individually have a higher risk of suicide compared to the general population, few studies have examined the impact of comorbid PTSD on suicidal ideation in patients with BD. Methods: We analyzed baseline data from the Clinical and Health Out...
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Objective The potential of clozapine in severe bipolar disorder is suggested by its efficacy in refractory schizophrenia, but the evidence is limited thus far. This report utilizes data from the standard care pathway of the Systematic Treatment Enhancement Program to examine the clinical impact of clozapine in bipolar disorder, comparing it to two...