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Paans O, Tilborg JL, Kamperman AM, Kupka RW, Kok RM. Psychotropic comedication trends in long-term lithium treatment for older adults with bipolar disorder: A 10-year analysis. J Affect Disord 2025; 380:366-374. [PMID: 40120957 DOI: 10.1016/j.jad.2025.03.091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Revised: 03/12/2025] [Accepted: 03/14/2025] [Indexed: 03/25/2025]
Abstract
OBJECTIVES The prescription of psychotropic comedications in patients with bipolar disorder (BD) evolved between 1995 and 2010. This study provides a comprehensive overview of prescription trends across various classes of psychotropic comedications, alongside lithium treatment, in older adults (aged ≥55 years) with BD, from 2010 to 2019. METHODS This naturalistic, retrospective cohort study included 166 older adults (mean age 67.4 years) treated with lithium. Medical files from a large mental healthcare provider in the Netherlands were used to construct Lifecharts. The average proportion of time that different classes of comedications were prescribed during follow-up was calculated. RESULTS Patients received psychotropic comedications next to lithium for 75.8 % of total follow-up time. Benzodiazepines were prescribed for 56.2 % of follow-up time, antidepressants for 31.6 %, atypical antipsychotics for 25.9 %, a second mood stabilizer for 18.4 %, and typical antipsychotics for 8.7 %. Most classes of comedications did not show significant changes in prescription trends over the 10-year observation period. Quetiapine at doses below 50 mg/day was prescribed significantly more over time (p = .033), its prescription duration increasing from 2.0 % of total follow-up time in 2010 to 8.1 % in 2019. LIMITATIONS Generalizability is limited due to focus on older lithium-treated BD patients, potential selection bias, and retrospective design. CONCLUSIONS Long-term lithium treatment in older adults is mostly combined with other psychotropic medications. Frequent and prolonged use of benzodiazepines and significant increase of low-dose quetiapine use are concerning, given their adverse effects and lack of long-term efficacy. Prescription trends observed before 2010 have largely stabilized. PLAIN LANGUAGE SUMMARY In this study, we examined what types of comedication were used alongside lithium in older adults with bipolar disorder between 2010 and 2019. For this purpose, we reviewed the medical records of 166 patients 55 years or older in the Netherlands. These patients were prescribed additional psychotropic medications along with lithium 75.8 % of the time. Benzodiazepines, often used to treat anxiety and sleep issues but not recommended for long-term use due to adverse effects, were the most frequently prescribed, namely 56.2 % of the time. Antidepressants were prescribed 31.6 % of the time, atypical antipsychotics 25.9 %, a second mood stabilizer 18.4 %, and typical antipsychotics 8.7 %. Although most prescription trends remained stable between 2010 and 2019, prescription time of low-dose quetiapine increased. We conclude that lithium maintenance treatment is mostly combined with other psychotropic comedications in older adults with bipolar disorder. Considering their potential adverse effects and lack of long-term benefits, the increasing use of low-dose quetiapine and the frequent long-term use of benzodiazepines are particularly concerning.
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Affiliation(s)
- Olaf Paans
- Parnassia Group, Rotterdam, the Netherlands.
| | | | - Astrid M Kamperman
- Erasmus Medical Center, Rotterdam, the Netherlands; Epidemiological and Social Psychiatric Research Institute (ESPRi), Department of Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands.
| | - Ralph W Kupka
- Amsterdam University Medical Center, Vrije Universiteit, dept. of Psychiatry, Amsterdam, the Netherlands.
| | - Rob M Kok
- Parnassia Group, Department of Old Age Psychiatry, The Hague, the Netherlands.
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Ljubic N, Ueberberg B, Grunze H, Assion HJ. Treatment of Bipolar Disorders in Older Adults: A Review. FOCUS (AMERICAN PSYCHIATRIC PUBLISHING) 2023; 21:434-443. [PMID: 38695000 PMCID: PMC11058944 DOI: 10.1176/appi.focus.23021024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/04/2024]
Abstract
Background Old age bipolar disorder has been an orphan of psychiatric research for a long time despite the fact that bipolar disorder (BD)-I and II together may affect 0.5-1.0% of the elderly. It is also unclear whether aetiology, course of illness and treatment should differ in patients with a first manifestation in older age and patients suffering from a recurrence of a BD known for decades. This narrative review will summarize the current state of knowledge about the epidemiology, clinical features, and treatment of BD in the elderly. Methods We conducted a Medline literature search from 1970 to 2021 using MeSH terms "Bipolar Disorder" × "Aged" or "Geriatric" or "Elderly". Search results were complemented by additional literature retrieved from examining cross references and by hand search in text books. Summary of findings Varying cut-off ages have been applied to differentiate old age from adult age BD. Within old age BD, there is a reasonable agreement of distinct entities, early and late-onset BD. They differ to some extent in clinical symptoms, course of illness, and some co-morbidities. Point prevalence of BD in older adults appears slightly lower than in working-age adults, with polarity of episodes shifting towards depression. Psychopharmacological treatment needs to take into account the special aspects of somatic gerontology and the age-related change of pharmacokinetic and pharmacodynamic characteristics. The evidence for commonly used treatments such as lithium, moodstabilizing antiepileptics, antipsychotics, and antidepressants remains sparse. Preliminary results support a role of ECT as well as psychotherapy and psychosocial interventions in old age BD. Conclusions There is an obvious need of further research for all treatment modalities of BD in old age. The focus should be pharmacological and psychosocial approaches, as well as their combination, and the role of physical treatment modalities such as ECT.Appeared originally in Ann Gen Psychiatry 2021; 20:1.
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Affiliation(s)
- Nemanja Ljubic
- Bereich Forschung & Wissenschaft, LWL-Klinik, Marsbruchstr. 179, 44287 Dortmund, Germany (Ljubic, Ueberberg, Assion); Psychiatrie Schwäbisch Hall, Ringstraße. 1, 74523 Schwäbisch Hall, Germany (Grunze); Paracelsus Medical University, Ernst-Nathan Straße 1, 90419 Nuremberg, Germany (Grunze)
| | - Bianca Ueberberg
- Bereich Forschung & Wissenschaft, LWL-Klinik, Marsbruchstr. 179, 44287 Dortmund, Germany (Ljubic, Ueberberg, Assion); Psychiatrie Schwäbisch Hall, Ringstraße. 1, 74523 Schwäbisch Hall, Germany (Grunze); Paracelsus Medical University, Ernst-Nathan Straße 1, 90419 Nuremberg, Germany (Grunze)
| | - Heinz Grunze
- Bereich Forschung & Wissenschaft, LWL-Klinik, Marsbruchstr. 179, 44287 Dortmund, Germany (Ljubic, Ueberberg, Assion); Psychiatrie Schwäbisch Hall, Ringstraße. 1, 74523 Schwäbisch Hall, Germany (Grunze); Paracelsus Medical University, Ernst-Nathan Straße 1, 90419 Nuremberg, Germany (Grunze)
| | - Hans-Jörg Assion
- Bereich Forschung & Wissenschaft, LWL-Klinik, Marsbruchstr. 179, 44287 Dortmund, Germany (Ljubic, Ueberberg, Assion); Psychiatrie Schwäbisch Hall, Ringstraße. 1, 74523 Schwäbisch Hall, Germany (Grunze); Paracelsus Medical University, Ernst-Nathan Straße 1, 90419 Nuremberg, Germany (Grunze)
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Eyler LT, Briggs FBS, Dols A, Rej S, Almeida OP, Beunders AJM, Blumberg HP, Forester BP, Patrick RE, Forlenza OV, Gildengers A, Jimenez E, Vieta E, Mulsant BH, Schouws S, Paans NPG, Strejilevich S, Sutherland A, Tsai S, Sajatovic M. Symptom Severity Mixity in Older-Age Bipolar Disorder: Analyses From the Global Aging and Geriatric Experiments in Bipolar Disorder Database (GAGE-BD). Am J Geriatr Psychiatry 2022; 30:1096-1107. [PMID: 35637088 PMCID: PMC10280310 DOI: 10.1016/j.jagp.2022.03.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 03/28/2022] [Accepted: 03/29/2022] [Indexed: 01/25/2023]
Abstract
OBJECTIVE Some individuals with bipolar disorder (BD) experience manic and depressive symptoms concurrently, but data are limited on symptom mixity in older age bipolar disorder (OABD). Using the Global Aging & Geriatric Experiments in Bipolar Disorder Database, we characterized mixity in OABD and associations with everyday function. METHODS The sample (n = 805), from 12 international studies, included cases with both mania and depression severity ratings at a single timepoint. Four mixity groups were created: asymptomatic (A), mixed (Mix), depressed only (Dep), and manic only (Man). Generalized linear mixed models used mixity group as the predictor variable; cohort was included as a random intercept. Everyday function was assessed with the Global Assessment of Functioning score. RESULTS Group proportions were Mix (69.6%; n = 560), followed by Dep (18.4%; n = 148), then A (7.8%; n = 63), then Man (4.2%; n= 34); levels of depression and mania were similar in Mix compared to Dep and Man, respectively. Everyday function was lowest in Mix, highest in A, and intermediate in Man and Dep. Within Mix, severity of depression was the main driver of worse functioning. Groups differed in years of education, with A higher than all others, but did not differ by age, gender, employment status, BD subtype, or age of onset. CONCLUSIONS Mixed features predominate in a cross-sectional, global OABD sample and are associated with worse everyday function. Among those with mixed symptoms, functional status relates strongly to current depression severity. Future studies should include cognitive and other biological variables as well as longitudinal designs to allow for evaluation of causal effects.
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Affiliation(s)
- Lisa T Eyler
- Department of Psychiatry (LTE), University of California San Diego, San Diego, CA; Desert-Pacific Mental Illness Research Education and Clinical Center, VA San Diego Healthcare System (LTE), San Diego, CA.
| | - Farren B S Briggs
- Department of Population and Quantitative Health Sciences (FBSB), Case Western Reserve University School of Medicine, Cleveland, OH
| | - Annemiek Dols
- GGZ inGeest, Amsterdam UMC, VU Medical Center, Amsterdam Public Health Research Institute (AD, AJMB, SS, NPGP), Amsterdam, the Netherlands; Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress program and Neurodegeneration program, Amsterdam, the Netherlands
| | - Soham Rej
- Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress program and Neurodegeneration program, Amsterdam, the Netherlands
| | | | - Alexandra J M Beunders
- GGZ inGeest, Amsterdam UMC, VU Medical Center, Amsterdam Public Health Research Institute (AD, AJMB, SS, NPGP), Amsterdam, the Netherlands
| | - Hilary P Blumberg
- Department of Psychiatry (HPB), Yale School of Medicine, New Haven, CT
| | - Brent P Forester
- Division of Geriatric Psychiatry (BPF), McLean Hospital, Belmont, MA; Harvard Medical School (BPF, REP), Boston, MA
| | - Regan E Patrick
- Harvard Medical School (BPF, REP), Boston, MA; Division of Geriatric Psychiatry (REP), McLean Hospital, Belmont, MA
| | - Orestes V Forlenza
- Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry (OVF), HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | - Ariel Gildengers
- Department of Psychiatry (AG), University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Esther Jimenez
- Bipolar and Depressive Disorders Unit, Hospital Clinic (EJ, EV), University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain
| | - Eduard Vieta
- Bipolar and Depressive Disorders Unit, Hospital Clinic (EJ, EV), University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain
| | - Benoit H Mulsant
- Department of Psychiatry (BHM), University of Toronto, Center for Addiction & Mental Health, Toronto, Canada
| | - Sigfried Schouws
- GGZ inGeest, Amsterdam UMC, VU Medical Center, Amsterdam Public Health Research Institute (AD, AJMB, SS, NPGP), Amsterdam, the Netherlands; GGZ inGeest, Amsterdam UMC (SS), VU Medical Center, Amsterdam, the Netherlands
| | - Nadine P G Paans
- GGZ inGeest, Amsterdam UMC, VU Medical Center, Amsterdam Public Health Research Institute (AD, AJMB, SS, NPGP), Amsterdam, the Netherlands; GGZ inGeest, Amsterdam UMC, VU Medical Center, Amsterdam Public Health Research Institute (NPGP), Amsterdam, the Netherlands
| | - Sergio Strejilevich
- AREA, Assistance and Research in Affective Disorders (SS), Buenos Aires, Argentina
| | - Ashley Sutherland
- Department of Psychiatry (AS), University of California San Diego, San Diego, CA
| | - Shangying Tsai
- Department of Psychiatry, School of Medicine (ST), College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Martha Sajatovic
- Case Western Reserve University School of Medicine (MS), University Hospitals Cleveland Medical Center, Cleveland, OH
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Chakrabarti S, Singh N. Psychotic symptoms in bipolar disorder and their impact on the illness: A systematic review. World J Psychiatry 2022; 12:1204-1232. [PMID: 36186500 PMCID: PMC9521535 DOI: 10.5498/wjp.v12.i9.1204] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 05/02/2022] [Accepted: 08/26/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Lifetime psychotic symptoms are present in over half of the patients with bipolar disorder (BD) and can have an adverse effect on its course, outcome, and treatment. However, despite a considerable amount of research, the impact of psychotic symptoms on BD remains unclear, and there are very few systematic reviews on the subject.
AIM To examine the extent of psychotic symptoms in BD and their impact on several aspects of the illness.
METHODS The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. An electronic literature search of six English-language databases and a manual search was undertaken to identify published articles on psychotic symptoms in BD from January 1940 to December 2021. Combinations of the relevant Medical Subject Headings terms were used to search for these studies. Articles were selected after a screening phase, followed by a review of the full texts of the articles. Assessment of the methodological quality of the studies and the risk of bias was conducted using standard tools.
RESULTS This systematic review included 339 studies of patients with BD. Lifetime psychosis was found in more than a half to two-thirds of the patients, while current psychosis was found in a little less than half of them. Delusions were more common than hallucinations in all phases of BD. About a third of the patients reported first-rank symptoms or mood-incongruent psychotic symptoms, particularly during manic episodes. Psychotic symptoms were more frequent in bipolar type I compared to bipolar type II disorder and in mania or mixed episodes compared to bipolar depression. Although psychotic symptoms were not more severe in BD, the severity of the illness in psychotic BD was consistently greater. Psychosis was usually associated with poor insight and a higher frequency of agitation, anxiety, and hostility but not with psychiatric comorbidity. Psychosis was consistently linked with increased rates and the duration of hospitalizations, switching among patients with depression, and poorer outcomes with mood-incongruent symptoms. In contrast, psychosis was less likely to be accompanied by a rapid-cycling course, longer illness duration, and heightened suicidal risk. There was no significant impact of psychosis on the other parameters of course and outcome.
CONCLUSION Though psychotic symptoms are very common in BD, they are not always associated with an adverse impact on BD and its course and outcome.
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Affiliation(s)
- Subho Chakrabarti
- Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, UT, India
| | - Navdeep Singh
- Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, UT, India
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Rajashekar N, Blumberg HP, Villa LM. Neuroimaging Studies of Brain Structure in Older Adults with Bipolar Disorder: A Review. JOURNAL OF PSYCHIATRY AND BRAIN SCIENCE 2022; 7:e220006. [PMID: 36092855 PMCID: PMC9453888 DOI: 10.20900/jpbs.20220006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Bipolar disorder (BD) is a common mood disorder that can have severe consequences during later life, including suffering and impairment due to mood and cognitive symptoms, elevated risk for dementia and an especially high risk for suicide. Greater understanding of the brain circuitry differences involved in older adults with BD (OABD) in later life and their relationship to aging processes is required to improve outcomes of OABD. The current literature on gray and white matter findings, from high resolution structural and diffusion-weighted magnetic resonance imaging (MRI) studies, has shown that BD in younger age groups is associated with gray matter reductions within cortical and subcortical brain regions that subserve emotion processing and regulation, as well as reduced structural integrity of white matter tracts connecting these brain regions. While fewer neuroimaging studies have focused on OABD, it does appear that many of the structural brain differences found in younger samples are present in OABD. There is also initial suggestion that there are additional brain differences, for at least a subset of OABD, that may result from more pronounced gray and white matter declines with age that may contribute to adverse outcomes. Preclinical and clinical data supporting neuro-plastic and -protective effects of mood-stabilizing medications, suggest that treatments may reverse and/or prevent the progression of brain changes thereby reducing symptoms. Future neuroimaging research implementing longitudinal designs, and large-scale, multi-site initiatives with detailed clinical and treatment data, holds promise for reducing suffering, cognitive dysfunction and suicide in OABD.
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Affiliation(s)
- Niroop Rajashekar
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA
| | - Hilary P. Blumberg
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06520, USA
- Child Study Center, Yale School of Medicine, New Haven, CT 06519, USA
| | - Luca M. Villa
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA
- Department of Psychiatry, University of Oxford, Oxford, OX37JX, UK
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Fico G, Oliva V, De Prisco M, Giménez-Palomo A, Sagué-Vilavella M, Gomes-da-Costa S, Garriga M, Solé E, Valentí M, Fanelli G, Serretti A, Fornaro M, Carvalho AF, Vieta E, Murru A. The U-shaped relationship between parental age and the risk of bipolar disorder in the offspring: A systematic review and meta-analysis. Eur Neuropsychopharmacol 2022; 60:55-75. [PMID: 35635997 DOI: 10.1016/j.euroneuro.2022.05.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 05/02/2022] [Accepted: 05/10/2022] [Indexed: 01/06/2023]
Abstract
Parenthood age may affect the risk for the development of different psychiatric disorders in the offspring, including bipolar disorder (BD). The present systematic review and meta-analysis aimed to appraise the relationship between paternal age and risk for BD and to explore the eventual relationship between paternal age and age at onset of BD. We searched the MEDLINE, Scopus, Embase, PsycINFO online databases for original studies from inception, up to December 2021. Random-effects meta-analyses were conducted. Sixteen studies participated in the qualitative synthesis, of which k = 14 fetched quantitative data encompassing a total of 13,424,760 participants and 217,089 individuals with BD. Both fathers [adjusted for the age of other parent and socioeconomic status odd ratio - OR = 1.29(95%C.I. = 1.13-1.48)] and mothers aged ≤ 20 years [(OR = 1.23(95%C.I. = 1.14-1.33)] had consistently increased odds of BD diagnosis in their offspring compared to parents aged 25-29 years. Fathers aged ≥ 45 years [adjusted OR = 1.29 (95%C.I. = 1.15-1.46)] and mothers aged 35-39 years [OR = 1.10(95%C.I. = 1.01-1.19)] and 40 years or older [OR = 1.2(95% C.I. = 1.02-1.40)] likewise had inflated odds of BD diagnosis in their offspring compared to parents aged 25-29 years. Early and delayed parenthood are associated with an increased risk of BD in the offspring. Mechanisms underlying this association are largely unknown and may involve a complex interplay between psychosocial, genetic and biological factors, and with different impacts according to sex and age range. Evidence on the association between parental age and illness onset is still tentative but it points towards a possible specific effect of advanced paternal age on early BD-onset.
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Affiliation(s)
- Giovanna Fico
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, 170 Villarroel st, 12-0, Barcelona, Catalonia 08036, Spain
| | - Vincenzo Oliva
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, 170 Villarroel st, 12-0, Barcelona, Catalonia 08036, Spain; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
| | - Michele De Prisco
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, 170 Villarroel st, 12-0, Barcelona, Catalonia 08036, Spain; Department of Neuroscience, Section of Psychiatry, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy
| | - Anna Giménez-Palomo
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, 170 Villarroel st, 12-0, Barcelona, Catalonia 08036, Spain
| | - Maria Sagué-Vilavella
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, 170 Villarroel st, 12-0, Barcelona, Catalonia 08036, Spain
| | - Susana Gomes-da-Costa
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, 170 Villarroel st, 12-0, Barcelona, Catalonia 08036, Spain
| | - Marina Garriga
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, 170 Villarroel st, 12-0, Barcelona, Catalonia 08036, Spain
| | - Eva Solé
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, 170 Villarroel st, 12-0, Barcelona, Catalonia 08036, Spain
| | - Marc Valentí
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, 170 Villarroel st, 12-0, Barcelona, Catalonia 08036, Spain
| | - Giuseppe Fanelli
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Alessandro Serretti
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
| | - Michele Fornaro
- Department of Neuroscience, Section of Psychiatry, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy
| | - Andre F Carvalho
- IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Vic., Australia 6 Perinatal Health Unit, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, Deakin University, Barcelona, Catalonia, Spain
| | - Eduard Vieta
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, 170 Villarroel st, 12-0, Barcelona, Catalonia 08036, Spain.
| | - Andrea Murru
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, 170 Villarroel st, 12-0, Barcelona, Catalonia 08036, Spain
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Bipolar Disorder Related Hospitalizations - a Descriptive Nationwide Study Using a Big Data Approach. Psychiatr Q 2022; 93:325-333. [PMID: 34581934 DOI: 10.1007/s11126-021-09951-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/11/2021] [Indexed: 10/20/2022]
Abstract
Bipolar Disorder (BD) is a mental disorder which frequently requires long hospitalizations and need for acute psychiatric care. The aim of this study was to describe a nationwide perspective of BD related hospitalizations and to use a BigData based approach in mental health research. We performed a retrospective observational study using a nationwide hospitalization database containing all hospitalizations registered in Portuguese public hospitals from 2008-2015. Hospitalizations with a primary diagnosis of BD were selected based on International Classification of Diseases version 9, Clinical Modification (ICD-9-CM) codes of diagnosis 296.xx (excluding 296.2x; 296.3x and 296.9x). From 20,807 hospitalizations belonging to 13,300 patients, around 33.4% occurred in male patients with a median length of stay of 16.0 days and a mean age of 47.9 years. The most common hospitalization diagnosis in BD has the code 296.4x (manic episode) representing 34.3% of all hospitalizations, followed by the code 296.5x (depressed episode) with 21.4%. The mean estimated hospitalization charge was 3,508.5€ per episode, with a total charge of 73M€ in the 8-year period of this study.This is a nationwide study giving a broad perspective of the BD hospitalization panorama at a national level. We found important differences in hospitalization characteristics by sex, age and primary diagnosis.
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Montejo L, Torrent C, Jiménez E, Martínez-Arán A, Blumberg HP, Burdick KE, Chen P, Dols A, Eyler LT, Forester BP, Gatchel JR, Gildengers A, Kessing LV, Miskowiak KW, Olagunju AT, Patrick RE, Schouws S, Radua J, Bonnín CDM, Vieta E. Cognition in older adults with bipolar disorder: An ISBD task force systematic review and meta-analysis based on a comprehensive neuropsychological assessment. Bipolar Disord 2022; 24:115-136. [PMID: 34978124 DOI: 10.1111/bdi.13175] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVES We aim to characterize the cognitive performance in euthymic older adults with bipolar disorder (OABD) through a comprehensive neuropsychological assessment to obtain a detailed neuropsychological profile. METHODS We conducted a systematic search in MEDLINE/Pubmed, Cochrane, and PsycInfo databases. Original studies assessing cognitive function in OABD (age ≥50 years ) containing, at a minimum, the domains of attention/processing speed, memory, and executive functions were included. A random-effects meta-analysis was conducted to summarize differences between patients and matched controls in each cognitive domain. We also conducted meta-regressions to estimate the impact of clinical and socio-demographic variables on these differences. RESULTS Eight articles, providing data for 328 euthymic OABD patients and 302 healthy controls, were included in the meta-analysis. OABD showed worse performance in comparison with healthy controls, with large significant effect sizes (Hedge's g from -0.77 to -0.89; p < 0.001) in verbal learning and verbal and visual delayed memory. They also displayed statistically significant deficits, with moderate effect size, in processing speed, working memory, immediate memory, cognitive flexibility, verbal fluency, psychomotor function, executive functions, attention, inhibition, and recognition (Hedge's g from -0.52 to -0.76; p < 0.001), but not in language and visuoconstruction domains. None of the examined variables were associated with these deficits. CONCLUSIONS Cognitive dysfunction is present in OABD, with important deficits in almost all cognitive domains, especially in the memory domain. Our results highlight the importance of including a routine complete neuropsychological assessment in OABD and also considering therapeutic strategies in OABD.
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Affiliation(s)
- Laura Montejo
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic of Barcelona, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Catalonia, Spain
| | - Carla Torrent
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic of Barcelona, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Catalonia, Spain
| | - Esther Jiménez
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic of Barcelona, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Catalonia, Spain
| | - Anabel Martínez-Arán
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic of Barcelona, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Catalonia, Spain
| | - Hilary P Blumberg
- Mood Disorders Research Program, Yale School of Medicine, New Haven, Connecticut, USA
| | - Katherine E Burdick
- Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Peijun Chen
- Section of Geriatric Psychiatry, Department of Psychiatry & VISN10 Geriatric Research, Education and Clinical Center, VA Northeast Ohio Healthcare System Cleveland VA Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Annemieke Dols
- GGZ inGeest, Department of Psychiatry, Amsterdam UMC, location VU Medical Center, Amsterdam Neuroscience, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
| | - Lisa T Eyler
- Department of Psychiatry, University of California, San Diego, California, USA
- Desert-Pacific Mental Illness Research, Education and Clinical Center, VA San Diego Healthcare System, San Diego, California, USA
| | - Brent P Forester
- Division of Geriatric Psychiatry, McLean Hospital, Belmont, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Jennifer R Gatchel
- Division of Geriatric Psychiatry, McLean Hospital, Belmont, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Ariel Gildengers
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Lars V Kessing
- Copenhagen Affective Disorder research Center (CADIC), Psychiatric Center Copenhagen, Copenhagen, Denmark
| | - Kamilla W Miskowiak
- Copenhagen Affective Disorder research Center (CADIC), Psychiatric Center Copenhagen, Copenhagen, Denmark
- Department of Psychology, University of Copenhagen, Copenhagen, Denmark
| | - Andrew T Olagunju
- Department of Psychiatry and Behavioral Neurosciences, McMaster University/St Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada
| | - Regan E Patrick
- Division of Geriatric Psychiatry, McLean Hospital, Belmont, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Sigfried Schouws
- GGZ inGeest, Department of Psychiatry, Amsterdam UMC, location VU Medical Center, Amsterdam Neuroscience, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
| | - Joaquim Radua
- Imaging of Mood- and Anxiety-Related Disorders (IMARD) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- CIBERSAM, Madrid, Spain
- Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
- Department of Clinical Neuroscience, Stockholm Health Care Services, Stockholm County Council, Karolinska Institutet, Stockholm, Sweden
| | - Caterina Del M Bonnín
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic of Barcelona, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Catalonia, Spain
| | - Eduard Vieta
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic of Barcelona, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Catalonia, Spain
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9
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Sajatovic M, Dols A, Rej S, Almeida OP, Beunders AJ, Blumberg HP, Briggs FB, Forester BP, Patrick RE, Forlenza OV, Gildengers A, Jimenez E, Vieta E, Mulsant B, Schouws S, Paans N, Strejilevich S, Sutherland A, Tsai S, Wilson B, Eyler LT. Bipolar symptoms, somatic burden, and functioning in older-age bipolar disorder: Analyses from the Global Aging & Geriatric Experiments in Bipolar Disorder Database project. Bipolar Disord 2022; 24:195-206. [PMID: 34314549 PMCID: PMC8792096 DOI: 10.1111/bdi.13119] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 06/22/2021] [Accepted: 07/20/2021] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Literature on older-age bipolar disorder (OABD) is limited. This first-ever analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated associations among age, BD symptoms, comorbidity, and functioning. METHODS This analysis used harmonized, baseline, cross-sectional data from 19 international studies (N = 1377). Standardized measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Global Assessment of Functioning (GAF). RESULTS Mean sample age was 60.8 years (standard deviation [SD] 12.2 years), 55% female, 72% BD I. Mood symptom severity was low: mean total YMRS score of 4.3 (SD 5.4) and moderate-to-severe depression in only 22%. Controlled for sample effects, both manic and depressive symptom severity appeared lower among older individuals (p's < 0.0001). The negative relationship between older age and symptom severity was similar across sexes, but was stronger among those with lower education levels. GAF was mildly impaired (mean =62.0, SD = 13.3) and somatic burden was high (mean =2.42, SD = 1.97). Comorbidity burden was not associated with GAF. However, higher depressive (p < 0.0001) and manic (p < 0.0001) symptoms were associated with lower GAF, most strongly among older individuals. CONCLUSIONS Findings suggest an attenuation of BD symptoms in OABD, despite extensive somatic burden. Depressive symptom severity was strongly associated with worse functioning in older individuals, underscoring the need for effective treatments of BD depression in older people. This international collaboration lays a path for the development of a better understanding of aging in BD.
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Affiliation(s)
- Martha Sajatovic
- Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Annemiek Dols
- GGZ inGeest, Amsterdam UMC, VU Medical Center, Amsterdam Neuroscience, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
| | - Soham Rej
- Lady Davis Institute, McGill University, Montreal, Canada
| | | | - Alexandra J.M. Beunders
- GGZ inGeest, Amsterdam UMC, VU Medical Center, Amsterdam Neuroscience, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
| | - Hilary P. Blumberg
- Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA
| | - Farren B.S. Briggs
- Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Brent P. Forester
- Division of Geriatric Psychiatry, McLean Hospital, Belmont, Massachusetts, USA and Harvard Medical School, Boston, MA
| | - Regan E. Patrick
- Division of Geriatric Psychiatry, McLean Hospital, Belmont, MA, USA
| | - Orestes V. Forlenza
- Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | - Ariel Gildengers
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Esther Jimenez
- Bipolar and Depressive Disorders Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain
| | - Eduard Vieta
- Bipolar and Depressive Disorders Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain
| | - Benoit Mulsant
- Department of Psychiatry, University of Toronto, Center for Addiction & Mental Health, Toronto, Canada
| | - Sigfried Schouws
- GGZ ingest, Amsterdam UMC, VU Medical Center, Amsterdam, the Netherlands
| | - Nadine Paans
- GGZ inGeest, Amsterdam UMC, VU Medical Center, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
| | - Sergio Strejilevich
- AREA, Assistance and Research in Affective Disorders, Buenos Aires, Argentina
| | - Ashley Sutherland
- Department of Psychiatry, University of California San Diego, San Diego, CA, USA
| | - Shangying Tsai
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Betsy Wilson
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Lisa T. Eyler
- Department of Psychiatry, University of California San Diego, San Diego, CA, USA and Desert-Pacific Mental Illness Research Education and Clinical Center, VA San Diego Healthcare System, San Diego, CA, USA
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10
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Functional Remediation for Older Adults with Bipolar Disorder (FROA-BD): study protocol for a randomized controlled trial. REVISTA DE PSIQUIATRIA Y SALUD MENTAL 2022. [DOI: 10.1016/j.rpsm.2022.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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11
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Ljubic N, Ueberberg B, Grunze H, Assion HJ. Treatment of bipolar disorders in older adults: a review. Ann Gen Psychiatry 2021; 20:45. [PMID: 34548077 PMCID: PMC8456640 DOI: 10.1186/s12991-021-00367-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 09/04/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Old age bipolar disorder has been an orphan of psychiatric research for a long time despite the fact that bipolar disorder (BD)-I and II together may affect 0.5-1.0% of the elderly. It is also unclear whether aetiology, course of illness and treatment should differ in patients with a first manifestation in older age and patients suffering from a recurrence of a BD known for decades. This narrative review will summarize the current state of knowledge about the epidemiology, clinical features, and treatment of BD in the elderly. METHODS We conducted a Medline literature search from 1970 to 2021 using MeSH terms "Bipolar Disorder" × "Aged" or "Geriatric" or "Elderly". Search results were complemented by additional literature retrieved from examining cross references and by hand search in text books. Varying cut-off ages have been applied to differentiate old age from adult age BD. Within old age BD, there is a reasonable agreement of distinct entities, early and late-onset BD. They differ to some extent in clinical symptoms, course of illness, and some co-morbidities. Point prevalence of BD in older adults appears slightly lower than in working-age adults, with polarity of episodes shifting towards depression. Psychopharmacological treatment needs to take into account the special aspects of somatic gerontology and the age-related change of pharmacokinetic and pharmacodynamic characteristics. The evidence for commonly used treatments such as lithium, mood-stabilizing antiepileptics, antipsychotics, and antidepressants remains sparse. Preliminary results support a role of ECT as well as psychotherapy and psychosocial interventions in old age BD. CONCLUSIONS There is an obvious need of further research for all treatment modalities of BD in old age. The focus should be pharmacological and psychosocial approaches, as well as their combination, and the role of physical treatment modalities such as ECT.
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Affiliation(s)
- Nemanja Ljubic
- Bereich Forschung & Wissenschaft, LWL-Klinik, Marsbruchstr. 179, 44287, Dortmund, Germany
| | - Bianca Ueberberg
- Bereich Forschung & Wissenschaft, LWL-Klinik, Marsbruchstr. 179, 44287, Dortmund, Germany
| | - Heinz Grunze
- Psychiatrie Schwäbisch Hall, Ringstraße. 1, 74523, Schwäbisch Hall, Germany.
- Paracelsus Medical University, Ernst-Nathan Straße 1, 90419, Nuremberg, Germany.
| | - Hans-Jörg Assion
- Bereich Forschung & Wissenschaft, LWL-Klinik, Marsbruchstr. 179, 44287, Dortmund, Germany
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12
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Tyler E, Lobban F, Long R, Jones SH. Developing a recovery-focused therapy for older people with bipolar disorder: a qualitative focus group study. BMJ Open 2021; 11:e049829. [PMID: 34348954 PMCID: PMC8340279 DOI: 10.1136/bmjopen-2021-049829] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVES As awareness of bipolar disorder (BD) increases and the world experiences a rapid ageing of the population, the number of people living with BD in later life is expected to rise substantially. There is no current evidence base for the effectiveness of psychological interventions for older adults with BD. This focus group study explored a number of topics to inform the development and delivery of a recovery-focused therapy (RfT) for older adults with BD. DESIGN A qualitative focus group study. SETTING Three focus groups were conducted at a university in the North West of England. PARTICIPANTS Eight people took part in the focus groups; six older adults with BD, one carer and one friend. RESULTS Participant's responses clustered into six themes: (1) health-related and age-related changes in later life, (2) the experience of BD in later life, (3) managing and coping with BD in later life, (4) recovery in later life, (5) seeking helping in the future and (6) adapting RfT for older people. CONCLUSIONS Participants reported a range of health-related and age-related changes and strategies to manage their BD. Participants held mixed views about using the term 'recovery' in later life. Participants were in agreement that certain adaptations were needed for delivering RfT for older adults, based on their experience of living with BD in later life. The data collected as part of the focus groups have led to a number of recommendations for delivering RfT for older adults with BD in a randomised controlled trial (Clinical Trial Registration: ISRCTN13875321).
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Affiliation(s)
- Elizabeth Tyler
- Division of Health Research, Lancaster University, Lancaster, UK
| | - Fiona Lobban
- Division of Health Research, Lancaster University, Lancaster, UK
| | - Rita Long
- Division of Health Research, Lancaster University, Lancaster, UK
| | - Steven H Jones
- Division of Health Research, Lancaster University, Lancaster, UK
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13
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Abstract
Further understanding of older age bipolar disorder (OABD) may lead to more specific recommendations for treatment adjusted to the specific characteristics and needs caused by age-related somatic and cognitive changes. Late-onset mania has a broad differential diagnosis and requires full psychiatric and somatic work-up, including brain imaging. Research on pharmacotherapy in OABD is limited. First-line treatment of OABD is similar to that for adult bipolar disorder (BD), with specific attention to vulnerability to side effects and somatic comorbidity. Because findings in younger adults with BD cannot be extrapolated to OABD, more research in OABD is warranted.
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Affiliation(s)
- Annemiek Dols
- Department of Old Age Psychiatry, GGZinGeest and VUmc University Medical Center, Amstelveenseweg 589, 1081 JC, Amsterdam, The Netherlands; Mental Health Program, Amsterdam Public Health Research Institute, Van der Boechorstsstraat 7, 1081 BT, Amsterdam, The Netherlands; Mood, Anxiety and Psychosis Program, Amsterdam Neuroscience, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
| | - Aartjan Beekman
- Department of Old Age Psychiatry, GGZinGeest and VUmc University Medical Center, Amstelveenseweg 589, 1081 JC, Amsterdam, The Netherlands; Mental Health Program, Amsterdam Public Health Research Institute, Van der Boechorstsstraat 7, 1081 BT, Amsterdam, The Netherlands; Mood, Anxiety and Psychosis Program, Amsterdam Neuroscience, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands; Department of Psychiatry, GGZinGeest and VUmc University Medical Center, Amstelveenseweg 589, 1081 JC, Amsterdam, The Netherlands
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14
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Vedel Kessing L, Ziersen SC, Andersen PK, Vinberg M. A nationwide population-based longitudinal study mapping psychiatric disorders during lifetime in siblings to patients with bipolar disorder. Acta Psychiatr Scand 2021; 143:284-293. [PMID: 33258104 DOI: 10.1111/acps.13263] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Accepted: 11/24/2020] [Indexed: 12/21/2022]
Abstract
OBJECTIVE The aim was to map rates and cumulative incidences of psychiatric disorders during lifetime for siblings to patients with a diagnosis of bipolar disorder compared with the general population. METHODS Danish nationwide population-based longitudinal register linkage study including 13,923 unaffected siblings to 19,955 patients with bipolar disorder and 278,460 unaffected control individuals from the general population matched according to year of birth and sex. Follow-up covered 22 years from 1995 to 2017. RESULTS Rates of 'any psychiatric disorder' among siblings compared with control individuals were constantly around twofold increased throughout lifespan whereas there was a bimodal age distribution of hazard ratios of bipolar disorder, unipolar disorder and use of alcohol or psychoactive drugs with the highest hazard ratios up to age 20 and above 60 years of age. Cumulative incidences from age 15 years of any psychiatric disorder were 44.2% at age 80 years for siblings versus 27.6% for control individuals and the corresponding numbers for bipolar disorder was 8.7% for siblings compared with 1.6% for control individuals. CONCLUSION Strategies to prevent onset of psychiatric illness in individuals with a first-generation family history of bipolar disorder should not be limited to adolescence and early adulthood but should be lifetime, likely with differentiated age-specific strategies.
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Affiliation(s)
- Lars Vedel Kessing
- Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Copenhagen, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Simon Christoffer Ziersen
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark
| | - Per Kragh Andersen
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark
| | - Maj Vinberg
- Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Copenhagen, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Psychiatric Research Unit, Psychiatric Centre North Zealand, Hillerød, Denmark
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15
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Millischer V, Matheson GJ, Martinsson L, Römer Ek I, Schalling M, Lavebratt C, Backlund L. AKT1 and genetic vulnerability to bipolar disorder. Psychiatry Res 2020; 284:112677. [PMID: 31810747 DOI: 10.1016/j.psychres.2019.112677] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 10/31/2019] [Accepted: 11/03/2019] [Indexed: 11/26/2022]
Abstract
AKT1 encodes a serine/threonine kinase that has as one of its best-known substrates glycogen synthase kinase-3 (GSK3), a primary target for lithium. AKT1 has been previously been implicated as a vulnerability gene for bipolar disorder (BD). We aimed to associate genetic variants in the AKT1 gene with subgroups of BD. BD patients from a Swedish cohort (N = 831) were phenotyped in regards to their psychotic episodes according to mood-congruence in depression and manias, and compared to controls (N = 1,496). All participants were genotyped for SNPs in AKT1 previously implicated to have a role: rs3730358, rs1130214 and rs3803300. None of the effects reported in earlier studies were statistically significant, including the association between rs3803300 and BD without any psychotic symptoms, rs3803300 and mood-congruent psychosis, rs3803300 and the combined groups, as well as the association between the haplotypes formed by rs3730358 and rs1130214 and risk for BD. In a Bayesian analysis, all Bayes' Factors using default priors supported the null hypothesis in the replication set by a factor of between 5 and 1300 times. Analysis of genome wide association data did not reveal any association between BD and the AKT1 region. We conclude AKT1 is less likely to be a vulnerability gene in BD.
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Affiliation(s)
- Vincent Millischer
- Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
| | - Granville J Matheson
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Psychiatric Research and Education, Stockholm City Council, Sweden
| | - Lina Martinsson
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Psychiatric Research and Education, Stockholm City Council, Sweden
| | - Inger Römer Ek
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Psychiatric Research and Education, Stockholm City Council, Sweden
| | - Martin Schalling
- Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Catharina Lavebratt
- Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Lena Backlund
- Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Psychiatric Research and Education, Stockholm City Council, Sweden
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16
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Sajatovic M, Eyler LT, Rej S, Almeida OP, Blumberg HP, Forester BP, Forlenza OV, Gildengers A, Mulsant BH, Strejilevich S, Tsai S, Vieta E, Young RC, Dols A. The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project: Understanding older-age bipolar disorder by combining multiple datasets. Bipolar Disord 2019; 21:642-649. [PMID: 31081573 DOI: 10.1111/bdi.12795] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
OBJECTIVE There is a dearth of research about the aging process among individuals with bipolar disorder (BD). One potential strategy to overcome the challenge of interpreting findings from existing limited older-age bipolar disorder (OABD) research studies is to pool or integrate data, taking advantage of potential overlap or similarities in assessment methods and harmonizing or cross-walking measurements where different measurement tools are used to evaluate overlapping construct domains. This report describes the methods and initial start-up activities of a first-ever initiative to create an integrated OABD-focused database, the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project. METHODS Building on preliminary work conducted by members of the International Society for Bipolar Disorders OABD taskforce, the GAGE-BD project will be operationalized in four stages intended to ready the dataset for hypothesis-driven analyses, establish a consortium of investigators to guide exploration, and set the stage for prospective investigation using a common dataset that will facilitate a high degree of generalizability. RESULTS Initial efforts in GAGE-BD have brought together 14 international investigators representing a broad geographic distribution and data on over 1,000 OABD. Start-up efforts include communication and guidance on meeting regulatory requirements, establishing a Steering Committee to guide an incremental analysis strategy, and learning from existing multisite data collaborations and other support resources. DISCUSSION The GAGE-BD project aims to advance understanding of associations between age, BD symptoms, medical burden, cognition and functioning across the life span and set the stage for future prospective research that can advance the understanding of OABD.
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Affiliation(s)
- Martha Sajatovic
- Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, Ohio
| | - Lisa T Eyler
- Department of Psychiatry, University of California San Diego, San Diego, California.,Desert-Pacific Mental Illness Research Education and Clinical Center, VA San Diego Healthcare System, San Diego, California
| | - Soham Rej
- Lady Davis Insitute, McGill University, Montreal, Canada
| | | | | | - Brent P Forester
- McLean Hospital, Belmont, Massachusetts.,Harvard Medical School, Boston, MA
| | - Orestes V Forlenza
- Laboratory of Neuroscience (LIM-27), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | - Ariel Gildengers
- Ariel Gildengers, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Benoit H Mulsant
- Department of Psychiatry, Center for Addiction & Mental Health, University of Toronto, Toronto, Canada
| | - Sergio Strejilevich
- AREA, Assistance and Research in Affective Disorders, Buenos Aires, Argentina
| | - Shangying Tsai
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Eduard Vieta
- Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain
| | - Robert C Young
- Weill Cornell Medicine and New York-Presbyterian Hospital, White Plains, New York
| | - Annemiek Dols
- GGZ inGeest, Amsterdam UMC, location VU Medical Center, Amsterdam Neuroscience, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
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17
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Panse S, Parikh D. Quality of life in elderly bipolar disorder patients. JOURNAL OF GERIATRIC MENTAL HEALTH 2019. [DOI: 10.4103/jgmh.jgmh_37_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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18
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Older men with bipolar disorder diagnosed in early and later life: Physical health morbidity and general hospital service use. J Affect Disord 2018; 241:269-274. [PMID: 30138812 DOI: 10.1016/j.jad.2018.08.035] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 08/01/2018] [Accepted: 08/07/2018] [Indexed: 01/05/2023]
Abstract
BACKGROUND Bipolar disorder (BD) has been associated with greater health morbidity burden, but it is unclear if this association is affected by age at the time of diagnosis and how this might impact on the use of general hospital services. METHODS Cross-sectional study investigating the prevalence of common medical morbidities among participants with early (EOBD) and late onset diagnosis of BD (LOBD - age at diagnosis ≥ 60 years) derived from a community-representative sample of 37,183 men aged 65-85 years. Cohort study over a follow up period of up to 17.7 years investigating the hazard of general hospital use among older men associated with EOBD and LOBD taking into account age and prevalent medical morbidities. RESULTS 250 older men had a recorded diagnosis of BD, 75 of whom had LOBD. Diabetes, stroke and diseases of the respiratory and digestive systems were more frequent in men with than without BD. There were no differences in the distribution of medical morbidities between men with EOBD and LOBD. The adjusted hazard ratio (HR) of contact with general hospital services was significantly higher among men with EOBD (HR = 1.33; 95%CI = 1.14, 1.54) and LOBD (HR = 1.27, 95%CI = 1.06, 1.51) compared with older men without BD. Older men with EOBD had the highest number of contacts with general hospital services during follow up, although men with EOBD and LOBD did not differ in the number of contacts due to episodes of mania or depression. The medical reasons for contact with general hospital services of men with EOBD and LOBD overlapped but were not identical. CONCLUSIONS Older men with BD experience greater health morbidity than men without BD. Older men with BD access hospital services for the management of physical morbidities earlier and more frequently than men without BD. Age at the time of diagnosis of BD has limited impact on the risk of contact with general medical services, although subtle differences in the physical morbidity of men with EOBD and LOBD warrant further investigation.
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19
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Rowland TA, Marwaha S. Epidemiology and risk factors for bipolar disorder. Ther Adv Psychopharmacol 2018; 8:251-269. [PMID: 30181867 PMCID: PMC6116765 DOI: 10.1177/2045125318769235] [Citation(s) in RCA: 229] [Impact Index Per Article: 32.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 03/13/2018] [Indexed: 12/20/2022] Open
Abstract
Bipolar disorder is a multifactorial illness with uncertain aetiology. Knowledge of potential risk factors enables clinicians to identify patients who are more likely to develop bipolar disorder, which directs further investigation, follow up and caution when prescribing. Ideally, identifying directly causative factors for bipolar disorder would enable intervention on an individual or population level to prevent the development of the illness, and improve outcomes through earlier treatment. This article reviews the epidemiology of bipolar disorder, along with putative demographic, genetic and environmental risk factors, while assessing the strength of these associations and to what extent they might be said to be 'causative'. While numerous genetic and environmental risk factors have been identified, the attributable risk of individual factors is often small, and most are not specific to bipolar disorder but are associated with several mental illnesses. Therefore, while some genetic and environmental factors have strong evidence supporting their association with bipolar disorder, fewer have sufficient evidence to establish causality. There is increasing interest in the role of specific gene-environment interactions, as well as the mechanisms by which risk factors interact to lead to bipolar disorder.
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Affiliation(s)
- Tobias A Rowland
- Unit of Mental Health and Wellbeing, Division of Health Sciences, University of Warwick, Coventry, CV4 7AL, UK
| | - Steven Marwaha
- Division of Health Sciences, University of Warwick, Coventry, UK
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20
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Abstract
Further understanding of older age bipolar disorder (OABD) may lead to more specific recommendations for treatment adjusted to the specific characteristics and needs caused by age-related somatic and cognitive changes. Late-onset mania has a broad differential diagnosis and requires full psychiatric and somatic work-up, including brain imaging. Research on pharmacotherapy in OABD is limited. First-line treatment of OABD is similar to that for adult bipolar disorder (BD), with specific attention to vulnerability to side effects and somatic comorbidity. Because findings in younger adults with BD cannot be extrapolated to OABD, more research in OABD is warranted.
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Affiliation(s)
- Annemiek Dols
- Department of Old Age Psychiatry, GGZinGeest and VUmc University Medical Center, Amstelveenseweg 589, 1081 JC, Amsterdam, The Netherlands; Mental Health Program, Amsterdam Public Health Research Institute, Van der Boechorstsstraat 7, 1081 BT, Amsterdam, The Netherlands; Mood, Anxiety and Psychosis Program, Amsterdam Neuroscience, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
| | - Aartjan Beekman
- Department of Old Age Psychiatry, GGZinGeest and VUmc University Medical Center, Amstelveenseweg 589, 1081 JC, Amsterdam, The Netherlands; Mental Health Program, Amsterdam Public Health Research Institute, Van der Boechorstsstraat 7, 1081 BT, Amsterdam, The Netherlands; Mood, Anxiety and Psychosis Program, Amsterdam Neuroscience, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands; Department of Psychiatry, GGZinGeest and VUmc University Medical Center, Amstelveenseweg 589, 1081 JC, Amsterdam, The Netherlands
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Serafini G, Gonda X, Monacelli F, Pardini M, Pompili M, Rihmer Z, Amore M. Possible predictors of age at illness onset and illness duration in a cohort study comparing younger adults and older major affective patients. J Affect Disord 2018; 225:691-701. [PMID: 28917196 DOI: 10.1016/j.jad.2017.08.077] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 07/18/2017] [Accepted: 08/27/2017] [Indexed: 11/29/2022]
Abstract
BACKGROUND Major affective conditions are associated with significant disability and psychosocial impairment. Whether specific socio-demographic and clinical characteristics may distinguish subgroups of patients in terms of prognosis and illness trajectories is a matter of debate. METHODS The sample of this naturalistic cohort study included 675 currently euthymic patients with major affective disorders of which 428 (63.4%) were diagnosed with unipolar and 247 (36.6%) with bipolar disorders. RESULTS Younger adults with a longer duration of untreated illness and residual inter-episodic symptoms were more likely to be single or divorced, students, with an earlier age of first treatment/hospitalization, longer duration of substance abuse and duration of illness than older patients who were, conversely, more likely to be widowed and retired. Multivariate analyses showed a significant positive contribution to age at illness onset by marital status, nonpsychiatric medications, substance abuse, psychiatric diagnosis (bipolar vs. unipolar), age at first treatment/hospitalization, duration of illness, and current age. According to a further analysis, we also found a significant positive contribution to duration of illness by marital status, educational level, positive history of psychiatric conditions in family, substance abuse, psychiatric diagnosis (bipolar vs. unipolar), age at illness onset, age at first treatment, and certain cardiovascular disorders. CONCLUSIONS There are substantial socio-demographic and clinical differences that may help to distinguish specific subgroups of patients; however, additional studies are requested to replicate these results and further investigate the main factors underlying our findings.
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Affiliation(s)
- Gianluca Serafini
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy.
| | - Xenia Gonda
- Department of Psychiatry and Psychotherapy, Kutvolgyi Clinical Center, Semmelweis University, Budapest, Hungary; MTA-SE Neurochemistry and Neuropsychopharmacology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary; NAP-A-SE New Antidepressant Target Research Group, Semmelweis University, Hungary
| | - Fiammetta Monacelli
- Department of Internal Medicine and Medical Specialties, DIMI, Section of Geriatrics, Genoa, Italy
| | - Matteo Pardini
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy; Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa, Genoa, Italy
| | - Maurizio Pompili
- Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, Sant'Andrea Hospital, Sapienza University of Rome, Italy
| | - Zoltan Rihmer
- Department of Psychiatry and Psychotherapy, Kutvolgyi Clinical Center, Semmelweis University, Budapest, Hungary
| | - Mario Amore
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy
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García-López A, Ezquiaga E, De Dios C, Agud JL. Depressive symptoms in early- and late-onset older bipolar patients compared with younger ones. Int J Geriatr Psychiatry 2017; 32:201-207. [PMID: 27017999 DOI: 10.1002/gps.4465] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2015] [Revised: 01/23/2016] [Accepted: 02/18/2016] [Indexed: 11/08/2022]
Abstract
OBJECTIVES The aim of this study was to determine clinical and outcome differences between older bipolar patients with early onset (EO) and late onset (LO) of the illness and between younger and EO older patients with a bipolar disorder under long-term treatment in an outpatient clinical setting. METHODS Three hundred ninety-five bipolar I and II outpatients were followed up for up to 7.7 years. Of these, 213 younger (<50 years) and 88 older (>60 years) patients were included. In the older subsample, 50 EO patients (onset <50 years) versus 38 LO patients (≥50 years) were analyzed. Likewise, younger versus EO older patients were compared. RESULTS The likelihood of LO older patients of being bipolar II was higher than for EO older patients. They were also diagnosed earlier than EO older patients. No other clinical differences at baseline and at the prospective follow-up were found. Compared with younger patients, EO older patients had more frequent depressive symptoms at baseline, suffered more major depressive episodes in the previous year and in the prospective follow-up, received more antidepressants at baseline, had higher rates of medical comorbid conditions and were less likely to be tobacco smokers. CONCLUSIONS Older patients constitute a meaningful proportion of bipolar patients under treatment. EO older patients suffered significantly from more frequent depressive symptoms than younger ones. LO older patients were predominantly bipolar II. So as bipolar illness progressed, depressive symptomatology became more frequent and manic episodes were less severe. Copyright © 2016 John Wiley & Sons, Ltd.
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Affiliation(s)
| | - Elena Ezquiaga
- Department of Psychiatry, University Hospital La Princesa, Madrid, Spain
| | - Consuelo De Dios
- Department of Psychiatry, University Hospital La Paz, Madrid, Spain
| | - Jose Luis Agud
- Department of Internal Medicine, University Hospital Severo Ochoa, Madrid, Spain
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Sajatovic M, Strejilevich SA, Gildengers AG, Dols A, Al Jurdi RK, Forester BP, Kessing LV, Beyer J, Manes F, Rej S, Rosa AR, Schouws SNTM, Tsai SY, Young RC, Shulman KI. A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force. Bipolar Disord 2015; 17:689-704. [PMID: 26384588 PMCID: PMC4623878 DOI: 10.1111/bdi.12331] [Citation(s) in RCA: 148] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2015] [Accepted: 07/24/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVES In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the International Society for Bipolar Disorder (ISBD) Task Force on Older-Age Bipolar Disorder (OABD). METHODS This task force report addresses the unique aspects of OABD including epidemiology and clinical features, neuropathology and biomarkers, physical health, cognition, and care approaches. RESULTS The report describes an expert consensus summary on OABD that is intended to advance the care of patients, and shed light on issues of relevance to BD research across the lifespan. Although there is still a dearth of research and health efforts focused on older adults with BD, emerging data have brought some answers, innovative questions, and novel perspectives related to the notion of late onset, medical comorbidity, and the vexing issue of cognitive impairment and decline. CONCLUSIONS Improving our understanding of the biological, clinical, and social underpinnings relevant to OABD is an indispensable step in building a complete map of BD across the lifespan.
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Affiliation(s)
- Martha Sajatovic
- Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, OH, USA
| | - Sergio A Strejilevich
- Bipolar Disorder Program, Neurosciences Institute, Favaloro University, Buenos Aires, Argentina
| | - Ariel G Gildengers
- Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA, USA
| | - Annemiek Dols
- GGZinGeest, VU Medical Center, Amsterdam, the Netherlands
| | - Rayan K Al Jurdi
- Michael E. DeBakey VA Medical Center, Houston, TX, USA
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA
| | - Brent P Forester
- Geriatric Psychiatry Research Program, McLean Hospital, Harvard Medical School, Boston, MA, USA
| | - Lars Vedel Kessing
- Psychiatric Centre Copenhagen, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - John Beyer
- Duke University Medical Center, Durham, NC, USA
| | - Facundo Manes
- Laboratory of Experimental Psychology and Neuroscience (LPEN), Institute of Cognitive Neurology (INECO), Favaloro University, Buenos Aires, Argentina
- UPD-INECO Foundation Core on Neuroscience (UNIFCoN), Chile
- National Scientific and Technical Rsearch Council (CONICET), Argentina
- Australian Research Council Centre of Excellence in Cognition and its Disorders, Australia
| | - Soham Rej
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Geri PARTy Research Group, Jewish General Hospital, Montreal, QC, Canada
| | - Adriane R Rosa
- Federal University of Rio Grande do Sul, Brazil
- Department of Pharmacology, Laboratory of Molecular Psychiatry, INCT for Translational Medicine–CNPq, Hospital de Clínicas de Porto Alegre, Brazil
| | - Sigfried NTM Schouws
- GGZ inGeest, Department of Psychiatry, EMGO Institute of Care and Health Research, VU University Medical Center, Amsterdam, the Netherlands
| | - Shang-Ying Tsai
- Department of Psychiatry, Taipei Medical University Hospital
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Robert C Young
- Weill Cornell Medical College and New York Presbyterian Hospital, White Plains, NY, USA
| | - Kenneth I Shulman
- Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
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Forester BP, Ajilore O, Spino C, Lehmann S. Clinical Characteristics of Patients with Late Life Bipolar Disorder in the Community: Data from the NNDC Registry. Am J Geriatr Psychiatry 2015; 23:977-84. [PMID: 25670662 PMCID: PMC4503521 DOI: 10.1016/j.jagp.2015.01.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Revised: 01/05/2015] [Accepted: 01/06/2015] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To compare clinical characteristics of older and younger patients with bipolar disorder enrolled in the United States' National Network of Depression Centers (NNDC) Clinical Care Registry (CCR). DESIGN Multicenter, de-identified naturalistic data from the National NNDC's CCR for all patients with a diagnosis of bipolar disorder who were enrolled in the registry as of April 25, 2013. PARTICIPANTS Community-dwelling patients (N = 218), ages 18 years or older, with bipolar disorder diagnosis recruited by NNDC-affiliated medical centers to participate in the NNDC CCR. Subjects aged 55 years or older were compared with subjects younger than age 55 years on clinical measures. MEASUREMENTS Patient Health Questionnaire; Quick Inventory of Depressive Symptomatology - Self-Report; Altman Self-Rating Mania Scale; Work and Social Adjustment Scale; Frequency and Intensity of Burden of Side Effects Rating; and the Self-Administered Comorbidity Questionnaire. RESULTS A greater percentage of older patients were prescribed antidepressant medications (71.9% versus 50.0%), and the younger cohort had significantly more psychostimulant use (16.7% versus 0%). Younger patients endorsed significantly more depressive symptoms compared with older patients. The mean number of psychotropic medications was not different in both older and younger patients with bipolar disorder. There was no statistically significant difference in frequency, intensity, or burden of psychotropic medication side effects as measured by the Frequency and Intensity of Burden of Side Effects Rating. CONCLUSION Findings of higher antidepressant use rates in the older cohort, combined with lower depression symptom severity and a similar degree of manic symptoms, suggests the possibility that older adults with bipolar disorder may have improved antidepressant efficacy and lower switch rates into manic or mixed states compared with younger cohorts. Ongoing data collection by the NNDC CCR will add to current knowledge to inform the care of older patients with bipolar disorder by providing multi-site data regarding phenomenology, treatment response, and longitudinal course of late life bipolar disorder in community settings.
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25
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Kessing LV, Vradi E, Andersen PK. Life expectancy in bipolar disorder. Bipolar Disord 2015; 17:543-8. [PMID: 25846854 DOI: 10.1111/bdi.12296] [Citation(s) in RCA: 122] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2014] [Revised: 01/02/2015] [Accepted: 01/23/2015] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Life expectancy in patients with bipolar disorder has been reported to be decreased by 11 to 20 years. These calculations are based on data for individuals at the age of 15 years. However, this may be misleading for patients with bipolar disorder in general as most patients have a later onset of illness. The aim of the present study was to calculate the remaining life expectancy for patients of different ages with a diagnosis of bipolar disorder. METHODS Using nationwide registers of all inpatient and outpatient contacts to all psychiatric hospitals in Denmark from 1970 to 2012 we calculated remaining life expectancies for values of age 15, 25, 35 ⃛ 75 years among all individuals alive in year 2000. RESULTS For the typical male or female patient aged 25 to 45 years, the remaining life expectancy was decreased by 12.0-8.7 years and 10.6-8.3 years, respectively. The ratio between remaining life expectancy in bipolar disorder and that of the general population decreased with age, indicating that patients with bipolar disorder start losing life-years during early and mid-adulthood. CONCLUSIONS Life expectancy in bipolar disorder is decreased substantially, but less so than previously reported. Patients start losing life-years during early and mid-adulthood.
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Affiliation(s)
- Lars Vedel Kessing
- Psychiatric Center Copenhagen, Department O, University of Copenhagen, Copenhagen, Denmark
| | - Eleni Vradi
- Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark
| | - Per Kragh Andersen
- Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark
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Sajatovic M, Dines P, Fuentes-Casiano E, Athey M, Cassidy KA, Sams J, Clegg K, Locala J, Stagno S, Tatsuoka C. Asenapine in the treatment of older adults with bipolar disorder. Int J Geriatr Psychiatry 2015; 30:710-9. [PMID: 25335125 PMCID: PMC4830381 DOI: 10.1002/gps.4213] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2014] [Accepted: 08/19/2014] [Indexed: 11/10/2022]
Abstract
OBJECTIVE In spite of growing numbers of older people, there are few treatment studies on late-life bipolar disorder (BD). This was a 12-week prospective, open-label trial to assess efficacy and tolerability of adjunct asenapine in non-demented older adults (≥ 60 years) with sub-optimal previous response to BD treatments. METHODS Asenapine was initiated at 5 mg/day and titrated as tolerated. Effects on global psychopathology were measured with Clinical Global Impression, bipolar version (CGI-BP), and the Brief Psychiatric Rating Scale (BPRS). Mood polarity severity was measured with the Hamilton Depression Rating Scale, Montgomery Asberg Depression Rating Scale, and Young Mania Rating Scale. Other outcomes included the World Health Organization Disability Assessment Schedule II. RESULTS Fifteen individuals were enrolled (mean age 68.6, SD 6.12; 53% female; 73% Caucasian, 13% African American, and 7% Asian). There were 4/15 (27%) individuals who prematurely terminated the study, whereas 11/15 (73%) completed the study. There were significant improvements from baseline on the BPRS (p < 0.05), on CGI-BP overall (p < 0.01), and on CGI-BP mania (p < 0.05) and depression (p < 0.01) subscales. The mean dose of asenapine was 11.2 (SD 6.2) mg/day. The most common reported side effects were gastrointestinal discomfort (n = 5, 33%), restlessness (n = 2, 13%), tremors (n = 2, 13%), cognitive difficulties (n = 2, 13%), and sluggishness (n = 2, 13%). CONCLUSIONS Older people with BD had global improvements on asenapine. Most reported adverse effects were mild and transient, but adverse effects prompted drug discontinuation in just over one quarter of patients. Although risks versus benefits in older people must always be carefully considered, asenapine may be a treatment consideration for some non-demented geriatric BD patients.
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Affiliation(s)
- Martha Sajatovic
- Department of Psychiatry and Neurological and Behavioral Outcomes Center, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, U.S.A
| | - Philipp Dines
- Department of Psychiatry, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, U.S.A
| | - Edna Fuentes-Casiano
- Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, Ohio
| | - Melanie Athey
- Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, Ohio, USA
| | - Kristin A. Cassidy
- Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, Ohio, USA
| | - Johnny Sams
- Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, Ohio, USA
| | - Kathleen Clegg
- Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, Ohio, USA
| | - Joseph Locala
- Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, Ohio, USA
| | - Susan Stagno
- Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, Ohio, USA
| | - Curtis Tatsuoka
- Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, Ohio
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Abstract
Psychosis is one of the most common conditions in later life with a lifetime risk of 23 %. Despite its high prevalence, late-onset psychosis remains a diagnostic and treatment dilemma. There are no reliable pathognomonic signs to distinguish primary or secondary psychosis. Primary psychosis is a diagnosis of exclusion and the clinician must rule out secondary causes. Approximately 60 % of older patients with newly incident psychosis have a secondary psychosis. In this article, we review current, evidence-based diagnostic and treatment approaches for this heterogeneous condition, emphasizing a thorough evaluation for the "six d's" of late-life psychosis (delirium, disease, drugs dementia, depression, delusions). Treatment is geared towards the specific cause of psychosis and tailored based on comorbid conditions. Frequently, environmental and psychosocial interventions are first-line treatments with the judicious use of pharmacotherapy as needed. There is an enormous gap between the prevalence of psychotic disorders in older adults and the availability of evidence-based treatment. The dramatic growth in the elderly population over the first half of this century creates a compelling need to address this gap.
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Oostervink F, Nolen WA, Kok RM. Two years' outcome of acute mania in bipolar disorder: different effects of age and age of onset. Int J Geriatr Psychiatry 2015; 30:201-9. [PMID: 24798245 DOI: 10.1002/gps.4128] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2013] [Accepted: 03/26/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND Information about differences between younger and older patients with bipolar disorder and between older patients with early and late age of onset of illness during long-term treatment is scarce. OBJECTIVES This study aimed to investigate the differences in treatment and treatment outcome between older and younger manic bipolar patients and between early-onset bipolar (EOB) and late-onset bipolar (LOB) older patients. METHOD The European Mania in Bipolar Longitudinal Evaluation of Medication study was a 2-year prospective, observational study in 3459 bipolar patients on the treatment and outcome of patients with an acute manic or mixed episode. Patients were assessed at 6, 12, 18, and 24 months post-baseline. We calculated the number of patients with a remission, recovery, relapse, and recurrence and the mean time to achieve this. RESULTS Older patients did not differ from younger bipolar patients in achieving remission and recovery or suffering a relapse and in the time to achieve this. However, more older patients recurred and in shorter time. Older patients used less atypical antipsychotics and more antidepressants and other concomitant psychiatric medication. Older EOB and LOB patients did not differ in treatment, but more older LOB patients tended to recover than older EOB patients. CONCLUSION Older bipolar manic patients did not differ from younger bipolar patients in short-term treatment outcome (remission and recovery), but in the long term, this may be more difficult to maintain. Distinguishing age groups in bipolar study populations may be useful when considering treatment and treatment outcome and warrants further study.
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Affiliation(s)
- Frits Oostervink
- Department of Old Age Psychiatry, GGZ Haagstreek (Rivierduinen), Leidschendam, The Netherlands
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29
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Nivoli AMA, Murru A, Pacchiarotti I, Valenti M, Rosa AR, Hidalgo D, Virdis V, Strejilevich S, Vieta E, Colom F. Bipolar disorder in the elderly: a cohort study comparing older and younger patients. Acta Psychiatr Scand 2014; 130:364-73. [PMID: 24702648 DOI: 10.1111/acps.12272] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/07/2014] [Indexed: 12/25/2022]
Abstract
OBJECTIVE The purpose of this study was to analyze differences in clinical and socio-demographic characteristics between older and younger bipolar outpatients paying special attention to depressive symptoms in a large, naturalistic cohort. METHOD Five hundred and ninety-three DSM-IV-TR bipolar outpatients were enrolled. Clinical characteristics were assessed according to DSM-IV-TR (SCID-I). Subjects were categorized into two groups according to current age (older OBD: age > 65 years; younger-YBD: age < 65 years). RESULTS About 80% of patients were younger (N = 470), and a fifth were older (N = 123), with a mean age of 77.30 years in OBD. Older patients were more likely to be married, not qualified, bipolar II, with depressive polarity of first episode, higher age at illness onset, higher age at first hospitalization. They were more likely to present with depressive predominant polarity, with lifetime history of catatonic, psychotic and melancholic features, age at illness onset >40 years, as well as suffering from more medical comorbidities when compared to younger bipolars. CONCLUSION The clinical presentation of bipolar disorder in late life would be defined more frequently by melancholic depressive features and a predominantly depressive polarity. These results suggest that treatment strategies for elderly bipolar patients should focus in the prevention of depressive episodes.
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Affiliation(s)
- A M A Nivoli
- Bipolar Disorders Unit, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; Department of Neuroscience, Institute of Psychiatry, University of Sassari, Sassari, Italy
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30
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Ostergaard SD, Bertelsen A, Nielsen J, Mors O, Petrides G. The association between psychotic mania, psychotic depression and mixed affective episodes among 14,529 patients with bipolar disorder. J Affect Disord 2013; 147:44-50. [PMID: 23122529 DOI: 10.1016/j.jad.2012.10.005] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2012] [Revised: 10/06/2012] [Accepted: 10/06/2012] [Indexed: 12/23/2022]
Abstract
BACKGROUND Psychotic and mixed affective episodes are prevalent in the course of bipolar disorder. Despite many studies on the implications of psychotic mania (PM), psychotic depression (PD) and mixed affective episodes (MAE), relatively little is known about the relationship between the three subtypes. The present study aimed to investigate whether the occurrence of PM, PD and MAE were associated with one another. METHODS This is a nationwide register-based, historical prospective cohort study. Data was obtained from the Danish Psychiatric Central Research Register. Subjects were defined as all individuals assigned with an ICD-10 diagnosis of bipolar disorder between January 1st 1994 and December 31st 2010. Potential associations among psychotic and mixed affective episodes were tested by means of logistic regression. RESULTS We identified 14,529 individuals with bipolar disorder with lifetime incidences of PM, PD and MAE of 19%, 15% and 17% respectively. We detected significant associations between PM and MAE (Adjusted Odds Ratio (AOR)=1.26, p=0.003), PD and MAE (AOR=1.24, p=0.001), and PM and PD (AOR=1.28, p=0.005). LIMITATIONS Diagnoses were assigned as part of routine clinical practice. CONCLUSIONS According to this register-based study, PD, PM and MAE are all associated with one another. This knowledge should be taken into consideration by clinicians when monitoring patients with bipolar disorder and by nosologists when defining the criteria and potential subtypes for mixed affective episodes for the upcoming DSM-5 and ICD-11.
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Affiliation(s)
- Søren Dinesen Ostergaard
- Unit For Psychiatric Research, Aalborg Psychiatric Hospital, Aarhus University Hospital, Aalborg, Denmark.
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Kroon JS, Wohlfarth TD, Dieleman J, Sutterland AL, Storosum JG, Denys D, de Haan L, Sturkenboom MCJM. Incidence rates and risk factors of bipolar disorder in the general population: a population-based cohort study. Bipolar Disord 2013; 15:306-13. [PMID: 23531096 DOI: 10.1111/bdi.12058] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2011] [Accepted: 10/20/2012] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To estimate the incidence rates (IRs) of bipolar I and bipolar II disorders in the general population according to sociodemographic population characteristics. METHODS A cohort study (during the years 1996-2007) was conducted in a general practitioners research database with a longitudinal electronic record of 800000 patients throughout the Netherlands [the Integrated Primary Care Information (IPCI) database]. Cases of bipolar disorder were identified and classified by systematic review of medical records. Age- and gender-specific IRs were calculated per calendar year, degree of urbanization, and degree of deprivation. RESULTS The overall IR of bipolar disorder was 0.70/10000 person-years (PY) [95% confidence interval (CI): 0.57-0.83]; the IR of bipolar I disorder was 0.43/10000 PY (95% CI: 0.34-0.55) and the IR of bipolar II disorder was 0.19/10000 PY (95% CI: 0.13-0.27). Two peaks in the age at onset of the disorder were noticed: one in early adulthood (15-24 years; 0.68/10000 PY) and a larger peak in later life (45-54 years; 1.2/10000 PY). In bipolar II disorder, only one peak, in the 45-54 year age category (IR 0.42/10000 PY), was found. The IRs of bipolar disorder were significantly higher in deprived areas. Similar rates were found for men compared to women and in urban compared to rural areas. No association was found between the onset of first (hypo)manic episode and month or season of birth. CONCLUSIONS We found two peaks in the age at onset of bipolar disorder, one in early adulthood and one in later life, the former consisting mainly of bipolar I disorder subjects. The incidence of bipolar disorder is higher in deprived areas. The onset of bipolar disorder is not associated with gender, urbanization, or month or season of birth.
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Affiliation(s)
- Jojanneke S Kroon
- Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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32
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Abstract
The ageing of the population brings particular challenges to psychiatric practice. Although the clinical presentation of common psychiatric disorders such as mood and psychotic disorders is largely similar to those in younger adults, late life presentations tend to be more complex as co-morbidity with dementia and physical illness is common. Suicide tends to increase with age in most countries. In this chapter we argue that the aetiology of disorders may be best understood within a stress vulnerability model in which neurobiological and psychosocial factors interplay. We further present that management strategies need to be comprehensive, incorporating physical, social, pharmacological, and psychological treatments appropriate to each case. We close with a call for the use of specialised multi-disciplinary services to improve the overall quality of care.
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Affiliation(s)
- C Wijeratne
- School of Psychiatry, University of New South Wales, Sydney, Australia
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33
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Abstract
Because the elderly are the fastest growing segment of the population, the number of older adults with bipolar disorder is increasing. Geriatric bipolar disorder is relatively rare, with an estimated lifetime prevalence of 0.5% to 1%, although approximately 4% to 17% of older patients in clinical psychiatric settings have bipolar disorder. Bipolar elders are disproportionately affected by medical burden. Given the complex nature of this disorder, comorbidity, and behavioral disturbances, various interventions may be indicated, including pharmacotherapies, electroconvulsive therapy, psychotherapies, and integrated care models. Additional research is needed to better understand the epidemiology, phenomenology, and treatment of geriatric bipolar disorder.
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Affiliation(s)
- Martha Sajatovic
- Department of Psychiatry, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
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34
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Retraso diagnóstico y diferencias por sexo y subtipo clínico en una cohorte de pacientes ambulatorios con trastorno bipolar. REVISTA DE PSIQUIATRIA Y SALUD MENTAL 2010; 3:79-89. [DOI: 10.1016/j.rpsm.2010.03.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2010] [Revised: 03/19/2010] [Accepted: 03/24/2010] [Indexed: 11/21/2022]
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The faultline activation process and the effects of activated faultlines on coalition formation, conflict, and group outcomes. ORGANIZATIONAL BEHAVIOR AND HUMAN DECISION PROCESSES 2010. [DOI: 10.1016/j.obhdp.2009.11.008] [Citation(s) in RCA: 168] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Oostervink F, Boomsma MM, Nolen WA. Bipolar disorder in the elderly; different effects of age and of age of onset. J Affect Disord 2009; 116:176-83. [PMID: 19087895 DOI: 10.1016/j.jad.2008.11.012] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2008] [Revised: 11/14/2008] [Accepted: 11/14/2008] [Indexed: 11/16/2022]
Abstract
BACKGROUND Information about differences between younger and elderly patients with bipolar disorder and between elderly patients with early and late age of onset of illness is limited. METHOD The European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) study was a 2-year prospective, observational study in 3459 bipolar patients on the treatment and outcome of patients with an acute manic or mixed episode. Within this study, elderly patients (>60 years of age; n=475) were compared with younger patients (<50 years of age; n=2286), and within the elderly group, Late Onset Bipolar (LOB) patients (onset > or =50 years; n=141) were compared with Early Onset Bipolar (EOB) patients (<50 years; n=323). RESULTS In the year prior to enrollment, elderly patients, especially those with EOB, more frequently reported a rapid cycling course of illness, but fewer suicide attempts. At baseline, elderly patients more often used one psychotropic medication and demonstrated less severe manic and psychotic symptoms, but no difference in depressive symptomatology. However, prior to enrollment and during the acute phase of treatment, elderly patients more frequently received antidepressants. Atypical antipsychotics were given less frequently. Regarding 12-week outcomes, there was no difference between elderly and younger patients, although LOB elderly recovered faster, and were discharged sooner than EOB elderly patients. LIMITATIONS Information about somatic conditions was not systematically collected nor was information about concurrent use of non-psychiatric medication which might have given some indication of somatic comorbidity. CONCLUSION Elderly bipolar manic patients differ from younger bipolar manic patients regarding treatment but not treatment outcome. LOB elderly patients demonstrated a more favourable outcome. The use of medication and the occurrence of rapid cycling in EOB elderly patients warrant further study.
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Affiliation(s)
- Frits Oostervink
- GGZ Haagstreek Department of Psychiatry, Leidschendam, The Netherlands.
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Abstract
PURPOSE OF REVIEW To follow up on reviews of case register research. Literature searches over a 2-year period were conducted to determine whether psychiatric case registers still have a role for research and service monitoring. RECENT FINDINGS Case register research covers a wide range of topics, and is most often found in Denmark where national databases support all kinds of record linkage studies. Typically, case registers are used in studies of treated prevalence and incidence of psychiatric disorders, in research on patterns of care, as sampling frames in epidemiological studies, and in studies on risk factors and treatment outcome. SUMMARY Despite a wide range of research based on administrative data, stakeholders in most countries are probably not well served by current priorities. Few studies investigate longitudinal patterns of service use to evaluate healthcare policies. There is a lack of comparative record linkage studies to inform local authorities on the cooperation between mental healthcare and public services. Implementing standard tools and procedures for routine outcome assessment seems still to be in an early phase in most register areas. When case register staff can capitalize on new opportunities, old and new case registers will continue to be important for research and service monitoring.
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