Depression and Depressive Symptoms in Advanced Cancer Patients - Assessment, Classification and Treatment

Summary in Norwegian: Depresjon og symptomer på depresjon – kartlegging, klassifisering og behandling Depresjon og depressive symptomer er en belastning for pasienter med langtkommen kreft. Anslag som er gjort av forekomsten av depresjon hos pasienter med langtkommen kreft, varierer veldig; fra 3 til 58 %. Depresjon er dessuten ofte underdiagnostisert og underbehandlet til tross for at det finnes diagnostiske systemer og kliniske retningslinjer for depresjon. Hovedmålet med denne avhandlingen er å bidra til å forbedre kartlegging, klassifisering og behandling av depresjon og depressive symptomer hos pasienter med langtkommen kreft. Tre forskjellige studier ble gjennomført: en systematisk litteraturgjennomgang, en tverrsnittstudie av et stort antall europeiske kreftpasienter og en retrospektiv studie basert på legers observasjon av kreftpasienter i deres siste levedøgn. Variasjonen i anslagene av forekomsten av depresjon hos pasienter med langtkommen kreft, kan være relatert til kartleggingsmetoder, men også til heterogeniteten til studiepopulasjonen med hensyn til for eksempel alder, diagnose, spredning av kreftsykdommen og overlevelse. Presis beskrivelse av pasientpopulasjonener nødvendig for å kunne sammenligne resultater på tvers av studier og overføre forskningsfunn til klinisk praksis. Hovedproblemstillingen i den systematiske litteraturgjennomgangen var: Hvordan blir populasjoner av pasienter med langtkommen kreft karakterisert i studier om depresjon og symptomer på depresjon? Den systematiske litteraturgjennomgangen viste at de hyppigst rapporterte variablene i de inkluderte studiene var alder (93 %), kjønn (90 %) og kreftstadium (95 %). Depresjonsrelaterte variabler, som bruk av antidepressiva, ble rapportert i 17 % av studiene, mens tidligere depresjonsepisoder ble rapportert i 12 %. En annen mulig årsak til variasjonen i anslagene av forekomst kan være mangel på en standard for å definere og kartlegge depresjon hos pasienter med langtkommen kreft. Derfor er tydelige beskrivelser av metoder for kartlegging og klassifisering nødvendig for å bedømme hvorvidt studiefunnene er relevante for klinisk praksis. Den andre problemstillingen for den systematiske litteraturstudien var: Hvordan blir depresjon kartlagt og klassifisert i kliniske studier av pasienter med langtkommen kreft? Litteraturstudien konkluderte med at 25 % av studiene brukte validerte diagnostiske systemer for å klassifisere depresjon, for eksempel DSM og ICD klassifiseringssystem som bruker strukturerte og semistrukturerte intervju. 75 % av studiene brukte ikke et validert diagnostiseringssystem. De brukte imidlertid selv-rapporteringsverktøy som Hospital Anxiety and Depression Scale og forskjellige versjoner av the Beck Depression Inventory. Det er altså stor variasjon i hvordan populasjonog kartleggingsmetoder blir beskrevet i studier av pasienter med langtkommen kreft og depresjon. En mer standardisert praksis er nødvendig for å forbedre generaliserbarheten og øke nytten av forskningsfunn. Sentrale aktører i fagfeltet bør oppmuntres til å utvikle anbefalinger for hvordan å beskrive pasientpopulasjon og hvilke kartleggingsmetoder som bør brukes i framtidige studier. Farmakologiske intervensjoner, som antidepressiva, behandler depressive lidelser hos kreftpasienter effektivt. Likevel blir langt fra alle kreftpasienter som har fått en depresjonsdiagnose, behandlet med antidepressiva. Hovedproblemstillingen i den andre studien, en internasjonal tverrsnittstudie (n=1048), var: Hva er forekomsten av bruken av antidepressiva blant pasienter med langtkommen kreft inkludert i en internasjonal multisenterstudie? Denne tverrsnittstudien rapporterte at forekomsten av bruken av antidepressiva var 14 % i et internasjonalt bekvemmelighetsutvalg av kreftpasienter med langtkommen kreft. Vi har manglet informasjon om hva som karakteriserer pasienter med langtkommen kreft som får behandling med antidepressiva. Derfor var den andre problemstillingen i tverrsnittstudien: Hvilke sosialdemografiske og medisinske variabler er assosiert med bruken av antidepressiva i pasienter med langtkommen kreft i en internasjonal multisenterstudie? I denne store internasjonale tverrsnittstudien ble følgende assosiert med bruk av antidepressiva mot depresjon hos pasienter med langtkommen kreft: ung alder, å være kvinne, bruk av smertestillende og tre eller flere komorbiditeter. Sykdomsrelaterte variabler som diagnose, stadium, allmenntilstand og overlevelsestid, var ikke assosiert med bruk av antidepressiva. Det mangler imidlertid fortsatt pålitelig informasjon om hvilke variabler som har innvirkning på legenes praksis med å foreskrive antidepressiva. Kreftpasienter som nærmer seg livets slutt, kan oppleve depresjon eller depressive symptomer. Det er imidlertid vanskelig å bedømme om pasientene opplever en normal dødsprosess, eller om det er en depresjon. Forskningsspørsmålet i den tredje studien, en retrospektiv dødsatteststudie (n=1363), var: Hva er forekomsten av depressive symptomer hos nederlandske pasienter med kreft det siste døgnet av livet i følge behandlende leges vurdering? Resultatene viste at forekomsten av depressive symptomer hos pasienter med kreft de siste 24 timene av livet var 37,6 %. Blant disse ble mild/moderat grad av depresjon registrert i 31,8 % og alvorlig/veldig alvorlig i 5,8 %. For å undersøke nærmere hva som kjennetegner kreftpasienter med depressive symptomer, ble følgende problemstilling adressert i samme studie: Er det en sammenheng mellom symptomer på depresjon og forskjellige sosialdemografiske variabler, kjennetegn ved pleie og symptomer i nederlandske kreftpasienter de siste 24 timene av levetiden? Det var en signifikant sammenheng mellom utmattelse og forvirring og milde/moderate symptomer på depresjon, mens angst var assosiert med både milde/moderate og alvorlige/veldig alvorlige symptomer på depresjon. Det at en spesialist i smerte eller palliasjon og psykiater/psykolog var involvet i behandlingen var assosiert med at legene hyppigere vurderte at pasientene hadde alvorlige/veldig alvorlige symptomer på depresjon. Det er fortsatt behov for økt oppmerksomhet mot subjektive symptomer, inkludert depressive symptomer, hos pasienter med langtkommen kreft. Denne avhandlingen viser at det er nødvendig å øke helsepersonells kunnskap om kartlegging, klassifisering og behandling av depresjon og depressive symptomer hos pasienter med langtkommen kreft. Dette vil bidra til å optimalisere behandling og pleie til pasienter med kreft gjennom hele sykdomsforløpet.Summary in English: Depression and depressive symptoms are burdensome in patients with advanced cancer. Prevalence rate estimates of depression in patients with advanced cancer vary greatly; from 3% to 58%.Furthermore, depression is often under diagnosed and under treated despite existing diagnostic systems and clinical guidelines for depression. The overall aim of this thesis is to contribute to improve assessment, classification and treatment of depression and depressive symptoms in patients with advanced cancer. Therefore, the steps described below were undertaken by three different studies; one systematic literature review, one cross-sectional study of a large sample of European patients with advanced cancer and one retrospective study based upon physicians’ observations of cancer patients at end of life. The variation in prevalence rates of depression in advanced cancer patients may be related to assessment methods, but also to the heterogeneity of the population studied with regard to for example age, diagnosis, extent of cancer disease, and survival. A precise characterisation of the study sample is needed to be able to compare results across studies and transfer research findings to clinical practice. The main research question in the systematic literature review was: How are populations of advanced cancer patients characterised in studies of depression and depressive symptoms? The systematic literature review revealed that the most frequently reported variables in the included studies were age (93%), gender (90%), and stage of cancer disease (95%). Depression-related variables such as use of antidepressants were reported in 17% of the studies and previous depressive episodes in 12%. Another possible reason for different prevalence rate estimates could be lack of agreed upon standards for defining and assessing depression in patients with advanced cancer. Therefore clear descriptions of the assessment and classification methods are necessary to judge the relevance of the study findings for clinical practice. A second research question in the systematic review was: How is depression assessed and classified in clinical studies in patients with advanced cancer? The systematic literature review concluded that 25% of the studies used validated diagnostic systems for classifying depression such as DSM and ICD classification system using structured and semi-structured interviews. 75% of the studies did not use a validated diagnostic system; however they used self-reported tools such as the Hospital Anxiety and Depression Scale and different versions of the Beck Depression Inventory. In summary, the current practice for describing sample characteristics and assessment methods for depression varies considerably between studies among patients with advanced cancer. More standardised practice is needed in order to enhance the generalizability and utility of research findings. Stakeholders should be encouraged to produce recommendations for sample descriptions and assessment methods in future studies. Pharmacologic interventions including antidepressant medication are effective in treating depressive disorders in cancer patients. However, far from all cancer patients with a diagnosis of depression receive treatment with antidepressants. The main research question in the second study, an international cross-sectional study (n=1048) was: What is the prevalence of use of antidepressants usage among advanced cancer patients included in an international multicentre study? This cross-sectional study reported that the prevalence of antidepressants use was 14% in an international convenience sample of advanced cancer patients. Information on characteristics of patients with advanced cancer that are treated with antidepressants was still lacking. Therefore, a second research question in the crosssectional study was the following: Which socio-demographic and medical variables are associated with the use of antidepressants in advanced cancer patients included in an international multicentre study? In this large international cross-sectional study, younger age, female gender, current medication for pain, and presence of three or more comorbidities were associated with antidepressant use other than as adjuvant for pain in advanced cancer patients. Disease-related variables such as diagnoses, stage, performance status, and survival length were not associated with the use of antidepressants. However, precise information on which variables that are guiding physicians in prescribing antidepressant medication is still lacking. Cancer patients at the end of life may experience depression or depressive symptoms. However, it is difficult to judge whether the patients experience a normal dying process or depression. The research question in the third study, a retrospective death certificate study (n=1363) was: What is the prevalence of depressive symptoms in Dutch cancer patients in the last 24 hours of their life according to treating physicians’ ratings? Results showed that the prevalence of depressive symptoms in cancer patients in the last 24 hours of life reported by physicians was 37.6%. Among them mild/moderate depression was registered in 31.8% and severe/very severe in 5.8%.To further investigate what is characterizing cancer patients with depressive symptoms, the following research question was addressed in the same study: Is there an association between depressive symptoms and different socio-demographic variables, characteristics of care and symptoms in Dutch cancer patients their last 24 hours of life? Fatigue and confusion were significantly associated with mild/moderate depressive symptoms, while anxiety with both mild/moderate and severe/very severe depressive symptoms. Involvement of pain specialists or palliative care consultants and psychiatrists or psychologists was associated with more frequent-ratings of severe or very severe depressive symptoms

Patient-reported depression measures in cancer: a meta-review

The patient-reported depression measures that perform best in oncology settings have not yet been identified. We did a meta-review to integrate the findings of reviews of more than 50 depression measures used in adults with, or recovering from, any type of cancer. We searched Medline, PsycINFO, Embase, and grey literature from 1999 to 2014 to identify 19 reviews representing 372 primary studies. 11 reviews were rated as being of high quality (defined as meeting at least 20 criteria in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement). The Hospital Anxiety Depression Scale (HADS) was the most thoroughly evaluated measure, but was limited by cutpoint variability. The HADS had moderate screening utility indices and was least recommended in advanced cancer or palliative care. The Beck Depression Inventory was more generalisable across cancer types and disease stages, with good indices for screening and case finding. The Center for Epidemiologic Studies Depression Scale was the best-weighted measure in terms of responsiveness. This meta-review provides a comprehensive overview of the strengths and limitations of available depression measures. It can inform the choice of the best measure for specific settings and purposes

Impact of palliative care consult service in inpatient hospital setting: a systematic literature review

ObjectivesDespite a number of studies on effectiveness of palliative care, there is a lack of complex updated review of the impact of in-hospital palliative care consult service. The objective is to update information on the impact of palliative care consult service in inpatient hospital setting.MethodsThis study was a systematic literature review, following the standard protocols (Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Joanna Briggs Institute tools) to ensure the transparent and robust review procedure. The effect of palliative care consult service was classified as being associated with improvement, no difference, deterioration or mixed results in specific outcomes. PubMed, Scopus, Academic Search Ultimate and SocINDEX were systematically searched up to February 2020. Studies were included if they focused on the impact of palliative care consult service caring for adult palliative care patients and their families in inpatient hospital setting.ResultsAfter removing duplicates, 959 citations were screened of which 49 full-text articles were retained. A total of 28 different outcome variables were extracted. 18 of them showed positive effects within patient, family, staff and healthcare system domains. No difference was observed in patient survival and depression. Inconclusive results represented patient social support and staff satisfaction with care.ConclusionsPalliative care consult service has a number of positive effects for patients, families, staff and healthcare system. More research is needed on factors such as patient spiritual well-being, social support, performance, family understanding of patient diagnosis or staff stress.</jats:sec

The use of antidepressants in patients with advanced cancer--results from an international multicentre study

OBJECTIVES: Depression is common in patients with advanced cancer; however, it is not often recognized and therefore not treated. The aims of this study were to examine the prevalence of the use of antidepressants (ADs) in an international cross-sectional study sample and to identify sociodemographic and medical variables associated with their use.METHODS: The study was conducted in patients with advanced cancer from 17 centres across eight countries. Healthcare professionals registered patient and disease-related characteristics. A dichotomous score (no/yes) was used to assess the use of ADs other than as adjuvant for pain. Self-report questionnaires from patients were used for the assessment of functioning and symptom intensity.RESULTS: Of 1051 patient records with complete data on ADs, 1048 were included (M:540/F:508, mean age 62 years, standard deviation [SD] 12). The majority were inpatients, and 85% had metastatic disease. The prevalence of AD use was 14%. Multivariate logistic regression analyses showed that younger age (odds ratio [OR] 2.46; confidence interval [CI] 1.32-4.55), female gender (OR 1.59; CI 1.09-2.33), current medication for pain (OR 2.68; CI 1.65-4.33) and presence of three or more co-morbidities (OR 4.74; CI 2.27-9.91) were associated with AD use for reasons other than pain. Disease-related variables (diagnoses, stage, Karnofsky Performance Status and survival) were not associated with the use of ADs.CONCLUSIONS: Female gender, younger age, analgesic use and multiple co-morbidities were associated with the use of ADs. However, information is still limited on which variables guide physicians in prescribing AD medication. Further longitudinal studies including details on psychiatric and medication history are needed to improve the identification of patients in need of ADs.</p

Additional file 1: of Mismatch between physicians and family members views on communications about patients with chronic incurable diseases receiving care in critical and intensive care settings in Georgia: a quantitative observational survey

Distribution of responses from physicians and patients’ family members to question 1.1 and 1.2. Figure S2. Distribution of responses from physicians and patients’ family members to question 1.2 and 2.2. Figure S3. Distribution of responses from physicians to question 1.3. Figure S4. Distribution of responses from physicians and patients’ family members to question 1.4 and 2.4. Figure S5. Distribution of responses from physicians and patients’ family members to question 1.5 and 2.5. Figure S6. Distribution of responses from physicians and patients’ family members to question 1.6 and 2.6. Figure S7. Distribution of responses from physicians and patients’ family members to question 1.7 and 2.7. Figure S8. Distribution of responses from physicians and patients’ family members to question 1.8 and 2.8. Figure S9. Distribution of responses from physicians and patients’ family members to question 1.9 and 2.9. Figure S10. Distribution of responses from physicians and patients’ family members to question 1.10 and 2.10. (ZIP 702 KB

Depressive symptoms in the last days of life of patients with cancer: a nationwide retrospective mortality study

Objectives: Depressive symptoms are common in patients with cancer and tend to increase as death approaches. The study aims were to examine the prevalence of depressive symptoms in patients with cancer in their final 24 h, and their association with other symptoms, sociodemographic and care characteristics. Methods: A stratified sample of deaths was drawn by Statistics Netherlands. Questionnaires on patient and care characteristics were sent to the physicians (N=6860) who signed the death certificates (response rate 77.8%). Adult patients with cancer with non-sudden death were included (n=1363). Symptoms during the final 24 h of life were assessed on a 1-5 scale and categorised as 1=no, 2-3=mild/moderate and 4-5=severe/very severe. Results: Depressive symptoms were registered in 37.6% of the patients. Patients aged 80 years or more had a reduced risk of having mild/moderate depressive symptoms compared with those aged 17-65 years (OR 0.70; 95% CI 0.50 to 0.99). Elderly care physicians were more likely to assess patients with severe/very severe depressive symptoms than patients with no depressive symptoms (OR 4.18; 95% CI 1.48 to 11.76). Involvement of pain specialists/palliative care consultants and psychiatrists/psychologists was associated with more ratings of severe/very severe depressive symptoms. Fatigue and confusion were significantly associated with mild/moderate depressive symptoms and anxiety with severe/very severe symptoms. Conclusions: More than one-third of the patients were categorised with depressive symptoms during the last 24 h of life. We recommend greater awareness of depression earlier in the disease trajectory to improve care