Pancreatic Cancer and Depression: A Narrative Review.

Depression is a common concomitant of pancreatic cancer, and, because it often occurs before the cancer is diagnosed, its occurrence is likely to be intrinsic to the condition rather than a reaction to such a diagnosis. Because pancreatic cancer is associated with a very high mortality, its early detection is a key task. We therefore review relevant literature to determine whether the depression is prototypically distinctive and whether its identification might lead to earlier diagnosis of pancreatic cancer. We report on the epidemiology and prognosis of pancreatic cancer and on the prevalence, description, and possible mechanisms involved for the occurrence of any associated depressive state, before reviewing the comparative utility of depression in relation to other risk factors in aiding diagnosis. Published studies fail to identify any distinct depressive prototypic phenotype to depression associated with pancreatic cancer. Although it is a relatively common concomitant of pancreatic cancer, the utility of depression as a marker of the condition is not suggested from a key study evaluating its contribution in relation to other symptoms and risk factors.

Vitamin D and depression.

OBJECTIVE: To examine whether vitamin D deficiency or insufficiency is associated with depression and whether vitamin D supplementation is an effective treatment for depression. METHOD: Empirical papers published in recent years were identified using three search engines and online databases - PubMed, Google Scholar and Cochrane Database. Specific search terms used were 'vitamin D', 'depression' and 'treatment' and articles were selected that examined the association between vitamin D deficiency/insufficiency and depression, vitamin D supplementation and Vitamin D as a treatment for depression. Our review weighted more recent studies (from 2011), although also considered earlier publications. RESULTS: Empirical studies appear to provide increasing evidence for an association between vitamin D insufficiency and depression, and for vitamin D supplementation and augmentation in those with clinical depression who are vitamin D deficient. Methodological limitations associated with many of the studies are detailed. LIMITATIONS: Articles were restricted to those in the English language while publication bias may have weighted studies with positive findings. CONCLUSIONS: There remains a need for empirical studies to move beyond cross-sectional designs to undertake more randomised controlled longitudinal trials so as to clarify the role of vitamin D in the pathogenesis of depression and its management, as well as to establish whether currently suggested associations are clinically significant and distinctive.

Psychostimulants for managing unipolar and bipolar treatment-resistant melancholic depression: a medium-term evaluation of cost benefits.

BACKGROUND: We earlier reported an open study of 50 unipolar and bipolar treatment resistant depressed patients indicating that psychostimulants may have differential superiority for the melancholic depressive sub-type. We designed an extension study to examine cost benefits of psychostimulants more closely for those only with melancholic depression. METHOD: The sample comprised patients clinically diagnosed with melancholic depression who had failed to respond to and/or experienced significant side-effects with at least two antidepressants. Data were collected for 61 unipolar and 51 bipolar II patients receiving a psyschostimulant for a mean interval of 69 weeks. Benefits and side-effects were assessed. RESULTS: Effectiveness ratings were similar across unipolar and bipolar sub-sets. Psychostimulants were judged as 'very' effective for 20% of patients and 'somewhat' effective for 50%. Forty percent judged the psychostimulant as being 'as effective' or as 'superior' to previously prescribed antidepressants, and worthy of being maintained. Significant side-effects were experienced by 40% of patients, requiring medication to be ceased in 12%. Twenty percent of the bipolar patients experienced a worsening of highs. LIMITATIONS: The study was uncontrolled and retrospective, no formal rater-completed or patient-completed interval measures of severity were completed, while diagnostic judgments about melancholic depression and bipolar disorder were clinically judged. CONCLUSIONS: This open study suggests that psychostimulants may be efficacious antidepressant options for managing unipolar and bipolar melancholia, often seemingly having very rapid onset and generally requiring only low doses, and arguing the need for controlled studies in melancholic patients.

GAD is good? Generalized anxiety disorder predicts a superior five-year outcome following an acute coronary syndrome.

While differing anxiety disorders have been reported to have quite variable impact on outcome following an acute coronary syndrome (ACS), a recent study quantified generalized anxiety disorder (GAD) as having a distinctly negative impact. We examined anxiety disorder status at baseline for any differential five-year impact on cardiac outcome following initial hospitalization for an ACS in 489 subjects. Of those initially assessed, 89% were examined at a five-year review. There were non-significant trends for all non-GAD anxiety disorders to be associated with a worse cardiac outcome. Meeting GAD criteria (both at baseline assessment and over the subjects' lifetime) was associated with a superior five-year cardiac outcome, particularly in the sub-set of those experiencing GAD as their only anxiety disorder, and after controlling for depression and medical comorbidities. As our results are at distinct variance with two previous studies specifically examining the impact of GAD on outcome in cardiac patients, we consider methodological and other explanations. We conclude that, if our findings are valid, then they may more reflect GAD patients having a 'constructive worrying' capacity and therefore being more likely to seek help in response to less severe somatic symptoms and to also be more adherent with cardiac rehabilitation programs.

Tolerance to desvenlafaxine in rapid metabolizing depressed patients.

The terms 'tolerance' and 'poop out' are commonly applied to describe the progressive loss of effectiveness of a previously effective antidepressant and where the individual may be a rapid metabolizer of those drugs as a consequence of possessing certain polymorphisms of P450 (CYP) liver enzymes, especially CYP2D6 and CYP2C19. As the antidepressant desvenlafaxine is not metabolized by those enzymes, it might be hypothesized that it would be less likely to be associated with tolerance or poop out, even for patients whose genotyping pattern is indicative of rapid metabolizing. In this study, we report on five patients who had a historical pattern suggestive of tolerance to other antidepressant drugs, whose genotyping test indicated that they were CYP2C19 rapid metabolizers, and who experienced 'poop out' again when commenced on desvenlafaxine. Although desvenlafaxine is theoretically an option in patients with a history of tolerance to antidepressants, these case reports indicate that this drug may not necessarily overcome the problem of tolerance in rapid metabolizing patients.

Specificity of depression following an acute coronary syndrome to an adverse outcome extends over five years.

Many studies have demonstrated that depression is associated with a worse cardiovascular outcome and increased risk of death in those experiencing an acute coronary syndrome (ACS). Recent studies have suggested, however, that any association is strongly influenced by the timing of the depression, with post-ACS depression providing the greatest risk. Establishing any timing impact should assist etiological clarification. We initially recruited 489 subjects hospitalized for an ACS, assessed lifetime and current depression, and then - at 1 and 12 months - assessed subsequent depression. Subjects were followed for up to 5 years to assess cardiovascular outcome and the impact of depression at differing time points, with three defined poor outcome categories (i.e. cardiac admission and/or cardiac rehospitalization). While outcome was associated with a number of non-depression variables, a poor outcome was most clearly associated with depressive episodes emerging at the time of the ACS but with some risk affected by episodes that commenced prior to the ACS and being persistent. Neither lifetime depressive episodes nor transient depressive episodes occurring around the baseline ACS event appeared to provide any risk. Study findings indicate that any differential deleterious impact of post-ACS depression has both short-term and longer-term outcomes, and, by implicating the centrality of post-ACS depression, should assist studies seeking to identify causal explanations.

Gender differences in depression.

It is commonly suggested that a female preponderance in depression is universal and substantial. This review considers that proposition and explanatory factors. The view that depression rates are universally higher in women is challenged with exceptions to the proposition helping clarify candidate explanations. 'Real' and artefactual explanations for any such phenomenon are considered, and the contribution of sex role changes, social factors and biological determinants are overviewed. While artefactual factors make some contribution, it is concluded that there is a higher order biological factor (variably determined neuroticism, 'stress responsiveness' or 'limbic system hyperactivity') that principally contributes to the gender differentiation in some expressions of both depression and anxiety, and reflects the impact of gonadal steroid changes at puberty. Rather than conclude that 'anatomy is destiny' we favour a diathesis stress model, so accounting for differential epidemiological findings. Finally, the impact of gender on response to differing antidepressant therapies is considered briefly.

The impact of differing anxiety disorders on outcome following an acute coronary syndrome: time to start worrying?

BACKGROUND: Both depression and anxiety have been implicated as influencing survival following an acute coronary syndrome (ACS). Studies evaluating the contribution of anxiety have produced varying results, perhaps reflecting the use of dimensional self-report measures of state anxiety and failure to control for co-morbid depression. We sought to assess the impact of anxiety on outcome in ACS patients using DSM-IV diagnoses, in addition to self-report measures, controlling for effects of concurrent depressive diagnosis as well as medical and socio-demographic variables. METHODS: Some 489 patients hospitalized with an ACS were assessed for lifetime and current DSM-IV anxiety disorders using both Composite International Diagnostic Interview (CIDI) decisions and such decisions complemented by clinical judgments of impairment. Patients were re-interviewed over the next 12 months to assess cardiac outcome (ACS readmission and cardiac mortality). RESULTS: Univariate analyses revealed a trend for those with a lifetime history of agoraphobia to experience poorer cardiac outcome and for those with a lifetime diagnosis of generalized anxiety disorder (GAD) to experience a superior cardiac outcome. After controlling for post-ACS depression and key medical and demographic covariates, agoraphobia was a significant predictor of poorer cardiac outcome while the trend for those with a history of GAD to experience a superior cardiac outcome remained. CONCLUSIONS: Any impact of "anxiety" on post-ACS outcome appears to be influenced by the clinical sub-type. The seemingly paradoxical finding that GAD might improve outcome may reflect "apprehensive worrying" being constructive, by improving self-management of the individual's cardiac problems.

[Major depression invites major concerns]. / Depressão maior suscita questionamento maior.

OBJECTIVE: To overview limitations to the concept and construct of major depression. METHOD: The objectives in initially conceptualizing major depression are examined against its subsequent utility and relevance to clinicians and researchers. RESULTS: It is argued that, as defined, major depression does not differentiate clinical depression well from expressions of non-clinical depression or sadness, that its criteria set do not generate reliable diagnoses, that a diagnosis of major depression means little in and of itself (as it effectively comprises multiple types of depression) and that it fails to inform us about cause, natural history or differential treatment response. CONCLUSION: Limitations to the concept of major depression would benefit from wider appreciation to advance changes to the clinical diagnosis of depressive sub-types.

Depressão maior suscita questionamento maior / Major depression invites major concerns

OBJETIVO: Revisar as limitações do conceito e do construto da depressão maior. MÉTODO: Os objetivos na conceitualização inicial da depressão maior são examinados em relação à sua subseqüente utilidade e relevância para os clínicos e pesquisadores. RESULTADOS: Afirma-se que, como definida, a depressão maior não diferencia bem a depressão clínica das expressões de depressão não clínica ou de tristeza; que seu conjunto de critérios não gera diagnósticos confiáveis; que um diagnóstico da depressão maior pouco significa por si só (na medida em que compreende efetivamente múltiplos tipos de depressão); e não nos informa sobre a causa, histórico natural ou resposta diferenciada ao tratamento. CONCLUSÃO: As limitações do conceito de depressão maior poderiam se beneficiar de uma avaliação mais ampla para impulsionar alterações no diagnóstico clínico dos subtipos depressivos.

OBJECTIVE: To overview limitations to the concept and construct of major depression. METHOD: The objectives in initially conceptualizing major depression are examined against its subsequent utility and relevance to clinicians and researchers. RESULTS: It is argued that, as defined, major depression does not differentiate clinical depression well from expressions of non-clinical depression or sadness, that its criteria set do not generate reliable diagnoses, that a diagnosis of major depression means little in and of itself (as it effectively comprises multiple types of depression) and that it fails to inform us about cause, natural history or differential treatment response. CONCLUSION: Limitations to the concept of major depression would benefit from wider appreciation to advance changes to the clinical diagnosis of depressive sub-types.

Timing is everything: the onset of depression and acute coronary syndrome outcome.

BACKGROUND: Conflicting findings have emerged from studies examining the impact of depression on death and readmission following a coronary event, possibly reflecting differences in the measurement of "depression" and the onset of depression in relation to the coronary event. The aim of this study was to examine the relationship between the timing of the depressive episode and 1-year cardiovascular outcome in recruited patients with acute coronary syndrome (ACS). METHODS: Patients hospitalized with ACS (N = 489) were recruited and assessed for lifetime and current depression by the Composite International Diagnostic Interview (CIDI) depression schedule. Patients were reinterviewed at 1 and 12 months by telephone to assess depression status and cardiovascular outcomes (ACS readmission and cardiac mortality). Mortality registers were also checked. RESULTS: Cardiovascular outcome was not associated with the presence of lifetime depression before the ACS admission or with existing depression at the time of the ACS admission. In contrast, depression that developed in the month after the ACS event showed a strong relationship with subsequent cardiovascular outcome, even after controlling for traditional cardiac risk factors. Outcome over the 12 months was more strongly predicted by the timing of depression onset than whether the depression was a first-ever (incident) or recurrent episode. CONCLUSIONS: Only a depressive episode that commenced following an ACS admission was associated with a poorer cardiovascular outcome. If confirmed, this finding would narrow the list of causal mechanisms previously proposed to account for the relationship between depression and coronary events.

Outcome in a specialist referral clinic for mood disorders: a qualitative and quantitative review.

OBJECTIVE: The aim of this study was to determine whether short-term outcome for those referred with a depressive disorder could be predicted from baseline clinical assessment and identify factors contributing to outcome in a clinic operating to a subtyping diagnostic and aetiologically weighted management model. METHOD: This pilot study involved a consecutive series of 85 patients referred to the Depression Clinic at the Black Dog Institute. RESULTS: Globally assessed baseline prediction was associated with short-term outcome. Comparably high rates of improvement were evident in those with bipolar, melancholic and non-melancholic subtypes, and somewhat lower in those diagnosed with a 'secondary depression'. Qualitative and quantitative analyses established that outcome was most clearly associated with referral source, degree of take up of recommendations and implementation of psychotropic drug strategies. CONCLUSIONS: Study results encourage more definitive and comparative study designs to be derived.

Omega-3 fatty acids and mood disorders.

OBJECTIVE: This article is an overview of epidemiological and treatment studies suggesting that deficits in dietary-based omega-3 polyunsaturated fatty acids may make an etiological contribution to mood disorders and that supplementation with omega-3 fatty acids may provide a therapeutic strategy. METHOD: Relevant published studies are detailed and considered. RESULTS: Several epidemiological studies suggest covariation between seafood consumption and rates of mood disorders. Biological marker studies indicate deficits in omega-3 fatty acids in people with depressive disorders, while several treatment studies indicate therapeutic benefits from omega-3 supplementation. A similar contribution of omega-3 fatty acids to coronary artery disease may explain the well-described links between coronary artery disease and depression. CONCLUSIONS: Deficits in omega-3 fatty acids have been identified as a contributing factor to mood disorders and offer a potential rational treatment approach. This review identifies a number of hypotheses and studies for consideration. In particular, the authors argue for studies clarifying the efficacy of omega-3 supplementation for unipolar and bipolar depressive disorders, both as individual and augmentation treatment strategies, and for studies pursuing which omega-3 fatty acid, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), is likely to provide the greatest benefit.

An increased proportional representation of bipolar disorder in younger depressed patients: analysis of two clinical databases.

OBJECTIVE: To pursue the suggested increased incidence of bipolar disorder by examining for a cohort effect in the proportional representation of Bipolar Disorder in two independent clinical samples of depressed patients. METHOD: Assessment of polarity status was undertaken with some consistency over defined collection periods in two independent samples. RESULTS: The lifetime proportional rates of bipolar disorder declined with age from some 60% to 30% in both samples. CONCLUSIONS: The strikingly similar age-related pattern in both samples and the linear trajectory support a cohort effect where the incidence of bipolar disorder may be increasing disproportionately in younger individuals.

Interpersonal psychotherapy for depression? The need to define its ecological niche.

BACKGROUND: Interpersonal psychotherapy (IPT) has long been viewed as an efficacious treatment for depression, with a large number of published studies allowing its efficacy and utility to be considered closely. METHODS: We review original studies and the one published meta-analysis of controlled efficacy trials, examining acute-phase and prophylactic studies, comparison studies with cognitive behaviour therapy, and studies evaluating its efficacy in combination with pharmacotherapy. RESULTS: We highlight difficulties in evaluating any psychotherapy, particularly when tested as having universal application for varying depressive conditions, but do identify circumstances where IPT may have specific salience. CONCLUSIONS: As for other treatments, IPT is unlikely to be a universal therapy for depression. This review offers suggestions as to where its preferential utility may lie, and argues for modified research paradigms to assist definition of its therapeutic niche.

Mood state effects of chocolate.

BACKGROUND: Chocolate consumption has long been associated with enjoyment and pleasure. Popular claims confer on chocolate the properties of being a stimulant, relaxant, euphoriant, aphrodisiac, tonic and antidepressant. The last claim stimulated this review. METHOD: We review chocolate's properties and the principal hypotheses addressing its claimed mood altering propensities. We distinguish between food craving and emotional eating, consider their psycho-physiological underpinnings, and examine the likely 'positioning' of any effect of chocolate to each concept. RESULTS: Chocolate can provide its own hedonistic reward by satisfying cravings but, when consumed as a comfort eating or emotional eating strategy, is more likely to be associated with prolongation rather than cessation of a dysphoric mood. LIMITATIONS: This review focuses primarily on clarifying the possibility that, for some people, chocolate consumption may act as an antidepressant self-medication strategy and the processes by which this may occur. CONCLUSIONS: Any mood benefits of chocolate consumption are ephemeral.

A validation study of two brief measures of depression in the cardiac population: the DMI-10 and DMI-18.

The authors report on the psychometric characteristics and clinical efficacy of two versions of a recently developed screening measure of depression (the DMI-18 and DMI-10) in the cardiac population. Patients with acute coronary syndrome or heart failure (N = 322) completed the DMI measures, psychosocial questionnaires, and a semistructured clinical interview during the hospital stay. The DMI-18 and DMI-10 measures have adequate psychometric properties, demonstrating high sensitivity and specificity when evaluated against clinical judgment based on a semistructured interview. The DMI-18 and DMI-10 are appropriate for use as screening instruments in cardiac patients.

Low levels of docosahexaenoic acid identified in acute coronary syndrome patients with depression.

As deficiencies in n-3 PUFAs have been linked separately to depression and to cardiovascular disease, they could act as a higher order variable contributing to the established link between depression and cardiovascular disease. We therefore examine the relationship between depression and omega-3 polyunsaturated fatty acids (n-3 PUFA), including total n-3 PUFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in patients with acute coronary syndrome (ACS). Plasma phospholipid levels of n-3 PUFA were measured in 100 patients hospitalized with ACS. Current major depressive episode was assessed by the Composite International Diagnostic Interview (CIDI). Depression severity was assessed by the 18-item Depression in the Medically Ill (DMI-18) measure. Patients clinically diagnosed with current depression had significantly lower mean total n-3 PUFA and DHA levels. Higher DMI-18 depression severity scores were significantly associated with lower DHA levels, with similar but non-significant trends observed for EPA and total n-3 PUFA levels. The finding that low DHA levels were associated with depression variables in ACS patients may explain links demonstrated between cardiovascular health and depression, and may have prophylactic and treatment implications.

Explicating links between acute coronary syndrome and depression: study design and methods.

OBJECTIVE: To describe a regional study seeking to replicate the suggested strong links whereby lifetime and post-coronary infarction depression are associated with a significant increase in mortality and cardiac morbidity, and consider the comparative influence of both depression and anxiety. METHOD: We detail relevant international studies and describe both the methodology as well as baseline and 1-month data from our study. RESULTS: Over a 3-year period we recruited 489 subjects admitted to a Sydney cardiac unit with an Acute Coronary Syndrome (ACS), and assessed by a range of cardiac variables and measures of current and lifetime depression. Ninety-eight per cent of the sample were assessed one month after baseline recruitment to establish depression rates. Long-term outcome reviews of mortality and morbidity and hospitalization rates are proceeding. For those subjects who were depressed in the post-ACS period and, even more so for those who had experienced lifetime depression, distinctly higher scores on anxiety variables (and lifetime caseness for anxiety disorders) were established. CONCLUSIONS: The strong interdependence between anxiety and depression in this sample of patients admitted with an ACS will allow examination of the comparative extent to which expressions of 'depression' and 'anxiety' contribute to post-ACS morbidity.

Is combination olanzapine and antidepressant medication associated with a more rapid response trajectory than antidepressant alone?

OBJECTIVE: The authors' goal was to determine if prescription of antidepressant medication plus olanzapine initiates a more rapid response than prescription of antidepressant alone. METHOD: Twenty patients with major depression were studied. For 2 weeks the patients were blindly assigned to receive antidepressant plus olanzapine or antidepressant plus placebo. After 2 weeks, olanzapine augmentation was initiated for patients who did not improve with placebo augmentation. Response to medication was measured primarily by Hamilton Depression Rating Scale score. Other measures were the CORE, Clinical Global Impression, Beck Depression Inventory, and Daily Rating Schedule. RESULTS: Hamilton depression scores improved nonsignificantly in response to olanzapine combination therapy, but that trend was not evident on any secondary measure. Four patients who did not improve while receiving antidepressant and placebo showed rapid remission following late olanzapine augmentation. CONCLUSIONS: Failure to demonstrate any benefit from initial combination therapy may reflect an underpowered rather than a negative study. The distinct impact of late olanzapine augmentation suggests that pretreatment with an antidepressant may be required to facilitate a rapid antidepressant response to combined treatment.