Annotated Abstracts of Journal Articles
2015, 3rd Quarter
Annotations by Jane Walker, MBChB, MSc, PhD, MRCPsych
September 2015
ANNOTATION (Jane Walker)
The Finding: There are few randomized controlled trials of the efficacy of antidepressants in people with cancer. The studies that have been published are of low quality.
Strengths and Weaknesses: The main strength of this study is its systematic and transparent approach to reviewing the relevant literature. The main weakness is that the authors included studies with heterogeneous samples (patients with major depressive disorder, adjustment disorder, dysthymic disorder, or depressive symptoms in the absence of a formal diagnosis) in the primary analysis.
Relevance: This review is of relevance to all PM/C-L psychiatrists working with patients who have cancer.
Background: Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap between medical and psychiatric symptoms, as described by diagnostic manuals such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). Moreover, it is particularly challenging to distinguish between pathological and normal reactions to such a severe illness. Depressive symptoms, even in subthreshold manifestations, have been shown to have a negative impact in terms of quality of life, compliance with anti-cancer treatment, suicide risk and likely even the mortality rate for the cancer itself. Randomised controlled trials (RCTs) on the efficacy and tolerability of antidepressants in this population group are few and often report conflicting results.
Objectives: To assess the effects and acceptability of antidepressants for treating depressive symptoms in adults (18 years or older) with cancer (any site and stage).
Search Methods: We searched the following electronic bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 3), MEDLINE Ovid (1946 to April week 3, 2014), EMBASE Ovid (1980 to 2014 week 17) and PsycINFO Ovid (1987 to April week 4, 2014). We additionally handsearched the trial databases of the most relevant national, international and pharmaceutical company trial registers and drug-approving agencies for published, unpublished and ongoing controlled trials.
Selection Criteria: We included RCTs allocating adults (18 years or above) with any primary diagnosis of cancer and depression (including major depressive disorder, adjustment disorder, dysthymic disorder or depressive symptoms in the absence of a formal diagnosis) comparing antidepressants versus placebo, or antidepressants versus other antidepressants.
Data Collection and Analysis: Two review authors independently checked eligibility and extracted data using a form specifically designed for the aims of this review. The two authors compared the data extracted and then entered data into RevMan 5 with a double-entry procedure. Information extracted included study and participant characteristics, intervention details, outcome measures for each time point of interest, cost analysis and sponsorship by a drug company. We used the standard methodological procedures expected by The Cochrane Collaboration.
Main Results: We retrieved a total of nine studies (861 participants), with seven studies contributing to the meta-analysis for the primary outcome. Four of these compared antidepressants and placebo, two compared two antidepressants and one-three armed study compared two antidepressants and a placebo arm. For the acute phase treatment response (6 to 12 weeks), we found very low quality evidence for the effect of antidepressants as a class on symptoms of depression compared with placebo when measured as a continuous outcome (standardised mean difference (SMD) -0.45, 95% confidence interval (CI) -1.01 to 0.11, five RCTs, 266 participants) or as a proportion of people who had depression (risk ratio (RR) 0.82, 95% CI 0.62 to 1.08, five RCTs, 417 participants). No trials reported data on the follow-up response (more than 12 weeks). In head-to-head comparisons we only retrieved data for selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants, providing very low quality evidence for the difference between these two classes (SMD -0.08, 95% CI -0.34 to 0.18, three RCTs, 237 participants). No clear evidence of an effect of antidepressants versus either placebo or other antidepressants emerged from the analyses of the secondary efficacy outcomes (dichotomous outcome, response at 6 to 12 weeks, very low quality evidence). We found very low quality evidence for the effect of antidepressants as a class in terms of dropouts due to any cause compared with placebo (RR 0.87, 95% CI 0.49 to 1.53, six RCTs, 455 participants), as well as between SSRIs and tricyclic antidepressants (RR 0.83, 95% CI 0.53 to 1.30, three RCTs, 237 participants). We downgraded the quality of the evidence because the included studies were at an unclear or high risk of bias due to poor reporting, imprecision arising from small sample sizes and wide confidence intervals, and inconsistency due to statistical or clinical heterogeneity.
Authors’ Conclusions: Despite the impact of depression on people with cancer, available studies were very few and of low quality. This review found very low quality evidence for the effects of these drugs compared with placebo. On the basis of these results clear implications for practice cannot be made. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which agent should be prescribed may be based on the data on antidepressant efficacy in the general population of individuals with major depression, also taking into account that data on medically ill patients suggest a positive safety profile for the SSRIs. Large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer with depressive symptoms, with or without a formal diagnosis of a depressive disorder, are urgently needed to better inform clinical practice.
ANNOTATION (Jane Walker)
The Finding: In this study the majority (78%) of bereaved parents had used mental health services following their loss. Despite this, a significant number had current unmet psychological needs.
Strengths and Weaknesses: The main strength of this study is its focus on both needs and use of services. Its main weaknesses are its cross-sectional approach and the low proportion of bereaved parents for whom the researchers gained physician approval to contact.
Relevance: This study is of particular relevance to psychiatrists working in cancer settings but is also relevant to all PM/C-L psychiatrists who work with bereaved patients.
Purpose: To examine bereavement mental health service use, barriers to use, and factors associated with use in parents bereaved by cancer.
Patients and Methods: A multicenter, cross-sectional study of 120 parents bereaved by cancer between 6 months and 6 years after their loss was performed. Parents completed self-report assessments of mental health service use and barriers, prolonged grief, depression, anxiety, attachment styles, and sense of meaning by phone, in person, or on their own.
Results: Forty-one percent of bereaved parents were currently using mental health services (talk therapy, psychotropic medication, and/or a support group), most commonly within the first 2 years after their loss. Talk therapy was the most frequently used service, although 36% of parents who discontinued therapy did so because it was not helpful. Forty percent of parents who wanted bereavement support reported they were not receiving services. The most common barriers to service use were that it was too painful to speak about the loss (64%) and too difficult to find help (60%). Factors associated with current mental health service use included more recent loss, prior mental health service use, subclinical/increased depression, insecure attachment styles, and a decreased sense of meaning. Minority parents were more likely to have unmet needs than nonminority parents.
Conclusion: Parents appear to need, want, and often access bereavement mental health services, which could be offered in oncology settings. However, barriers to service use must be addressed, particularly for those with more debilitating grief symptoms and for minorities. High treatment dropout rates suggest the importance of improving retention, training providers, and developing effective grief interventions.
ANNOTATION (Jane Walker)
The Finding: Chronic depressive symptoms did not increase the risk of cancer incidence. People with new depressive symptoms did have an increased risk of cancer in the next nine years.
Strengths and Weaknesses: The strengths of this study are its large sample size and long-term follow-up. The main weakness is the lack of data on other symptoms which would assist the interpretation of the findings.
Relevance: The findings of this study are relevant to psychiatrists who work with depressed patients in any medical setting.
Objective: To explore the association between depressive symptom history and cancer incidence.
Methods: Affective/emotional depressive symptoms were assessed using the General Health Questionnaire (GHQ-30) depression sub-scale across phase 1 (1985-1988), phase 2 (1989-1990), and phase 3 (1991-1994) of the Whitehall II prospective cohort study; ‘chronic’=depressive episode at phase 1, 2 and 3; ‘new’=depressive episode at phase 3 only. Cancer incidence was obtained from the National Health Service Central Register with an average follow-up of 15.6 years (range 0.08-17.4). The study sample consisted of 6983 participants, aged 35-55years at baseline. Results were adjusted for age, sex, socio-economic position, health behaviours, health status/conditions, medication, and social support.
Results: Over a 17.4 year follow-up, chronic depressive symptoms did not increase the risk of cancer incidence compared to those who never experienced symptoms (hazard ratio (HR)=1.03, 95% confidence interval (CI): 0.71-1.49). Participants who experienced new depressive symptoms had an increased risk of cancer incidence in the first 9 years of follow-up (HR=1.89, 95% CI: 1.23-2.90) but no increased risk in later years (HR=0.84, 95% CI: 0.52-1.35).
Conclusion: Chronic depressive symptoms were not associated with cancer incidence. In contrast, new-onset symptoms were associated with a substantially increased risk, possibly due to reverse causality.