Neurology Central

Knowns and unknowns of identifications management of depressed brain tumor patients

Malignant brain tumors (BT) are often devastating diseases associated with short life expectancy and progressive impairment of functional status and quality of life. Depression is a highly prevalent complication among patients with established BT diagnosis, with reported point-prevalence rates approaching 50% [1]. A constantly increasing body of evidence suggests that depression is related to significant impairment of health-related quality of life [2], worse treatment outcomes [3] and shorter survival [4] of BT patients. Furthermore, depressed patients are at risk for adverse health behaviors and impaired compliance with treatment recommendations [5]. From a clinical perspective, early recognition of depressed BT patients or patients at high risk for depression, followed by effective management of depressed patients, is expected to translate into improved clinical and patient-oriented outcomes. However, to date there are no evidence-based recommendations to guide identification and management of depressed BT patients.

Depression screening versus case-finding

Both screening (assessment of all patients) and case-finding (assessment of patients who are at elevated risk) strategies can be employed to identify patients suffering from mental disorders. However, due to a wide range (from 5% to 44%) of reported point prevalence rates of depressed BT patients, it remains largely unclear if all BT patients should be screened for depression irrespectively from clinical characteristics such as BT localization and grade, past histories of mental disorders and other risk factors for mental disorders. The alternative case-finding strategy largely depends on clinicians’ awareness, as only patients who are at elevated risk for mental disorders based on clinical impression are referred for detailed evaluation by a mental health professional [6].

Varying opinions are held on the use of these strategies. For example, the Canadian Task Force on Preventive Health Care [7] and National Institute for Health and Care Excellence [8] do not recommend routine depression screening in the general adult population unless clinical clues exist. On the other hand, major national and international cancer and palliative care societies, such as the National Comprehensive Cancer Network [9], American Society of Clinical Oncology [10] and European Palliative Care Research Collaborative [11], stress the importance of routine screening for depression in cancer patients. According to guidelines from the latter societies, symptoms of depression should be discussed during the initial visit and at later visits at appropriate time intervals, especially when there are changes in disease and/or treatment status.

Routine screening for depression at presentation of BT patients seems to be reasonable, because depression often occurs early in the disease trajectory [12] and BT patients with a past history of depression are at increased risk for depression recurrence during the course of their illness [13]. Significant reduction of depressive and anxiety symptom severity has been reported immediately following neurosurgical removal of BT [14,15]; however, other longitudinal studies have documented high rates of depression during all stages of illness [6,13]. These findings suggest that depressive symptom severity fluctuates and remains a serious problem throughout the course of the disease.

Potential caveats of the depression screening approach for depression detection in a neuro-oncology setting include a lack of validated depression screening instruments for the patient population, as well as the significant socioeconomic costs. These costs arise due to the fact that all patients need to be referred for screening intervention from which high false-positive screening instrument rates can result in unnecessary psychiatric consultations. The cost-effectiveness of a screening approach could be improved by employing depression screening scales which were previously validated in the BT patient population and by using cut-off values with optimal psychometric properties (high sensitivity and positive predictive values) for depression screening purposes. Screening intervention could be completed prior to a clinic visit by using paper-and-pencil or online depression screening scales.

A case-finding strategy could also potentially reduce economic healthcare burden, as only patients at risk would be referred for mental health evaluation. On the other hand, such an approach carries a risk for under-recognition of depressed patients if the primary healthcare provider is not trained to identify depression symptoms and/or depression risk factors. Further research is needed to better delineate BT patient subgroups that are at high risk of developing depression.

Alternatively, a stepped-care model can be considered in order to improve recognition and optimize costs-effectiveness of depression screening. In a stepped-care model, a short scale or just a single screening question is used for initial screening purposes and patients at elevated risk for depression are referred for subsequent comprehensive assessment by a mental health specialist. The American Society of Clinical Oncology [10] recommends that all cancer patients should be assessed for the presence of current depressive symptoms or risk factors for depression, such as personal or family history of depression, concurrent life stresses, absence of social support, advanced disease, poorly controlled symptoms, poor performance status or physical disabilities. Patients with depressive symptoms and/or depression risk factors are then subjected to a second-step assessment intervention that includes two core symptoms of depressive disorder, namely low mood and anhedonia. Patients who score positive on at least one of the two questions are asked to complete the Personal Health Questionnaire (PHQ-9). Subsequently, patients with moderate or severe depressive symptoms on the PHQ-9 or those at risk for self-harm should be referred for psychological and psychiatric evaluation to confirm the diagnosis and to establish treatment regimens and initiation.

Although these guidelines and instruments might be adapted for the screening of BT patients, the optimal depression screening algorithm is still under debate. Our recent review showed that widely-used depression screening tools are still not sufficiently validated in the BT patient population for depressive symptom evaluation purposes [1]. Therefore, diagnostic properties and optimal cut-off values of self-rating depressive symptom scales remain to be determined in BT patients prior to recommending a specific instrument. Diagnosis of depression and the decision for treatment initiation should not be based solely on scores of self-rating scales but should be grounded on comprehensive psychological and psychiatric evaluation. To the best of our knowledge, there are no studies to date examining clinical value of depression screening intervention in BT patients. Therefore, it is urgently needed to estimate if depression screening intervention can indeed improve recognition of depressed patients and antidepressant treatment availability, and improve quality of life and prognosis of BT patients.

Integrated management programs for depressed BT patients

Integration of evidence-based depression treatment methods in comprehensive depression management algorithms is expected to improve health status of depressed BT patients. Optimal treatment method(s) should be carefully selected in patients with established BT diagnosis, as unnecessary psychiatric treatment(s) can significantly increase the risk of serious adverse events and complications such as lowered seizure threshold and elevated fatigue symptom severity. Therefore, depression management strategies should be chosen with regards to psychiatric presentation, clinical symptoms imposed by BT, adjuvant BT treatments (chemotherapy, radiotherapy, anti-seizure treatment and others) and previous antidepressant treatments.

Principles of stepped care might also be applied in the management of depressed BT patients. According to Chambers and colleagues, management of psychological distress should start from brief support and information focused interventions that should be followed by more intensive, in-depth, specialized, and multidisciplinary approaches for patients with high levels of distress [16]. The American Society of Clinical Oncology [10] established a structured algorithm for depression management in cancer patients. These guidelines are very useful for deciding mode and intensity of the interventions, but less is known about the efficacy of specific treatment or intervention options for depression management in BT patients. Currently there are no evidence-based recommendations regarding the optimal management strategy of depressed BT patients. Numerous pharmacological and/or psychosocial treatment (individual and group psychotherapy, self-help groups, online counseling, etc) modalities have been shown to be effective for treatment of depression, but it remains unclear if these interventions are effective and safe for BT patients. Pharmacological treatments of depression in BT patients remain terra incognita because little is known about safety, efficacy and possible side effects of antidepressant treatment in patients with BT [17]. Research on efficacy of psychosocial interventions for BT patients is also in an initial stage of its development. A recent review of psychotherapy interventions in patients with BT [18] reported only one randomized controlled trial of psychosocial intervention for primary BT patients, which indicated positive effects of psychosocial intervention with regards to depressive symptom severity and quality of life. Thus, further research studies are urgently needed in order to develop an evidence-based background for depression management in BT patients.

Recommendations for current practice

Healthcare professionals should be aware that emotional problems are common complications among BT patients and are associated with poor quality of life and clinical outcomes. Despite the presence of numerous depression identification strategies directed for primary care and cancer patient settings, there are no evidence-based recommendations to suggest optimal depression screening/case-finding strategies among BT patients. Therefore, in line with already established recommendations, we recommend using self-rating scales for initial depression screening purposes in BT patients. Ideally, adequately translated and validated depression symptom scales should be used whenever possible. Patients identified at high risk for mood disorders should be referred for evaluation by mental health professionals and for establishment of optimal depression treatment and follow-up strategies.


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