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      Twelve Chinese herbal preparations for the treatment of depression or depressive symptoms in cancer patients: a systematic review and meta-analysis of randomized controlled trials

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          Abstract

          Background

          Patients with cancer are vulnerable to depression or other depressive conditions. The aim of this paper was to evaluate the efficacy and safety of Chinese herbal medicine (CHM) for the treatment of depression or depressive symptoms in cancer patients.

          Methods

          CENTRAL, MEDLINE, EMBASE, PsycINFO, CNKI, VIP, SinoMed, and online clinical trial registry websites were searched for relevant RCTs until May 2017. The methodological quality of each included study was assessed with the “risk of bias” tool. Review Manager 5.3.5 was used to analyze the data.

          Results

          We identified 18 RCTs that included data from 1441 participants. Twelve different types of Chinese herbal preparations were investigated by these studies, and they showed a better therapeutic effect in most comparisons when measured in terms of depression rating scale scores, with SMDs (95% CI) of − 2.30 (− 3.54, − 1.05) (CHM versus no treatment), − 0.61 (− 1.03, − 0.18) (CHM versus antidepressants), and − 0.55 (− 1.07, − 0.02) (CHM plus psychological treatments versus psychological treatments), or when measured in terms of treatment response rate, with RRs (95% CI) of 1.65 (1.19, 2.29) (CHM versus no treatment), 1.15 (1.03, 1.28) (CHM versus psychological treatments), 1.32 (1.07, 1.63) (CHM plus antidepressants versus antidepressants), and 1.70 (1.02, 2.85) (CHM plus psychological treatments versus psychological treatments). Compared with antidepressants, these CHMs showed borderline superiority for improving the response rate, with an RR (95% CI) of 1.08 (0.93, 1.26). Subgroup analysis based on psychiatric diagnosis (depression versus depressive symptoms) did not modify the direction of these estimates and neither could it explain the high level of heterogeneity. Patients in the CHM group experienced fewer adverse events of cardiac toxicity ( P = 0.02), functional gastrointestinal disorders ( P = 0.008), sleep disturbances (P = 0.02), blurred vision (P = 0.02) and fatigue ( P = 0.03) than the patients in the no treatment group or the antidepressants group.

          Conclusions

          According to the investigation of the twelve herbal preparations, the CHM intervention appears to alleviate depressive symptoms in cancer patients, either alone or combined with antidepressants or psychological treatments. However, a high risk of bias and high heterogeneity made the mean estimates uncertain. Well-designed trials with comprehensive and transparent reporting are warranted in the future.

          Electronic supplementary material

          The online version of this article (10.1186/s12906-019-2441-8) contains supplementary material, which is available to authorized users.

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          Most cited references37

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          Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials.

          Several studies have reported antidepressant effects of anti-inflammatory treatment; however, the results have been conflicting and detrimental adverse effects may contraindicate the use of anti-inflammatory agents. To systematically review the antidepressant and possible adverse effects of anti-inflammatory interventions. Trials published prior to December, 31, 2013, were identified searching Cochrane Central Register of Controlled Trials, PubMed, EMBASE, PsychINFO, Clinicaltrials.gov, and relevant review articles. Randomized placebo-controlled trials assessing the efficacy and adverse effects of pharmacologic anti-inflammatory treatment in adults with depressive symptoms, including those who fulfilled the criteria for depression. Data were extracted by 2 independent reviewers. Pooled standard mean difference (SMD) and odds ratios (ORs) were calculated. Depression scores after treatment and adverse effects. Ten publications reporting on 14 trials (6262 participants) were included: 10 trials evaluated the use of nonsteroidal anti-inflammatory drugs (NSAIDs) (n=4,258) and 4 investigated cytokine inhibitors (n=2,004). The pooled effect estimate suggested that anti-inflammatory treatment reduced depressive symptoms (SMD, -0.34; 95% CI, -0.57 to -0.11; I2=90%) compared with placebo. This effect was observed in studies including patients with depression (SMD, -0.54; 95% CI, -1.08 to -0.01; I2=68%) and depressive symptoms (SMD, -0.27; 95% CI, -0.53 to -0.01; I2=68%). The heterogeneity of the studies was not explained by differences in inclusion of clinical depression vs depressive symptoms or use of NSAIDs vs cytokine inhibitors. Subanalyses emphasized the antidepressant properties of the selective cyclooxygenase 2 inhibitor celecoxib (SMD, -0.29; 95% CI, -0.49 to -0.08; I2=73%) on remission (OR, 7.89; 95% CI, 2.94 to 21.17; I2=0%) and response (OR, 6.59; 95% CI, 2.24 to 19.42; I2=0%). Among the 6 studies reporting on adverse effects, we found no evidence of an increased number of gastrointestinal or cardiovascular events after 6 weeks or infections after 12 weeks of anti-inflammatory treatment compared with placebo. All trials were associated with a high risk of bias owing to potentially compromised internal validity. Our analysis suggests that anti-inflammatory treatment, in particular celecoxib, decreases depressive symptoms without increased risks of adverse effects. However, a high risk of bias and high heterogeneity made the mean estimate uncertain. This study supports a proof-of-concept concerning the use of anti-inflammatory treatment in depression. Identification of subgroups that could benefit from such treatment might be warranted.
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            Association of depression and anxiety on quality of life, treatment adherence, and prognosis in patients with advanced non-small cell lung cancer.

            Symptoms of depression and anxiety are common in patients with lung cancer and may produce an impact on both health-related quality of life (HRQL) and survival. The aim of the present study was to evaluate the association of depression and anxiety on HRQL, treatment adherence, and prognosis in patients with non-small cell lung cancer (NSCLC). This is a prospective study of patients with stage IIIB or IV NSCLC. Depression and anxiety were measured using the hospital anxiety and depression scale, the International Neuropsychiatric Interview, and the HRQL with the EORTC QLQ-C30 and QLQ-LC13 questionnaires. Instruments were applied before treatment and repeated at 3 and 6 months. Lack of treatment adherence was considered as patients who stopped going to their consultation appointments. A total of 82 patients were included. At the initial evaluation, depression and anxiety were found in 32.9 and 34.1 % of patients, respectively. Depression was associated with feminine gender (p = 0.034) and poor performance status (p = 0.048). Depression and anxiety showed an association with HRQL. Patients with depression showed median overall survival of 6.8 months, whereas that for nondepressed patients was 14 months (hazard ratio [HR], 1.9; 95 % confidence interval (95 % CI), 1.03-3.7; p = 0.042). The 58 % of patients with depression had poor treatment adherence versus 42 % of patients without depression (p = 0.004). Depression and anxiety were present in one-third of patients with recently diagnosed NSCLC. Depression and anxiety were associated with decreased HRQL scales, and depression was independently associated with treatment adherence and with poor prognosis.
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              Oncologists' recognition of depression in their patients with cancer.

              This study was performed as part of a large depression screening project in cancer patients to determine the degree of physician recognition of levels of depressive symptoms in cancer patients and to describe patient characteristics that influence the accuracy of physician perception of depressive symptoms. Twenty-five ambulatory oncology clinics affiliated with Community Cancer Care, Inc of Indiana enrolled and surveyed 1,109 subjects treated by 12 oncologists. Subjects completed the Zung Self-Rating Depression Scale (ZSDS) and physicians were asked to rate their patients' level of depressive symptoms, anxiety, and pain using numerical rating scales. Subjects' sex, age, primary tumor type, medications, primary caregiver, and disease stage at diagnosis were also recorded. Physician ratings of depression were significantly associated with their patients' levels of endorsement of depressive symptoms on the ZSDS. However, agreement between physicians and patients is most frequently clustered when patients report little or no depressive symptoms. While physician ratings are concordant with patient endorsement of no significant depressive symptomatology 79% of the time, they are only concordant 33% and 13% of the time in the mild-to-moderate/severe ranges, respectively. Physician ratings were most influenced by patient endorsement of frequent and obvious mood symptoms, ie, sadness, crying, and irritability. Physician ratings also appeared to be influenced by medical correlates of patients' level of depressive symptoms (functional status, stage of disease, and site of tumor). Additionally, patients whose depression was inaccurately classified reported significantly higher levels of pain and had higher levels of disability. Physicians' ratings of depression were most highly correlated with physicians' ratings of patients' anxiety and pain. Physicians' perceptions of depressive symptoms in their patients are correlated with patient's ratings, but there is a marked tendency to underestimate the level of depressive symptoms in patients who are more depressed. They are most influenced by symptoms such as crying and depressed mood, and medical factors that are useful, but not the most reliable, indicators of depression in this population. Physicians' ratings of their patients' distress symptoms seem to be global in nature--they are highly correlated with anxiety, pain, and global dysfunction. Physician assessment might be improved if they were instructed to assess and probe for the more reliable cognitive symptoms such as anhedonia, guilt, suicidal thinking, and hopelessness. Screening instruments and the use of brief follow-up interviews would help to identify patients who are depressed.
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                Author and article information

                Contributors
                13811097397@163.com
                zijie2002@163.com
                982374153@qq.com
                zhangning_bucm@163.com
                821235640@qq.com
                66841633@qq.com
                452786371@qq.com
                1261229074@qq.com
                jinwen1119@foxmail.com
                liuzhe625@hbtcm.edu.cn
                63206873@qq.com
                zsq2098@163.com
                Journal
                BMC Complement Altern Med
                BMC Complement Altern Med
                BMC Complementary and Alternative Medicine
                BioMed Central (London )
                1472-6882
                23 January 2019
                23 January 2019
                2019
                : 19
                : 28
                Affiliations
                [1 ]ISNI 0000 0001 1431 9176, GRID grid.24695.3c, School of Chinese Medicine, , Beijing University of Chinese Medicine, ; Beijing, 100029 China
                [2 ]ISNI 0000 0004 1772 1285, GRID grid.257143.6, College of Basic Medicine, , Hubei University of Chinese Medicine, ; Hubei, 430065 China
                [3 ]ISNI 0000 0004 0604 6392, GRID grid.410612.0, College of Traditional Chinese Medicine, , Inner Mongolia Medical University, ; Hohhot, 010110 China
                Author information
                http://orcid.org/0000-0002-7226-3577
                Article
                2441
                10.1186/s12906-019-2441-8
                6345004
                30674300
                287ec79d-b306-4b3f-acdb-f4bade8c23df
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 3 May 2018
                : 16 January 2019
                Funding
                Funded by: Development Funds from Beijing University of Chinese Medicine
                Funded by: National Programme on Key Basic Research Project
                Award ID: 2013CB532001
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Complementary & Alternative medicine
                chinese herbal medicine,depression,depressive symptoms,cancer

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