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1.
Curcumin for depression: a meta-analysis.
Fusar-Poli, L, Vozza, L, Gabbiadini, A, Vanella, A, Concas, I, Tinacci, S, Petralia, A, Signorelli, MS, Aguglia, E
Critical reviews in food science and nutrition. 2020;(15):2643-2653
Abstract
Curcumin is the principal curcuminoid found in turmeric (Curcuma longa), a spice frequently used in Asian countries. Given its anti-inflammatory and antioxidant properties, it has been hypothesized that curcumin might be effective in treating symptoms of a variety of neuropsychiatric disorders, such as depression. We conducted a systematic review following the PRISMA guidelines. In August 2019, we screened 930 articles, of which 9 were eligible for the meta-analysis. In 7 articles, participants were affected by major depressive disorder (MDD), while in other two they suffered from depression secondary to a medical condition. We found an overall significant effect of curcumin on depressive (10 studies, 531 participants, Hedge's g = -0.75, 95% CI -1.11 to -0.39, p < 0.001) and anxiety symptoms (5 studies, 284 participants, Hedge's g = -2.62, 95% CI -4.06 to -1.17, p < 0.001), with large effect size. Curcumin was generally well-tolerated by patients. Our findings suggest that curcumin, if added to standard care, might improve depressive and anxiety symptoms in people with depression. However, given the small sample size, our results should be cautiously interpreted. Further trials should be implemented, particularly in Western countries, where curcumin does not represent a usual component of dietary regimens.
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Probability of major depression diagnostic classification based on the SCID, CIDI and MINI diagnostic interviews controlling for Hospital Anxiety and Depression Scale - Depression subscale scores: An individual participant data meta-analysis of 73 primary studies.
Wu, Y, Levis, B, Sun, Y, Krishnan, A, He, C, Riehm, KE, Rice, DB, Azar, M, Yan, XW, Neupane, D, et al
Journal of psychosomatic research. 2020;:109892
Abstract
OBJECTIVE Two previous individual participant data meta-analyses (IPDMAs) found that different diagnostic interviews classify different proportions of people as having major depression overall or by symptom levels. We compared the odds of major depression classification across diagnostic interviews among studies that administered the Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). METHODS Data accrued for an IPDMA on HADS-D diagnostic accuracy were analysed. We fit binomial generalized linear mixed models to compare odds of major depression classification for the Structured Clinical Interview for DSM (SCID), Composite International Diagnostic Interview (CIDI), and Mini International Neuropsychiatric Interview (MINI), controlling for HADS-D scores and participant characteristics with and without an interaction term between interview and HADS-D scores. RESULTS There were 15,856 participants (1942 [12%] with major depression) from 73 studies, including 15,335 (97%) non-psychiatric medical patients, 164 (1%) partners of medical patients, and 357 (2%) healthy adults. The MINI (27 studies, 7345 participants, 1066 major depression cases) classified participants as having major depression more often than the CIDI (10 studies, 3023 participants, 269 cases) (adjusted odds ratio [aOR] = 1.70 (0.84, 3.43)) and the semi-structured SCID (36 studies, 5488 participants, 607 cases) (aOR = 1.52 (1.01, 2.30)). The odds ratio for major depression classification with the CIDI was less likely to increase as HADS-D scores increased than for the SCID (interaction aOR = 0.92 (0.88, 0.96)). CONCLUSION Compared to the SCID, the MINI may diagnose more participants as having major depression, and the CIDI may be less responsive to symptom severity.
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The Accuracy of the Patient Health Questionnaire-9 Algorithm for Screening to Detect Major Depression: An Individual Participant Data Meta-Analysis.
He, C, Levis, B, Riehm, KE, Saadat, N, Levis, AW, Azar, M, Rice, DB, Krishnan, A, Wu, Y, Sun, Y, et al
Psychotherapy and psychosomatics. 2020;(1):25-37
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Abstract
BACKGROUND Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results. OBJECTIVE To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10. METHODS Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview. RESULTS Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22-0.24 lower compared to fully structured interviews and 0.06-0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of ≥10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82-0.92) and 0.86 (0.82-0.88). CONCLUSIONS The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression.
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Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis.
Köhler, CA, Freitas, TH, Stubbs, B, Maes, M, Solmi, M, Veronese, N, de Andrade, NQ, Morris, G, Fernandes, BS, Brunoni, AR, et al
Molecular neurobiology. 2018;(5):4195-4206
Abstract
Mounting evidence suggests that aberrations in immune-inflammatory pathways contribute to the pathophysiology of major depressive disorder (MDD), and individuals with MDD may have elevated levels of predominantly pro-inflammatory cytokines and C-reactive protein. In addition, previous meta-analyses suggest that antidepressant drug treatment may decrease peripheral levels of interleukin-1 beta (IL-1β) and IL-6. Recently, several new studies examining the effect of antidepressants on these cytokines have been published, and so we performed an updated meta-analysis of studies that measured peripheral levels of cytokines and chemokines during antidepressant treatment in patients with MDD. The PubMed/MEDLINE, EMBASE, and PsycInfo databases were searched from inception through March 9, 2017. Forty-five studies met inclusion criteria (N = 1517). Peripheral levels of IL-6, tumor necrosis factor-alpha (TNF-α), IL-1β, IL-10, IL-2, IL-4, interferon-γ, IL-8, the C-C motif ligand 2 chemokine (CCL-2), CCL-3, IL-1 receptor antagonist, IL-13, IL-17, IL-5, IL-7, and the soluble IL-2 receptor were measured in at least three datasets and thus were meta-analyzed. Antidepressant treatment significantly decreased peripheral levels of IL-6 (Hedges g = -0.454, P <0.001), TNF-α (g = -0.202, P = 0.015), IL-10 (g = -0.566, P = 0.012), and CCL-2 (g = -1.502, P = 0.006). These findings indicate that antidepressants decrease several markers of peripheral inflammation. However, this meta-analysis did not provide evidence that reductions in peripheral inflammation are associated with antidepressant treatment response although few studies provided separate data for treatment responders and non-responders.
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N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials.
Zheng, W, Zhang, QE, Cai, DB, Yang, XH, Qiu, Y, Ungvari, GS, Ng, CH, Berk, M, Ning, YP, Xiang, YT
Acta psychiatrica Scandinavica. 2018;(5):391-400
Abstract
OBJECTIVE This systematic review and meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive N-acetylcysteine (NAC), an antioxidant drug, in treating major depressive disorder (MDD), bipolar disorder, and schizophrenia. METHODS The PubMed, Cochrane Library, PsycINFO, CNKI, CBM, and WanFang databases were independently searched and screened by two researchers. Standardized mean differences (SMDs), risk ratios, and their 95% confidence intervals (CIs) were computed. RESULTS Six RCTs (n = 701) of NAC for schizophrenia (three RCTs, n = 307), bipolar disorder (two RCTs, n = 125), and MDD (one RCT, n = 269) were identified and analyzed as separate groups. Adjunctive NAC significantly improved total psychopathology (SMD = -0.74, 95% CI: -1.43, -0.06; I2 = 84%, P = 0.03) in schizophrenia, but it had no significant effect on depressive and manic symptoms as assessed by the Young Mania Rating Scale in bipolar disorder and only a small effect on major depressive symptoms. Adverse drug reactions to NAC and discontinuation rates between the NAC and control groups were similar across the three disorders. CONCLUSIONS Adjunctive NAC appears to be a safe treatment that has efficacy for schizophrenia, but not for bipolar disorder or MDD. Further higher quality RCTs are warranted to determine the role of adjunctive NAC in the treatment of major psychiatric disorders.
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Efficacy and safety of levomilnacipran, vilazodone and vortioxetine compared with other second-generation antidepressants for major depressive disorder in adults: A systematic review and network meta-analysis.
Wagner, G, Schultes, MT, Titscher, V, Teufer, B, Klerings, I, Gartlehner, G
Journal of affective disorders. 2018;:1-12
Abstract
BACKGROUND Second-generation antidepressants dominate the medical management of major depressive disorder (MDD). Levomilnacipran, vilazodone and vortioxetine are the latest therapeutic options approved for the treatment of MDD. This systematic review aims to compare the benefits and harms of vilazodone, levomilnacipran, and vortioxetine with one another and other second-generation antidepressants. METHODS We searched electronic databases up to September 2017 and reviewed reference lists and pharmaceutical dossiers to detect published and unpublished studies. Two reviewers independently screened abstracts and full text articles, and rated the risk of bias of included studies. Randomized controlled trials (RCTs) and controlled observational studies including adult outpatients with MDD were eligible for inclusion. We conducted network meta-analyses on response to treatment using frequentist multivariate meta-analyses models. Placebo- and active-controlled trials were eligible for network meta-analyses. RESULTS Twenty-four studies met our inclusion criteria. Direct comparisons were limited to vilazodone versus citalopram, and vortioxetine versus duloxetine, paroxetine, or venlafaxine XR (extended release). Results of head-to-head trials and network meta-analyses, overall, indicated similar efficacy among levomilnacipran, vilazodone, or vortioxetine and other second-generation antidepressants. Although rates of overall adverse events and discontinuation due to adverse events were similar, RCTs reported several differences in specific adverse events. For most outcomes the strength of evidence was low. LIMITATIONS Limitations are the focus of literature searches on studies published in English, possible reporting biases, and general methodological limitations of network meta-analyses. CONCLUSIONS Overall, the available evidence does not indicate greater benefits or fewer harms of levomilnacipran, vilazodone, and vortioxetine compared with other second-generation antidepressants.
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Comparative Benefits and Harms of Complementary and Alternative Medicine Therapies for Initial Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis.
Asher, GN, Gartlehner, G, Gaynes, BN, Amick, HR, Forneris, C, Morgan, LC, Coker-Schwimmer, E, Boland, E, Lux, LJ, Gaylord, S, et al
Journal of alternative and complementary medicine (New York, N.Y.). 2017;(12):907-919
Abstract
OBJECTIVES To report the comparative benefits and harms of exercise and complementary and alternative medicine (CAM) treatments with second-generation antidepressants (SGA) for major depressive disorder (MDD). DESIGN Systematic review and meta-analysis. SETTINGS Outpatient clinics. SUBJECTS Adults, aged 18 years and older, with MDD receiving an initial treatment attempt with SGA. INTERVENTIONS Any CAM or exercise intervention compared with an SGA. OUTCOME MEASURES Treatment response, remission, change in depression rating, adverse events, treatment discontinuation, and treatment discontinuation due to adverse events. RESULTS We found 22 randomized controlled trials for direct comparisons and 127 trials for network meta-analyses, including trials of acupuncture, omega-3 fatty acids, S-adenosyl methionine, St. John's wort, and exercise. For most treatment comparisons, we found no differences between treatment groups for response and remission. However, the risk of bias of these studies led us to conclude that the strength of evidence for these findings was either low or insufficient. The risk of treatment harms and treatment discontinuation attributed to adverse events was higher for selective serotonin receptor inhibitors than for St. John's wort. CONCLUSIONS Although we found little difference in the comparative efficacy of most CAM therapies or exercise and SGAs, the overall poor quality of the available evidence base tempers any conclusions that we might draw from those trials. Future trials should incorporate patient-oriented outcomes, treatment expectancy, depressive severity, and harms assessments into their designs; antidepressants should be administered over their full dosage ranges; and larger trials using methods to reduce sampling bias are needed.
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Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies.
Köhler, CA, Freitas, TH, Maes, M, de Andrade, NQ, Liu, CS, Fernandes, BS, Stubbs, B, Solmi, M, Veronese, N, Herrmann, N, et al
Acta psychiatrica Scandinavica. 2017;(5):373-387
Abstract
OBJECTIVE To conduct a systematic review and meta-analysis of studies that measured cytokine and chemokine levels in individuals with major depressive disorder (MDD) compared to healthy controls (HCs). METHOD The PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched up until May 30, 2016. Effect sizes were estimated with random-effects models. RESULT Eighty-two studies comprising 3212 participants with MDD and 2798 HCs met inclusion criteria. Peripheral levels of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, IL-10, the soluble IL-2 receptor, C-C chemokine ligand 2, IL-13, IL-18, IL-12, the IL-1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HCs, whereas interferon-gamma levels were lower in MDD (Hedge's g = -0.477, P = 0.043). Levels of IL-1β, IL-2, IL-4, IL-8, the soluble IL-6 receptor (sIL-6R), IL-5, CCL-3, IL-17, and transforming growth factor-beta 1 were not significantly altered in individuals with MDD compared to HCs. Heterogeneity was large (I2 : 51.6-97.7%), and sources of heterogeneity were explored (e.g., age, smoking status, and body mass index). CONCLUSION Our results further characterize a cytokine/chemokine profile associated with MDD. Future studies are warranted to further elucidate sources of heterogeneity, as well as biosignature cytokines secreted by other immune cells.
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Statins for the treatment of depression: A meta-analysis of randomized, double-blind, placebo-controlled trials.
Salagre, E, Fernandes, BS, Dodd, S, Brownstein, DJ, Berk, M
Journal of affective disorders. 2016;:235-42
Abstract
BACKGROUND In epidemiological studies, statins appear to benefit mood, and there are now some randomized controlled trials examining the efficacy of statins. However, the role of statins in depression remains uncertain. Thus the aim of this paper was to assess the effect of statins on depressive symptoms by performing a meta-analysis of all double-blind, randomized, placebo controlled clinical trials (RCT) conducted in subjects with depression. METHODS A systematic search was executed using PubMed and ClinicalTrials.gov in November 30th, 2015 for all double-blind, RCT of statins versus placebo in persons with depressive symptoms. Sixty-seven potential articles were identified through search of electronic databases, of those three met inclusion criteria and were included in the meta-analysis. The outcome measure was change in Hamilton Depression Rating Scale (HDRS) scores associated with statin use. A meta-analysis was conducted and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. GRADE was used to assess study quality. RESULTS The three articles included provided data on 165 participants with moderate to severe depression. Of these, 82 were randomized to statins as an adjuvant therapy to antidepressant treatment (i.e., citalopram or fluoxetine) and 83 to the placebo arm. All studies were double-blind RCTs, with a follow-up of 6-12 weeks. The statin agents evaluated were lovastatin, atorvastatin, and simvastatin. When compared to placebo, statins, as add-on to treatment as usual, largely improved depressive symptoms as assessed by the HDRS (SMD=-0.73, 95% IC -1.04 to -0.42, p<0.001, 3 between-group comparisons, n=165). No serious adverse effects were reported. CONCLUSIONS Our results suggest that adjunctive treatment with statins could be useful for the treatment of depressive symptoms. Additional double-blind, randomised, placebo-controlled trials are necessary to settle the matter.
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Lamotrigine compared to placebo and other agents with antidepressant activity in patients with unipolar and bipolar depression: a comprehensive meta-analysis of efficacy and safety outcomes in short-term trials.
Solmi, M, Veronese, N, Zaninotto, L, van der Loos, ML, Gao, K, Schaffer, A, Reis, C, Normann, C, Anghelescu, IG, Correll, CU
CNS spectrums. 2016;(5):403-418
Abstract
OBJECTIVES To meta-analytically summarize lamotrigine's effectiveness and safety in unipolar and bipolar depression. METHODS We conducted systematic PubMed and SCOPUS reviews (last search =10/01/2015) of randomized controlled trials comparing lamotrigine to placebo or other agents with antidepressant activity in unipolar or bipolar depression. We performed a random-effects meta-analysis of depression ratings, response, remission, and adverse effects calculating standardized mean difference (SMD) and risk ratio (RR) ±95% confidence intervals (CIs). RESULTS Eighteen studies (n=2152, duration=9.83 weeks) in patients with unipolar depression (studies=4, n=187; monotherapy vs lithium=1, augmentation of antidepressants vs placebo=3) or bipolar depression (studies=14, n=1965; monotherapy vs placebo=5, monotherapy vs lithium or olanzapine+fluoxetine=2, augmentation of antidepressants vs placebo=1, augmentation of mood stabilizers vs placebo=3, augmentation of mood stabilizers vs trancylpromine, citalopram, or inositol=3) were meta-analyzed. Lamotrigine's efficacy for depressive symptoms did not differ significantly in monotherapy vs augmentation studies (vs. placebo: p=0.98, I2=0%; vs active agents: p=0.48, I2=0%) or in unipolar vs bipolar patients (vs placebo: p=0.60, I2=0%), allowing pooling of each placebo-controlled and active-controlled trials. Lamotrigine outperformed placebo regarding depressive symptoms (studies=11, n=713 vs n=696; SMD=-0.15, 95% CI=-0.27, -0.02, p=0.02, heterogeneity: p=0.24) and response (after removing one extreme outlier; RR=1.42, 95% CI=1.13-1.78; p=0.003, heterogeneity: p=0.08). Conversely, lamotrigine did not differ regarding efficacy on depressive symptoms, response, or remission from lithium, olanzapine+fluoxetine, citalopram, or inositol (studies=6, n=306 vs n=318, p-values=0.85-0.92). Adverse effects and all-cause/specific-cause discontinuation were similar across all comparisons. CONCLUSIONS Lamotrigine was superior to placebo in improving unipolar and bipolar depressive symptoms, without causing more frequent adverse effects/discontinuations. Lamotrigine did not differ from lithium, olanzapine+fluoxetine, citalopram, or inositol.