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Brain, Behavior, and Immunity Mar 2022COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome.
OBJECTIVE
To quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome.
DATA SOURCES
Systematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists.
STUDY SELECTION
Primary research articles which evaluated individuals at least 12 weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected.
DATA EXTRACTION & SYNTHESIS
Two reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Tukey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model.
MAIN OUTCOMES & MEASURES
The co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks following COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences associated with post-COVID-19 syndrome.
RESULTS
The literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32 (95% CI, 0.27, 0.37; p < 0.001; n = 25,268; I = 99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001; n = 13,232; I = 98.0). Moreover, narrative synthesis revealed elevations in proinflammatory markers and considerable functional impairment in a subset of individuals.
CONCLUSIONS & RELEVANCE
A significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena.
STUDY REGISTRATION
PROSPERO (CRD42021256965).
Topics: COVID-19; COVID-19 Testing; Cognitive Dysfunction; Fatigue; Humans; SARS-CoV-2; Post-Acute COVID-19 Syndrome
PubMed: 34973396
DOI: 10.1016/j.bbi.2021.12.020 -
European Neuropsychopharmacology : the... Jan 2022The aim of the study was to systematically review the hard evidence alone, concerning lithium efficacy separately for the phases and clinical facets of Bipolar disorder... (Review)
Review
The aim of the study was to systematically review the hard evidence alone, concerning lithium efficacy separately for the phases and clinical facets of Bipolar disorder (BD). The PRISMA method was followed to search the MEDLINE for Randomized Controlled trials, Post-hoc analyses and Meta-analyses and review papers up to August 1st 2020, with the combination of the words 'bipolar', 'manic', 'mania', 'manic depression' and 'manic depressive' and 'randomized'. Trials and meta-analyses concerning the use of lithium either as monotherapy or in combination with other agents in adults were identified concerning acute mania (Ν=64), acute bipolar depression (Ν=78), the maintenance treatment (Ν=73) and the treatment of other issues (N = 93). Treatment guidelines were also identified. Lithium is efficacious for the treatment of acute mania including concomitant psychotic symptoms. In acute bipolar depression it is efficacious only in combination with specific agents. For the maintenance phase, it is efficacious as monotherapy mainly in the prevention of manic while its efficacy for the prevention of depressive episodes is unclear. Its combinations increase its therapeutic value. It is equaly efficacious in rapid and non-rapid cycling patients, in concomitant obsessive-compulsive symptoms, alcohol and substance abuse, the neurocognitive deficit, suicidal ideation and fatigue The current systematic review provided support for the usefulness of lithium against a broad spectrum of clinical issues in Bipolar disorder. Its efficacy is comparable to that of more recently developed agents.
Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium; Lithium Compounds; Mania; Randomized Controlled Trials as Topic
PubMed: 34980362
DOI: 10.1016/j.euroneuro.2021.10.003 -
Acta Psychiatrica Scandinavica May 2018To provide an update on the evidence base for the nature of the relationship between negative symptoms and depressive features in people with schizophrenia, and propose...
OBJECTIVE
To provide an update on the evidence base for the nature of the relationship between negative symptoms and depressive features in people with schizophrenia, and propose new models that reflect their complex relationship.
METHOD
A systematic review following PRISMA guidelines. A total of 2210 articles were identified from EMBASE, PsychInfo and MEDLINE, and further two articles were hand-searched from references. Twenty-seven met inclusion criteria and were included in the review.
RESULTS
In schizophrenia, primary evidence suggests symptoms of low mood, suicidal ideation and pessimism have more specificity for depression whereas alogia and blunted affect may have more specificity as negative symptoms. Anhedonia, anergia and avolition may be common to both.
CONCLUSION
It may be possible to further distinguish depressive features from negative symptoms in schizophrenia when detailed phenomenology is considered. However, in a proposed dimensional model, these two domains continue to share certain phenomena, highlighting their close relationship.
Topics: Comorbidity; Depressive Disorder; Humans; Schizophrenia
PubMed: 29532909
DOI: 10.1111/acps.12873 -
Progress in Neuro-psychopharmacology &... Jun 2019Anhedonia is defined as a diminished ability to experience interest or pleasure, and is a critical psychopathological dimension of major depressive disorder (MDD). The...
Anhedonia is defined as a diminished ability to experience interest or pleasure, and is a critical psychopathological dimension of major depressive disorder (MDD). The purpose of the current systematic review is to evaluate the therapeutic efficacy of pharmacological treatments on measures of anhedonia in adults with MDD. Electronic databases Cochrane Library (CENTRAL), Ovid MEDLINE, PubMed, PsycINFO, and Google Scholar were searched from inception to June 1, 2018 for longitudinal studies utilizing pharmacotherapy for the treatment of anhedonia in patients with MDD. A total of 17 eligible studies were identified (i.e., evaluated the effects of pharmacotherapy on a measure of anhedonia). Among the identified studies, the efficacy of 14 different pharmacotherapies on measures of anhedonia were evaluated, including melatonergic agents (i.e. agomelatine), monoaminergic agents (i.e. moclobemide, clomipramine, bupropion, venlafaxine, fluoxetine, amitifadine and levomilnacipran, escitalopram, and sertraline), glutamatergic agents (i.e., ketamine and riluzole), stimulants (i.e., methylphenidate), and psychedelics (i.e., psilocybin). Based on the available evidence, most antidepressants demonstrated beneficial effects on measures of anhedonia as well as the other depressive symptoms. Only escitalopram/riluzole combination treatment was ineffective in treating symptoms of anhedonia in MDD. Continued research is warranted to further support the efficacy of mechanistically-distinct antidepressants in treating symptoms of anhedonia in MDD. Future research should also aim to parse out the heterogeneous effects of different pharmacotherapies on anhedonic symptoms.
Topics: Anhedonia; Antidepressive Agents; Depressive Disorder, Major; Humans
PubMed: 30611836
DOI: 10.1016/j.pnpbp.2019.01.002 -
JAMA Jun 2020The Patient Health Questionnaire depression module (PHQ-9) is a 9-item self-administered instrument used for detecting depression and assessing severity of depression.... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The Patient Health Questionnaire depression module (PHQ-9) is a 9-item self-administered instrument used for detecting depression and assessing severity of depression. The Patient Health Questionnaire-2 (PHQ-2) consists of the first 2 items of the PHQ-9 (which assess the frequency of depressed mood and anhedonia) and can be used as a first step to identify patients for evaluation with the full PHQ-9.
OBJECTIVE
To estimate PHQ-2 accuracy alone and combined with the PHQ-9 for detecting major depression.
DATA SOURCES
MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PsycINFO, and Web of Science (January 2000-May 2018).
STUDY SELECTION
Eligible data sets compared PHQ-2 scores with major depression diagnoses from a validated diagnostic interview.
DATA EXTRACTION AND SYNTHESIS
Individual participant data were synthesized with bivariate random-effects meta-analysis to estimate pooled sensitivity and specificity of the PHQ-2 alone among studies using semistructured, fully structured, or Mini International Neuropsychiatric Interview (MINI) diagnostic interviews separately and in combination with the PHQ-9 vs the PHQ-9 alone for studies that used semistructured interviews. The PHQ-2 score ranges from 0 to 6, and the PHQ-9 score ranges from 0 to 27.
RESULTS
Individual participant data were obtained from 100 of 136 eligible studies (44 318 participants; 4572 with major depression [10%]; mean [SD] age, 49 [17] years; 59% female). Among studies that used semistructured interviews, PHQ-2 sensitivity and specificity (95% CI) were 0.91 (0.88-0.94) and 0.67 (0.64-0.71) for cutoff scores of 2 or greater and 0.72 (0.67-0.77) and 0.85 (0.83-0.87) for cutoff scores of 3 or greater. Sensitivity was significantly greater for semistructured vs fully structured interviews. Specificity was not significantly different across the types of interviews. The area under the receiver operating characteristic curve was 0.88 (0.86-0.89) for semistructured interviews, 0.82 (0.81-0.84) for fully structured interviews, and 0.87 (0.85-0.88) for the MINI. There were no significant subgroup differences. For semistructured interviews, sensitivity for PHQ-2 scores of 2 or greater followed by PHQ-9 scores of 10 or greater (0.82 [0.76-0.86]) was not significantly different than PHQ-9 scores of 10 or greater alone (0.86 [0.80-0.90]); specificity for the combination was significantly but minimally higher (0.87 [0.84-0.89] vs 0.85 [0.82-0.87]). The area under the curve was 0.90 (0.89-0.91). The combination was estimated to reduce the number of participants needing to complete the full PHQ-9 by 57% (56%-58%).
CONCLUSIONS AND RELEVANCE
In an individual participant data meta-analysis of studies that compared PHQ scores with major depression diagnoses, the combination of PHQ-2 (with cutoff ≥2) followed by PHQ-9 (with cutoff ≥10) had similar sensitivity but higher specificity compared with PHQ-9 cutoff scores of 10 or greater alone. Further research is needed to understand the clinical and research value of this combined approach to screening.
Topics: Adult; Depressive Disorder, Major; Female; Humans; Interviews as Topic; Male; Mass Screening; Patient Health Questionnaire; ROC Curve; Sensitivity and Specificity
PubMed: 32515813
DOI: 10.1001/jama.2020.6504 -
EClinicalMedicine Aug 2023Intranasal esketamine has received regulatory approvals for the treatment of depression. Recently a large trial of repeated dose racemic ketamine also demonstrated...
BACKGROUND
Intranasal esketamine has received regulatory approvals for the treatment of depression. Recently a large trial of repeated dose racemic ketamine also demonstrated efficacy in severe depression. However, uncertainties remain regarding comparative efficacy, dosage, and the time course of response.
METHODS
In this systematic review and meta-analysis, we searched Embase, Medline, Pubmed, PsycINFO, and CENTRAL up to April 13, 2023, for randomised controlled trials (RCTs) investigating ketamine for depression. Two investigators independently assessed study eligibility and risk of bias and extracted the data on depression severity scores, response and remission rates, and all-cause dropouts. Multivariable mixed-effects meta-regressions incorporated drug formulation (racemic (Rac) or esketamine (Esket)) and dose (Low or High) as covariates. Treatment effects were assessed: immediately following the first dose, during further repeated dosing, and follow-up after the final dose of a treatment course. This study is registered with PROSPERO (CRD42021221157).
FINDINGS
The systematic review identified 687 articles, of which 49 RCTs were eligible for analysis, comprising 3299 participants. Standardised mean differences (95% confidence intervals) immediately following the first/single treatment were moderate-high for all conditions (Rac-High: -0.73, -0.91 to -0.56; Esket-High: -0.48, -0.75 to -0.20; Rac-Low: -0.33, -0.54 to -0.12; Esket-Low: -0.55, -0.87 to -0.24). Ongoing effects during repeated dosing were significantly greater than the control for Rac-High (-0.61; -1.02 to -0.20) and Rac-Low (-0.55, -1.09 to -0.00), but not Esket-Low (-0.15, -0.49 to 0.19) or Esket-High (-0.22, -0.54 to 0.10). At follow-up effects remained significant for racemic ketamine (-0.65; -1.23 to -0.07) but not esketamine (-0.33; -0.96 to 0.31). All-cause dropout was similar between experiment and control conditions for both formulations combined (Odds Ratio = 1.18, 0.85-1.64). Overall heterogeneity varied from 5.7% to 87.6.
INTERPRETATION
Our findings suggested that effect sizes for depression severity, as well as response and remission rates, were numerically greater for racemic ketamine than esketamine. Higher doses were more effective than low doses. Differences were evident in initial effects, ongoing treatment, and lasting effects after the final dose.
FUNDING
None.
PubMed: 37593223
DOI: 10.1016/j.eclinm.2023.102127 -
Expert Opinion on Emerging Drugs Mar 2021The large percentage of adults with major depressive disorder (MDD) insufficiently responding and/or tolerating conventional monoamine-based antidepressants invites the...
INTRODUCTION
The large percentage of adults with major depressive disorder (MDD) insufficiently responding and/or tolerating conventional monoamine-based antidepressants invites the need for mechanistically novel treatments. Convergent evidence implicates glutamatergic signaling as a potential therapeutic target in MDD.
AREAS COVERED
The synthesis herein of preclinical and clinical studies indicates that dextromethorphan (DXM) is well tolerated and exhibits clinically significant antidepressant effects; DXM combined with bupropion has demonstrated replicated and relatively rapid onset efficacy in adults with MDD. DXM efficacy has been preliminarily reported in adults with bipolar depression. The combination of DXM and bupropion represents a pharmacokinetic and pharmacodynamic synergy which may account for the rapidity of action in MDD.
EXPERT OPINION
The combination of DXM and bupropion is a safe, well tolerated and efficacious treatment option in adults with MDD. Priority questions are whether DXM/bupropion is uniquely effective across discrete domains of psychopathology (e.g. anhedonia, reward processing, general cognitive systems) and/or whether it is able to significantly improve patient-reported outcomes (e.g. quality of life, psychosocial functioning). The availability of ketamine/esketamine and DXM/bupropion instantiates the relevance of glutamate as a treatment target in MDD. Studies in bipolar depression with DXM/bupropion are warranted as well as in MDD with suicidality.
Topics: Adult; Animals; Antidepressive Agents; Bipolar Disorder; Bupropion; Depressive Disorder, Major; Dextromethorphan; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Humans; Molecular Targeted Therapy
PubMed: 33682569
DOI: 10.1080/14728214.2021.1898588 -
Schizophrenia Bulletin Mar 2022Anhedonia, the reduced capacity to experience pleasure, has long been considered a prominent feature of schizophrenia spectrum disorders. Many domain-specific... (Meta-Analysis)
Meta-Analysis
Anhedonia, the reduced capacity to experience pleasure, has long been considered a prominent feature of schizophrenia spectrum disorders. Many domain-specific conceptualizations of anhedonia and pleasure capacity have been developed, and there currently exist a variety of self-report assessment tools that purport to assess these various domains. The current systematic review and meta-analysis (PROSPERO: CRD42020156169) aimed to quantify overall and domain-specific self-reported anhedonia in people with schizophrenia compared to nonpsychiatric controls. We performed a literature search of PsycINFO, MEDLINE, and Embase databases for dissertations and peer-reviewed articles published in English prior to June 2021. Studies employing a psychometrically validated self-report measure of anhedonia, pleasure experience or affect in people with schizophrenia, schizoaffective, or schizophreniform disorders; studies utilizing at least one clearly defined healthy or community control group for comparison; and studies providing sufficient data to calculate effect sizes were included in this review. Random and mixed effects meta-analyses, meta-regressions, and subgroup comparisons were run across domains of anhedonia to explore weighted mean effect sizes and their associated moderators. In total, 146 studies met inclusion criteria, yielding 390 Hedges' g effect sizes from the included comparisons. People with schizophrenia reported moderate-to-large elevations in overall and domain-specific anhedonia. A sensitivity analysis accounting for high risk of bias studies did not significantly impact results. Lastly, patient sex, education, negative symptom severity, antipsychotic class, and trait negative affect differentially moderated effect sizes across domains of anhedonia. Despite the heterogeneity inherent in schizophrenia spectrum disorders, self-reported anhedonia is ubiquitously reported across self-report measures in this population.
Topics: Adult; Anhedonia; Female; Humans; Male; Psychometrics; Schizophrenia; Self Report
PubMed: 34891171
DOI: 10.1093/schbul/sbab136 -
The International Journal of Eating... Feb 2022Anhedonia, or loss of pleasure, is related to deficits in reward processing across a variety of psychiatric disorders. In light of research suggesting abnormal reward... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Anhedonia, or loss of pleasure, is related to deficits in reward processing across a variety of psychiatric disorders. In light of research suggesting abnormal reward processing in eating disorders (EDs), the study of anhedonia in EDs may yield important insights into the role of reward in eating pathology. This meta-analysis and review aimed to provide both a quantitative and qualitative synthesis of the existing literature on this topic.
METHOD
We conducted this research (or these meta-analyses) according to PRISMA guidelines. We searched four databases for both peer-reviewed and unpublished literature, and included studies only if a self-report or clinical interview measure of anhedonia was administered to a sample with an ED diagnosis.
RESULTS
We included 21 studies in the systematic review, and 10 studies in two meta-analyses that compared anhedonia between ED and control samples (n = 9 studies) and within different ED diagnoses (n = 5 studies). Meta-analyses revealed that anhedonia was significantly higher in ED groups compared to healthy controls, but there was no significant difference in anhedonia between ED diagnostic groups. A qualitative review of the literature also suggested that anhedonia may be correlated with increased ED symptom severity.
DISCUSSION
Findings indicated that anhedonia is elevated in EDs and may be a relevant treatment target. Future research should examine how self-reported anhedonia may correlate with components of reward processing in EDs in order to improve theoretical models as well as targeted interventions.
Topics: Anhedonia; Anorexia Nervosa; Feeding and Eating Disorders; Humans; Reward; Self Report
PubMed: 34811779
DOI: 10.1002/eat.23645 -
Nutrients Jan 2020Abnormally high levels of physical activity have been documented throughout the literature in patients with eating disorders (ED), especially those diagnosed with...
Abnormally high levels of physical activity have been documented throughout the literature in patients with eating disorders (ED), especially those diagnosed with anorexia nervosa (AN). Yet no clear definition, conceptualization, or treatment of the problematic use of physical activity (PPA) in ED patients exists. The aim of this review is to propose a new classification of PPA, report the prevalence, triggers, predictors, maintainers and other related factors of PPA in ED patients, in addition to proposing a comprehensive model of the development of PPA in AN. A total of 47 articles, retrieved from Medline and Web of Science, met the inclusion criteria and were included in the analysis. As a result, the new approach of PPA was divided into two groups (group 1 and group 2) according to the dimension (quantitative vs qualitative approach) of physical activity that was evaluated. The prevalence of PPA in ED was reported in 20 out of 47 studies, the comparison of PPA between ED versus controls in 21 articles, and the links between PPA and psychological factors in ED in 26 articles, including depression (16/26), anxiety (13/26), obsessive-compulsiveness (9/26), self-esteem (4/26), addictiveness (1/26), regulation and verbal expression of emotions (1/26) and anhedonia (1/26). The links between PPA and ED symptomatology, PPA and weight, body mass index (BMI) and body composition in ED, PPA and age, onset, illness duration and lifetime activity status in ED, PPA and ED treatment outcome were reported in 18, 15, 7, 5 articles, respectively. All of the factors have been systematically clustered into group 1 and group 2. Results focused more on AN rather than BN due to the limited studies on the latter. Additionally, a model for the development of PPA in AN patients was proposed, encompassing five periods evolving into three clinical stages. Thus, two very opposite components of PPA in AN were suggested: voluntarily PPA increased in AN was viewed as a conscious strategy to maximize weight loss, while involuntarily PPA increased proportionally with weight-loss, indicating that exercise might be under the control of a subconscious biological drive and involuntary cognition.
Topics: Adolescent; Adult; Anorexia Nervosa; Bulimia Nervosa; Compulsive Behavior; Exercise; Female; Humans; Male; Young Adult
PubMed: 31936525
DOI: 10.3390/nu12010183