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Pharmacological Reports : PR Dec 2023Treatment-resistant depression (TRD) is a subgroup of major depressive disorder in which the use of classical antidepressant treatments fails to achieve satisfactory... (Review)
Review
Treatment-resistant depression (TRD) is a subgroup of major depressive disorder in which the use of classical antidepressant treatments fails to achieve satisfactory treatment results. Although there are various definitions and grading models for TRD, common criteria for assessing TRD have still not been established. However, a common feature of any TRD model is the lack of response to at least two attempts at antidepressant pharmacotherapy. The causes of TRD are not known; nevertheless, it is estimated that even 60% of TRD patients are so-called pseudo-TRD patients, in which multiple biological factors, e.g., gender, age, and hormonal disturbances are concomitant with depression and involved in antidepressant drug resistance. Whereas the phenomenon of TRD is a complex disorder difficult to diagnose and successfully treat, the search for new treatment strategies is a significant challenge of modern pharmacology. It seems that despite the complexity of the TRD phenomenon, some useful animal models of TRD meet the construct, the face, and the predictive validity criteria. Based on the literature and our own experiences, we will discuss the utility of animals exposed to the stress paradigm (chronic mild stress, CMS), and the Wistar Kyoto rat strain representing an endogenous model of TRD. In this review, we will focus on reviewing research on existing and novel therapies for TRD, including ketamine, deep brain stimulation (DBS), and psychedelic drugs in the context of preclinical studies in representative animal models of TRD.
Topics: Rats; Animals; Humans; Depression; Depressive Disorder, Major; Antidepressive Agents; Depressive Disorder, Treatment-Resistant; Rats, Inbred WKY
PubMed: 37882914
DOI: 10.1007/s43440-023-00542-9 -
JAMA Pediatrics Nov 2023The COVID-19 pandemic has contributed to poorer mental health and a greater need for treatment. Nationally representative estimates of major depressive disorder (MDD)...
IMPORTANCE
The COVID-19 pandemic has contributed to poorer mental health and a greater need for treatment. Nationally representative estimates of major depressive disorder (MDD) and mental health treatment among US adolescents during the pandemic are needed.
OBJECTIVE
To estimate MDD prevalence among adolescents, evaluate mental health treatment use among adolescents with MDD, and assess differences by race and ethnicity.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional analysis of the nationally representative 2021 National Survey on Drug Use and Health included noninstitutionalized US adolescents between the ages of 12 and 17 years (n = 10 743). Analytic weights were applied to all rates and model estimates to be nationally representative and account for sample design and survey nonresponse. Data were collected from January 14 to December 20, 2021, and analyzed from February 11 to April 3, 2023.
EXPOSURES
Self-reported race and ethnicity.
MAIN OUTCOMES AND MEASURES
Dichotomous outcomes of MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition), MDD-specific mental health treatment, any type of mental health treatment, telehealth visits, and delays in mental health treatment.
RESULTS
The sample included 10 743 adolescents (51.1% male). Self-reported race and ethnicity included 5.1% Asian, 14.1% Black, 23.3% Latinx, 51.2% White, and 6.3% more than 1 race. Ages were evenly distributed: 34.0% aged 12 to 13 years; 33.3% aged 14 to 15 years; and 32.7% aged 16 to 17 years. Adolescents of more than 1 race or ethnicity had the highest MDD rate (26.5%). Compared with White adolescents, the lowest rates of any MDD treatment overall were found among Latinx adolescents (29.2% [95% CI, 22.2%-36.2%]) and those of more than 1 race or ethnicity (21.1% [95% CI, 11.6%-30.7%]). Similar results were found for treatment by any clinician (Latinx, 25.6% [95% CI, 18.8%-32.4%]; >1 race or ethnicity, 19.1% [95% CI, 9.7%-28.6%]), treatment by a mental health specialist (Latinx, 22.9% [95% CI, 16.9%-28.9%]; >1 race or ethnicity, 16.7% [95% CI, 7.1%-26.3%]), treatment by a nonspecialist clinician (Latinx, 7.3% [95% CI, 3.3%-11.3%]; >1 race or ethnicity, 4.8% [95% CI, 1.9%-7.7%]), and use of any psychotropic medication prescription (Latinx, 11.6% [95% CI, 7.3%-15.9%]; >1 race or ethnicity, 8.3% [95% CI, 2.8%-13.7]). Compared with White adolescents, Black adolescents had lower rates of MDD treatment by any clinician (31.7% [95% CI, 23.7%-39.8%]) and by nonspecialist clinicians (8.4% [95% CI, 3.8%-13.2%]) and experienced lower prescription rates for any psychotropic medication (12.6 [95% CI, 4.6%-20.6%]). Asian (16.0% [95% CI, 5.0%-27.2%]) and Latinx (17.8% [95% CI, 12.6%-23.0%]) adolescents had lower rates of virtual mental health treatment compared with White adolescents. Black (19.1% [95% CI, 14.1%-24.2%]) and Latinx (17.9% [95% CI, 15.0%-21.1%]) adolescents had lower rates of appointments transition to telehealth, while Black adolescents (14.1% [95% CI, 10.7%-17.4%]) experienced delays getting their prescriptions.
CONCLUSIONS AND RELEVANCE
During the first full calendar year of the pandemic, approximately 1 in 5 adolescents had MDD, and less than half of adolescents who needed treatment had any mental health treatment. Adolescents in racial and ethnic minority groups, particularly Latinx, experienced the lowest treatment rates. Federal policy should target adolescents as a whole, and minority populations in particular, to ensure equitable treatment access. Efforts should consider the social, racial, ethnic, and cultural determinants of health.
Topics: Humans; Male; Adolescent; Child; Female; Ethnicity; Depressive Disorder, Major; Cross-Sectional Studies; Pandemics; Minority Groups
PubMed: 37812424
DOI: 10.1001/jamapediatrics.2023.3996 -
Neuroscience and Biobehavioral Reviews May 2024Major depressive, bipolar, or psychotic disorders are preceded by earlier manifestations in behaviours and experiences. We present a synthesis of evidence on... (Meta-Analysis)
Meta-Analysis Review
Major depressive, bipolar, or psychotic disorders are preceded by earlier manifestations in behaviours and experiences. We present a synthesis of evidence on associations between person-level antecedents (behaviour, performance, psychopathology) in childhood, adolescence, or early adulthood and later onsets of major depressive disorder, bipolar disorder, or psychotic disorder based on prospective studies published up to September 16, 2022. We screened 11,342 records, identified 460 eligible publications, and extracted 570 risk ratios quantifying the relationships between 52 antecedents and onsets in 198 unique samples with prospective follow-up of 122,766 individuals from a mean age of 12.4 to a mean age of 24.8 for 1522,426 person years of follow-up. We completed meta-analyses of 12 antecedents with adequate data. Psychotic symptoms, depressive symptoms, anxiety, disruptive behaviors, affective lability, and sleep problems were transdiagnostic antecedents associated with onsets of depressive, bipolar, and psychotic disorders. Attention-deficit/hyperactivity and hypomanic symptoms specifically predicted bipolar disorder. While transdiagnostic and diagnosis-specific antecedents inform targeted prevention and help understand pathogenic mechanisms, extensive gaps in evidence indicate potential for improving early risk identification.
Topics: Adolescent; Humans; Adult; Child; Young Adult; Bipolar Disorder; Depressive Disorder, Major; Prospective Studies; Psychotic Disorders; Anxiety Disorders
PubMed: 38494121
DOI: 10.1016/j.neubiorev.2024.105625 -
Current Opinion in Psychiatry Jan 2024Major depressive disorder (MDD) is a common and burdensome severe mental disorder, which is expected to become the leading cause of disease burden worldwide. Most... (Review)
Review
PURPOSE OF REVIEW
Major depressive disorder (MDD) is a common and burdensome severe mental disorder, which is expected to become the leading cause of disease burden worldwide. Most patients with MDD remain untreated/undertreated. For many decades "a trial and error" approach has been adopted for selecting the best treatment plan for each individual patient, but more recently a personalized treatment approach has been proposed, by taking into account several individual and clinical factors (e.g., clinical stage, comorbidity, duration of illness). Therefore, the aim of this study is to address the most relevant innovations in the personalized treatment plan for patients with MDD.
RECENT FINDINGS
In recent years, several pharmacological and nonpharmacological innovations have been introduced in the treatment of patients with MDD. As regards pharmacological treatments, the newly developed drugs have an innovative mechanism of action, targeting the glutamatergic systems. These drugs are highly effective in improving depressive symptoms, with a good level of safety and tolerability. As regards nonpharmacological interventions, innovations include both new strategies targeting different domains (e.g., lifestyle interventions aiming to improve the physical symptoms of depression or virtual reality) and classical interventions provided through innovative mechanisms (e.g., web-based psychotherapies and use of digital approaches). Patients globally report a good level of acceptability of these interventions.
SUMMARY
Depression is a heterogeneous, complex and multidimensional disorder, representing one of the leading causes of disability worldwide. The final aim of the management of patients is functional recovery, which can be achieved by using personalized, integrated and recovery-oriented interventions. Several innovative pharmacological and nonpharmacological treatments are now available; interventions should be selected on the basis of the patient's needs and preferences in order to tailor the treatment, according to a shared decision-making approach.
Topics: Humans; Depressive Disorder, Major; Depression; Precision Medicine; Psychotherapy; Comorbidity
PubMed: 37865845
DOI: 10.1097/YCO.0000000000000903 -
Medicine Nov 2023Depression affects millions globally and often coexists with cognitive deficits. This study explored the potential of probiotics in enhancing cognition and ameliorating... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Depression affects millions globally and often coexists with cognitive deficits. This study explored the potential of probiotics in enhancing cognition and ameliorating depressive symptoms in major depressive disorder patients.
METHODS
Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and the Population, Intervention, Comparator, Outcome, and Study design framework, we systematically reviewed randomized controlled trials examining probiotic effects on cognition and depressive symptoms. Searches spanned 7 databases from January 2010 to May 2022. Risk of bias was assessed using Revised Cochrane Risk of Bias 2.0, and meta-analysis was conducted with RevMan 5.4.1. Publication bias was evaluated via Egger test.
RESULTS
In a systematic review on the effects of probiotic supplementation on cognition and depressive symptoms in depression patients, 635 records were initially identified, with 4 studies ultimately included. These randomized controlled trials were conducted across diverse regions, primarily involving females, with assessment periods ranging from 1 to 2 months. Concerning cognitive outcomes, a statistically significant moderate improvement was found with probiotic supplementation, based on the mean difference and its 95% confidence interval. However, for depressive symptoms, the overall effect was negligible and not statistically significant. A heterogeneity test indicated consistent findings across studies for both cognitive and depressive outcomes (I² = 0% for both). The potential for publication bias was evaluated using the Egger linear regression test, suggesting no significant bias, though caution is advised due to the limited number of studies.
CONCLUSION
Probiotics may enhance cognitive domains and mitigate depressive symptoms, emphasizing the gut-brain axis role. However, methodological variations and brief intervention durations call for more standardized, extensive research.
Topics: Female; Humans; Depressive Disorder, Major; Depression; Probiotics; Cognition; Research Design
PubMed: 38013351
DOI: 10.1097/MD.0000000000036005 -
Journal of Affective Disorders Jun 2024Despite the high prevalence of comorbid hypertension in patients with major depressive disorder (MDD), the relationship between the two diseases has received little...
BACKGROUND
Despite the high prevalence of comorbid hypertension in patients with major depressive disorder (MDD), the relationship between the two diseases has received little attention. Previous observational studies have descripted the association between MDD and hypertension, the causality from MDD on hypertension remained unknown. The present Mendelian randomization (MR) study aimed to assess the causal effect of MDD on hypertension.
METHODS
A set of genetics instrument was used for analysis, derived from publicly available genetic meta-analysis data. A total of 44 single-nucleotide polymorphisms (SNPs) associated with MDD. The largest genome-wide association study (GWAS) for hypertension (54,358 cases and 408,652 controls) was used to assess the effect of MDD on hypertension. Inverse variance weighted method (IVW), weighted median method (WM), and MR-Egger regression were used for MR analyses. The MR-Egger_intercept test and Cochran's Q statistic were used to determine the pleiotropy and the heterogeneity, respectively.
RESULTS
A total of 28 independent and effective MDD genetic instrumental variables were extracted from the hypertension GWAS summary statistics. Pleiotropy analysis suggested no significant pleiotropic variant among the 28 selected MDD genetic instrument variants in hypertension GWAS datasets. As MDD based on genetic changes increased, the risk of hypertension increased using MR-Egger (OR = 1.004436, 95%CI 0.9884666-1.020663, P = 0.5932928), WM (OR = 1.000499, 95%CI 1.0000188-1.000980, P = 0.0416871), and IVW (OR = 1.000573, 95%CI 1.0000732-1.001074, P = 0.0246392). Our results were robust, with no obvious bias based on investigating the single MDD SNP on hypertension.
CONCLUSIONS
Our result suggested a causal associated between genetically increased MDD and increased hypertension risk in European population.
Topics: Humans; Depressive Disorder, Major; Genome-Wide Association Study; Hypertension; Mendelian Randomization Analysis; Nonoxynol
PubMed: 38556096
DOI: 10.1016/j.jad.2024.03.144 -
Translational Psychiatry Sep 2023Treatment response and resistance in major depressive disorder (MDD) are suggested to be heritable. Due to significant challenges in defining treatment-related...
Treatment response and resistance in major depressive disorder (MDD) are suggested to be heritable. Due to significant challenges in defining treatment-related phenotypes, our understanding of their genetic bases is limited. This study aimed to derive a stringent definition of treatment resistance and to investigate the genetic overlap between treatment response and resistance in MDD. Using electronic medical records on the use of antidepressants and electroconvulsive therapy (ECT) from Swedish registers, we derived the phenotype of treatment-resistant depression (TRD) and non-TRD within ~4500 individuals with MDD in three Swedish cohorts. Considering antidepressants and lithium are first-line treatment and augmentation used for MDD, respectively, we generated polygenic risk scores (PRS) of antidepressants and lithium response for individuals with MDD and evaluated their associations with treatment resistance by comparing TRD with non-TRD. Among 1778 ECT-treated MDD cases, nearly all (94%) used antidepressants before their first ECT and the vast majority had at least one (84%) or two (61%) antidepressants of adequate duration, suggesting these MDD cases receiving ECT were resistant to antidepressants. We did not observe a significant difference in the mean PRS of antidepressant response between TRD and non-TRD; however, we found that TRD cases had a significantly higher PRS of lithium response compared to non-TRD cases (OR = 1.10-1.12 under various definitions). The results support the evidence of heritable components in treatment-related phenotypes and highlight the overall genetic profile of lithium-sensitivity in TRD. This finding further provides a genetic explanation for lithium efficacy in treating TRD.
Topics: Humans; Depressive Disorder, Major; Lithium; Antidepressive Agents; Electroconvulsive Therapy; Depressive Disorder, Treatment-Resistant
PubMed: 37770441
DOI: 10.1038/s41398-023-02602-3 -
Journal of Affective Disorders Jul 2023To explore clinical characteristics and symptomatology of major depressive disorder (MDD) with atypical features based on DSM criteria or only reversed vegetative...
OBJECTIVE
To explore clinical characteristics and symptomatology of major depressive disorder (MDD) with atypical features based on DSM criteria or only reversed vegetative symptoms.
METHOD
A total of 3187 patients who met DSM-IV TR criteria for MDD were enrolled. Demographics and symptomatology covering multiple symptom domains were assessed and compared between three groups of cases: those who met DSM criteria for atypical specifier (the DAD group), those who had at least one reversed vegetative symptoms (hypersomnia or hyperphagia) (the SAD group) without meeting DSM atypical specifier criteria, and those without any reversed vegetative symptoms (the NAD group).
RESULTS
The DAD and SAD group accounted for 4.4% and 14.4% of the participants, respectively. The DAD cases were characterized by a highest proportion of hospitalizations, longest duration of current episode and worst quality of life. The DAD and SAD cases were more likely to adopt unhealthy behaviors (smoking and alcohol drinking). Most depressive symptoms related to higher illness severity and treatment resistance were more frequent in the DAD cases, followed by the SAD cases, and least frequent in the NAD cases.
LIMITATIONS
A cross-sectional design and a non-validated questionnaire were used.
CONCLUSIONS
The findings support the role of DSM defined atypical depression as a valid MDD subtype and provide evidence for clinical utility of the simplified approach of defining atypical features based on only reversed vegetative symptoms. This has implications for illness screening, public health, suicide prevention and better treatment planning for depressed individuals with atypical features even below syndromal level.
Topics: Humans; Depressive Disorder, Major; Cross-Sectional Studies; NAD; Quality of Life; Depression; Syndrome
PubMed: 37086803
DOI: 10.1016/j.jad.2023.04.062 -
Journal of Affective Disorders Nov 2023Identifying and managing major depressive disorder (MDD) patients with suicidal ideation or behavior (MDSI) is critical for reducing the disease burden. This scoping... (Review)
Review
Major depressive disorder with suicidal ideation or behavior in Chinese population: A scoping review of current evidence on disease assessment, burden, treatment and risk factors.
BACKGROUND
Identifying and managing major depressive disorder (MDD) patients with suicidal ideation or behavior (MDSI) is critical for reducing the disease burden. This scoping review aims to map the existing evidence related to MDSI in the Chinese population.
METHOD
A scoping review was conducted to summarize the published evidence regarding epidemiology or disease burden, evaluation, diagnosis, management, and prognosis of MDSI. The search strategy imposed restriction on English or Chinese publications between 1 January 2011 and 28 February 2022.
RESULTS
Of the 14,005 identified records, 133 met the eligibility criteria and were included for analysis. The included studies were characterized as high heterogeneity in evaluation of suicidal ideation or behavior. Compared with MDD patients without suicidal ideation or behavior, MDSI patients were more likely to suffer from psychological and somatic symptoms, social function impairment, and lower quality of life. Younger age, female gender, longer disease course, and comorbid psychological or physical symptoms were consistently found to be risk factors of suicidal ideation or behavior. Relevant research gaps remain regarding comprehensive evaluation of standard clinical diagnosis, disease burden, social-cultural risk factors, and effectiveness of interventions targeting MDSI. Studies with large sample size, representative population are warranted to provide high-quality evidence.
CONCLUSIONS
MDD patients with suicidal ideation or behavior should be prioritized in treatment and resource allocation. Heterogeneity exists in the definition and evaluation of MDSI in different studies. To better inform clinical practice, it is imperative to establish a unified standard for evaluation and diagnosis of suicidal ideation or behavior among MDD population.
Topics: Humans; Depressive Disorder, Major; East Asian People; Quality of Life; Risk Factors; Suicidal Ideation
PubMed: 37619652
DOI: 10.1016/j.jad.2023.08.106 -
The New England Journal of Medicine Dec 2023
Review
Topics: Humans; Depressive Disorder; Technology; Wearable Electronic Devices
PubMed: 38157501
DOI: 10.1056/NEJMra2215898