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The New England Journal of Medicine Dec 2023
Review
Topics: Humans; Depressive Disorder; Technology; Wearable Electronic Devices
PubMed: 38157501
DOI: 10.1056/NEJMra2215898 -
Expert Opinion on Pharmacotherapy 2023Longer treatment times, more comorbidity, more severe impairments in social, psychological, and emotional functioning, increased healthcare use, and more... (Review)
Review
INTRODUCTION
Longer treatment times, more comorbidity, more severe impairments in social, psychological, and emotional functioning, increased healthcare use, and more hospitalizations are all factors that are related to dysthymia. Given the significant prevalence of dysthymia (including persistent depressive disorder) worldwide, its comorbidity with several mental disorders, and the detrimental effects of these comorbidities, it is important to conduct a systematic review to compare the effects of pharmacological acute and maintenance treatments for dysthymia with placebo and standard care in the last 10 years, based on the publication of DSM5.
AREAS COVERED
This systematic review was performed according to PRISMA guidelines. Databases, including PubMed and Cochrane Central Register of Controlled Trials, were searched to assess the effects of pharmacological acute and maintenance treatments for dysthymia in comparison with placebo and treatment as usual.
EXPERT OPINION
Our review shows that SSRIs and SNRIs present efficacy for dysthymia treatment, and L-Acetylcarnitine should be investigated further for this condition in elderly patients. The comparison of antidepressant medication versus placebo showed coherent results based on three studies favoring pharmacotherapy as an effective treatment for participants with dysthymia. However, the scarcity of research on continuation and maintenance therapy in people with dysthymia highlights the need for more primary research.
Topics: Aged; Humans; Antidepressive Agents; Comorbidity; Depressive Disorder; Dysthymic Disorder; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 37787056
DOI: 10.1080/14656566.2023.2265809 -
Psychopharmacology Bulletin Aug 2023The first monoamine oxidase inhibitors (MAOIs) used for the treatment of depression in the 1950-60s were credited with treating severe melancholic depression (MeD)... (Review)
Review
The first monoamine oxidase inhibitors (MAOIs) used for the treatment of depression in the 1950-60s were credited with treating severe melancholic depression (MeD) successfully and greatly reducing the need for electroconvulsive therapy (ECT). Following the hiatus caused by the then ill-understood cheese reaction, MAOI use was relegated to atypical and treatment-resistant depressions only, based on data from insufficiently probing research studies suggesting their comparatively lesser effectiveness in MeD. The siren attraction of new 'better' drugs with different mechanisms amplified this trend. Following a re-evaluation of the data, we suggest that MAOIs are effective in MeD. Additionally, the broad unitary conceptualisation of major depressive disorder (MDD) in the DSM model diminished the chance of demonstrating distinctive responses to different antidepressant drugs (ADs) such as SSRIs, TCAs, and MAOIs, thereby further reducing the interest in MAOIs. More reliable categorical distinction of MeD, disentangling it from MDD, may be possible if more sensitive measuring instruments (CORE, SMPI) are used. We suggest these issues will benefit from re-appraisement via an inductive reasoning process within a binary (rather than a unitary) model for defining the different depressive disorders, allowing for the use of more reliable diagnostic criteria for MeD in particular. We conclude that MAOIs remain essential for, , TCA-resistant MeD, and should typically be used prior to ECT; additionally, they have a role in maintaining remission in cases treated with ECT (and ketamine/esketamine). We suggest that MAOIs should be utilized earlier in treatment algorithms and with greater regularity than is presently the case.
Topics: Humans; Monoamine Oxidase Inhibitors; Depressive Disorder, Major; Depression; Depressive Disorder, Treatment-Resistant; Electroconvulsive Therapy
PubMed: 37601082
DOI: No ID Found -
Psychiatry Research Oct 2023Our meta-analysis demonstrated that intermittent theta burst stimulation (iTBS)/bilateral-TBS (Bi-TBS) and high-frequency repetitive transcranial magnetic stimulation... (Meta-Analysis)
Meta-Analysis
Our meta-analysis demonstrated that intermittent theta burst stimulation (iTBS)/bilateral-TBS (Bi-TBS) and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS)/bilateral-rTMS (Bi-rTMS) had similar efficacy, acceptability, and safety profiles for antidepressant treatment-resistant major depressive disorder (AD-TRD). In our sensitivity analysis that excluded a study that compared Bi-TBS with Bi-rTMS for older adults, all efficacy outcomes were also comparable between iTBS and HF-rTMS. Because iTBS does not require higher stimulation intensity and a longer stimulus time than conventional HF-rTMS protocols, we speculated that for those with AD-TRD, iTBS/Bi-TBS is a more helpful therapeutic modality in clinical practice than HF-rTMS/Bi-rTMS.
Topics: Humans; Aged; Depressive Disorder, Major; Transcranial Magnetic Stimulation; Depressive Disorder, Treatment-Resistant; Antidepressive Agents; Treatment Outcome
PubMed: 37657200
DOI: 10.1016/j.psychres.2023.115452 -
Genes Dec 2023Major depressive disorder (MDD) is a complex disorder and a leading cause of disability in 280 million people worldwide. Many environmental factors, such as microbes,... (Review)
Review
Major depressive disorder (MDD) is a complex disorder and a leading cause of disability in 280 million people worldwide. Many environmental factors, such as microbes, drugs, and diet, are involved in the pathogenesis of depressive disorders. However, the underlying mechanisms of depression are complex and include the interaction of genetics with epigenetics and the host immune system. Modifications of the gut microbiome and its metabolites influence stress-related responses and social behavior in patients with depressive disorders by modulating the maturation of immune cells and neurogenesis in the brain mediated by epigenetic modifications. Here, we discuss the potential roles of a leaky gut in the development of depressive disorders via changes in gut microbiota-derived metabolites with epigenetic effects. Next, we will deliberate how altering the gut microbiome composition contributes to the development of depressive disorders via epigenetic alterations. In particular, we focus on how microbiota-derived metabolites such as butyrate as an epigenetic modifier, probiotics, maternal diet, polyphenols, drugs (e.g., antipsychotics, antidepressants, and antibiotics), and fecal microbiota transplantation could positively alleviate depressive-like behaviors by modulating the epigenetic landscape. Finally, we will discuss challenges associated with recent therapeutic approaches for depressive disorders via microbiome-related epigenetic shifts, as well as opportunities to tackle such problems.
Topics: Humans; Depressive Disorder, Major; Microbiota; Gastrointestinal Microbiome; Probiotics; Epigenesis, Genetic
PubMed: 38137038
DOI: 10.3390/genes14122217 -
Drug Discovery Today Sep 2023Current treatments modalities for major depressive disorder (MDD) mainly target the monoaminergic neurotransmission. However, the therapeutic inadequacy and adverse... (Review)
Review
Current treatments modalities for major depressive disorder (MDD) mainly target the monoaminergic neurotransmission. However, the therapeutic inadequacy and adverse effects confine the use of these conventional antidepressants to a limited subset of MDD patients. The classical antidepressants are increasingly proving unsatisfactory in tackling the treatment-resistant depression (TRD). Hence, the focus of treatment is shifting to alternative pathogenic pathways involved in depression. Preclinical and clinical evidences accumulated across the last decades have unequivocally affirmed the causative role of immuno-inflammatory pathways in the progression of depression. There is an upsurge in the clinical evaluations of the drugs having anti-inflammatory effects as antidepressants. This review highlights the molecular mechanisms connecting the inflammatory pathways to the MDD and current clinical status of inflammation modulating drugs in the treatment of MDD.
Topics: Humans; Depressive Disorder, Major; Antidepressive Agents; Depressive Disorder, Treatment-Resistant; Inflammation
PubMed: 37422168
DOI: 10.1016/j.drudis.2023.103697 -
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 -
The Journal of Clinical Psychiatry Aug 2023Perinatal depression (PND) is one of the most common medical conditions associated with pregnancy, with 1 in 7 women impacted by PND symptoms and 1 in 13 meeting...
Perinatal depression (PND) is one of the most common medical conditions associated with pregnancy, with 1 in 7 women impacted by PND symptoms and 1 in 13 meeting criteria for major depressive disorder. Unfortunately, half of postpartum depression (PPD) cases begin during pregnancy but are not diagnosed until postpartum. Delayed diagnosis and treatment of PND lead to poor outcomes for both mother and child. The American College of Obstetricians and Gynecologists recently updated its recommendation that screening for perinatal depression and anxiety occur at the initial prenatal visit, later in pregnancy, and at postpartum. Several hypotheses have been developed to explain the pathophysiology of PND including endocrine, epigenetic, synaptic transmission, neural network, neurosteroid, stress, and inflammatory mechanisms. Researchers believe that the answer lies in a synthesized mechanism of all of these models. Novel and emerging therapeutics are focusing on the neurosteroid mechanism within the integrated hypothesis. Neuroactive steroids are changing the understanding of the pathophysiology of depression and PPD, and novel and emerging therapeutics with new mechanisms of action based on these findings are impacting the treatment paradigm for this widespread and burdensome disorder.
Topics: Female; Humans; Pregnancy; Anxiety; Depression; Depression, Postpartum; Depressive Disorder, Major; Neurosteroids; Postpartum Period
PubMed: 37585246
DOI: 10.4088/JCP.sagppd3003sho -
Neuroscience Jun 2024Major depressive disorder is one of the most prevalent psychiatric diseases, and up to 30-40% of patients remain symptomatic despite treatment. Novel therapies are... (Review)
Review
Major depressive disorder is one of the most prevalent psychiatric diseases, and up to 30-40% of patients remain symptomatic despite treatment. Novel therapies are sorely needed, and animal models may be used to elucidate fundamental neurobiological processes that contribute to human disease states. We conducted a systematic review of current preclinical approaches to investigating treatment resistance with the goal of describing a path forward for improving our understanding of treatment resistant depression. We conducted a broad literature search to identify studies relevant to the preclinical investigation of treatment resistant depression. We followed PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) guidelines and included all relevant studies. We identified 467 studies in our initial search. Of these studies, we included 69 in our systematic review after applying our inclusion/exclusion criteria. We identified 10 broad strategies for investigating treatment resistance in animal models. Stress hormone administration was the most commonly used model, and the most common behavioral test was the forced swim test. We systematically identified and reviewed current approaches for gaining insight into the neurobiology underlying treatment resistant depression using animal models. Each approach has its advantages and disadvantages, but all require careful consideration of their potential limitations regarding therapeutic translation. An enhanced understanding of treatment resistant depression is sorely needed given the burden of disease and lack of effective therapies.
Topics: Animals; Disease Models, Animal; Antidepressive Agents; Depressive Disorder, Treatment-Resistant; Humans; Depressive Disorder, Major
PubMed: 38697464
DOI: 10.1016/j.neuroscience.2024.04.013 -
Journal of Affective Disorders Apr 2024Over the course of the 19th century, the concept of melancholia morphed from a partial insanity defined by disorders of judgment to a disorder characterized primarily by... (Review)
Review
Over the course of the 19th century, the concept of melancholia morphed from a partial insanity defined by disorders of judgment to a disorder characterized primarily by mood disturbances. The francophone Belgian psychiatrist Joseph Guislain, whose work has not been previously translated into English, played an important role in this transition. We translate and comment upon two of his key descriptions of melancholia from 1835 and 1852, emphasizing the following 5 features. First, his concept of melancholia is quite "modern" meeting all DSM-5 criteria for major depression. Second, his clinical descriptions are vivid, often giving voice to his patients. Third, other aspects of his text reflect older concepts, including 17th century melancholic subtypes. Fourth, and of particular historical import, he was, in 1835, likely the first major European alienist to argue that nonpsychotic melancholia was an important form of the disorder and a legitimate mental illness. This represented key step in the transition of melancholia from a psychotic to a mood disorder and also helped expand the 18th century model of insanity which was as restricted solely to disturbances of judgment/imagination. Fifth, beginning with his 1835 writings, but more prominently in his 1852 text, Guislain emphasizes that melancholia is a form of phrenalgia - mental pain. In so doing, he played an important role in helping initiate this influential psychophysiological theory of melancholia that was championed by Wilhelm Griesinger and other important German and English psychiatrists later in the 19th century.
Topics: Humans; Depression; Psychotic Disorders; Mood Disorders; Depressive Disorder, Major; Writing
PubMed: 38253135
DOI: 10.1016/j.jad.2024.01.195