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JAMA Psychiatry Nov 2022Treatment-resistant depression (TRD) is common in older adults. Bilateral repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex for... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of Standard Sequential Bilateral Repetitive Transcranial Magnetic Stimulation vs Bilateral Theta Burst Stimulation in Older Adults With Depression: The FOUR-D Randomized Noninferiority Clinical Trial.
IMPORTANCE
Treatment-resistant depression (TRD) is common in older adults. Bilateral repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex for 48 minutes has demonstrated efficacy in TRD. Theta burst stimulation (TBS), a newer form of rTMS, can also be delivered bilaterally using left intermittent TBS and right continuous TBS for only 4 minutes.
OBJECTIVE
To establish the effectiveness and tolerability of TBS compared with standard rTMS in older adults with TRD.
DESIGN, SETTING, AND PARTICIPANTS
In this randomized noninferiority trial with open treatment and blinded assessors, recruitment occurred between December 2016 and March 2020. The trial was conducted at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada and included outpatients 60 years and older with a diagnosis of depression, moderate severity, and nonresponse to 1 or more antidepressant trial of adequate dosage and duration or intolerance of 2 or more trials.
INTERVENTIONS
Participants were randomized to receive a course of 4 to 6 weeks of either bilateral standard rTMS or TBS.
MAIN OUTCOMES AND MEASURES
The primary outcome measure was change in Montgomery-Åsberg Depression Rating Scale; secondary outcome measures included the 17-item Hamilton Rating Scale for Depression, Quick Inventory of Depressive Symptomatology (16-item) (self-report), and dropout rates. A noninferiority margin of 2.75 points was used for the primary outcome. All participants who attained the primary completion point of 4 weeks were analyzed.
RESULTS
A total of 87 participants (mean [SD] age, 67.1 [6.7] years; 47 [54.0%] female) were randomized to standard bilateral rTMS and 85 (mean [SD] age, 66.3 [5.3] years; 45 [52.9%] female) to TBS, of whom 85 (98%) and 79 (93%) were assessed for the primary outcome, respectively, whereas tolerability was assessed in all randomized participants. In the rTMS group, 4 (4.6%) were American Indian, reported other, or preferred not to answer; 5 (5.8%) were Asian; and 78 (89.7%) were White. In the TBS group, 6 (7.1%) were Asian, 2 (2.4%) were Black or reported other, and 77 (90.3%) were White. Mean (SD) Montgomery-Åsberg Depression Rating Scale total scores improved from 25.6 (4.0) to 17.3 (8.9) for rTMS and 25.7 (4.7) to 15.8 (9.1) for TBS (adjusted difference, 1.55; lower 95% CI -0.67), establishing noninferiority for TBS. The all-cause dropout rates were relatively similar between groups (rTMS: 2 of 87 [2.3%]; TBS: 6 of 85 [7.1%]; P = .14; χ2 = 2.2).
CONCLUSIONS AND RELEVANCE
In older adults with TRD, bilateral TBS compared with standard bilateral rTMS achieved noninferior reduction in depression symptoms. Both treatments had low and similar dropout rates. Using TBS rather than rTMS could increase access to treatment several-fold for older adults with TRD.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02998580.
Topics: Female; Humans; Aged; Male; Transcranial Magnetic Stimulation; Depression; Depressive Disorder, Major; Prefrontal Cortex; Depressive Disorder, Treatment-Resistant; Ontario; Treatment Outcome
PubMed: 36129719
DOI: 10.1001/jamapsychiatry.2022.2862 -
Psychoneuroendocrinology Nov 2020Depression is one of the most prevalent, disabling, and costly mental illnesses currently affecting over 300 million people worldwide. A subset of depressed patients... (Review)
Review
Depression is one of the most prevalent, disabling, and costly mental illnesses currently affecting over 300 million people worldwide. A subset of depressed patients display inflammation as indicated by increased levels of proinflammatory mediators in the blood and cerebrospinal fluid. Longitudinal and experimental studies suggest that this inflammatory profile may causally contribute to the initiation, maintenance, or recurrence of depressive episodes in the context of major depressive disorder (MDD). While the mechanistic pathways that mediate these depressogenic effects have not yet been fully elucidated, toll-like receptor (TLR) signaling is one potential common inflammatory pathway. In this review, we focus on the role that inflammation plays in depression, TLR signaling and its plasticity as a candidate pathway, its regulation by micro ribonucleic acids (miRNAs), and their potential as diagnostic biomarkers for identification of inflammatory subtypes of depression. Pre-clinical and clinical studies have demonstrated that TLR expression and TLR signaling regulators are associated with MDD. Further, TLR expression and signaling is in-turn, regulated in part by miRNAs and some TLR-responsive miRNAs indirectly modulate pathways that are implicated in MDD pathophysiology. These data suggest an intersection between TLR signaling regulation and MDD-linked pathways. While these studies suggest that miRNAs play a role in the pathophysiology of MDD via their regulatory effects on TLR pathways, the utility of miRNAs as biomarkers and potential treatment targets remains to be determined. Developing new and innovative techniques or adapting established immunological approaches to mental health, should be at the forefront in moving the field forward, especially in terms of categorization of inflammatory subtypes in MDD.
Topics: Biomarkers; Depression; Depressive Disorder, Major; Humans; Inflammation; MicroRNAs; Signal Transduction; Toll-Like Receptors
PubMed: 32911436
DOI: 10.1016/j.psyneuen.2020.104843 -
The Psychiatric Clinics of North America Jun 2023Major depressive disorder (MDD) is considered a global crisis. Conventional treatments for MDD consist of pharmacotherapy and psychotherapy, although a significant... (Review)
Review
Major depressive disorder (MDD) is considered a global crisis. Conventional treatments for MDD consist of pharmacotherapy and psychotherapy, although a significant number of patients with depression respond poorly to conventional treatments and are diagnosed with treatment-resistant depression (TRD). Transcranial photobiomodulation (t-PBM) therapy uses near-infrared light, delivered transcranially, to modulate the brain cortex. The aim of this review was to revisit the antidepressant effects of t-PBM, with a special emphasis on individuals with TRD. A search on PubMed and ClinicalTrials.gov tracked clinical studies using t-PBM for the treatment of patients diagnosed with MDD and TRD.
Topics: Humans; Depressive Disorder, Major; Depression; Brain; Psychotherapy; Antidepressive Agents; Depressive Disorder, Treatment-Resistant
PubMed: 37149348
DOI: 10.1016/j.psc.2023.02.013 -
Journal of Affective Disorders Oct 2023Children and adolescents with major depressive disorder (MDD) are at increased risk for premature cardiovascular disease (CVD). Whether adolescents with MDD manifest...
BACKGROUND
Children and adolescents with major depressive disorder (MDD) are at increased risk for premature cardiovascular disease (CVD). Whether adolescents with MDD manifest evidence of dyslipidemia, a key risk factor for CVD, is unknown.
METHODS
Youth recruited through an ambulatory psychiatry clinic and the community, were categorized following diagnostic interview as MDD or as healthy controls [HC]. CVD risk factors including high density lipoprotein (HDL), low density lipoprotein (LDL), and triglyceride concentrations were collected. Depression severity was measured using the Center for Epidemiological Studies Depression Scale for Children. The associations of diagnostic group as well as depressive symptom severity with lipid concentrations were examined using multiple regression analyses. Models were adjusted for age, sex, and standardized Body Mass Index.
RESULTS
Participants (n = 243) were 68 % female with a mean age of 15.04 ± 1.81 years. MDD and HC participants had comparable levels of dyslipidemia (MDD: 48 %, HC: 46 %, p > .7) and hypertriglyceridemia (MDD: 34 %, HC: 30 %, p > .7). Among depressed adolescents, greater depressive symptoms were associated with higher total cholesterol concentrations in unadjusted models only. Greater depressive symptoms were associated with higher HDL concentrations and a lower triglyceride-to-HDL ratio, after adjusting for covariates.
LIMITATIONS
Cross-sectional design.
CONCLUSIONS
Adolescents with clinically significant depressive symptoms manifested similar levels of dyslipidemia as healthy youth. Future studies examining the prospective trajectories of depressive symptoms and lipid concentrations are needed to determine the point at which dyslipidemia emerges in the course of MDD, and the mechanism of the association that imparts increased CVD risk for depressed youth.
Topics: Child; Humans; Adolescent; Female; Male; Depressive Disorder, Major; Depression; Prospective Studies; Cross-Sectional Studies; Triglycerides; Dyslipidemias; Cardiovascular Diseases; Lipoproteins, HDL; Cholesterol, HDL
PubMed: 37302507
DOI: 10.1016/j.jad.2023.06.017 -
American Journal of Psychotherapy Mar 2020This review details the history of the development of interpersonal psychotherapy (IPT), beginning at Yale University when Dr. Gerald Klerman led a maintenance study of... (Review)
Review
This review details the history of the development of interpersonal psychotherapy (IPT), beginning at Yale University when Dr. Gerald Klerman led a maintenance study of the treatment of depression. The trial aimed to mimic clinical practice and, therefore, included psychotherapy. This review describes the first IPT clinical trial, subsequent trials, and numerous IPT adaptations for different age groups, formats (group, telephone, computer), disorders, and educational levels of mental health trainees. As of 2017, at least 133 clinical trials of IPT had been carried out worldwide. This review also describes challenges associated with training clinicians to deliver evidence-based psychotherapy. It concludes with a discussion of future directions for IPT, which include expanding training to community health workers and testing IPT in low- and middle-income countries.
Topics: Depression; Depressive Disorder; Humans; Interpersonal Psychotherapy; Interpersonal Relations; Treatment Outcome
PubMed: 31752510
DOI: 10.1176/appi.psychotherapy.20190032 -
Journal of Affective Disorders Oct 2023Debate is ongoing as to whether burnout can be differentiated from depression. This study evaluated whether burnout and depression could be distinguished using a new...
BACKGROUND
Debate is ongoing as to whether burnout can be differentiated from depression. This study evaluated whether burnout and depression could be distinguished using a new burnout measure and other variables.
METHODS
Scores on the Sydney Burnout Measure (SBM) were compared between participants with self-diagnosed burnout (BO-all group; n = 622) and clinically-diagnosed depression (DEP-all group; n = 90). The latter group was split into melancholic (DEP-mel; n = 56) and non-melancholic (DEP-nonmel; n = 34) depression subgroups for subsequent analyses. Differences in reporting of depressive symptoms and causal attributions were also evaluated.
RESULTS
While total SBM scores showed poor differentiation, the BO-all group had lower social withdrawal and higher empathy loss subscale scores than the depression groups. Odds ratios were significant for several of the depressive symptoms and causal attribution items when comparing the BO-all group to the DEP-all and DEP-mel groups, while only a few items were significant when comparing the BO-all and DEP-nonmel groups.
LIMITATIONS
Participants in the depression group were assigned by clinician-based depression diagnoses, rather than by a standardised diagnostic interview, and the group had a relatively small sample size. Participants in the burnout group were self-diagnosed and not assessed for comorbid psychiatric diagnoses.
CONCLUSIONS
There were some nuanced symptoms differences between burnout and depression, but many of the SBM symptoms were not specific to burnout. Results also suggested that burnout overlaps more with non-melancholic than melancholic depression, and that differentiation of burnout and depression may rely more on weighting causal factors over symptoms.
Topics: Humans; Depression; Depressive Disorder; Comorbidity; Burnout, Professional; Sample Size
PubMed: 37479038
DOI: 10.1016/j.jad.2023.07.095 -
Journal of Neuroscience Research Mar 2020Brain-derived neurotrophic factor (BDNF) is well known to play a critical role in cognition. Its role in mood disorders, including post stroke depression (PSD), is also... (Review)
Review
Brain-derived neurotrophic factor (BDNF) is well known to play a critical role in cognition. Its role in mood disorders, including post stroke depression (PSD), is also recognized with more evidence surfacing. In patients with PSD, their serum BNDF level is lower than in those without depression. Furthermore, antidepressants could enhance BDNF expression in the brain, resulting in an alleviation of depression symptoms. Such therapeutic effect can be abolished in animals with the BDNF gene deleted. In PSD patients, the presence of stroke may contribute to the development of depression, including affecting the expression of BDNF. However, the mechanisms of BDNF in the development of PSD remain largely unknown. Lower BDNF levels may have existed in some patients before stroke onset, making them vulnerable to develop depressive symptoms. Meanwhile, the hypoxic environment induced by stroke could possibly downregulate BDNF expression in the brain. Current antidepressant treatments are not specific for PSD and there is a lack of treatments to address the linkage between stroke and PSD. This review summarizes the current knowledge of BDNF in PSD. By regulating BDNF expression, a synergistic effect may be achieved when such treatments are applied together with existing antidepressants.
Topics: Animals; Brain; Brain-Derived Neurotrophic Factor; Depression; Depressive Disorder; Humans; Stroke
PubMed: 31385340
DOI: 10.1002/jnr.24510 -
The American Journal of Geriatric... Jan 2023
Topics: Humans; Depression; Aging; Depressive Disorder
PubMed: 36216691
DOI: 10.1016/j.jagp.2022.09.003 -
Pharmacogenomics Aug 2019
Topics: Anxiety; Child; Depression; Depressive Disorder; Humans; Pharmacogenetics; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 31453769
DOI: 10.2217/pgs-2019-0088 -
Therapeutische Umschau. Revue... Aug 2021Post stroke depression Post stroke depression is a common psychiatric disorder after a cerebrovascular insult. It effects the outcome of the rehabilitation after the...
Post stroke depression Post stroke depression is a common psychiatric disorder after a cerebrovascular insult. It effects the outcome of the rehabilitation after the stroke and leads to an increased mortality. The symptomatic description of the depressive symptoms is done according to the ICD-10 criteria. The following article aims to provide an overview of the etiologic theories, diagnostic approaches, and therapeutic strategies regarding PSD.
Topics: Depression; Depressive Disorder; Humans; Stroke
PubMed: 34291664
DOI: 10.1024/0040-5930/a001274