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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 -
JAMA Psychiatry Feb 2023The totality of the societal and individual impact of treatment-resistant depression (TRD) is unknown, as is the potential to prognosticate TRD. The generalizability of... (Observational Study)
Observational Study
IMPORTANCE
The totality of the societal and individual impact of treatment-resistant depression (TRD) is unknown, as is the potential to prognosticate TRD. The generalizability of many observational studies on TRD is limited.
OBJECTIVE
To estimate the burden of TRD in a large population-wide cohort in an area with universal health care by including data from both health care types (psychiatric and nonpsychiatric) and, further, to develop a prognostic model for clinical use.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study, a population-based observational study, assessed data from the Stockholm MDD Cohort for episodes of major depressive disorder (MDD) between 2010 and 2017 that fulfilled predefined criteria for TRD (≥3 consecutive antidepressant treatments). Data analysis was performed from August 2020 to May 2022.
MAIN OUTCOMES AND MEASURES
Outcomes were psychiatric and nonpsychiatric comorbid conditions, antidepressant treatments, health care resource utilization, lost workdays, all-cause mortality, and intentional self-harm and, in the prognostic model, TRD.
RESULTS
A total of 158 169 unipolar MDD episodes (in 145 577 patients) were identified between January 1, 2012, and December 31, 2017 (64.7% women; median [IQR] age, 42 years [30-56]). Of these, 12 793 episodes (11%) fulfilled criteria for TRD. The median (IQR) time from the start of MDD episode to TRD was 552 days (294-932). Selective serotonin reuptake inhibitor was the most common class of antidepressant treatment in all treatment steps, and 5907 patients (46.2%) received psychotherapy at some point before initiation of the third pharmacological antidepressant treatment. Compared with matched non-TRD episodes, TRD episodes had more inpatient bed-days (mean, 3.9 days; 95% CI, 3.6-4.1, vs 1.3 days; 95% CI, 1.2-1.4) and more lost workdays (mean, 132.3 days; 95% CI, 129.5-135.1, vs 58.7 days; 95% CI, 56.8-60.6) 12 months after the index date. Anxiety, stress, sleep disorder, and substance use disorder were all more common comorbid conditions in TRD episodes. Intentional self-harm was more than 4 times more common in TRD episodes. The all-cause mortality rate for patients with MDD with TRD episodes was 10.7/1000 person-years at risk, compared with 8.7/1000 person-years at risk for patients with MDD without TRD episodes (hazard ratio, 1.23; 95% CI, 1.07-1.41). Median time from start of the first antidepressant treatment to start of the second, and from start of the second antidepressant treatment to start of the third, was 165 and 197 days, respectively. The severity of MDD, defined using the self-rating Montgomery-Åsberg Depression Rating Scale (MADRS-S) at time of MDD diagnosis, was found to be the most important prognostic factor for TRD (C index = 0.69).
CONCLUSIONS AND RELEVANCE
In this cohort study, TRD was a common variant of MDD when including patients from both health care types, which is associated with a high disease burden for both patients and society. The median time between initiation of new antidepressant treatments was longer than recommended in current treatment guidelines, suggesting room for more structured and timely depression care.
Topics: Humans; Female; Adult; Male; Cohort Studies; Depression; Depressive Disorder, Major; Delivery of Health Care; Antidepressive Agents; Depressive Disorder, Treatment-Resistant; Retrospective Studies
PubMed: 36515938
DOI: 10.1001/jamapsychiatry.2022.3860 -
Progress in Brain Research 2023Patients with major depressive disorder (MDD) often exhibit an inadequate treatment response or failure to achieve remission following treatment with antidepressant... (Comparative Study)
Comparative Study
Patients with major depressive disorder (MDD) often exhibit an inadequate treatment response or failure to achieve remission following treatment with antidepressant drugs. Treatment-resistant depression (TRD) is proposed to identify this clinical scenario. Compared to those without TRD, patients with TRD have significantly lower health-related quality of life in mental and physical dimensions, more functional impairment and productivity loss, and higher healthcare costs. TRD imposes a massive burden on the individual, family, and society. However, a lack of consensus on the TRD definition limits the comparison and interpretation of TRD treatment efficacy across trials. Furthermore, because of the various TRD definitions, there is scarce treatment guideline specifically for TRD, in contrast to the rich treatment guidelines for MDD. In this chapter, common issues related to TRD, such as proper definitions of an adequate antidepressant trial and TRD, were carefully reviewed. Prevalence of and clinical outcomes related to TRD were summarized. We also summarized the staging models ever proposed for the diagnosis of TRD. Furthermore, we highlighted variations in the definition regarding the lack of or an inadequate response in treatment guidelines for depression. Up-to-date treatment options for TRD, including pharmacological strategies, psychotherapeutic interventions, neurostimulation techniques, glutamatergic compounds, and even experimental agents were reviewed.
Topics: Humans; Antidepressive Agents; Depression; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Quality of Life
PubMed: 37414489
DOI: 10.1016/bs.pbr.2023.03.007 -
Clinics in Geriatric Medicine May 2020This article covers current research on the relationship between depression and cognitive impairment in older adults. First, it approaches the clinical assessment of... (Review)
Review
This article covers current research on the relationship between depression and cognitive impairment in older adults. First, it approaches the clinical assessment of late-life depression and comorbid cognitive impairment. Cognitive risk factors for suicide are discussed. Research is then provided on neuropsychological changes associated with depression, discussing subjective cognitive impairment, mild cognitive impairment, and dementia profiles. In addition, literature regarding neuroimaging and biomarker findings in depressed older adults is presented. Finally, therapeutic models for treatment of late-life depression are discussed, including psychotherapy models, holistic treatments, pharmacologic approaches, and brain stimulation therapies.
Topics: Aged; Aging; Cognitive Dysfunction; Depressive Disorder, Major; Humans; Neuropsychological Tests; Patient Care Management
PubMed: 32222303
DOI: 10.1016/j.cger.2019.11.009 -
Expert Opinion on Pharmacotherapy Oct 2019: Persistent Depressive Disorder (PDD) is a nosological entity introduced with DSM-5, encompassing numerous different conditions including Dysthymia, recurrent Major... (Review)
Review
: Persistent Depressive Disorder (PDD) is a nosological entity introduced with DSM-5, encompassing numerous different conditions including Dysthymia, recurrent Major Depressive Disorder, Double Depression and Chronic Major Depression. PDD is a particularly significant cause of disease burden in the general population. : In the present paper, the authors explore the controversies surrounding the definition of PDD, the current approach to its treatment endorsed by the major scientific bodies, along with the available evidence on the efficacy of said treatments. : Clinicians need to be particularly vigilant and always gather a thorough history. In this diagnostic group, there is a relevant risk of having an undiagnosed Bipolar Disorder as affected individuals typically fail to recognize the pathological components of hypomanic episodes. In this setting, it is crucial to reconsider the diagnosis and to frequently verify compliance with the treatment plan. Numerous technological advances, particularly in the neuroimaging field, offer new insight and new challenges in defining the pathophysiological mechanisms of depressive syndromes. In the future, these advances may offer guidance towards an improved treatment approach and diagnostic process.
Topics: Amisulpride; Antidepressive Agents; Antipsychotic Agents; Depressive Disorder, Major; Dysthymic Disorder; Humans; Psychotherapy; Quality of Life; Treatment Outcome
PubMed: 31290333
DOI: 10.1080/14656566.2019.1637419 -
International Journal of Molecular... Sep 2020This review analyzes the current scientific literature on the role of the Sigma1R chaperone in the pathogenesis of depressive disorders and pharmacodynamics of... (Review)
Review
This review analyzes the current scientific literature on the role of the Sigma1R chaperone in the pathogenesis of depressive disorders and pharmacodynamics of antidepressants. As a result of ligand activation, Sigma1R is capable of intracellular translocation from the endoplasmic reticulum (ER) into the region of nuclear and cellular membranes, where it interacts with resident proteins. This unique property of Sigma1R provides regulation of various receptors, ion channels, enzymes, and transcriptional factors. The current review demonstrates the contribution of the Sigma1R chaperone to the regulation of molecular mechanisms involved in the antidepressant effect.
Topics: Animals; Antidepressive Agents; Depressive Disorder; Humans; Receptors, sigma; Sigma-1 Receptor
PubMed: 32992988
DOI: 10.3390/ijms21197088 -
Fortschritte Der Neurologie-Psychiatrie Apr 2022
Topics: Depression; Depressive Disorder; Humans; Parkinson Disease
PubMed: 35443281
DOI: 10.1055/a-1683-1840 -
Scientific Reports Mar 2021Although depression and glaucoma share several common pathophysiology, the risk of glaucoma in patients with depression has not been reported. Thus, we investigated the...
Although depression and glaucoma share several common pathophysiology, the risk of glaucoma in patients with depression has not been reported. Thus, we investigated the effect of depressive symptom and depressive disorder on glaucoma incidence. In this nationwide population-based cohort study, all subjects receiving the National Screening Program at the age of 66 during 2009-2014 were included. These subjects were divided into depression group and no depression group based on subjective depressive symptoms and clinically diagnosed depressive disorder and were tracked until 2017 for development of glaucoma. Of the 922,769 subjects included in the study, 191,636 (20.77%) subjects were categorized as depression group. Subjects with depression showed increased hazard of developing glaucoma (adjusted HR = 1.12[95% confidence interval (CI), 1.09-1.15]) than those without depression. The risk of glaucoma increased sequentially from those with no depression to those with subjective depressive symptom (adjusted HR = 1.09[95% CI, 1.06-1.13]), those with clinically diagnosed depressive disorder (adjusted HR = 1.23[95% CI, 1.14-1.32]), and those with both subjective depressive symptom and clinically diagnosed depressive disorder (adjusted HR = 1.36[95% CI, 1.22-1.52]). Our analyses suggest that individuals with depression had a greater risk of developing glaucoma than those without depression. Subjective depressive symptoms and clinically diagnosed depressive disorder independently and synergistically increased the risk of glaucoma incidence.
Topics: Aged; Depressive Disorder; Female; Glaucoma; Humans; Incidence; Male; Risk Factors
PubMed: 33723349
DOI: 10.1038/s41598-021-85380-6 -
Bipolar Disorders May 2024The perinatal period is an extremely delicate phase that can involve a high risk for onset of depressive disorders. The Edinburgh Postnatal Depression Scale (EPDS) is a... (Review)
Review
The perinatal period is an extremely delicate phase that can involve a high risk for onset of depressive disorders. The Edinburgh Postnatal Depression Scale (EPDS) is a widely validated instrument for assessing perinatal depressive symptoms, including the dimension of anhedonia. There are studies suggesting that the neural mechanism underlying the occurrence of anhedonia in patients with major depressive disorder (MDD) and bipolar depression (BD) might be distinct. Anhedonia seems to represent a more stable and frequent symptom in women with postpartum bipolar relative to unipolar depressive disorder and is associated with significantly higher depressive symptom severity. Perinatal medicine is an important component of women's health. Treatment of anhedonia can be challenging, and the most effective treatment can be a combination of psychotherapy and medication, but the screening of anhedonia in peripartum women can prevent the development of other psychiatric disorders and maladaptive behaviors.
Topics: Humans; Female; Anhedonia; Peripartum Period; Pregnancy; Bipolar Disorder; Depressive Disorder, Major; Depression, Postpartum
PubMed: 38302845
DOI: 10.1111/bdi.13408 -
European Neuropsychopharmacology : the... Sep 2021Depressive Disorders are the most common psychiatric diagnoses in the general population. To estimate the frequency, costs associated with Depressive Disorders in usual... (Observational Study)
Observational Study
Depressive Disorders are the most common psychiatric diagnoses in the general population. To estimate the frequency, costs associated with Depressive Disorders in usual clinical practice, and in the whole Spanish population, a longitudinal, retrospective, observational study was carried out using data from the BIG-PAC database®. Study population: all patients aged ≥ 18 years with a diagnosis of a Depressive Disorder in 2015-2017. Prevalence was computed as the proportion of Depressive Disorder cases in the adult general population, and the incidence rate, as the number of new Depressive Disorder cases diagnosed per 1,000 person-years in the population using health services, during 2015-2017. We collected demographic variables, comorbidity, direct health costs, and indirect costs (temporary and permanent disability). Health costs related to Depressive Disorders were estimated according to the annual resource use rate (resource/patient/year). Indirect costs were calculated according to the human capital method. Using the study data and information from the Spanish National Institute of Statistics, we estimated the cost of Depressive Disorders corresponding to the Spanish adult population, including premature mortality. 69,217 Depressive Disorder patients aged ≥ 18 years who met the inclusion/exclusion criteria were studied (mean age: 56.8 years; female: 71.4%). Prevalence of Depressive Disorders in the general population was 4.73% (95% CI: 4.70-4.76%). Annual incidence rates (2015-2017) were 7.12, 7.35 and 8.02 per 1,000 person-years, respectively. Total costs observed in our Depressive Disorder patients were € 223.9 million (corresponding to a mean of € 3,235.3; mean/patient/year), of which, 18.4% were direct health care costs and 81.6%, non-health indirect costs (18% temporary occupational disability, 63.6% permanent disability). Considering also the cost of premature death, the mean cost per patient/year was € 3,402 and the estimated societal costs of Depressive Disorders in Spain were € 6,145 million. The prevalence and incidence of Depressive Disorders are consistent with other series reviewed. Resource use and total costs (especially non-health costs) were high.
Topics: Adult; Cost of Illness; Delivery of Health Care; Depressive Disorder; Female; Health Care Costs; Humans; Middle Aged; Retrospective Studies; Spain
PubMed: 34058711
DOI: 10.1016/j.euroneuro.2021.04.022