Mortality in treatment-resistant unipolar depression: A register-based cohort study in Sweden

Reutfors, Johan; Andersson, Therése; Brenner, Philip; Brandt, Lena; DiBernardo, Allitia; Li, Gang; Hägg, David; Wingård, Louise; Bodén, Robert

doi:10.1016/j.jad.2018.06.030

Cited by 72 publications

(80 citation statements)

References 39 publications

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“…The MRS voxel thus had faces parallel to each of these MRI volumes and was positioned in the cortex directly under the vitamin E capsule, with care taken to ensure that no part of the voxel exited the brain. The voxel measured an initial 30 × 20 × 10 mm 3 , adjusted in size and orientation to maximize local DLPFC grey matter content. We acquired an identical, non-watersuppressed scan (8 excitations) immediately afterward from the same site.…”

Section: Mri Proceduresmentioning

confidence: 99%

“…1 Among patients with MDD, those with TRD have appreciably higher morbidity and mortality. 2,3 Repetitive transcranial magnetic stimulation (rTMS) is effective for TRD, resulting in remission in approximately 35% of patients and appreciable improvement in about another 30%. 4 Research interest remains high in elucidating the mechanism of action of rTMS to increase its efficacy for TRD and other conditions.…”

Section: Introductionmentioning

confidence: 99%

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Dorsolateral prefrontal γ-aminobutyric acid in patients with treatment-resistant depression after transcranial magnetic stimulation measured with magnetic resonance spectroscopy

Levitt¹,

Kalender²,

O’Neill³

et al. 2019

JPN

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Background: The therapeutic mechanism of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) may involve modulation of γ-aminobutyric acid (GABA) levels. We used proton magnetic resonance spectroscopy (MRS) to assess changes in GABA levels at the site of rTMS in the left dorsolateral prefrontal cortex (DLPFC). Methods: In 26 adults with TRD, we used Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) spectral-editing MRS to measure GABA in the left DLPFC before and after standard clinical treatment with rTMS. All participants but 1 were medicated, including 12 patients on GABA agonist agents. Results: Mean GABA in the DLPFC increased 10.0% (p = 0.017) post-rTMS in the overall sample. As well, GABA increased significantly in rTMS responders (n = 12; 23.6%, p = 0.015) but not in nonresponders (n = 14; 4.1%, p = not significant). Changes in GABA were not significantly affected by GABAergic agonists, but clinical response was less frequent (p = 0.005) and weaker (p = 0.035) in the 12 participants who were receiving GABA agonists concomitant with rTMS treatment. Limitations: This study had an open-label design in a popu lation receiving naturalistic treatment. Conclusion: Treatment using rTMS was associated with increases in GABA levels at the stimulation site in the left DLPFC, and the degree of GABA change was related to clinical improvement. Participants receiving concomitant treatment with a GABA agonist were less likely to respond to rTMS. These findings were consistent with earlier studies showing the effects of rTMS on GABA levels and support a GABAergic model of depression.

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Section: Mri Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dorsolateral prefrontal γ-aminobutyric acid in patients with treatment-resistant depression after transcranial magnetic stimulation measured with magnetic resonance spectroscopy

Levitt¹,

Kalender²,

O’Neill³

et al. 2019

JPN

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“…At least a third of all MDD patients experience treatment-resistant depression (TRD), defined as a failure to respond to two adequate medication trials [3]. Those suffering from TRD are left suffering from a significant decline in their social and occupational functioning and higher rates of all-cause mortality [4]. Persistent symptoms in TRD often translate into exponential increases in work loss and medical costs compared to more responsive forms of illness [5].…”

Section: Introductionmentioning

confidence: 99%

Minocycline as adjunctive treatment for treatment-resistant depression: study protocol for a double blind, placebo-controlled, randomized trial (MINDEP2)

et al. 2020

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Background: Available evidence suggests that adjunctive treatment with immunomodulatory medications may be effective in the treatment of major depressive disorder (MDD). A pilot trial of the tetracycline minocycline as adjunctive treatment in treatment-resistant depression (TRD), produced promising results, however, a larger scale trial is needed to confirm the antidepressant actions of this drug. Methods: This is a 12-week double blind, placebo-controlled, randomized trial of minocycline as an add-on to standard antidepressants for adults (age > 18) with DSM-5 major depressive episode, who have failed to respond to at least two adequate trials of antidepressant treatment. It is a parallel-arm study with 50 participants in each group. The primary outcome measure is change in 17-item Hamilton Depression Rating Scale (HRSD-17) total scores from baseline to week 12. Secondary measures include the Clinical Global Impression (CGI) scale, World Health Organization Quality of Life Short Version (WHOQOL-BREF) and the Generalized Anxiety Disorder scale (GAD-7). Peripheral inflammatory biomarkers will be collected at baseline, week 6 and 12.Discussion: If minocycline is well tolerated and effective in reducing depressive symptoms in patients with TRD, it would warrant genuine consideration as a treatment option for TRD. Additionally, if results demonstrate that minocycline has antidepressant properties, and that changes in inflammatory status are associated with its antidepressant action, it will inform the development of individualized treatment for a subset of patients with MDD. Trial registration: Clinicaltrials.gov identifier: NCT03947827. Registered 13th May, 2019.

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“…For example, the administrative data must contain information of deaths and their causes, records of suicide attempts, as well as data on MDD diagnosis and treatment trials during a sufficient follow-up time in order to identify patients with TRD. As a proxy for identifying treatment resistance, the method of using prescription data in modeling TRD has been increasingly used in register studies Risk Factors for Suicide and Suicide Attempts (Corey-Lisle, Birnbaum, Greenberg, Marynchenko, & Claxton, 2002;Fife et al, 2017;Gronemann, Jorgensen, Nordentoft, Andersen, & Osler, 2018;Reutfors et al, 2018;Thomas et al, 2013). In these studies, the rate of TRD among antidepressant initiators has consistently been lower compared to in clinical studies, ranging from 12 to 20%.…”

Section: Introductionmentioning

confidence: 99%

“…In a recent study, we investigated mortality among patients with TRD in a large register-based cohort of Swedish patients with MDD and found that the risk of death from external causes, including suicide, was almost doubled among the patients defined as having TRD (Reutfors et al, 2018). Thus, investigating potential risk factors for both suicide and suicide attempts in this particular group seems a priority.…”

Section: Introductionmentioning

confidence: 99%

Risk Factors for Suicide and Suicide Attempts Among Patients With Treatment-Resistant Depression: Nested Case-Control Study

Reutfors

Andersson

Tanskanen

et al. 2019

Archives of Suicide Research

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The risk of suicide is elevated among patients with treatment-resistant depression (TRD). Risk factors for suicide and suicide attempts among cases and controls with TRD were investigated using data from nationwide Swedish registers. Among 119,407 antidepressant initiators with a diagnosis of depression, 15,631 patients who started a third sequential treatment trial during the same depressive episode were classified with TRD. A nested casecontrol study compared cases with suicide and suicide attempts with up to three closely matched controls. Sociodemographic and clinical risk factors were assessed using conditional logistic regression analyses. In all, 178 patients died by suicide and 1,242 experienced a suicide attempt during follow-up. History of suicide attempts, especially if <1 year after the attempt, was a significant independent risk factor for suicide (adjusted odds ratio [aOR], 8.9; 95% confidence interval [CI], 5.1-15.7) as were 10 to 12 years of education compared to lower education (aOR, 1.69; 95% CI, 1.02-2.81). For attempted suicide, the strongest independent risk factors were history of suicide attempts (<1 year aOR, 5.1; 95% CI, 4.0-6.5), substance abuse (aOR, 2.6; 95% CI, 2.2-3.1), personality disorders (aOR, 1.9; 95% CI, 1.5-2.3), and somatic comorbidity (aOR, 2.0; 95% CI, 1.04-3.9). Suicide attempts, especially if recent, are strong risk factors for completed suicide among patients with TRD. Established risk factors for suicide attempts were confirmed for patients with TRD.

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Mortality in treatment-resistant unipolar depression: A register-based cohort study in Sweden

Cited by 72 publications

References 39 publications

Dorsolateral prefrontal γ-aminobutyric acid in patients with treatment-resistant depression after transcranial magnetic stimulation measured with magnetic resonance spectroscopy

Dorsolateral prefrontal γ-aminobutyric acid in patients with treatment-resistant depression after transcranial magnetic stimulation measured with magnetic resonance spectroscopy

Minocycline as adjunctive treatment for treatment-resistant depression: study protocol for a double blind, placebo-controlled, randomized trial (MINDEP2)

Risk Factors for Suicide and Suicide Attempts Among Patients With Treatment-Resistant Depression: Nested Case-Control Study

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