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BACKGROUND: Major depressive disorder (MDD) poses a significant global health burden with available treatments limited by inconsistent efficacy and notable side effects. Classic psychedelics, including lysergic acid diethylamide (LSD), have garnered attention for their potential in treating psychiatric disorders. Microdosing, the repeated consumption of sub-hallucinogenic doses of psychedelics, has emerged as a self-treatment approach for depression within lay communities. Building upon preliminary evidence and the successful completion of an open-label pilot trial of microdosing LSD for depression (LSDDEP1), this protocol outlines a phase 2b randomised controlled trial (LSDDEP2). The main objective of LSDDEP2 is to assess the modification of depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), following a regimen of LSD microdoses versus placebo. METHODS: This is a randomised, double-dummy, triple-blind, active placebo-controlled, parallel groups trial of LSD microdosing in patients meeting DSM-5 criteria for major depressive disorder. Participants will undergo an 8-week LSD microdosing regimen using the titratable MB-22001 formulation taking two doses a week. All doses will be self-administered at home and will be titratable from 4 to 20 µg based on subjective perception and tolerability. In addition to depression symptoms, outcome will include psychiatric and personality inventories, sleep and activity tracking, electroencephalography (EEG), blood biomarkers, semi-structured interviews, and safety (e.g. adverse event, laboratory exam) measures. DISCUSSION: This study will be the first randomised controlled trial to administer controlled microdoses of LSD for treatment of MDD in participants' naturalistic environment. The measures included are designed to assess the drug's safety, mechanism, and treatment efficacy over placebo in this population. The results of this study will be important for assessing the viability of psychedelic microdosing as an additional treatment option and for informing the direction of future clinical trials. TRIAL REGISTRATION: ANZCTR, ACTRN12624000128594. Prospectively Registered on 13 February 2024.
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Trastorno Depresivo Mayor , Alucinógenos , Dietilamida del Ácido Lisérgico , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Dietilamida del Ácido Lisérgico/administración & dosificación , Dietilamida del Ácido Lisérgico/efectos adversos , Alucinógenos/administración & dosificación , Alucinógenos/efectos adversos , Método Doble Ciego , Resultado del Tratamiento , Adulto , Ensayos Clínicos Fase II como Asunto , Masculino , Femenino , Persona de Mediana Edad , Adulto Joven , Factores de TiempoRESUMEN
Microdosing psychedelic drugs at a level below the threshold to induce hallucinations is an increasingly common lifestyle practice. However, the effects of microdosing on sleep have not been previously reported. Here, we report results from a Phase 1 randomized controlled trial in which 80 healthy adult male volunteers received a 6-week course of either LSD (10 µg) or placebo with doses self-administered every third day. Participants used a commercially available sleep/activity tracker for the duration of the trial. Data from 3231 nights of sleep showed that on the night after microdosing, participants in the LSD group slept an extra 24.3 min per night (95% Confidence Interval 10.3-38.3 min) compared to placebo-with no reductions of sleep observed on the dosing day itself. There were no changes in the proportion of time spent in various sleep stages or in participant physical activity. These results show a clear modification of the physiological sleep requirements in healthy male volunteers who microdose LSD. The clear, clinically significant changes in objective measurements of sleep observed are difficult to explain as a placebo effect. Trial registration: Australian New Zealand Clinical Trials Registry: A randomized, double-blind, placebo-controlled trial of repeated microdoses of lysergic acid diethylamide (LSD) in healthy volunteers; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381476 ; ACTRN12621000436875.
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Alucinógenos , Duración del Sueño , Adulto , Humanos , Masculino , Australia , Alucinógenos/farmacología , Sueño , Voluntarios Sanos , Método Doble CiegoRESUMEN
BACKGROUND: An advanced cancer diagnosis can be associated with a significant profile of distress. Psychedelic compounds have shown clinically significant effects in the treatment of psychological distress in patients with advanced-stage cancer. Given the challenges of delivering timely and effective intervention in the advanced cancer context, it is possible that an alternative, more pragmatic, approach lies in psychedelic 'microdosing'. Microdosing refers to repeated administration of psychedelics in sub-hallucinogenic doses. The purpose of this study is to evaluate the feasibility of conducting a full-scale randomised controlled trial comparing psychedelic microdose-assisted-meaning-centred psychotherapy (PA-MCP) to standard meaning-centred psychotherapy (MCP) in New Zealand indigenous (Maori) and non-indigenous people with advanced cancer and symptoms of anxiety and/or depression. Although MCP is a well-established psychotherapeutic treatment in advanced cancer populations, the potential efficacy and effectiveness of this therapy when delivered alongside a standardised microdose regimen of a psychedelic compound have not been investigated. METHODS: Participants with advanced-stage cancer and symptoms of anxiety and/or depression (N = 40; 20 Maori, 20 non-Maori) will be randomised under double-blind conditions to receive 7 sessions of MCP alongside 13 doses of either an LSD microdose (4-20 µg) (PA-MCP) or inactive placebo (placebo-MCP). The feasibility, acceptability, and safety of this intervention and physiological and psychological measures will be recorded at baseline, at each session of MCP, and at a 1-month and 6-month follow-up. DISCUSSION: Our findings will evaluate the feasibility, acceptability, and safety of a larger randomised controlled trial and provide an initial indication of the potential benefits of psychedelic microdosing for psychological distress in advanced-stage indigenous and non-indigenous cancer patients. TRIAL REGISTRATION: NZCTR, ACTRN12623000478617. Registered 11 May 2023. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385810&isReview=true .
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Repetitive transcranial magnetic stimulation (rTMS) has shown efficacy and tolerability in Major Depressive Disorder (MDD). However, the underlying mechanisms of its antidepressant effects remain unclear. This open-label study investigated electroencephalography (EEG) functional connectivity markers associated with response and the antidepressant effects of rTMS. Resting-state EEG data were collected from 28 participants with MDD before and after a four-week rTMS course. Source-space functional connectivity between 38 cortical regions was compared using an orthogonalised amplitude approach. Depressive symptoms significantly improved following rTMS, with 43 % of participants classified as responders. While the study's functional connectivity findings did not withstand multiple comparison corrections, exploratory analyses suggest an association between theta band connectivity and rTMS treatment mechanisms. Fronto-parietal theta connectivity increased after treatment but did not correlate with antidepressant response. Notably, low baseline theta connectivity was associated with greater response. However, due to the exploratory nature and small sample size, further replication is needed. The findings provide preliminary evidence that EEG functional connectivity, particularly within the theta band, may reflect the mechanisms by which rTMS exerts its therapeutic effects.
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Trastorno Depresivo Mayor , Estimulación Magnética Transcraneal , Humanos , Antidepresivos/farmacología , Trastorno Depresivo Mayor/terapia , ElectroencefalografíaRESUMEN
BACKGROUND: The role of neuroinflammation in psychiatric disorders is not well-elucidated. A noninvasive technique sensitive to low-level neuroinflammation may improve understanding of the pathophysiology of these conditions. PURPOSE: To test the ability of quantitative magnetization transfer (QMT) MR at 3 T for detection of low-level neuroinflammation induced by typhoid vaccine within a clinically reasonable scan time. STUDY TYPE: Randomized, crossover, placebo-controlled. SUBJECTS: Twenty healthy volunteers (10 males; median age 34 years). FIELD STRENGTH/SEQUENCE: Magnetization prepared rapid gradient-echo and MT-weighted 3D fast low-angle shot sequences at 3 T. ASSESSMENT: Participants were randomized to either vaccine or placebo first with imaging, then after a washout period received the converse with a second set of imaging. MT imaging, scan time, and blood-based inflammatory marker concentrations were assessed pre- and post-vaccine and placebo. Mood was assessed hourly using the Profile of Mood States questionnaire. QMT parameter maps, including the exchange rate from bound to free pool (kba) were generated using a two-pool model and then segmented into tissue type. STATISTICAL TESTS: Voxel-wise permutation-based analysis examined inflammatory-related alterations of QMT parameters. The threshold-free cluster enhancement method with family-wise error was used to correct voxel-wise results for multiple comparisons. Region of interest averages were fed into mixed models and Bonferroni corrected. Spearman correlations assessed the relationship between mood scores and QMT parameters. Results were considered significant if corrected P < 0.05. RESULTS: Scan time for the MT-weighted acquisition was approximately 11 minutes. Blood-based analysis showed higher IL-6 concentrations post-vaccine compared to post-placebo. Voxel-wise analysis found three clusters indicating an inflammatory-mediated increase in kba in cerebellar white matter. Cerebellar kba for white matter was negatively associated with vigor post-vaccine but not post-placebo. DATA CONCLUSION: This study suggested that QMT at 3 T may show some sensitivity to low-level neuroinflammation. Further studies are needed to assess the viability of QMT for use in inflammatory-based disorders. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.
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Trastornos Mentales , Vacunas Tifoides-Paratifoides , Masculino , Humanos , Adulto , Estudios Cruzados , Enfermedades Neuroinflamatorias , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: Globally, an estimated 260 million people suffer from depression [1], and there is a clear need for the development of new, alternative antidepressant therapies. In light of problems with the tolerability and efficacy of available treatments [2], a global trend is emerging for patients to self-treat depression with microdoses of psychedelic drugs such as lysergic acid diethylamide (LSD) and psilocybin [3]. Beyond anecdotal reports from those who self-medicate in this way, few clinical trials have evaluated this practice. In our recently published phase 1 study in healthy volunteers [4], we determined that LSD microdosing was relatively safe and well tolerated in that cohort. Furthermore, the data demonstrated that conducting such microdosing trials is broadly feasible, with excellent adherence and compliance to the regimen observed. In this open-label pilot trial of patients with major depressive disorder (LSDDEP1), we will test the tolerability and feasibility of an 8-week regimen of LSD microdosing in this patient group prior to a larger subsequent randomised controlled trial (LSDDEP2). METHODS: Twenty patients meeting the DSM-5 criteria for major depressive disorder will receive an 8-week LSD microdosing treatment regimen. The treatment protocol will use a sublingual formulation of LSD (MB-22001) delivered twice per week under a titration schedule using a dose of 5-15 µg. Tolerability will be assessed by quantifying the percentage of participants who withdraw from the trial due to adverse events attributable to the treatment regimen, while feasibility will be assessed by quantifying the percentage of attended clinic visits once enrolled. To determine whether there is any antidepressant response to the LSD microdosing regimen, MADRS scores will be assessed at baseline and 2, 4, 6, and 8 weeks after the commencement of the regimen. DISCUSSION: The results of LSDDEP1 will provide valuable information regarding the tolerability and feasibility of a proposed LSD microdosing regimen in patients with MDD. Such information is critically important to optimise trial design prior to commencing a subsequent and more resource-intensive randomised controlled trial. TRIAL REGISTRATION: ANZCTR, ACTRN12623000486628. Registered on 12 May 2023.
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AIM: To explore the importance of health workforce training, particularly in newly regulated healthcare practices such as assisted dying (AD). This study aims to analyse the socio-demographic factors associated with health professionals' completion of the e-learning module and attendance at the two webinars provided by the New Zealand Ministry of Health - Manatu Hauora (MH) and whether completion of the e-learning module and webinars supported health professionals' understanding of the End of Life Choices Act 2019. METHOD: Secondary analysis of the MH workforce surveys conducted in July 2021. RESULTS: The study findings indicate that health professionals who are older, of Pakeha/European ethnicity and work in hospice settings are more likely to complete the e-learning module, while females are more likely to attend webinars. CONCLUSION: Despite low completion and attendance rates, the study highlights the positive association between training and health professionals' overall understanding of the Act. These results emphasise the need for enhancing training programmes to increase health professionals' knowledge and competence with AD. Furthermore, the research proposes focussing on healthcare practitioners in the early stages of their careers and not directly engaged in offering AD services, as well as Maori and Pasifika health practitioners.
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Instrucción por Computador , Fuerza Laboral en Salud , Cuidado Terminal , Femenino , Humanos , Muerte , Pueblo Maorí , Nueva Zelanda , Recursos HumanosRESUMEN
OBJECTIVES: People with terminal illnesses often experience psychological distress and associated disability. Recent clinical trial evidence has stimulated interest in the therapeutic use of psychedelics at end of life. Much uncertainty remains, however, mainly due to methodological difficulties that beset existing trials. We conducted a scoping review of pipeline clinical trials of psychedelic treatment for depression, anxiety, and existential distress at end of life. METHODS: Proposed, registered, and ongoing trials were identified from 2 electronic databases (ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform). Recent reviews and both commercial and non-profit organization websites were used to identify additional unregistered trials. RESULTS: In total, 25 studies were eligible, including 13 randomized controlled trials and 12 open-label trials. Three trials made attempts beyond randomization to assess expectancy and blinding effectiveness. Investigational drugs included ketamine (n = 11), psilocybin (n = 10), 3,4-methylenedioxymethamphetamine (n = 2), and lysergic acid diethylamide (n = 2). Three trials involved microdosing, and fifteen trials incorporated psychotherapy. SIGNIFICANCE OF RESULTS: A variety of onging or upcoming clinical trials are expected to usefully extend evidence regarding psychedelic-assisted group therapy and microdosing in the end-of-life setting. Still needed are head-to-head comparisons of different psychedelics to identify those best suited to specific indications and clinical populations. More extensive and rigorous studies are also necessary to better control expectancy, confirm therapeutic findings and establish safety data to guide the clinical application of these novel therapies.
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Alucinógenos , Cuidado Terminal , Humanos , Alucinógenos/farmacología , Alucinógenos/uso terapéutico , Dietilamida del Ácido Lisérgico , Psilocibina/farmacología , Psilocibina/uso terapéutico , MuerteRESUMEN
AIM: To determine socio-demographic factors associated with health professionals' understanding of the End of Life Choice Act (the Act), support for assisted dying (AD), and willingness to provide AD in New Zealand. METHOD: Secondary analysis of two Manatu Hauora - Ministry of Health workforce surveys conducted in February and July 2021. RESULTS: Our analysis showed (1) older health professionals (age>55) had a better overall understanding of the Act than their young colleagues (ageâ¢35), (2) female health professionals were less likely to support and be willing to provide AD, (3) Asian health professionals were less likely to support AD compared to their Pakeha/European counterparts, (4) nurses were more likely to support AD and be willing to provide AD when compared to medical practitioners, and (5) pharmacists were more willing to provide AD when compared to medical practitioners. CONCLUSION: Several socio-demographic factors, including age, gender, ethnicity, and professional background, are significantly associated with health professionals' support and willingness to provide AD, with likely consequences for the AD workforce availability and service delivery in New Zealand. Future review of the Act could consider enhancing the roles of those professional groups with higher support and willingness to assist in providing AD services in caring for people requesting AD.
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Actitud del Personal de Salud , Fuerza Laboral en Salud , Humanos , Femenino , Persona de Mediana Edad , Nueva Zelanda , Encuestas y Cuestionarios , Recursos Humanos , MuerteRESUMEN
BACKGROUND: Microdosing psychedelic drugs is a widespread social phenomenon with diverse benefits claimed for mood and cognition. Randomized controlled trials have failed to support these claims, but the laboratory-based dosing in trials conducted to date may have limited ecological validity. METHODS: Healthy male volunteers were randomized into lysergic acid diethylamide (LSD) (n = 40) and placebo (n = 40) groups and received 14 doses of either 10 µg LSD or an inactive placebo every 3 days for 6 weeks. First doses were given in a supervised laboratory setting, with other doses self-administered in a naturalistic setting. Results of safety data, blinding, daily questionnaires, expectancy, and pre-/postintervention psychometrics and cognitive tasks are presented here. RESULTS: The most notable reported adverse event was treatment-related anxiety, which prompted the withdrawal of 4 participants from the LSD group. Daily questionnaires showed credible evidence (>99% posterior probability) of improved ratings of creativity, connectedness, energy, happiness, irritability, and wellness on dose days compared with nondose days, and these effects remained when controlling for preintervention expectancy. No questionnaire or cognitive task showed a credible change between baseline and 6-week assessment time points. CONCLUSIONS: Microdosing LSD appears to be relatively safe in healthy adult men, notwithstanding a risk of anxiety. While microdosing elicited transient increases in scales associated with mood-elevating effects, it was not sufficient to promote enduring changes to overall mood or cognition in healthy adults. Future microdosing trials in clinical populations will require the use of active placebos to control for placebo effects and dose titration to adjust for interindividual variability in drug response.
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Alucinógenos , Dietilamida del Ácido Lisérgico , Adulto , Humanos , Masculino , Afecto , Ansiedad/tratamiento farmacológico , Cognición , Alucinógenos/efectos adversos , Voluntarios SanosRESUMEN
OBJECTIVES: A resurgence of research investigating the administration of psychedelic compounds alongside psychotherapy suggests that this treatment is a promising intervention for anxiety, depression, and existential distress in people with cancer. However, psychedelic treatment that induces a mind-altering experience potentially poses barriers to vulnerable cancer patients, and health-care practitioners may have concerns about referring their patients to trials investigating this approach. The aim of the current study was to investigate the perceptions of cancer health-care practitioners based in New Zealand and the USA related to psychedelic-assisted therapy. METHODS: This study utilized a cross-sectional survey of cancer health-care practitioners in New Zealand and the USA via convenience sampling to identify their perceptions about the concept of conducting psychedelic-assisted therapy with cancer patients. RESULTS: Participants perceived that (1) psychedelic-assisted therapy has the potential to provide benefit for cancer patients, (2) research in this area across a variety of domains is important, (3) work should consider spiritual and indigenous perspectives of health, and (4) there was willingness to refer patients to trials in this area, especially patients with advanced disease who were no longer going through curative treatment. Participants in the USA had greater awareness of psychedelics than the New Zealand sample; however, New Zealand participants more strongly believed that spiritual/indigenous factors should be considered in psychedelic-assisted therapy. SIGNIFICANCE OF RESULTS: Cancer health-care practitioners in our sample considered research investigating the potential for psychedelic-assisted therapies to be important and may be more open to studies that start in palliative and end-of-life contexts.
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BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide. The current treatments are ineffective in approximately one-third of patients, resulting in a large economic burden and reduced quality of life for a significant proportion of the global population. There is considerable evidence that increased inflammation may distinguish a sub-type of MDD, and there are no validated diagnostic tools or treatments for neuroinflammation in MDD patients. The current study aims to explore the potential role of low-dose naltrexone (LDN), a drug with purported anti-inflammatory properties in the central nervous system, as an adjunctive treatment in patients with MDD. METHODS/DESIGN: This double-blind placebo-controlled hybrid parallel arm study enables the exploration of peripheral and central inflammatory markers with LDN as an approach to investigate inflammation as a pathophysiological contributor to MDD. Eligible participants with MDD (n = 48) will be stratified into the high and low inflammatory groups according to the levels of high-sensitivity C-reactive protein (hs-CRP) and then randomized to receive LDN or placebo for an initial 12 weeks, followed by a further 12 weeks during which all participants will receive LDN. The primary outcome measure will be the Montgomery-Åsberg Depression Rating Scale (MADRS) administered at baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 14 weeks, 16 weeks, 20 weeks, and 24 weeks, to assess the effectiveness of the anti-depressant response. The secondary outcomes include the use of MRI techniques including quantitative magnetization transfer (qMT), echo-planar spectroscopic imaging (EPSI), and diffusion-weighted imaging (DWI) to help to elucidate the neurobiological mechanism of LDN, and the inflammatory mechanisms in action in MDD. Electroencephalography, blood samples, cognitive tasks, and additional questionnaires will also be used to determine if there is a specific profile of symptoms in individuals with inflammatory MDD. Healthy participants (n = 24) will be recruited for baseline outcome measures only, to enable comparison with patients with MDD. DISCUSSION: This trial contributes to the literature on inflammation in MDD, including the understanding of the pathophysiology and efficacy of anti-inflammatory treatments. The investigation of inflammatory mechanisms in MDD is an important first step in the development of biomarkers to classify patient sub-groups, increase the accuracy of diagnosis, and tailor the approach to patients in clinical practice. This study may provide evidence of the benefit of LDN for the groups in whom conventional anti-depressants are ineffective and lead the way for translation into clinical practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12622000881730 . Registered on 21 June 2022.
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Antiinflamatorios , Trastorno Depresivo Mayor , Naltrexona , Antiinflamatorios/uso terapéutico , Australia , Biomarcadores , Proteína C-Reactiva , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/tratamiento farmacológico , Método Doble Ciego , Humanos , Inflamación/diagnóstico , Inflamación/tratamiento farmacológico , Naltrexona/uso terapéutico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Objective: To investigate scopolamine's rapid-acting antidepressant effects using an active placebo comparator. Most prior intravenous scopolamine studies reduced depressive symptomatologies compared to saline placebo infusions within 3 days. However, the confounding effect of placebo is unknown given that only saline placebo has been used in prior studies.Methods: In this trial, 40 patients with major depressive disorder were randomized to receive single intravenous doses of either scopolamine hydrobromide (4-6 µg/kg) or glycopyrronium bromide (4 µg/kg) between August 2019 and April 2021 in Auckland, New Zealand. Glycopyrronium was chosen as the active placebo due to its similar antimuscarinic properties to scopolamine but inability to cross the blood-brain barrier. The primary mood outcome measure was the Montgomery-Åsberg Depression Rating Scale (MADRS) administered pre-infusion and 1, 3, 7, 14, 28, and 42 days post-infusion.Results: Per protocol, this trial was abandoned for futility at n = 40. While scopolamine reduced MADRS scores by 12.6 (± 8.7 SD) points at day 3, glycopyrronium showed similar reductions (11.2 ± 9.6 SD). Frequentist linear mixed models showed no antidepressant effects of scopolamine versus placebo (d = 0.17), and Bayesian mixed effect models showed moderate evidence in favor of the null hypothesis at day 3 (Bayes factor = 0.32). Participants remained well-blinded to drug allocation, with 50% of participants correctly guessing their allocation.Conclusions: The observed MADRS improvement was larger than in prior studies, but no antidepressant effects were observed. This study using an active placebo confirms recent studies demonstrating the lack of antidepressant efficacy of scopolamine.Trial Registration: Australian New Zealand Clinical Trials Registry identifier: ACTRN12619000569101.
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Trastorno Depresivo Mayor , Antidepresivos/uso terapéutico , Australia , Teorema de Bayes , Trastorno Depresivo Mayor/tratamiento farmacológico , Método Doble Ciego , Glicopirrolato/farmacología , Glicopirrolato/uso terapéutico , Humanos , Escopolamina/uso terapéutico , Resultado del TratamientoRESUMEN
Prior studies indicate a pathogenic role of neuroinflammation in psychiatric disorders; however, there are no accepted methods that can reliably measure low-level neuroinflammation non-invasively in these individuals. Magnetic resonance spectroscopic imaging (MRSI) is a versatile, non-invasive neuroimaging technique that demonstrates sensitivity to brain inflammation. MRSI in conjunction with echo-planar spectroscopic imaging (EPSI) measures brain metabolites to derive whole-brain and regional brain temperatures, which may increase in neuroinflammation. The validity of MRSI/EPSI for measurement of low level neuroinflammation was tested using a safe experimental model of human brain inflammation - intramuscular administration of typhoid vaccine. Twenty healthy volunteers participated in a double-blind, placebo-controlled crossover study including MRSI/EPSI scans before and 3 h after vaccine/placebo administration. Body temperature and mood, assessed using the Profile of Mood States, were measured every hour up to four hours post-treatment administration. A mixed model analysis of variance was used to test for treatment effects. A significant proportion of brain regions (44/47) increased in temperature post-vaccine compared to post-placebo (p < 0.0001). For temperature change in the brain as a whole, there was no significant treatment effect. Significant associations were seen between mood scores assessed at 4 h and whole brain and regional temperatures post-treatment. Findings indicate that regional brain temperature may be a more sensitive measure of low-level neuroinflammation than whole-brain temperature. Future work where these measurement techniques are applied to populations with psychiatric disorders would be of clinical interest.
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Encefalitis , Vacunas Tifoides-Paratifoides , Encéfalo/patología , Estudios Cruzados , Encefalitis/metabolismo , Encefalitis/patología , Humanos , Espectroscopía de Resonancia Magnética/métodos , Enfermedades Neuroinflamatorias , Temperatura , Vacunas Tifoides-Paratifoides/metabolismoRESUMEN
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a treatment shown to be effective in treating major depressive disorder (MDD). However, the effect of rTMS therapy on functional connectivity within the brains of patients being treated for MDD remains poorly understood. Few studies have investigated the effects of a course of rTMS on resting-state network activity. METHODS: In an open-label naturalistic study, resting-state fMRI was collected prior to and following a four-week course of rTMS in 24 participants with MDD and 2 with bipolar disorder. Montgomery-Asberg depression rating scale scores showed a response rate of 42%. RESULTS: Clinical response to rTMS was correlated with reduced functional connectivity from baseline to post-rTMS within the salience network (SN). This indicates SN connectivity may be functionally relevant to how rTMS produces antidepressant effects. In an exploratory inter-network analysis, connectivity between the SN and posterior default mode network (pDMN) was higher following treatment. However this difference was not correlated with the antidepressant response. Local BOLD activity within these networks was also assessed using the fractional amplitude of low-frequency fluctuations (fALFF) technique. Local activity increased in both the SN and pDMN following rTMS. However this increase was also not correlated with antidepressant response. LIMITATIONS: The sample population was heterogeneous, continuing current use of medications, and the study lacked a healthy control or sham stimulation comparison group. CONCLUSIONS: Together, these results provide evidence for the involvement of the SN in the antidepressant response to rTMS treatment.
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Trastorno Depresivo Mayor , Trastorno Depresivo Resistente al Tratamiento , Depresión , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Resistente al Tratamiento/diagnóstico por imagen , Trastorno Depresivo Resistente al Tratamiento/terapia , Humanos , Imagen por Resonancia Magnética/métodos , Estimulación Magnética Transcraneal/métodosRESUMEN
Alterations in levels of neurotransmitters γ-aminobutyric acid (GABA) and glutamate may underlie the mechanism by which repetitive transcranial magnetic stimulation (rTMS) has efficacy as a treatment for major depressive disorder (MDD). This study used proton magnetic resonance spectroscopy (H1MRS) to investigate the effect of rTMS on levels of GABA and combined glutamate/glutamine measure (Glx). Treatment-resistant, currently depressed individuals participated in a naturalistic open-label study with rTMS treatment administered at 10 Hz and 120% of resting motor threshold to the left dorsolateral prefrontal cortex (DLPFC) for 20 sessions. H1 MRS measures were collected at baseline and after four weeks of daily treatment. GABA and Glx were measured from both the left DLPFC and a control region (right motor cortex). Twenty-seven participants completed the study and were included in the analysis. Contrary to previous studies, no difference in GABA was observed following treatment. Glx levels were found to significantly increase in both the left DLPFC and right motor cortex voxels but this increase did not correlate with antidepressant response. Glx levels were found to increase following rTMS, not only underlying the site of stimulation but also at a distant control voxel suggesting a degree of non-specificity in response to therapy.