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2.
Medicine (Baltimore) ; 99(45): e22958, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157937

RESUMO

INTRODUCTION: Treatment-resistant depression (TRD) has a high prevalence and can be exacerbated by poor physical health and economic hardships, which have become common stressors during the current COVID-19 pandemic. The therapeutic approaches used to treat these patients are not always available, may be not be accepted by some patients, and often require face-to-face interactions. OBJECTIVE: The main aim of this study will be to evaluate the effectiveness of an Internet-based adjuvant lifestyle-based intervention for patients with TRD. METHODS: This will be a parallel, randomized, and controlled clinical trial. A total of 180 patients with TRD will be randomly allocated (1:1:1) to 1 of 3 groups: treatment prescribed by the mental health team and written suggestions for lifestyle changes (placebo control group); treatment prescribed by the mental health team, written suggestions for lifestyle changes, and an 8-week mindfulness-based cognitive therapy program (active control group); or treatment prescribed by the mental health team, written suggestions for lifestyle changes, and an 8-week lifestyle change promotion program (intervention group). We will perform this study during the COVID-19 pandemic, and will administer interventions by teletherapy, and contact participants by telephone calls, text messages, and/or teleconferences. We will collect patient data using questionnaires administered at baseline, immediately after the intervention, and after 6 and 12 months. The primary outcome will be score on the Beck Depression Inventory-II. The secondary outcomes will be score on the Clinical Global Impressions Scale (used to quantify and track patient progress and treatment response over time) and health-related quality of life measured using the European Quality of Life-5 Dimensions Questionnaire. DISCUSSION: Patients with TRD are especially vulnerable when face-to-face psychotherapy is unavailable. The main strength of the proposed study is the novelty of the intervention to be used as an adjuvant therapy. Our results may provide guidance for treatment of patients with TRD in future situations that require lockdown measures. CLINICALTRIALS REGISTRATION NUMBER: NCT04428099.


Assuntos
Infecções por Coronavirus/epidemiologia , Transtorno Depressivo Resistente a Tratamento/terapia , Estilo de Vida Saudável , Pneumonia Viral/epidemiologia , Telemedicina , Terapia Cognitivo-Comportamental , Promoção da Saúde , Humanos , Atenção Plena , Pandemias , Ensaios Clínicos Pragmáticos como Assunto , Qualidade de Vida , Inquéritos e Questionários
3.
Am J Geriatr Psychiatry ; 28(10): 1025-1029, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32753340

RESUMO

OBJECTIVE: Electroconvulsive therapy (ECT) is an essential psychiatric service with an important role in treating older adults with severe or treatment-resistant depression. During the COVID-19 pandemic, ECT services have be constrained by infection control measures. We report a case of a 66-year-old female patient with a severe major depressive episode who had previously responded to right unilateral ECT and was treated with two modified accelerated intermittent theta-burst stimulation (aiTBS) protocols. METHODS: The two aiTBS courses consisted of eight daily sessions over five consecutive days, followed by gradual tapering, using 1,800 pulses per session pre-COVID-19 (first course), and 600 pulses per session during the pandemic (second course). RESULTS: Moderate to severe baseline depressive symptoms reached remission levels after both courses. CONCLUSION: The 600-pulses aiTBS treatment protocol reported here warrants further study and evaluation, but may be a potential option in cases where older adults with severe depressive symptoms cannot access ECT during the COVID-19 pandemic.


Assuntos
Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/terapia , Estimulação Magnética Transcraniana/métodos , Idoso , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Resistente a Tratamento/psicologia , Eletroconvulsoterapia , Feminino , Acesso aos Serviços de Saúde , Humanos , Pandemias , Questionário de Saúde do Paciente , Pneumonia Viral/epidemiologia , Resultado do Tratamento
6.
Brain Stimul ; 13(3): 850-857, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32289716

RESUMO

BACKGROUND: To determine if an accelerated rTMS protocol results in distinct depressive symptom response trajectories, compared to a standard rTMS protocol. We also sought to validate previous analyses that identified distinct depressive symptom response trajectories with rTMS treatment using an external dataset. METHOD: Data from two recent clinical trials comparing accelerated rTMS protocol delivered to the left dorsolateral prefrontal cortex (DLPFC) with standard once-daily rTMS protocol were used to identify depressive symptom response trajectories. The accelerated protocol in Trial 1 was conventional 10-Hz rTMS, while Trial 2 employed intermittent theta burst stimulation (iTBS). Participants were adult outpatients (18-70 years old) with bipolar or unipolar depression and moderate-severe depression (Montgomery Asberg Depression Rating Scale score >19) who had failed to respond to adequate courses of two different antidepressants. We used group-based trajectory modeling to identify MADRS response trajectories, and regression techniques adjusting for baseline depressive symptom severity to determine the association between treatment protocol and depressive symptom response trajectory. RESULTS: Treatment outcomes of 189 participants were analysed. We identified four distinct response trajectories: "nonresponse" (N = 59; 30.7%), "minimal response" (N = 65; 34.1%), "higher symptoms, response" (N = 26; 14.6%), "lower symptoms, response" (N = 39; 20.6%). We failed to find an association between rTMS protocol (accelerated vs standard) with depressive symptom response trajectory even after adjusting for baseline depressive symptom severity. CONCLUSION: The accelerated rTMS protocol in this study did not impact depressive symptom response trajectories. This work provides further confirmatory evidence that there are distinct depressive symptom response trajectories with rTMS delivered to the left DLPFC. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12616000443493 and ACTRN12613000044729.


Assuntos
Transtorno Depressivo Resistente a Tratamento/psicologia , Transtorno Depressivo Resistente a Tratamento/terapia , Córtex Pré-Frontal/fisiologia , Estimulação Magnética Transcraniana/métodos , Adolescente , Adulto , Idoso , Antidepressivos/uso terapêutico , Austrália , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
7.
Am J Psychiatry ; 177(8): 716-726, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32252538

RESUMO

OBJECTIVE: New antidepressant treatments are needed that are effective, rapid acting, safe, and tolerable. Intermittent theta-burst stimulation (iTBS) is a noninvasive brain stimulation treatment that has been approved by the U.S. Food and Drug Administration for treatment-resistant depression. Recent methodological advances suggest that the current iTBS protocol might be improved through 1) treating patients with multiple sessions per day at optimally spaced intervals, 2) applying a higher overall pulse dose of stimulation, and 3) precision targeting of the left dorsolateral prefrontal cortex (DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. The authors examined the feasibility, tolerability, and preliminary efficacy of Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an accelerated, high-dose resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for treatment-resistant depression. METHODS: Twenty-two participants with treatment-resistant depression received open-label SAINT. fcMRI was used to individually target the region of the left DLPFC most anticorrelated with sgACC in each participant. Fifty iTBS sessions (1,800 pulses per session, 50-minute intersession interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT. RESULTS: One participant withdrew, leaving a sample size of 21. Nineteen of 21 participants (90.5%) met remission criteria (defined as a score <11 on the Montgomery-Åsberg Depression Rating Scale). In the intent-to-treat analysis, 19 of 22 participants (86.4%) met remission criteria. Neuropsychological testing demonstrated no negative cognitive side effects. CONCLUSIONS: SAINT, an accelerated, high-dose, iTBS protocol with fcMRI-guided targeting, was well tolerated and safe. Double-blinded sham-controlled trials are needed to confirm the remission rate observed in this initial study.


Assuntos
Transtorno Depressivo Resistente a Tratamento , Giro do Cíngulo/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Estimulação Magnética Transcraniana/métodos , Adulto , Protocolos Clínicos , Cognição , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/fisiopatologia , Transtorno Depressivo Resistente a Tratamento/terapia , Feminino , Neuroimagem Funcional/métodos , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Monitorização Fisiológica/métodos , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Indução de Remissão/métodos
9.
Psychiatry Res ; 287: 112907, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32179210

RESUMO

New methods for using ketamine in patients with propofol-electroconvulsive therapy-resistant depression (ECT-RD) are needed in the clinic. This study aimed to investigate the therapeutic efficacy of ketamine plus ECT in ECT-RD patients, along with the treatment-induced brain alterations. A total of 28 ECT-RD patients were intravenously injected with ketamine six times and treated with propofol-ECT six times alternately within two weeks. The Hamilton Depression Scale was used to assess the treatment effect. Global functional connectivity density (gFCD) and functional connectivity strength (FCS) were used to evaluate functional brain alterations. As compared with the propofol-ECT treatment group, the addition of ketamine could improve the therapeutic outcomes in patients with ECT-RD. The treatment increased gFCD in the left temporal and subgenual anterior cingulated cortex. Simultaneously, the treatment decreased FCS within the default mode network. Although increased functional connectivity could be sustained for 10 days, the clinical effect was only sustained 7 days, indicating that the clinical effect and functional brain alterations were disjointed. Ketamine plus propofol-ECT can obviously improve the effects of propofol-ECT in ECT-RD patients. However, the effect is limited in 7 days, suggesting the benefit is short-term.


Assuntos
Antidepressivos/administração & dosagem , Encéfalo/diagnóstico por imagem , Transtorno Depressivo Resistente a Tratamento/terapia , Eletroconvulsoterapia/métodos , Ketamina/administração & dosagem , Propofol/administração & dosagem , Adulto , Anestésicos Intravenosos/administração & dosagem , Encéfalo/efeitos dos fármacos , Terapia Combinada/métodos , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/psicologia , Eletroconvulsoterapia/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
10.
Brain Stimul ; 13(3): 931-938, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32205066

RESUMO

BACKGROUND: Investigating approaches for determining a functionally meaningful dorsolateral prefrontal cortex (DLPFC) stimulation site is imperative for optimising repetitive transcranial magnetic stimulation (rTMS) response rates for treatment-resistant depression. One proposed approach is neuro-cardiac-guided rTMS (NCG-TMS) in which high frequency rTMS is applied to the DLPFC to determine the site of greatest heart rate deceleration. This site is thought to index a frontal-vagal autonomic pathway that intersects a key pathway believed to underlie rTMS response. OBJECTIVE: We aimed to independently replicate previous findings of high-frequency NCG-TMS and extend it to evaluate the use of low-frequency rTMS for NCG-TMS. METHODS: Twenty healthy participants (13 female; aged 38.6 ± 13.9) underwent NCG-TMS on frontal, fronto-central (active) and central (control) sites. For high-frequency NCG-TMS, three 5 s trains of 10 Hz were provided at each left hemisphere site. For low-frequency NCG-TMS, 60 s trains of 1 Hz were applied to left and right hemispheres and heart rate and heart rate variability outcome measures were analysed. RESULTS: For high-frequency NCG-TMS, heart rate deceleration was observed at the left frontal compared with the central site. For low-frequency NCG-TMS, accelerated heart rate was found at the right frontal compared with central sites. No other site differences were observed. CONCLUSION: Opposite patterns of heart rate activity were found for high- and low-frequency NCG-TMS. The high-frequency NCG-TMS data replicate previous findings and support further investigations on the clinical utility of NCG-TMS for optimising rTMS site localisation. Further work assessing the value of low-frequency NCG-TMS for rTMS site localisation is warranted.


Assuntos
Frequência Cardíaca/fisiologia , Córtex Pré-Frontal/fisiologia , Estimulação Magnética Transcraniana/métodos , Nervo Vago/fisiologia , Adulto , Transtorno Depressivo Resistente a Tratamento/fisiopatologia , Transtorno Depressivo Resistente a Tratamento/terapia , Eletrocardiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiologia , Adulto Jovem
11.
PLoS One ; 15(1): e0227614, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31935237

RESUMO

BACKGROUND: The present study aimed to develop a new scale to evaluate the level of difficulty in treating major depressive disorder with antidepressants based on the lifetime treatment profile. METHODS: In addition to evaluating the difficulty of treatment with antidepressants (A subscale), the Treatment Resistance to Antidepressants Evaluation Scale (TRADES) is comprised of a subscale to account for the attributes that compromise the efficacy of treatment (B subscale). One hundred and six participants aged 18 to 65 years with remitted major depressive disorder were enrolled. Eligible cases were those with at least 2 years from disease onset until the scoring date of the TRADES (the index date), with a complete treatment record. Various psychosocial and clinical features, such as neuroticism, harm avoidance, and utilization of psychiatric services, were used to validate the TRADES. RESULTS: The mean duration of the course before and after the index date were 5.5 ± 3.5 and 3.1 ± 1.7 years, respectively. In a multiple regression analysis, the final total scores of the TRADES independently correlated with higher levels of neuroticism and harm avoidance. Total scores were also associated with a higher utilization of psychiatric outpatient and admission services before the index date. Furthermore, it is thought that total scores could predict a higher number of visits to psychiatric outpatient, emergency, and admission services following the index date. CONCLUSIONS: The TRADES has acceptable validity and could help to quantify the level of treatment difficulty with antidepressants in major depressive disorder.


Assuntos
Transtorno Depressivo Maior/classificação , Transtorno Depressivo Resistente a Tratamento/classificação , Psicometria/métodos , Adulto , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Inibidores de Captação de Serotonina/uso terapêutico
12.
Curr Pharm Des ; 26(2): 244-252, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31924151

RESUMO

In this narrative review, we intended to summarize the evidence of pharmacological and somatic treatment choices for treatment-resistant depression (TRD). There are several types of therapeutic strategies to improve inadequate response to antidepressant treatment. The first step for patients with TRD is to optimize the dosage and duration of antidepressants as well as to ensure their drug compliance. The shift to antidepressant and antidepressant combination therapy for patients with TRD cannot be regarded as an evidence-based strategy. Only the combination of a monoamine reuptake inhibitor with a presynaptic α2-autoreceptor antagonist might have better efficacy than other antidepressant combinations. Currently, the most evidence-based treatment options for TRD are augmentation strategies. Among augmentative agents, second-generation antipsychotics and lithium have the strongest evidence for the management of TRD. Further studies are needed to evaluate the augmentative efficacy of anticonvulsants, thyroid hormone, glutamatergic agents, anti-inflammatory agents, and nutraceuticals for TRD. Among somatic therapies, electroconvulsive therapy and repetitive transcranial magnetic stimulation are effective for TRD. Further studies are warranted to provide clinicians with a better recommendation in making treatment choices in patients with TRD.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/terapia , Eletroconvulsoterapia , Quimioterapia Combinada , Humanos
13.
Fortschr Neurol Psychiatr ; 88(1): 40-51, 2020 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-31986551

RESUMO

Vagus nerve stimulation (VNS) is a minimally invasive neurostimulation method and was approved for drug-resistant epilepsy in children and adults in Europe in 1994. The observation that depression -the most common comorbidity in epilepsy - improved with VNS prompted trials of VNS in treatment-resistant depression (TRD) leading to European approval of VNS for TRD in 2001. Use of VNS for TRD patients in Germany is currently limited to a few highly specialized tertiary centers and the method is largely unknown in psychiatric clinical practice. We therefore systematically review the most recent publications on VNS in TRD as well as recommendations in guidelines and discuss the use of VNS in clinical practice. In the past 5 years, 5 level-2 studies and 4 level-3 studies were published on the effect of VNS in TRD patients. Clinical studies have failed to demonstrate short-term efficacy of VNS in TRD patients. Long-term efficacy of VNS in TRD patients is documented by multiple studies: the recently published largest ever investigation on the subject confirms favorable outcomes in TRD patients receiving adjunctive VNS in addition to treatment-as-usual compared to patients receiving treatment-as-usual-only over a 5-year period. Long-term efficacy of VNS is documented by level-2 evidence; however, it is not known which TRD patients have a higher probability of responding to VNS, which may complicate patient selection in clinical practice. Additionally, the unclear and variable definition of TRD may hinder or postpone adequate use of neurostimulation treatments.


Assuntos
Transtorno Depressivo Resistente a Tratamento/terapia , Estimulação do Nervo Vago , Europa (Continente) , Humanos , Resultado do Tratamento
14.
J Consult Clin Psychol ; 88(2): 106-118, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894993

RESUMO

OBJECTIVE: The sudden gain (SG; large symptom improvements in one between-session interval) has been identified as a consistent predictor of better outcomes at posttreatment and over follow-up in cognitive-behavioral therapy (CBT) for depression. Other defined trajectories of symptom change in CBT, including linear (consistent changes in depression), log-linear (symptom change concentrated in early or late sessions), one-step (substantial change in depression symptoms between two adjacent sessions), and cubic (symptom decrease, increase, and decrease), also predict better treatment outcomes. METHOD: We explored whether these patterns of symptom change occurred and predicted outcome in a sample of 156 adults with treatment-resistant depression who participated in a randomized controlled trial of CBT as an adjunct to pharmacotherapy (Wiles et al., 2013). Depression symptoms were assessed weekly with the Beck Depression Inventory-II. RESULTS: Multilevel modeling revealed that both SGs and having a defined trajectory predicted lower depression severity at 6- and 12-month follow-up, even controlling for baseline depression symptoms, early slopes of change, and symptom variability. CONCLUSIONS: These findings highlight the importance of examining longitudinal data and the robustness of the sudden gain pattern. They further suggest that having a defined symptom trajectory might confer its own advantages in predicting depression outcomes. Clinicians could use weekly depression scores to identify these key patterns of change to guide treatment decisions. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Assuntos
Terapia Cognitivo-Comportamental , Transtorno Depressivo Resistente a Tratamento/terapia , Adulto , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Sintomas , Resultado do Tratamento
15.
J Psychosoc Nurs Ment Health Serv ; 58(1): 11-16, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31895965

RESUMO

Treatment resistance continues to challenge and frustrate mental health clinicians and provoke psychiatric researchers to seek additional explanatory theories for psychopathology. Because the inflammatory process activates symptoms of depression, anxiety, and psychosis, it is a reasonable route to follow for primary and/or indirect contribution to mental disorders. The current article reviews the research literature regarding the role the inflammatory process and immune system play in mental disorders as well as novel treatments under investigation for resistant depression, anxiety, substance use, and psychotic disorders. [Journal of Psychosocial Nursing and Mental Health Services, 58(1), 11-16.].


Assuntos
Transtornos Mentais/fisiopatologia , Transtornos Mentais/terapia , Psiconeuroimunologia , Transtornos de Ansiedade/terapia , Transtorno Depressivo Resistente a Tratamento/terapia , Humanos , Transtornos Mentais/imunologia , Transtornos Psicóticos/terapia
16.
J Neurol Neurosurg Psychiatry ; 91(2): 189-195, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31801845

RESUMO

OBJECTIVE: Deep brain stimulation (DBS) reduces depressive symptoms in approximately 40%-60% of patients with treatment-resistant depression (TRD), but data on long-term efficacy and safety are scarce. Our objective was to assess the efficacy and safety of DBS targeted at the ventral anterior limb of the internal capsule (vALIC) in 25 patients with TRD during a 1-year, open-label, maintenance period, which followed a 1-year optimisation period. METHODS: Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAM-D-17), Montgomery-Asberg Depression Rating Scale (MADRS) and self-reported Inventory of Depressive Symptomatology (IDS-SR). Primary outcomes were response rate (≥50% HAM-D-17 score reduction) after the maintenance phase, approximately 2 years after DBS surgery, and changes in depression scores and occurrence of adverse events during the maintenance phase. RESULTS: Of 25 operated patients, 21 entered and 18 completed the maintenance phase. After the maintenance phase, eight patients were classified as responder (observed response rate: 44.4%; intention-to-treat: 32.0%). During the maintenance phase, HAM-D-17 and MADRS scores did not change, but the mean IDS-SR score decreased from 38.8 (95% CI 31.2 to 46.5) to 35.0 (95% CI 26.1 to 43.8) (p=0.008). Non-responders after optimisation did not improve during the maintenance phase. Four non-DBS-related serious adverse events occurred, including one suicide attempt. CONCLUSIONS: vALIC DBS for TRD showed continued efficacy 2 years after surgery, with symptoms remaining stable after optimisation as rated by clinicians and with patient ratings improving. This supports DBS as a viable treatment option for patients with TRD. TRIAL REGISTRATION NUMBER: NTR2118.


Assuntos
Estimulação Encefálica Profunda/métodos , Transtorno Depressivo Resistente a Tratamento/terapia , Cápsula Interna , Estimulação Encefálica Profunda/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
17.
Lancet Psychiatry ; 7(1): 29-40, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31860455

RESUMO

BACKGROUND: Stimulation adjustment is required to optimise outcomes of deep brain stimulation (DBS) for treatment-resistant depression, but controlled data for ideal stimulation parameters are poor or insufficient. We aimed to establish the efficacy and safety of short pulse width (SPW) and long pulse width (LPW) subcallosal cingulate DBS in depression. METHODS: We did a double-blind, randomised, crossover trial in an academic hospital in Calgary, AB, Canada. Patients had DSM IV-defined major depressive disorder and bipolar depression (20-70 years old, both sexes) and did not respond to treatment for more than 1 year, with a score of 20 or more on the 17-item Hamilton Depression Rating Scale (HDRS) at recruitment. Patients underwent bilateral DBS implantation into the subcallosal cingulate white matter using diffusion tensor imaging tractography. Patients were randomly assigned 1:1 without stratification using a computerised list generator to receive either SPW (90 µs) or LPW (210-450 µs) stimulation for 6 months. Patients and the clinician assessing outcomes were masked to the stimulation group. Keeping frequency constant (130 Hz), either pulse width or voltage was increased monthly, based on response using the HDRS. Patients who did not respond to treatment (<50% reduction in HDRS from baseline) at 6 months crossed over to the opposite stimulation for another 6 months. All patients received individualised cognitive behavioural therapy (CBT) for 12 weeks. The primary outcome was change in HDRS at 6 months and 12 months using intention-to-treat analysis. This study is registered with ClinicalTrials.gov, NCT01983904. FINDINGS: Between Dec 5, 2013, and Sept 30, 2016, of 225 patients screened for eligibility, 23 patients were selected for DBS surgery. After one patient withdrew, 22 (mean age 46·4 years, SEM 3·1; 10 [45%] female, 12 [55%] male) were randomly assigned, ten (45%) to LPW stimulation and 12 (55%) to SPW stimulation. Patients were followed up at 6 months and 12 months. There was a significant reduction in HDRS scores (p<0·0001) with no difference between SPW and LPW groups (p=0·54) in the randomisation phase at 6 months. Crossover groups did not show a significant decrease in HDRS within groups (p=0·15) and between groups (p=0·21) from 6-12 months. Adverse events were equal between groups. Worsening anxiety and depression were the most common psychological adverse events. One patient in the SPW group died by suicide. INTERPRETATION: Both LPW and SPW stimulation of subcallosal cingulate white matter tracts carried similar risks and were equally effective in reducing depressive symptoms, suggesting a role for both pulse width and amplitude titration in optimising clinical outcomes in patients with treatment-resistant depression. FUNDING: Alberta Innovates Health Solutions.


Assuntos
Transtorno Bipolar/terapia , Estimulação Encefálica Profunda , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/terapia , Imagem de Tensor de Difusão , Córtex Pré-Frontal , Canadá , Terapia Cognitivo-Comportamental , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
18.
Int J Neuropsychopharmacol ; 23(1): 20-25, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-31740958

RESUMO

BACKGROUND: Treatment-resistant depression is among the most debilitating conditions in psychiatry. Recent studies have associated alterations in white matter microstructure measured with magnetic resonance imaging with poor antidepressant response. Therefore, the extent to which electroconvulsive therapy, the most effective therapeutic option for treatment-resistant depression, affects white matter microstructure warrants investigation. METHODS: A total 13 patients suffering from severe unipolar treatment-resistant depression underwent magnetic resonance imaging with a diffusion tensor imaging sequence before and after undergoing a series of right unilateral electroconvulsive therapy. Diffusivity metrics were compared voxel-wise using tract-based spatial statistics and repeated-measures ANOVA. RESULTS: A total 12 patients responded to electroconvulsive therapy and 9 were classified as remitters. An increase in axial diffusivity was observed in the posterior limb of the internal capsule of the right hemisphere (PFWE ≤ .05). The increase in this area was higher in the right compared with the left hemisphere (P < .05). No correlation of this effect with treatment response could be found. CONCLUSIONS: The strong lateralization of effects to the hemisphere of electrical stimulation suggests an effect of electroconvulsive therapy on diffusivity metrics which is dependent of electrode placement. Investigation in controlled studies is necessary to reveal to what extent the effects of electroconvulsive therapy on white matter microstructure are related to clinical outcomes and electrode placement.


Assuntos
Transtorno Depressivo Resistente a Tratamento/diagnóstico por imagem , Transtorno Depressivo Resistente a Tratamento/terapia , Imagem de Tensor de Difusão , Eletroconvulsoterapia , Substância Branca/diagnóstico por imagem , Adolescente , Adulto , Feminino , Humanos , Cápsula Interna/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Brain Stimul ; 13(2): 337-340, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31711880

RESUMO

BACKGROUND: Dorsomedial prefrontal cortex (DMPFC) repetitive transcranial magnetic stimulation (rTMS) is a novel intervention for treatment-refractory depression (TRD). To date, many open-label case series and one randomized controlled trial of modest sample size have provided preliminary evidence that DMPFC-rTMS is an effective treatment for TRD. Here, we report the results of a large, double-blinded, sham-controlled trial of DMPFC-rTMS for TRD. OBJECTIVE: The primary aim of this study was to determine the efficacy of DMPFC-rTMS for TRD under sham-controlled conditions. METHODS: 120 TRD patients were randomized to receive 30 twice-daily sessions of either active high-frequency, active low-frequency, or sham DMPFC-rTMS using a novel bent active/sham double-cone coil. Placebo stimulation also involved the use of surface electrodes placed above the eyebrows. The 17-item Hamilton Rating Scale for Depression served as the primary outcome measure. RESULTS: Although there was a significant main effect of treatment across all arms, active DMPFC-rTMS was not superior to sham. Both participants and assessors were unable to accuracy determine whether patients received active or placebo stimulation. However, technicians' treatment arm guesses were significantly above chance. CONCLUSION: DMPFC rTMS did not result in improvement of depressive symptoms greater than sham stimulation. We cannot rule out that the sham apparatus may also have elicited an antidepressant effect via electrical trigeminal stimulation; future DMPFC-rTMS trials are therefore warranted.


Assuntos
Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/terapia , Estimulação Magnética Transcraniana/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/fisiopatologia
20.
Behav Cogn Psychother ; 48(3): 376-381, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31625500

RESUMO

BACKGROUND: One-third of patients with depression do not respond satisfactorily to treatment, and approximately 20% of all patients treated for depression develop a chronic depression. One approach to more effective treatment of chronic and treatment-resistant depression is to target rumination - an underlying mechanism implicated in the development and maintenance of depression. AIM: The purpose of this uncontrolled group study was to investigate the feasibility of individual rumination-focused cognitive behavioural therapy (RfCBT) for patients with chronic and treatment-resistant depression. METHOD: A total of 10 patients with chronic and treatment-resistant depression were offered 12-16 individual sessions of RfCBT. The primary outcome was depressive symptoms as measured by Hamilton Depression Scale at pre-, post- and 3-month follow-up. Secondary symptoms measured included self-reported rumination and worry. RESULTS: There was a significant reduction in depressive symptoms (p < 0.05), rumination (p < 0.01) and worry (p < 0.5) from pre- to post-treatment. Half of the participants (n = 5) showed significant reliable change on levels of depressive symptoms post-treatment. The reduction in depressive symptoms, rumination and worry were maintained at follow-up. CONCLUSIONS: RfCBT was associated with significant reductions in depressive symptoms in a small sample with chronic and treatment-resistant depression. Despite limitations of being a small uncontrolled study with limited follow-up, these results are promising in a difficult to treat population. RfCBT warrants further systematic evaluation.


Assuntos
Terapia Cognitivo-Comportamental , Transtorno Depressivo Resistente a Tratamento , Ansiedade , Depressão/terapia , Transtorno Depressivo Resistente a Tratamento/terapia , Humanos , Resultado do Tratamento
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