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1.
Psychopharmacology (Berl) ; 238(4): 1157-1169, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33483802

RESUMO

Ketamine produces a rapid antidepressant response in over 50% of adults with treatment-resistant depression. A long infusion of ketamine may provide durable remission of depressive symptoms, but the safety, efficacy, and neurobiological correlates are unknown. In this open-label, proof-of-principle study, adults with treatment-resistant depression (N = 23) underwent a 96-h infusion of intravenous ketamine (0.15 mg/kg/h titrated toward 0.6 mg/kg/h). Clonidine was co-administered to reduce psychotomimetic effects. We measured clinical response for 8 weeks post-infusion. Resting-state functional magnetic resonance imaging was used to assess functional connectivity in patients pre- and 2 weeks post-infusion and in matched non-depressed controls (N = 27). We hypothesized that responders to therapy would demonstrate response-dependent connectivity changes while all subjects would show treatment-dependent connectivity changes. Most participants completed infusion (21/23; mean final dose 0.54 mg/kg/h, SD 0.13). The infusion was well tolerated with minimal cognitive and psychotomimetic side effects. Depressive symptoms were markedly reduced (MADRS 29 ± 4 at baseline to 9 ± 8 one day post-infusion), which was sustained at 2 weeks (13 ± 8) and 8 weeks (15 ± 8). Imaging demonstrated a response-dependent decrease in hyperconnectivity of the subgenual anterior cingulate cortex to the default mode network, and a treatment-dependent decrease in hyperconnectivity within the limbic system (hippocampus, amygdala, medial thalamus, nucleus accumbens). In exploratory analyses, connectivity was increased between the limbic system and frontal areas, and smaller right hippocampus volume at baseline predicted larger MADRS change. A single prolonged infusion of ketamine provides a tolerated, rapid, and sustained response in treatment-resistant depression and normalizes depression-related hyperconnectivity in the limbic system and frontal lobe. ClinicalTrials.gov : Treatment Resistant Depression (Pilot), NCT01179009.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/uso terapêutico , Sistema Límbico/efeitos dos fármacos , Adolescente , Adulto , Idoso , Antidepressivos/administração & dosagem , Clonidina/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/diagnóstico por imagem , Transtorno Depressivo Resistente a Tratamento/psicologia , Feminino , Giro do Cíngulo/efeitos dos fármacos , Alucinógenos/efeitos adversos , Humanos , Infusões Intravenosas , Ketamina/administração & dosagem , Ketamina/antagonistas & inibidores , Sistema Límbico/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/efeitos dos fármacos , Escalas de Graduação Psiquiátrica , Simpatolíticos/uso terapêutico , Resultado do Tratamento , Adulto Jovem
2.
Psychopharmacology (Berl) ; 238(3): 857-865, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33471146

RESUMO

BACKGROUND: Interest and activity are part of the positive mood domain. Evidence suggests the symptom domain of interest-activity at baseline as a clinical predictor for treatment response to traditional antidepressants. However, whether this domain is related to the response to a single low-dose ketamine infusion remains unclear. METHODS: Seventy-one patients with treatment-resistant depression were randomized to 3 treatment groups: a single 0.5 or 0.2 mg/kg ketamine or normal saline placebo infusion. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale before infusions and at postinfusion period (at 40 min and up to 2 weeks). Low (mild) versus medium versus high (severe) interest-activity symptom domain groups were classified on the basis of the cutoff point of ± 0.4 standard deviation. The effect of baseline interest-activity symptoms on outcomes was tested using generalized estimating equation models. RESULTS: The interest-activity symptom domain as a continuous variable (ß = 8.413, p = .016) was related to the trajectory of depressive symptoms. Stratified by levels of the interest-activity symptom domain, in the low interest-activity, 0.2 mg/kg ketamine infusion (ß = 0.013) demonstrated the greatest antidepressant effect (p < .01) compared with 0.5 mg/kg ketamine (ß = 0.739) and placebo infusions; however, in the high interest-activity, 0.5 mg/kg ketamine infusion (ß = 0.001) demonstrated the best antidepressant effect (p < .01) compared with 0.2 mg/kg ketamine (ß = 1.372) and placebo infusions. DISCUSSION: The symptom domain of interest-activity was an independent predictor for the treatment response to a single low-dose ketamine infusion.


Assuntos
Anedonia/efeitos dos fármacos , Antidepressivos/administração & dosagem , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/administração & dosagem , Escalas de Graduação Psiquiátrica , Adulto , Transtorno Depressivo Resistente a Tratamento/psicologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
5.
Hu Li Za Zhi ; 67(5): 56-64, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-32978766

RESUMO

BACKGROUND: The COVID-19 pandemic has had a disastrous impact globally. For the general public and for people with mental illnesses, this pandemic may cause mental/physical stress and major life impacts. PURPOSE: This study was designed to explore the related changes in daily life and impacts on the well-being of a group of patients with chronic treatment-resistant depression (TRD) during the COVID-19 pandemic. METHODS: This study was a part of a long-term, follow-up study of a cohort of patients with TRD collected in 2018. All of the subjects who were diagnosed with major depression and fit the inclusion criteria were referred by the psychiatrists from two teaching hospitals. Structured interviews were used to collect data on physical and psychological changes during the pandemic period between January and May 2020. The researchers organized the key points by recording or note taking. Thematic analysis was used to summarize and classify themes and units. RESULTS: The 116 respondents revealed that the COVID-19 pandemic affected their health in the biological, psychological, and social dimensions. The three emerging themes included: The threatening of homogeneity in the whole person's health, the interaction between bio-psycho-social aspects, and positive growth of individuals with TRD. Although the participants had confidence in the prevention strategies of the government related to COVID-19, they expressed feelings of distress and restlessness with regard to COVID-19-related news reports. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The COVID-19 pandemic has affected the health of patients with TRD in both positive and negative ways. As the goal of government preventive strategies is to protect and promote public health, regular attention should be paid to the negative effects of long-term exposure to pandemic-related news on this vulnerable population.


Assuntos
Adaptação Psicológica , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/psicologia , Transtorno Depressivo Resistente a Tratamento/epidemiologia , Transtorno Depressivo Resistente a Tratamento/psicologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/psicologia , Seguimentos , Humanos , Meios de Comunicação de Massa , Pesquisa Qualitativa
6.
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
7.
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
8.
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
9.
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
10.
J Clin Psychopharmacol ; 40(1): 75-79, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31834094

RESUMO

PURPOSE: There is a practical need for the identification of pretreatment clinical and epidemiological response predictors to repeat ketamine infusions. Response predictors can serve to guide clinical inclusion of patients and weigh risks versus benefits for those receiving maintenance ketamine. Previous studies indicate a link between obesity, depression, and treatment response. We sought to investigate if body mass index (BMI) or metabolic syndrome could predict treatment response to ketamine. METHODS: Patients aged 18 to 72 years who were electroconvulsive therapy nonresponders were given a subanesthetic ketamine hydrochloride dose of 0.5 mg/kg delivered intravenously for 40 minutes for an acute series of 3 to 6 infusions every other day. If patients reported at least a 50% decrease in depression symptoms after the acute series, they were moved to a maintenance series of infusions, on an individualized basis. To assess if BMI or metabolic syndrome could predict response, logistic regression models were run to analyze initial responders, sustained responders, and nonresponders. Models were adjusted for age, sex, and baseline depression severity. RESULTS: Of the 150 patients analyzed, 56 did not respond to the acute phase, 38 initially responded to the acute phase but relapsed during the maintenance phase, and 56 sustained their response for 1 year. In unadjusted models, BMI was not shown to be a predictor of initial or sustained response. Alternatively, metabolic syndrome defined by a diagnosis of hypertension, hyperglycemia, or hyperlipidemia was determined to be significantly associated with diminished initial response but not sustained response. CONCLUSIONS: In our patient group, results support the literature that outcome in antidepressant therapy is affected by the presence of metabolic syndrome rather than obesity itself. Although BMI did not predict initial response to ketamine, the presence of metabolic syndrome was significantly negatively associated with the initial response to an acute series of ketamine infusions.


Assuntos
Afeto/efeitos dos fármacos , Antidepressivos/administração & dosagem , Índice de Massa Corporal , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/administração & dosagem , Síndrome Metabólica/complicações , Obesidade/complicações , Adolescente , Adulto , Idoso , Antidepressivos/efeitos adversos , Transtorno Depressivo Resistente a Tratamento/complicações , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/psicologia , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Ketamina/efeitos adversos , Masculino , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Obesidade/diagnóstico , Sistema de Registros , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
J Affect Disord ; 260: 323-328, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521869

RESUMO

BACKGROUND: There are many putative mechanisms by which ketamine has its effect and many unanswered questions about risks and benefits of long-term ketamine therapy. A research imperative is the identification of predictors of response to intravenous ketamine, especially a sustained response to maintenance ketamine. Temperament is an inherited aspect of personality and is a predictive factor for outcome in treatment resistant depressed (TRD) patients. METHODS: We analyzed which domains of personality impacted initial and sustained ketamine response. Utilizing the Neuroticism Extraversion Openness Five Factor Inventory (NEO-FFI) on 125 participants with TRD, we tested (1) whether the degree of neuroticism predicted initial and/or sustained response to ketamine; and (2) whether extraversion, agreeableness, openness to experience, and conscientiousness had an impact on response. RESULTS: Our findings confirmed previous literature that elevated neuroticism, low conscientiousness, and low extraversion was the pattern of our TRD population regardless of response. Openness was the only factor to significantly predict sustained treatment outcome. LIMITATIONS: Our findings are limited by the lack of placebo control, small sample size, non- standardized infusion intervals, polypharmacy rather than ketamine monotherapy, a select TRD population in that they had all failed ECT, and a primarily Caucasian population. CONCLUSIONS: Our registry adds to the literature that factors making up temperament may have predictive value in regard to treatment response, specifically the outcome for TRD patients receiving long-term ketamine infusion therapy. If confirmed, assessing for Openness could reduce inappropriate exposure to ketamine with its attendant unknown long-term risks.


Assuntos
Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/psicologia , Extroversão Psicológica , Ketamina/uso terapêutico , Neuroticismo , Adulto , Feminino , Humanos , Infusões Intravenosas , Masculino , Personalidade , Inventário de Personalidade , Sistema de Registros , Resultado do Tratamento
12.
Brain Stimul ; 13(1): 15-19, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31492631

RESUMO

BACKGROUND: Lithium is a helpful adjunct to patients undergoing ECT. However, only case reports and limited data suggest increase risk of delirium. Thus, this continues to be a controversial issue. OBJECTIVE: In this study, we examine 1) The association and odds of delirium and cognitive problems with ECT and lithium (ECT + Li) combination compared to ECT alone, 2) If positively associated, would this association vary by both type of mood episode and type of disorder? METHODS: A national sample of 64,728 adult psychiatric inpatients across the US (identified from a total data of about 70 million total discharges annually) was analyzed using linear-by-linear association and logistic regression to assess the odds ratio (OR) for delirium and cognitive impairment for those treated with lithium (N = 158), ECT (N = 64148), or ECT + Li (N = 422) after adjusting for demographics and psychiatric diagnoses. RESULTS: The prevalence of delirium was higher in the ECT + Lithium group (5.7%) vs. ECT only (0.6%) or lithium only groups (0%). Patients managed with ECT + Lithium have 11.7-fold higher odds (95% CI 7.55-17.99, P < 0.001) of delirium compared to ECT alone. In the ECT + Li group, delirium prevalence was 7.8% in unipolar depression, 3.4% in bipolar depressed, 0% in bipolar mania. CONCLUSION: These results are surprising given the fading concern about delirium association with ECT + lithium combination. The high odds in the combination group warrant clinical caution, use of lower lithium doses (if combinations cannot be avoided), and vigilance regarding early signs of delirium. These results warrant replication in future studies.


Assuntos
Disfunção Cognitiva/etiologia , Delírio/etiologia , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/terapia , Eletroconvulsoterapia/efeitos adversos , Carbonato de Lítio/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Delírio/epidemiologia , Delírio/psicologia , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Resistente a Tratamento/epidemiologia , Transtorno Depressivo Resistente a Tratamento/psicologia , Eletroconvulsoterapia/métodos , Feminino , Humanos , Carbonato de Lítio/administração & dosagem , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
13.
J Manag Care Spec Pharm ; 26(1): 16-20, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31880219

RESUMO

DISCLOSURES: Funding for this summary was contributed by the Laura and John Arnold Foundation, National Institute for Health Care Management, California Health Care Foundation, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Healthcare, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, AstraZeneca, Allergan, Alnylam, Biogen, Blue Shield of California, Cambia Health Services, CVS Caremark, Editas, Express Scripts, Genentech, GlaxoSmithKline, Harvard Pilgrim Health Care, Health Care Service Corporation, HealthPartners, HealthFirst, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinkrodt Pharmaceuticals, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Agboola, Fazioli, and Pearson are employed by ICER. Touchette reports grants from ICER during the course of this work and personal fees from Monument Analytics, unrelated to this work. Atlas has nothing to disclose.


Assuntos
Afeto/efeitos dos fármacos , Antidepressivos/administração & dosagem , Antidepressivos/economia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/economia , Custos de Medicamentos , Ketamina/administração & dosagem , Ketamina/economia , Administração Intranasal , Adolescente , Adulto , Aerossóis , Idoso , Antidepressivos/efeitos adversos , Pesquisa Comparativa da Efetividade , Análise Custo-Benefício , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/psicologia , Medicina Baseada em Evidências , Feminino , Humanos , Ketamina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Formulação de Políticas , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
15.
Psychol Med ; 50(2): 264-272, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30674359

RESUMO

BACKGROUND: Few studies focused on the relationship between psychological measures, major depressive disorder (MDD) and repetitive transcranial magnetic stimulation (rTMS) response. This study investigated several psychological measures as potential predictors for rTMS treatment response. Additionally, this study employed two approaches to evaluate the robustness of our findings by implementing immediate replication and full-sample exploration with strict p-thresholding. METHODS: This study is an open-label, multi-site study with a total of 196 MDD patients. The sample was subdivided in a Discovery (60% of total sample, n = 119) and Replication sample (40% of total sample, n = 77). Patients were treated with right low frequency (1 Hz) or left high frequency (10 Hz) rTMS at the dorsolateral prefrontal cortex. Clinical variables [Beck Depression Inventory (BDI), Neuroticism, Extraversion, Openness Five-Factor Inventory, and Depression, Anxiety, and Stress Scale, and BDI subscales] were obtained at baseline, post-treatment, and at follow-up. Predictors were analyzed in terms of statistical association, robustness (independent replication), as well as for their clinical relevance [positive predictive value (PPV) and negative predictive value (NPV)]. RESULTS: Univariate analyses revealed that non-responders had higher baseline anhedonia scores. Anhedonia scores at baseline correlated negatively with total BDI percentage change over time. This finding was replicated. However, anhedonia scores showed to be marginally predictive of rTMS response, and neither PPV nor NPV reached the levels of clinical relevance. CONCLUSIONS: This study suggests that non-responders to rTMS treatment have higher baseline anhedonia scores. However, anhedonia was only marginally predictive of rTMS response. Since all other psychological measures did not show predictive value, it is concluded that psychological measures cannot be used as clinically relevant predictors to rTMS response in MDD.


Assuntos
Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/psicologia , Transtorno Depressivo Resistente a Tratamento/terapia , Estimulação Magnética Transcraniana , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inventário de Personalidade , Valor Preditivo dos Testes , Córtex Pré-Frontal/fisiopatologia , Curva ROC , Resultado do Tratamento
16.
Stereotact Funct Neurosurg ; 97(5-6): 369-380, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31865344

RESUMO

INTRODUCTION: Bilateral anterior capsulotomy (BAC) is an effective surgical procedure for patients with treatment-resistant major depression (TRMD). In this work, we analyze the connectivity of the BAC lesions to identify connectivity "fingerprints" associated with clinical outcomes in patients with TRMD. METHODS: We performed a retrospective study of ten patients following BAC surgery. These patients were divided into "responders" and "non-responders" based on the relative change in the Beck depression inventory (BDI) score after surgery. We generated the dorsolateral prefrontal associative (DLPFC) pathways and the ventromedial prefrontal limbic (vmPFC) pathways going through the anterior limb of the internal capsule and analyzed if the overlap of the BAC lesions with these pathways was associated with either outcome. Finally, we used the BAC lesions of our patients to generate group-averaged connectivity "fingerprints" associated with either outcome. RESULTS: Six patients were responders (≥50% improvement in BDI), four patients were non-responders (<50% improvement). No significant impairments were found in most neuropsychological tests after surgery. The overlap analysis showed that in the responder group, there was less involvement of the DLPFC pathways than the vmPFC pathways (p = 0.001). Conversely, in the non-responder group, there was no significant difference between the involvement of both pathways (p = 0.157). The responder and non-responder connectivity fingerprint showed significant connections with the vmPFC limbic areas. However, the non-responder connectivity fingerprint also showed stronger connectivity to associative areas including the DLPFC and lateral orbitofrontal cortices. CONCLUSIONS: The optimum outcome following BAC surgery in this cohort was associated with interruption of vmPFC pathways and the relative preservation of DLPFC pathways.


Assuntos
Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/cirurgia , Transtorno Depressivo Resistente a Tratamento/diagnóstico por imagem , Transtorno Depressivo Resistente a Tratamento/cirurgia , Cápsula Interna/diagnóstico por imagem , Cápsula Interna/cirurgia , Adulto , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Resistente a Tratamento/psicologia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/cirurgia , Estudos Retrospectivos , Adulto Jovem
17.
J Clin Psychiatry ; 80(6)2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31846575

RESUMO

OBJECTIVE: To determine the likelihood of antidepressant response in older adults with major depression as a function of their prior antidepressant trials. METHODS: 500 older adults with major depression as diagnosed by DSM-IV criteria for major depressive episode were treated with venlafaxine extended release for 12 weeks. Participants were recruited from July 2009 to January 2014. For each participant, we collected detailed data on prior antidepressant trials for the current episode of depression. We examined the prospective remission rates as a function of number and class of prior antidepressant trials in a post hoc analysis of pooled data from 2 prior trials. RESULTS: Remission rates with venlafaxine were inversely correlated with the number of prior adequate medication trials (66% for no prior adequate trials, 45% for 1 prior adequate trial, 23% for 2 or more prior adequate trials; P < .0001). Additionally, if prior treatment trials included a serotonin-norepinephrine reuptake inhibitor, participants were even less likely to achieve remission with venlafaxine (32% for 1 prior adequate trial, 18% for 2 or more prior adequate trials; P < .0001). Those with prior adequate trials were also more likely to require a higher dosage of venlafaxine to achieve remission. CONCLUSIONS: Information on an individual patient's number and class of prior adequate antidepressant trials can be used to predict the likelihood of a successful treatment outcome with a given antidepressant in older adults with major depression. Further work is needed to refine this approach to provide personalized antidepressant treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00892047 and NCT02263248.


Assuntos
Algoritmos , Antidepressivos/uso terapêutico , Regras de Decisão Clínica , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Cloridrato de Venlafaxina/uso terapêutico , Antidepressivos/efeitos adversos , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/psicologia , Aripiprazol/efeitos adversos , Aripiprazol/uso terapêutico , Comorbidade , Preparações de Ação Retardada , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/psicologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Funções Verossimilhança , Estudos Prospectivos , Recidiva , Resultado do Tratamento , Cloridrato de Venlafaxina/efeitos adversos
18.
BMJ Open ; 9(12): e032507, 2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31874880

RESUMO

INTRODUCTION: Depressive disorders are very common diseases entailing a great burden on affected people. However, comprehensive information on long-term disease course in patients with severe depression is lacking so far. The objectives of the DELTA study are to examine long-term outcomes and their predicting factors, to assess clinical response of antidepressant pharmacotherapy by applying therapeutic drug monitoring, to identify predictors of therapeutic non-response, to describe the long-term healthcare utilisation and to investigate the role of biomarkers in disease course. METHODS AND ANALYSIS: A cohort study including all adult hospitalised cases (age range 18 to 75 years) of severe major depression who are admitted to the Bezirkskrankenhaus Augsburg is established. It is planned to include 300 patients. During the hospital stay, information is gathered through personal interview, self-administered questionnaires, cognitive tests and chart review. Furthermore, biomaterials are collected. After hospital discharge, patients are repeatedly re-examined over time (3, 6, 12, 24 and 36 months) to collect information about mortality, relapse, depression severity, health-related quality of life (HRQOL), perceived stigma, cognitive functions, diet, physical activity, treatment and healthcare utilisation. Follow-up blood samples are collected to determine therapeutic drug levels. The primary study aim is to investigate long-term therapeutic response, survival, relapse, HRQOL and cognitive functions. Survival time and time to relapse or re-hospitalisation will be analysed using Cox regression models. Changes of HRQOL, depressive symptoms and cognitive functions over time will be examined using generalised linear regression models for repeated measures or mixed models. Correlates of the disease course will be modelled using suitable generalised linear, mixed, estimating equation and growth curve models. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Ludwig-Maximilians-Universität München (date of approval: 23 October 2017, reference number: 17-625). Study results will be presented at scientific conferences and published in peer-reviewed scientific journals.


Assuntos
Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Resistente a Tratamento/psicologia , Progressão da Doença , Qualidade de Vida , Adolescente , Adulto , Idoso , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/terapia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Estudos Prospectivos , Adulto Jovem
20.
J Psychiatry Neurosci ; 44(6): 384-385, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573153

RESUMO

A growing body of literature has shown the effectiveness of ketamine for treating chronic depression. How long the beneficial effects of repeated ketamine last once infusions are stopped, however, remains largely unknown. Understanding the challenges that ensue after ketamine cessation can help clinicians optimally guide patients who opt for ketamine treatment and minimize the associated risks. In this commentary, we discuss some unexpected data gathered from participants of a pilot study on the effects of adjunctive ketamine infusion for resistant depression.


Assuntos
Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Duração da Terapia , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Ketamina/uso terapêutico , Adulto , Doença Crônica , Transtorno Depressivo Resistente a Tratamento/psicologia , Feminino , Acesso aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Ideação Suicida , Tentativa de Suicídio
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