RESUMO
BACKGROUND: Major depressive disorder (MDD) is commonly treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs inhibit the serotonin transporter (5-HTT), but the downstream antidepressant mechanism of action of these drugs is poorly understood. The serotonin 1B (5-HT1B) receptor is functionally linked to 5-HTT and 5-HT1B receptor binding and 5-HT1B receptor mRNA is reduced in the raphe nuclei after SSRI administration in primates and rodents, respectively. The effect of SSRI treatment on 5-HT1B receptor binding in patients with MDD has not been examined previously. This positron emission tomography (PET) study aimed to quantify brain 5-HT1B receptor binding changes in vivo after SSRI treatment for MDD in relation to treatment effect. METHODS: Eight unmedicated patients with moderate to severe MDD underwent PET with the 5-HT1B receptor radioligand [11C]AZ10419369 before and after 3 to 4 weeks of treatment with the SSRI escitalopram 10 mg daily. Depression severity was assessed at time of PET and after 6 to 7 weeks of treatment with the Montgomery-Åsberg Depression Rating Scale. RESULTS: We observed a significant reduction in [11C]AZ10419369 binding in a dorsal brainstem (DBS) region containing the median and dorsal raphe nuclei after escitalopram treatment (P = .036). Change in DBS [11C]AZ10419369 binding correlated with Montgomery-Åsberg Depression Rating Scale reduction after 3-4 (r = 0.78, P = .021) and 6-7 (r = 0.94, P < .001) weeks' treatment. CONCLUSIONS: Our findings align with the previously reported reduction of 5-HT1B receptor binding in the raphe nuclei after SSRI administration and support future studies testing change in DBS 5-HT1B receptor binding as an SSRI treatment response marker.
Assuntos
Transtorno Depressivo Maior , Escitalopram , Tomografia por Emissão de Pósitrons , Receptor 5-HT1B de Serotonina , Inibidores Seletivos de Recaptação de Serotonina , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Benzopiranos , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Citalopram/farmacologia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/diagnóstico por imagem , Escitalopram/metabolismo , Escitalopram/farmacologia , Escitalopram/uso terapêutico , Morfolinas , Piperazinas/farmacologia , Ligação Proteica/efeitos dos fármacos , Receptor 5-HT1B de Serotonina/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Resultado do TratamentoRESUMO
OBJECTIVES: This study aims to evaluate the safety and efficacy of escitalopram and sertraline in post-stroke depression (PSD) patients, to provide more reliable therapeutics for cardiovascular and psychiatric clinical practice. METHODS: We recruited 60 patients (aged 40-89 years old) with an ICD-10 diagnosis of PSD, who were then randomly assigned to two groups and treated with flexible doses of escitalopram (10 to 20 mg/day, n = 30) or sertraline (50 to 200 mg/day, n = 30) for consecutive 8 weeks, respectively. The 24-item Hamilton Depression Rating Scale (HAMD-24), the 14-item Hamilton Anxiety Rating Scale (HAMA-14), the Treatment Emergent Symptom Scale (TESS), the Montreal Cognitive Assessment Scale (MOCA), and the Activity of Daily Living scale (ADL) were used to assess patients before, during, and after treatment for depression, anxiety, adverse effects, cognitive function, and daily living activities. Repeated measures ANOVA, the Mann-Whitney U test, the chi-square test (χ2), or Fisher's exact test was employed to assess baseline demographics, response rate, adverse effects rate, and changes in other clinical variables. RESULTS: Significant reduction in HAMD-24 and HAMA-14 scores was evaluated at baseline, as well as 1, 3, 4, 6, and 8 weeks of drug intervention (p < 0.01). There was a significant group difference in post-treatment HAMD-24 scores (p < 0.05), but no difference was observed in HAMA-14 scores (p > 0.05). Further analysis showed a significant variance in the HAMD-24 scores between the two groups at the end of the first week (p < 0.01). The incidence of adverse effects in both patient groups was mild, but there was a statistically significant difference between the two groups (p < 0.05). The improvement in cognitive function and the recovery of daily living abilities were comparable between both groups (p > 0.05). CONCLUSION: Escitalopram and sertraline showed comparable efficacy for anxiety symptoms, cognitive function, and daily living abilities in PSD patients. In addition, escitalopram was more appropriate for alleviating depressive symptoms. To validate the conclusion, trials with a larger sample size are in demand in the future. The registration number is ChiCTR1800017373.
Assuntos
Atividades Cotidianas , Escitalopram , Sertralina , Acidente Vascular Cerebral , Humanos , Sertralina/uso terapêutico , Sertralina/efeitos adversos , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Adulto , Idoso de 80 Anos ou mais , Escitalopram/uso terapêutico , Escitalopram/efeitos adversos , Depressão/tratamento farmacológico , Depressão/etiologia , Resultado do Tratamento , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Escalas de Graduação Psiquiátrica , Antidepressivos/uso terapêutico , Antidepressivos/efeitos adversos , Citalopram/uso terapêutico , Citalopram/efeitos adversosRESUMO
OBJECTIVE: Late-life depression is associated with substantial heterogeneity in clinical presentation, disability, and response to antidepressant treatment. We examined whether self-report of severity of common symptoms, including anhedonia, apathy, rumination, worry, insomnia, and fatigue were associated with differences in presentation and response to treatment. We also examined whether these symptoms improved during treatment with escitalopram. DESIGN: Eighty-nine older adults completed baseline assessments, neuropsychological testing and providing self-reported symptom and disability scales. They then entered an 8-week, placebo-controlled randomized trial of escitalopram, and self-report scales were repeated at the trial's end. Raw symptom scale scores were combined into three standardized symptom phenotypes and models examined how symptom phenotype severity was associated with baseline measures and depression improvement over the trial. RESULTS: While rumination/worry appeared independent, severity of apathy/anhedonia and fatigue/insomnia were associated with one another and with greater self-reported disability. Greater fatigue/insomnia was also associated with slower processing speed, while rumination/worry was associated with poorer episodic memory. No symptom phenotype severity score predicted a poorer overall response to escitalopram. In secondary analyses, escitalopram did not improve most phenotypic symptoms more than placebo, aside for greater reductions in worry and total rumination severity. CONCLUSION: Deeper symptom phenotype characterization may highlight differences in the clinical presentation of late-life depression. However, when compared to placebo, escitalopram did not improve many of the symptoms assessed. Further work is needed to determine whether symptom phenotypes inform longer-term course of illness, and which treatments may best benefit specific symptoms.
Assuntos
Depressão , Distúrbios do Início e da Manutenção do Sono , Humanos , Idoso , Depressão/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Escitalopram , Anedonia , Resultado do Tratamento , Cognição , Fadiga/tratamento farmacológico , Citalopram/uso terapêuticoRESUMO
OBJECTIVE: Aim: Evaluation of the effectiveness of the early 8-week monotherapy with escitalopram as a form of proactive psychosomatic intervention for patients with post-COVID depression. PATIENTS AND METHODS: Materials and methods: 44 patients with post-COVID depression were involved in a proactive psychosomatic intervention in the form of an 8-week intake of escitalopram (Medogram, Medochemiе Ltd) for 2-8 weeks in the case of a diagnosis of severe depression. Hamilton Depression Scale (HAM-D), Somatic Symptom Scale (SSS-8), Quality of Life Scale (CQLS) were used to assess symptoms and status dynamics. RESULTS: Results: Patients with post-COVID depression after an 8-week course of escitalopram therapy showed a significant reduction in mental and somatic symptoms of depression and an improvement in quality of life. At the time of enrollment in the study, 12 (28.58%) individuals had mild depression, 15 (35.71%) had moderate depression, and 15 (35.71%) had severe depression. At the end of the 8th weeks of taking the drug in 24 (57.14%) there were no signs of depression on the HAM-D scale, in 18 people there were subclinical manifestations of depression. The effectiveness of escitalopram in reducing the symptoms of depression in this study was 66%. CONCLUSION: Conclusions: With the introduction of pharmacotherapy with escitalopram there was a significant reduction in mental and so¬matic symptoms of depression and an improvement in quality of life. Escitalopram (Medochemie Ltd) may be an effective drug for psychopharmacotherapy of depressive symptoms in patients who have had COVID-19. Further studies are promising its effective¬ness in the treatment of post-COVID depression.
Assuntos
COVID-19 , Depressão , Humanos , COVID-19/complicações , Depressão/tratamento farmacológico , Depressão/etiologia , Escitalopram/uso terapêutico , Qualidade de Vida , Resultado do TratamentoRESUMO
OBJECTIVES: Depression is often accompanied by various degrees of cognitive decline, with a high incidence. Guidelines recommend medication combined with psychological therapy. Solution focused group therapy (SFGT) is a newer group psychotherapy technique. This study aims to explore the difference between SFGT combined with escitalopram and only use escitalopram in treating depression. METHODS: A total of 84 patients who met the diagnostic criteria of international classification of diseases-10 (ICD-10) were enrolled into the combined group (SFGT combined with escitalopram, n=42) and the control group (only escitalopram, n=42) for an 8-week treatment. Patients were measured with the 24-item Hamilton Depression Scale (HAMD-24) and the Cognitive Flexibility Inventory (CFI) at baseline (T0), week 4 (T1), and week 8 (T2), respectively. Differences in depressive symptoms and cognitive flexibility between the 2 groups were compared and analyzed. RESULTS: At T2, 8 patients were dislodged in the combined group and 10 in the control group. There was no difference in the subscales and total scores of HAMD-24 and CFI between the 2 groups at T0 (all P>0.05). At T1 and T2, compared with the control group, the total scores and anxiety somatization, cognitive impairment, delay, and a sense of despair subscales scores of HAMD-24 were lower, and the total scores and subscales scores of CFI in the combined group were higher (all P<0.05). CONCLUSIONS: SFGT combined with escitalopram is more effective than monotherapy for improving the anxiety somatization symptoms, cognitive impairment, retardation symptoms and despair symptoms, and increasing the cognitive flexibility.
Assuntos
Transtorno Depressivo , Psicoterapia de Grupo , Humanos , Citalopram/uso terapêutico , Citalopram/efeitos adversos , Depressão/terapia , Escitalopram , Transtorno Depressivo/complicações , Transtorno Depressivo/terapia , Cognição , Resultado do TratamentoRESUMO
OBJECTIVE: We assessed pharmacokinetic correlates of treatment response to escitalopram using a large therapeutic drug monitoring database. METHODS: A large naturalistic sample of patients receiving escitalopram was analyzed. Responders were defined as 'very much improved' or 'much improved' based on the Clinical Global Impression - Improvement score, CGI-I. We compared responders (n = 83) vs. non-responders (n = 388) with the primary outcome being the escitalopram plasma concentration and concentration corrected by the daily dose (C/D ratio). Effects of age, sex, body-mass-index (BMI), and C/D ratio were assessed in a multivariate logistic regression model predicting response. RESULTS: There were no statistically significant differences in clinical and demographic characteristics between responders vs. non-responders. There were also no differences between escitalopram daily doses or plasma concentrations, while C/D ratios were significantly higher in non-responders than in responders (1.6 ± 1.7 vs. 1.2 ± 0.9 (ng/mL)/(mg/day), p = 0.007); C/D ratios (odds ratio 0.52, 95% confidence interval 0.34-0.80, p < 0.003) were associated with response to escitalopram, after controlling for age, sex, and BMI. CONCLUSIONS: Patients with low clearance of escitalopram as reflected upon high C/D ratios may be less likely respond to escitalopram. Identifying these patients during dose titration may support clinical decision-making, including switching to a different antidepressant instead of increasing daily dose.
Assuntos
Citalopram , Escitalopram , Humanos , Citalopram/efeitos adversos , Antidepressivos/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: There is growing evidence for the therapeutic effects of the psychedelic drug psilocybin for major depression. However, due to the lack of safety data on combining psilocybin with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and concerns that there may be a negative interaction on efficacy, participants enrolling in psychedelic trials are usually required to discontinue SNRI/SNRIs prior to enrolling. AIMS: Using data from a recent clinical trial examining the comparative efficacy the psychedelic drug psilocybin (P) combined with approximately 20 h of psychological support to a 6-week (daily) course of the SSRI escitalopram plus matched psychological support for major depressive disorder, we explored the effects of discontinuing SSRI/SNRIs prior to study enrolment on study outcomes. METHODS: Exploratory post hoc analyses using linear mixed effects model were performed to investigate the discontinuation effect on various validated depression symptom severity scales and well-being. The impact of SSRI/SNRIs discontinuation on the acute psychedelic experience was also explored. RESULTS/OUTCOMES: In the psilocybin group, there was a reduced treatment effect on all outcome measures for SSRI/SNRIs discontinuers compared with unmedicated patients at trial entry. However, no effects of discontinuation on measures of the acute psychedelic experience were found. CONCLUSION: Discontinuation of SSRI/SNRIs before psilocybin might diminish response to treatment; however, as we did not test SSRI/SNRI continuation in our trial, we cannot infer such causation. Moreover, the exploratory nature of the analyses makes them hypothesis generating, and not confirmatory. A controlled trial of SSRI/SNRI discontinuation versus continuation prior to psilocybin is urgently required.
Assuntos
Transtorno Depressivo Maior , Escitalopram , Alucinógenos , Psilocibina , Inibidores Seletivos de Recaptação de Serotonina , Humanos , Psilocibina/administração & dosagem , Psilocibina/farmacologia , Psilocibina/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Adulto , Masculino , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Feminino , Alucinógenos/administração & dosagem , Alucinógenos/efeitos adversos , Alucinógenos/farmacologia , Escitalopram/administração & dosagem , Escitalopram/farmacologia , Pessoa de Meia-Idade , Resultado do Tratamento , Quimioterapia CombinadaRESUMO
EEG brain abnormalities, such as slowing and isolated epileptiform discharges (IEDs), has previously been associated with non-response to antidepressant treatment with escitalopram and venlafaxine, suggesting a potential need for treatment with anticonvulsant property in some patients. The current study aims to replicate the reported association of EEG abnormality and treatment outcomes in an open-label trial of escitalopram for major depressive disorder (MDD) and explore its relationship to mood and cognition. Pretreatment, 6 min eyes-closed resting-state 256-channel EEG was recorded in 91 patients with MDD (age 18-57) who were treated with 10-20 mg escitalopram for 12 weeks; patients could switch to duloxetine after four weeks. A certified clinical neurophysiologist rated the EEGs. IED and EEG slowing was seen in 13.2%, and in 6.6% there were findings with unclear significance (i.e., Wicket spikes and theta activity). We saw no group-difference in remission or response rates after 8 and 12 weeks of treatment or switching to duloxetine. Patients with EEG abnormalities had higher pretreatment mood disturbances driven by greater anger (p=.039) and poorer verbal memory (p=.012). However, EEG abnormality was not associated with improved mood or verbal memory after treatment. Our findings should be interpreted in light of the rarity of EEG abnormalities and the sample size. While we cannot confirm that EEG abnormalities are associated with non-response to treatment, including escitalopram, abnormal EEG activity is associated with poor mood and verbal memory. The clinical utility of EEG abnormality in antidepressant treatment selection needs careful evaluation before deciding if useful for clinical implementation.
Assuntos
Transtorno Depressivo Maior , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Cloridrato de Duloxetina/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Citalopram/uso terapêutico , Escitalopram , Antidepressivos/uso terapêutico , Eletroencefalografia , Resultado do TratamentoRESUMO
Depression is a leading global cause of disability, yet about half of patients do not respond to initial antidepressant treatment. This treatment difficulty may be in part due to the heterogeneity of depression and corresponding response to treatment. Unsupervised machine learning allows underlying patterns to be uncovered, and can be used to understand this heterogeneity by finding groups of patients with similar response trajectories. Prior studies attempting this have clustered patients using a narrow range of data primarily from depression scales. In this work, we used unsupervised machine learning to cluster patients receiving escitalopram therapy using a wide variety of subjective and objective clinical features from the first eight weeks of the Canadian Biomarker Integration Network in Depression-1 trial. We investigated how these clusters responded to treatment by comparing changes in symptoms and symptom categories, and by using Principal Component Analysis (PCA). Our algorithm found three clusters, which broadly represented non-responders, responders, and remitters. Most categories of features followed this response pattern except for objective cognitive features. Using PCA with our clusters, we found that subjective mood state/anhedonia is the core feature of response with escitalopram, but there exists other distinct patterns of response around neurovegetative symptoms, activation, and cognition.
Assuntos
Transtorno Depressivo Maior , Humanos , Canadá , Transtorno Depressivo Maior/psicologia , Escitalopram , Resultado do TratamentoRESUMO
Importance: Anxiety disorders are common, highly distressing, and impairing conditions. Effective treatments exist, but many patients do not access or respond to them. Mindfulness-based interventions, such as mindfulness-based stress reduction (MBSR) are popular and can decrease anxiety, but it is unknown how they compare to standard first-line treatments. Objective: To determine whether MBSR is noninferior to escitalopram, a commonly used first-line psychopharmacological treatment for anxiety disorders. Design, Setting, and Participants: This randomized clinical trial (Treatments for Anxiety: Meditation and Escitalopram [TAME]) included a noninferiority design with a prespecified noninferiority margin. Patients were recruited between June 2018 and February 2020. The outcome assessments were performed by blinded clinical interviewer at baseline, week 8 end point, and follow-up visits at 12 and 24 weeks. Of 430 individuals assessed for inclusion, 276 adults with a diagnosed anxiety disorder from 3 urban academic medical centers in the US were recruited for the trial, and 208 completed the trial. Interventions: Participants were 1:1 randomized to 8 weeks of the weekly MBSR course or the antidepressant escitalopram, flexibly dosed from 10 to 20 mg. Main Outcomes and Measures: The primary outcome measure was anxiety levels as assessed with the Clinical Global Impression of Severity scale (CGI-S), with a predetermined noninferiority margin of -0.495 points. Results: The primary noninferiority sample consisted of 208 patients (102 in MBSR and 106 in escitalopram), with a mean (SD) age of 33 (13) years; 156 participants (75%) were female; 32 participants (15%) were African American, 41 (20%) were Asian, 18 (9%) were Hispanic/Latino, 122 (59%) were White, and 13 (6%) were of another race or ethnicity (including Native American or Alaska Native, more than one race, or other, consolidated owing to low numbers). Baseline mean (SD) CGI-S score was 4.44 (0.79) for the MBSR group and 4.51 (0.78) for the escitalopram group in the per-protocol sample and 4.49 (0.77) vs 4.54 (0.83), respectively, in the randomized sample. At end point, the mean (SD) CGI-S score was reduced by 1.35 (1.06) for MBSR and 1.43 (1.17) for escitalopram. The difference between groups was -0.07 (0.16; 95% CI, -0.38 to 0.23; P = .65), where the lower bound of the interval fell within the predefined noninferiority margin of -0.495, indicating noninferiority of MBSR compared with escitalopram. Secondary intent-to-treat analyses using imputed data also showed the noninferiority of MBSR compared with escitalopram based on the improvement in CGI-S score. Of patients who started treatment, 10 (8%) dropped out of the escitalopram group and none from the MBSR group due to adverse events. At least 1 study-related adverse event occurred for 110 participants randomized to escitalopram (78.6%) and 21 participants randomized to MBSR (15.4%). Conclusions and Relevance: The results from this randomized clinical trial comparing a standardized evidence-based mindfulness-based intervention with pharmacotherapy for the treatment of anxiety disorders found that MBSR was noninferior to escitalopram. Trial Registration: ClinicalTrials.gov Identifier: NCT03522844.
Assuntos
Atenção Plena , Humanos , Adulto , Feminino , Masculino , Atenção Plena/métodos , Escitalopram , Estresse Psicológico/terapia , Transtornos de Ansiedade/tratamento farmacológico , Ansiedade , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the effectiveness and safety of escitalopram in the form of oral dispersible tablets (Elicea Q-Tab) in real-life clinical practice in patients with depressive and anxiety disorders. MATERIAL AND METHODS: The study included 1.892 outpatient patients, 1.860 of whom completed participation in accordance with the protocol and entered the statistical analysis. Most patients were diagnosed with depressive and anxiety disorders of varying severity, as a rule, these diagnoses were established for the first time. The drug was most often prescribed at a dosage of 10 mg/day. The patients were monitored for 90 days and at each of the 3 visits, scales were used to assess the clinical condition (CGI-S and CGI-I), scales «Interaction with people, maintaining relationships (social functioning)¼ and «Availability of work, task completion, school attendance (professional functioning)¼, scales satisfaction with the convenience of admission/appointment and the effectiveness of treatment, various indicators of quality of life (autonomy, social and professional functioning, hobbies and hobbies), as well as the severity of cognitive disorders were measured. RESULTS: Patients treated with escitalopram in the form of oral tablets dispersible in the oral cavity (Elicea Q-Tab) showed an improvement in their clinical condition (a decrease in CGI-S scores from 3.65 at visit 1 to 2.63 by visit 3, by 28%; a decrease in CGI-I scores from 2.39 at visit 1 to 1.57 to visit 3, by 34%), as well as improving the quality of life, social (from 2.74 points on 1 visit to 4.32 on 2 visits, by 58%) and professional functioning (from 2.81 on 1 visit to 4.35 on 2 visits, by 55%), the level of concentration (from 3.28 points on 1 visit up to 4.5 on 3 visits, by 37%). Doctors and patients noted high satisfaction with the effectiveness and convenience of using the drug, the frequency of adverse events was low. CONCLUSION: The study showed that escitalopram in the form of oral tablets dispersible in the oral cavity (Elicea Q-Tab) is an efficient and safe treatment for depressive and anxiety disorders in real-world clinical settings. Patients and physicians have evaluated the drug positively and it can be considered as an effective agent in psychiatric practice.
Assuntos
Transtorno Depressivo Maior , Escitalopram , Humanos , Qualidade de Vida , Transtorno Depressivo Maior/tratamento farmacológico , Resultado do Tratamento , Transtornos de Ansiedade/tratamento farmacológico , Citalopram/uso terapêutico , Citalopram/efeitos adversosRESUMO
Despite considerable efforts to study the relationship between insomnia and depression, there is minimal research investigating whether insomnia symptoms change over time during a course of antidepressant pharmacotherapy. This study investigated the course of insomnia symptoms during the acute treatment of major depressive disorder (MDD) using a secondary analysis of data from MDD patients (N = 180) who were treated with open-label escitalopram (10-20 mg/day) for 8-weeks. Montgomery-Asberg Depression Rating Scale without sleep item (modified-MADRS) assessed depression and Self-reported Quick Inventory Depressive Scale (QIDS-SR) measured subjective sleep-onset, mid-nocturnal, and early-morning insomnia throughout 8-weeks of treatment. Pittsburgh Sleep Quality Index (PSQI) was used to assess subjective sleep quality, duration, onset latency, and efficiency throughout 8-weeks of treatment. Remission of depression was defined as modified-MADRS ≤10 at week-8. Mixed model repeated measures (MMRMs) were conducted with remission status as an independent variable and each sleep variable as a dependent variable. MMRMs demonstrated that remitters had significantly lower QIDS-SR sleep-onset and mid-nocturnal insomnia scores as well as a significantly lower PSQI sleep quality score than non-remitters throughout 8-weeks of treatment. Monitoring subjective sleep-onset and mid-nocturnal insomnia during the course of treatment with serotonergic antidepressants may be useful for predicting acute remission of depression.
Assuntos
Transtorno Depressivo Maior , Distúrbios do Início e da Manutenção do Sono , Humanos , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/diagnóstico , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Antidepressivos/uso terapêutico , Sono , Escitalopram , Resultado do TratamentoRESUMO
BACKGROUND: In spite of numerous options, the most efficacious treatment for major depressive disorder (MDD) remains elusive. Algorithm-guided treatments (AGTs) are proposed to address inadequate remission and optimize treatment delivery. This study aimed to evaluate the clinical benefit of AGTs for MDD, and to explore specific moderators of treatment outcomes for individual patients. METHODS: The study recruited 987 patients with MDD across eight hospitals who were randomly assigned to AGT with escitalopram (AGT-E), AGT with mirtazapine (AGT-M), or treatment-as-usual (TAU). The outcomes were symptom remission, response rate, early improvement rate, subsymptom clusters improvement over time, the mean time to first remission, relapse rate at 6-months posttreatment follow-up, quality of life (QOL), and adverse events. RESUTLS: No significant differences were observed across groups in outcome, except that TAU showed significantly poorer QOL, higher relapse rates at 6-months posttreatment follow-up, and marginally significantly worse maximal burden of adverse events than the AGT groups. After 6 weeks of treatment initiation, remission rate did not significantly increase with extended treatment. AGT-M outperformed the TAU and AGT-E in treating sleep symptoms. AGT-E was less effective than AGT-M and TAU in patients with severe depression and somatic symptoms (DSSS). The superiority of TAU over AGTs was observed in recurrent MDD patients. CONCLUSION: Although the superiority of AGTs over TAU was limited by failure of alternative subsequent treatment, AGTs outperformed in QOL and relapse rate. Types of disease episode and DSSS were regarded as specific moderators in treatment of depression. These findings might contribute to future research on targeted antidepressant treatment.
Assuntos
Transtorno Depressivo Maior , Algoritmos , Antidepressivos/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Escitalopram , Humanos , Qualidade de Vida , Resultado do TratamentoRESUMO
OBJECTIVE: To report side effect frequency and severity in patients with major depressive disorder (MDD) receiving escitalopram and aripiprazole adjunctive therapy and to examine whether pretreatment anxious depression is associated with the number and presence of specific side effects. METHODS: 188 of the 211 trial participants provided information on side effects during treatment with escitalopram (10-20 mg) for 8 weeks, and nonresponders received further augmentation on aripiprazole (2-10 mg) adjunctive therapy for another 8 weeks, whereas responders remained on escitalopram. Participants completed the Toronto Side Effects Scale at weeks 2, 4, 10, and 12. Covariate-adjusted negative binomial regression and Wilcoxon tests examined the association between anxious depression (GAD-7 ≥ 10) and number of side effects. Covariate-adjusted logistic regression and chi-square tests explored the association between anxious depression and specific side effects. RESULTS: For both therapies, the most frequent side effects were also the most severe. They mostly related to the central nervous system (CNS) (i.e., drowsiness and nervousness). Between baseline and week 2, the number of side effects participants experienced (incidence rate ratio [IRR] = 1.38, p = .010) or had trouble with (IRR = 1.34, p = .026) was significantly higher among those with anxious depression for escitalopram but not adjunctive aripiprazole. Further, odds of experiencing and having trouble with nervousness and agitation were also significantly higher in anxious depression for escitalopram only (p < .05). CONCLUSION: Patients on escitalopram and aripiprazole adjunctive therapy may experience and have trouble with CNS side effects. Pretreatment anxious depression may predispose escitalopram recipients with MDD to developing side effects, especially those related to anxiety.
Assuntos
Transtorno Depressivo Maior , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Aripiprazol/efeitos adversos , Depressão , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/tratamento farmacológico , Quimioterapia Combinada , Escitalopram , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: There is little real-world evidence about effectiveness of different antidepressants on geriatric depression. METHODS: We used population-based claims data in Taiwan between 1997 and 2013 to include older patients (≥ 60 years of age) who were diagnosed with depression and started to use antidepressants. All patients were followed up until discontinuation of antidepressant use or the end of the study period. Treatment outcomes were set as the risk of switching to another antidepressant, receiving augmentation therapy, and psychiatric hospitalization. We used cox proportional hazards regression models to calculate hazard ratios with 95% confidence intervals (CIs) and adjust for several confounding factors (aHRs). RESULTS: During the study period, a total of 207,946 elderly patients with depression received one of the following 11 antidepressants: sertraline, fluoxetine, paroxetine, escitalopram, citalopram, fluvoxamine, venlafaxine, duloxetine, moclobemide, mirtazapine, and bupropion. Compared to the patients treated with sertraline, those treated with fluvoxamine / venlafaxine had significantly but modestly higher risks of switching (aHR [95% CI]: 1.16 [1.11-1.21] / 1.10 [1.06-1.14]), augmentation (1.06 [1.02-1.10] / 1.08 [1.05-1.12]), and hospitalization (1.28 [1.03-1.58] / 1.37 [1.16-1.62]). Otherwise, the remaining 9 antidepressants yielded no consistent result in the three outcomes. LIMITATIONS: This study is a multi-arm and active controlled trial, lacking a placebo group. CONCLUSION: As treating geriatric depression, no individual antidepressant posed consistently better effectiveness in the outcomes of switching antidepressant, receiving augmentation, and psychiatric hospitalization than any other one, whereas clinicians should be cautious when prescribing fluvoxamine and venlafaxine.
Assuntos
Antidepressivos , Depressão , Idoso , Antidepressivos/uso terapêutico , Citalopram/uso terapêutico , Depressão/tratamento farmacológico , Escitalopram/uso terapêutico , Humanos , Sertralina/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: Although anxiety symptoms frequently co-occur with major depressive disorder, few studies examined the prediction of treatment outcomes among participants with anxious depression receiving antidepressants. We investigated whether baseline anxiety, and early improvements in anxiety and depression symptoms predict eventual treatment outcomes. METHODS: 111 participants with anxious depression, defined using ≥ 10 on GAD-7, received escitalopram (10-20 mg) for 8 weeks. Covariate-adjusted logistic regression was conducted to examine the impact of baseline anxiety, and to assess the extent week 2 anxiety (GAD-7) and depression (QIDS-SR) percentage improvement associates with week 8 anxiety (GAD-7) and depression (MADRS) response/remission. Optimum improvement thresholds were identified using receiving-operating-curve analysis and their predictive values assessed. RESULTS: Greater percentage improvement in anxiety and depression after the first 2 weeks of treatment significantly increased odds of achieving week 8 anxiety and depression response/remission (OR:1.01-1.04, p<0.05). Early anxiety (68.4%/87.2%) and depression (52.2%/83.0%) improvement thresholds around 30 and 40% provided moderate to high positive predictive value (PPV) for predicting week 8 anxiety response/remission, as well as moderate to high negative predictive value (NPV) for predicting week 8 depression response/remission (anxiety:70.8%/91.7%; depression:72.2%/90.1%). Baseline anxiety severity predicted anxiety outcomes at weeks 2 and 8. LIMITATIONS: Trial lacked placebo group. CONCLUSION: In anxious depression, early improvement in anxiety may be better than depression in predicting anxiety outcomes, with similar or higher PPVs. Both improvement types perform similarly in predicting depression outcomes, with the lack of improvement predictive of non-response and non-remission. Finally, baseline anxiety predicts eventual anxiety but not depression outcomes.
Assuntos
Transtorno Depressivo Maior , Escitalopram , Ansiedade/complicações , Ansiedade/tratamento farmacológico , Depressão , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Non-response to first-line treatment for major depressive disorder (MDD) is common; for such individuals, quality of life (QoL) impairments can be severe. Identifying predictors of QoL changes may support the management of cases with persistent depressive symptoms despite adequate initial pharmacological/psychological treatment. OBJECTIVE: The present study aimed to explore predictors of domain-specific QoL improvement following adjunctive aripiprazole treatment for inadequate response to initial antidepressant therapy. METHODS: We evaluated secondary QoL outcomes from a CAN-BIND (Canadian Biomarker Integration Network in Depression) study in patients with MDD who did not respond to an initial 8 weeks of escitalopram and received a further 8 weeks of adjunctive aripiprazole (n = 96). Physical, psychological, social, and environmental QoL domains were assessed using the World Health Organization QoL Scale Brief Version (WHOQOL-BREF). Clinician-rated depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Functioning was measured with the Sheehan Disability Scale (SDS). Satisfaction with medication was assessed with a single item from the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Exploratory t-tests were used to describe domain score changes. A hierarchical linear regression was used to explore demographic, clinical, and treatment-related predictors of improvement. RESULTS: Across domains, QoL improved with adjunctive aripiprazole treatment. Satisfaction with medication and MADRS and SDS scores similarly improved. Symptom reduction was a predictor for positive change to physical and psychological QoL; functioning improvements were predictive of increases to all QoL domains. Satisfaction with medication predicted improvements to physical and psychological domains, whereas number of medication trials was a predictor of worsening QoL in the physical domain. CONCLUSION: The final model explained the most variance in psychological (68%) and physical (67%) QoL. Less variance was explained for environmental (43%) and social QoL (33%), highlighting a need for further exploration of predictors in these domains. Strategies such as functional remediation may have potential to support QoL for individuals with persistent depressive symptoms. CLINICAL TRIALS REGISTRY: ClinicalTrials.gov identifier: NCT016557.