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2.
Autoimmun Rev ; 19(5): 102504, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32173514

RESUMEN

Major depressive disorder (MDD) is a common condition that afflicts the general population across a broad spectrum of ages and social backgrounds. MDD has been identified by the World Health Organization as a leading cause of disability worldwide. Approximately 30% of patients are poor responsive to standard of care (SOC) treatment and novel therapeutic approaches are warranted. Since chronic inflammation, as it is often observed in certain cancers, type 2 diabetes, psoriasis and chronic arthritis, are accompanied by depression, it has been suggested that immunoinflammatory processes may be involved in the pathogenesis of MDD. Cytokines are a group of glycoproteins secreted from lymphoid and non-lymphoid cells that orchestrate immune responses. It has been suggested that a dysregulated production of cytokines may be implicated in the pathogenesis and maintenance of MDD. On the basis of their functions, cytokines can be subdivided in pro-inflammatory and anti-inflammatory cytokines. Since abnormal blood and cerebrospinal fluid of both pro and anti-inflammatory cytokines are altered in MDD, it has been suggested that abnormal cytokine homeostasis may be implicated in the pathogenesis of MDD and possibly to induction of therapeutic resistance. We review current data that indicate that cytokines may represent a useful tool to identify MDD patients that may benefit from tailored immunotherapeutic approaches and may represent a potential tailored therapeutic target.


Asunto(s)
Citocinas/inmunología , Citocinas/metabolismo , Trastorno Depresivo Mayor/inmunología , Trastorno Depresivo Mayor/psicología , Antiinflamatorios/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/patología , Humanos , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Inflamación/metabolismo
3.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 42(1): 14-21, Jan.-Feb. 2020. tab
Artículo en Inglés | LILACS | ID: biblio-1055366

RESUMEN

Objective: This study aimed to determine if personality disorder (PD) predicted functional outcomes in patients with major depressive disorder (MDD). Methods: Data (n=71) from a double-blind, randomized, placebo-controlled 12-week trial assessing the efficacy of 200 mg/day adjunctive minocycline for MDD were examined. PD was measured using the Standardized Assessment of Personality Abbreviated Scale. Outcome measures included Clinical Global Impression - Improvement (CGI-I), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Social and Occupational Functioning Scale (SOFAS), and Range of Impaired Functioning (RIFT). Analysis of covariance was used to examine the impact of PD (dichotomized factor [≥ 3] or continuous measure) on the outcome measures-treatment group correlation. Results: PD was identified in 69% of the sample. After adjusting for age, sex, and baseline scores for each of the outcome measures, there was no significant difference between participants with and without PD on week 12 scores for any of the outcome measures (all p > 0.14). Conclusion: In this secondary analysis of a primary efficacy study, PD was a common comorbidity among those with MDD, but was not a significant predictor of functional outcomes. This study adds to the limited literature on PD in randomized controlled trials for MDD. Clinical trial registration: ACTRN12612000283875.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Anciano , Trastornos de la Personalidad/psicología , Trastorno Depresivo Mayor/psicología , Trastorno Depresivo Mayor/tratamiento farmacológico , Minociclina/administración & dosificación , Antidepresivos/administración & dosificación , Satisfacción Personal , Pruebas de Personalidad , Escalas de Valoración Psiquiátrica , Calidad de Vida , Comorbilidad , Efecto Placebo , Método Doble Ciego , Resultado del Tratamiento , Autoinforme , Persona de Mediana Edad
6.
Gene ; 734: 144333, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-31972309

RESUMEN

Multiple antidepressive treatment methods are widely used in the clinic, but different patients showed considerable differences in response to the same treatment. The catechol-O-methyltransferase (COMT) rs4680 polymorphism is involved in the antidepressive treatment reaction; however, the results in different studies are inconsistent. Thus, we performed a meta-analysis to explore the association of the COMT rs4680 polymorphism with the treatment response in major depressive disorder (MDD) patients. An online search was performed through PubMed, EMBASE and the Cochrane library up to December 2018. The odds ratios (ORs), 95% confidence intervals (95% CI) and heterogeneity were calculated in four genetic models. Subgroup analysis and Galbraith plot were carried out to detect the potential source of heterogeneity. Sensitivity and publication bias analyses were performed to identify the reliability of the results. A total of 11 studies involving 2845 individuals were included in this meta-analysis. The results of the subgroup analysis indicated that patients who carried the G allele had remission or a better response to electroconvulsive therapy (ECT) in four genetic models. Excluding the studies that might lead to heterogeneity, overall ORs were recalculated, and no obvious association between rs4680 polymorphism and therapeutic reaction was detected in the allelic, recessive and additive models. In the dominant model, COMT rs4680 variants showed significant associations with antidepressive treatment, but the result was highly dependent on the individual study. In addition, the patients with the GG or AG + GG genotype in comparison to AA were associated with a better response to ECT treatment. However, due to the small number of studies using ECT treatment, we suggest that more research should be performed to verify this result.


Asunto(s)
Antidepresivos/uso terapéutico , Catecol O-Metiltransferasa/genética , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/genética , Polimorfismo Genético , Biomarcadores Farmacológicos , Estudios de Asociación Genética , Humanos , Metionina , Resultado del Tratamiento , Valina
7.
PLoS One ; 15(1): e0227614, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31935237

RESUMEN

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.


Asunto(s)
Trastorno Depresivo Mayor/clasificación , Trastorno Depresivo Resistente al Tratamiento/clasificación , Psicometría/métodos , Adulto , Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Inhibidores de la Captación de Serotonina/uso terapéutico
8.
J Altern Complement Med ; 26(1): 8-24, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31328996

RESUMEN

Objectives: Bupleurum chinense (BC; Radix Bupleuri) formulae are widely used in herbal medicine clinical practice for major depressive disorder (MDD). This study provides an up-to-date and comprehensive systematic review and meta-analysis of BC formula for MDD. Design: Randomized controlled trials were retrieved from English and Chinese databases, from their inceptions to March 2019. Included studies compared BC formula alone or as integrative medicine to selective serotonin reuptake inhibitor (SSRI) antidepressants. Studies included adults 18-65 years of age. People with other types of depression or physical comorbidities, such as poststroke depression, bipolar, and other mental or physical disorders, were excluded. Meta-analysis was performed using STATA software. Grading of Recommendations Assessment, Development, and Evaluation was also conducted to assess the quality of evidence. Results: Thirty studies compared BC formula to antidepressants and 25 studies compared BC formula plus antidepressants to antidepressants alone. BC formula was more effective than antidepressants at improving depression severity measured on the Hamilton Rating Scale for Depression (HRSD) (standardized mean difference [SMD] -0.35, 95% confidence interval [CI] -0.52 to -0.18, I2 = 81.2%). Integrative use of BC formula plus SSRIs was also superior to SSRIs alone at improving HRSD scores (SMD -1.03, 95% CI -1.43 to -0.62, I2 = 94.2%). However, heterogeneity of the included studies was high and quality was low. The total number and severity of adverse events in the BC formula groups were less than that in the antidepressant groups. Conclusions: BC formula alone or given as integrative medicine with antidepressants reduced depression severity. However, the evidence is low quality and at risk of bias. Well-designed studies are needed to validate the results we identified in this review.


Asunto(s)
Bupleurum , Depresión/tratamiento farmacológico , Trastorno Depresivo Mayor/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
9.
J Agric Food Chem ; 68(7): 1808-1815, 2020 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-31532659

RESUMEN

Major depressive disorder (MDD) is associated with stress-induced immune dysregulation and reduced brain-derived neurotrophic factor (BDNF) levels in sensitive brain regions associated with depression. Elevated levels of proinflammatory cytokines and reduced BDNF levels lead to impaired synaptic plasticity mechanisms that contribute to the pathophysiology of MDD. There is accumulating evidence that the administration of polyphenols at doses ranging from 5 to 180 mg/kg of body weight can normalize elevated levels of proinflammatory cytokines and abnormal levels of BDNF and, thus, restore impaired synaptic plasticity mechanisms that mediate depressive behavior in animal models of stress. This review will focus on the mechanisms by which grape-derived polyphenols normalize impaired synaptic plasticity and reduce depressive behavior in animal models of stress.


Asunto(s)
Trastorno Depresivo Mayor/tratamiento farmacológico , Plasticidad Neuronal/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Polifenoles/administración & dosificación , Vitis/química , Animales , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Humanos , Extractos Vegetales/química , Polifenoles/química
10.
Mini Rev Med Chem ; 20(1): 24-38, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31288718

RESUMEN

Tricyclic Antidepressants (TCAs) are a group of the main category of antidepressant drugs, which are commonly prescribed to treat major depressive disorder. Determination of TCA drugs is very important for clinical and forensic toxicology, especially for therapeutic drug monitoring in various biofluids. High Performance Liquid Chromatography (HPLC) is a well-established technique for this purpose. A lot of progress has been made in this field since the past 10 years. Novel extraction techniques, and novel materials for sample preparation, novel columns and novel applications of analysis of various biofluids for the determination of TCAs in combination with other drugs are some typical examples. Moreover, advances have been performed in terms of Green Analytical Chemistry principles. Herein, we aim to discuss the developed HPLC methods that were reported in the literature for the time span of 2008-2018.


Asunto(s)
Antidepresivos Tricíclicos/análisis , Antidepresivos Tricíclicos/farmacocinética , Cromatografía Líquida de Alta Presión/métodos , Animales , Antidepresivos Tricíclicos/aislamiento & purificación , Trastorno Depresivo Mayor/tratamiento farmacológico , Monitoreo de Drogas/métodos , Humanos , Extracción Líquido-Líquido/métodos , Extracción en Fase Sólida/métodos
11.
Expert Opin Pharmacother ; 21(1): 9-20, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31663783

RESUMEN

Introduction: In March 2019, intranasal esketamine was approved by the Food and Drug Administration (FDA) for the treatment of treatment-resistant depression (TRD) in adults. This review presents the results of clinical trials underlying the FDA approval of intranasal esketamine.Areas covered: Esketamine's efficacy and safety in TRD were assessed in 5 phase III studies: three 4-week, placebo-controlled studies, and two long-term trials. One short-term trial showed statistically significant antidepressant effects of esketamine vs placebo, while a long-term withdrawal study showed that esketamine is significantly beneficial in terms of extending time to relapse, compared to placebo. Two other short-term trials did not meet the prespecified statistical tests for showing efficacy, although improvement in depressive symptoms from baseline to the end of week 4 favors esketamine over placebo.Expert opinion: Intranasal esketamine is a new treatment option for people with TRD. The main benefit of esketamine is rapid onset of antidepressant activity, but the effects of prolonged treatment are still preliminary. The main concerns relate to the safety aspects of prolonged esketamine therapy, when considering its abuse potential. While data for esketamine use over a long period of time is lacking, its use should be carefully monitored.


Asunto(s)
Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Ketamina/administración & dosificación , Administración Intranasal , Adulto , Antidepresivos/efectos adversos , Antidepresivos/uso terapéutico , Humanos , Ketamina/efectos adversos
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(12): 1230-1234, 2019 Dec 10.
Artículo en Chino | MEDLINE | ID: mdl-31813155

RESUMEN

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) CHRNA4 gene with response to selective serotonin re-uptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD). METHODS: For 304 patients receiving drug treatment for major depression, 2 SNPs, namely rs4522666 and rs4603829, of the CHRNA4 gene were determined by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry. HAMD-17 was adopted as the primary rating tool to evaluate the severity of depression on the baseline and at the end of 1st, 2nd, 4th and 6th weeks treatment. RESULTS: The frequency of GG genotype/G allele for rs4522666 differed significantly from that of TT and GT genotypes/T allele between responders and non-responders (P=0.015 and P=0.006, respectively). No significant difference was found in genotypic and allelic frequencies of rs4603829 between the two groups (P> 0.05). CONCLUSION: SNPs of the CHRNA4 gene may play an important role in the response to antidepressant drugs among ethnic Han Chinese with MDD.


Asunto(s)
Antidepresivos/farmacología , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/genética , Receptores Nicotínicos/genética , Grupo de Ascendencia Continental Asiática , China , Frecuencia de los Genes , Genotipo , Humanos , Polimorfismo de Nucleótido Simple
16.
J Opioid Manag ; 15(4): 342-344, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31637686

RESUMEN

A 49-year-old male with major depressive disorder well-managed with venlafaxine [serotonin and norepinephrine reuptake inhibitor (SNRI)] and no history of manic episodes developed his first manic episode following use of tramadol. Tramadol-induced mania has been described with selective serotonin reuptake inhibitors but not SNRIs. In addition, mania is not listed as a potential clinical side effect-further illustrating this relative rarity. Due to tramadol's SNRI activity, there is definitive risk for mood lability in individuals managed with tramadol and other serotonergic medications as seen in this patient. The authors findings suggest the need for greater risk consideration when prescribing tramadol with other related agents such as venlafaxine.


Asunto(s)
Trastorno Bipolar , Trastorno Depresivo Mayor , Tramadol , Clorhidrato de Venlafaxina , Analgésicos Opioides , Trastorno Bipolar/inducido químicamente , Trastorno Depresivo Mayor/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de la Captación de Serotonina/efectos adversos , Tramadol/efectos adversos , Tramadol/uso terapéutico , Clorhidrato de Venlafaxina/efectos adversos , Clorhidrato de Venlafaxina/uso terapéutico
17.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 41(5): 441-446, Sept.-Oct. 2019. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1039113

RESUMEN

We conducted a narrative literature review on studies that specifically addressed the pharmacokinetics of antidepressants in patients on hemodialysis. The search included the MEDLINE, LILACS, and Web of Knowledge databases and combined Medical Subject Headings and free-text search terms for chronic kidney disease, end-stage renal disease, renal replacement therapy, depression, and antidepressants; it was limited to studies conducted in humans, with no language or time constraints. The search yielded 212 studies. After screening titles and abstracts, 32 studies were read in full and 11 ultimately met the inclusion criteria and were included in the review. Most of the studies showed no difference in the pharmacokinetics of antidepressant drugs between patients with normal renal function and patients undergoing hemodialysis. However, studies with fluvoxamine and amitriptyline showed that variations in albumin levels might affect serum concentrations of these agents. The included studies have several limitations, and there are many obstacles to the adequate treatment of depression in patients undergoing hemodialysis. Further studies on this topic are needed to support proper treatment of these patients, improving their quality of life and reducing mortality.


Asunto(s)
Humanos , Diálisis Renal/psicología , Trastorno Depresivo Mayor/tratamiento farmacológico , Insuficiencia Renal Crónica/psicología , Insuficiencia Renal Crónica/terapia , Antidepresivos/farmacocinética , Resultado del Tratamiento
18.
Nat Hum Behav ; 3(12): 1319-1331, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31548678

RESUMEN

The efficacy of antidepressant treatment for depression is controversial due to the only modest superiority demonstrated over placebo. However, neurobiological heterogeneity within depression may limit overall antidepressant efficacy. We sought to identify a neurobiological phenotype responsive to antidepressant treatment by testing pretreatment brain activation during response to, and regulation of, emotional conflict as a moderator of the clinical benefit of the antidepressant sertraline versus placebo. Using neuroimaging data from a large randomized controlled trial, we found widespread moderation of clinical benefits by brain activity during regulation of emotional conflict, in which greater downregulation of conflict-responsive regions predicted better sertraline outcomes. Treatment-predictive machine learning using brain metrics outperformed a model trained on clinical and demographic variables. Our findings demonstrate that antidepressant response is predicted by brain activity underlying a key self-regulatory emotional capacity. Leveraging brain-based measures in psychiatry will forge a path toward better treatment personalization, refined mechanistic insights and improved outcomes.


Asunto(s)
Antidepresivos de Segunda Generación/metabolismo , Antidepresivos/metabolismo , Encéfalo/diagnóstico por imagen , Trastorno Depresivo Mayor/tratamiento farmacológico , Antidepresivos/uso terapéutico , Antidepresivos de Segunda Generación/uso terapéutico , Encéfalo/efectos de los fármacos , Ensayos Clínicos como Asunto , Depresión , Trastorno Depresivo Mayor/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Resultado del Tratamiento
19.
N Engl J Med ; 381(10): 903-911, 2019 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-31483961

RESUMEN

BACKGROUND: Altered neurotransmission of γ-aminobutyric acid (GABA) has been implicated in the pathogenesis of depression. Whether SAGE-217, an oral, positive allosteric modulator of GABA type A receptors, is effective and safe for the treatment of major depressive disorder is unknown. METHODS: In this double-blind, phase 2 trial, we enrolled patients with major depression and randomly assigned them in a 1:1 ratio to receive 30 mg of SAGE-217 or placebo once daily. The primary end point was the change from baseline to day 15 in the score on the 17-item Hamilton Depression Rating Scale (HAM-D; scores range from 0 to 52, with higher scores indicating more severe depression). Secondary efficacy end points, which were assessed on days 2 through 8 and on days 15, 21, 28, 35, and 42, included changes from baseline in scores on additional depression and anxiety scales, a reduction from baseline of more than 50% in the HAM-D score, a HAM-D score of 7 or lower, and a Clinical Global Impression of Improvement score of 1 (very much improved) or 2 (much improved) (on a scale of 1 to 7, with a score of 7 indicating that symptoms are very much worse). RESULTS: A total of 89 patients underwent randomization: 45 patients were assigned to the SAGE-217 group, and 44 to the placebo group. The mean baseline HAM-D score was 25.2 in the SAGE-217 group and 25.7 in the placebo group. The least-squares mean (±SE) change in the HAM-D score from baseline to day 15 was -17.4±1.3 points in the SAGE-217 group and -10.3±1.3 points in the placebo group (least-squares mean difference in change, -7.0 points; 95% confidence interval, -10.2 to -3.9; P<0.001). The differences in secondary end points were generally in the same direction as those of the primary end point. There were no serious adverse events. The most common adverse events in the SAGE-217 group were headache, dizziness, nausea, and somnolence. CONCLUSIONS: Administration of SAGE-217 daily for 14 days resulted in a reduction in depressive symptoms at day 15. Adverse events were more common in the SAGE-217 group than in the placebo group. Further trials are needed to determine the durability and safety of SAGE-217 in major depressive disorder and to compare SAGE-217 with available treatments. (Funded by Sage Therapeutics; ClinicalTrials.gov number, NCT03000530.).


Asunto(s)
Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Moduladores del GABA/uso terapéutico , Pregnanos/uso terapéutico , Pirazoles/uso terapéutico , Receptores de GABA-A/metabolismo , Administración Oral , Adulto , Regulación Alostérica , Antidepresivos/efectos adversos , Trastorno Depresivo Mayor/clasificación , Mareo/inducido químicamente , Método Doble Ciego , Femenino , Moduladores del GABA/efectos adversos , Humanos , Análisis de los Mínimos Cuadrados , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Pregnanos/efectos adversos , Escalas de Valoración Psiquiátrica , Pirazoles/efectos adversos
20.
Turk Psikiyatri Derg ; 30(2): 142-144, 2019.
Artículo en Turco | MEDLINE | ID: mdl-31487380

RESUMEN

Erectile dysfunction is a sexual dysfunction which is commonlycomorbid with major depression. Antidepressant treatment does notalways improve comorbid sexual dysfunctions in major depression. Infact, sexual dysfunction may worsen or get complicated following theintroduction of antidepressants. Modafinil is a drug with stimulanteffect on the central nervous system by binding to norepinephrineand dopamine transporters and consequently increasing synapticnorepinephrine and dopamine levels. Modafinil is primarily used inthe treatment of narcolepsy and chronic fatigue syndrome. In addition,it is known for its effectiveness in attention deficit hyperactivitydisorder and as an add-on option for major depression. In this paper,we report the case of a 39-year-old man with major depression whosecomorbid erectile dysfunction improved after addition of modafinilto antidepressant treatment. Fluoxetine 20 mg/day was initiatedand despite the improvement of most of the depressive symptomsand the sexual desire, his complaints of fatigue, weakness and erectiledysfunction continued. With the addition of modafinil (200 mg /day),improvement was observed not only in psychomotor symptoms but alsoin erectile dysfunction of the patient.


Asunto(s)
Estimulantes del Sistema Nervioso Central/uso terapéutico , Trastorno Depresivo Mayor/psicología , Disfunción Eréctil/psicología , Modafinilo/uso terapéutico , Adulto , Estimulantes del Sistema Nervioso Central/administración & dosificación , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/tratamiento farmacológico , Esquema de Medicación , Disfunción Eréctil/complicaciones , Disfunción Eréctil/tratamiento farmacológico , Humanos , Masculino , Modafinilo/administración & dosificación
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