Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits
Palabras clave
Abstracto
Descripción
The goal of the proposed research is to determine the mechanism of action of an antidepressant of known efficacy (bupropion) and to tie this mechanism of action to a biomarker of inflammation in support of precision medicine for the treatment of major depression (MD). MD is a devastating disease affecting approximately 10% of US adults and being the leading cause of disability worldwide. Despite availability of several classes of antidepressant medications, initial treatment response is low (around 30%), and approximately 1/3 of depressed patients are non-responsive to conventional antidepressant therapies. Although extensive reviews of the literature suggest that available antidepressant medications are equally effective, recent studies suggest that there may be differential responsiveness to conventional antidepressants among subgroups of depressed patients. One subgroup of depressed patients who may exhibit differential antidepressant responsiveness are those with increased markers of inflammation. Data from previous studies support the notion that differential responsiveness to conventional antidepressants exists and may be revealed by pretreatment levels of inflammation as indexed by the inflammatory biomarker C-reactive protein (CRP).
This study proposes to use a mechanistic clinical trial design with drugs of known efficacy to take the first step toward establishing whether antidepressants that target dopamine (e.g. bupropion) might be a better choice for depressed patients with increased inflammation and anhedonia than an selective serotonin reuptake inhibitor (SSRI). Accordingly, 50 depressed patients with a CRP>2mg/L and increased anhedonia will be randomized to 8 weeks of bupropion or escitalopram in order to analyze data from 40 patients (accounting for drop outs). All depressed patients will undergo functional magnetic resonance imaging (fMRI) to examine functional connectivity in reward-related circuits at baseline and 4 and 8 weeks along with objective and clinical assessments of Research Domain Criteria (RDoC) positive (motivational) valence constructs at baseline and 2, 4, 6 and 8 weeks.
The researchers hypothesize that patients who receive bupropion versus escitalopram will exhibit increased functional connectivity between ventral striatum and ventromedial prefrontal cortex in association with decreased motivational deficits and anhedonia.
fechas
| Verificado por última vez: | 06/30/2020 |
| Primero enviado: | 04/15/2020 |
| Inscripción estimada enviada: | 04/15/2020 |
| Publicado por primera vez: | 04/19/2020 |
| Última actualización enviada: | 07/08/2020 |
| Última actualización publicada: | 07/09/2020 |
| Fecha de inicio real del estudio: | 07/31/2020 |
| Fecha estimada de finalización primaria: | 02/28/2022 |
| Fecha estimada de finalización del estudio: | 02/28/2022 |
Condición o enfermedad
Intervención / tratamiento
Drug: Bupropion
Drug: Escitalopram
Fase
Grupos de brazos
| Brazo | Intervención / tratamiento |
|---|---|
| Experimental: Bupropion Participants randomized to take bupropion for 8 weeks. | Drug: Bupropion Participants will take 150 milligrams per day (mg/d) of bupropion XL for two weeks, then the dose will be increased to 300mg/d, as tolerated, for the remaining 6 weeks of the study. |
| Active Comparator: Escitalopram Participants randomized to take escitalopram for 8 weeks. | Drug: Escitalopram Participants will take 10mg/d of escitalopram for two weeks, then the dose will be increased to 20mg/d, as tolerated, for the remaining 6 weeks of the study. |
Criterio de elegibilidad
| Edades elegibles para estudiar | 25 Years A 25 Years |
| Sexos elegibles para estudiar | All |
| Acepta voluntarios saludables | si |
| Criterios | Inclusion Criteria: - willing and able to give written informed consent - a primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders (DSM-V) MD, current as diagnosed by the Structured Clinical Interview for DSM-V Axis I Disorders (SCID-V) - score of ≥16 on the 16-item Quick Inventory of Depressive Symptomatology (QIDS)-SR - off all antidepressant or other psychotropic therapy (e.g. mood stabilizers, antipsychotics, and sedative hypnotics) for at least 4 weeks prior to baseline visit (8 weeks for fluoxetine); concomitant administration of up to 2 mg of clonazepam or its equivalent per day will be allowed, but not within 12 hours of study assessments - CRP>2mg/L - IDS-SR anhedonia subscale score ≥5 Exclusion Criteria: - history of any autoimmune disorder - history of hepatitis B or C infection or human immunodeficiency virus infection - history of any type of cancer requiring treatment with more than minor surgery - unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination and laboratory testing) - history of any (non-mood-related) psychotic disorder; active psychotic symptoms of any type; substance abuse/dependence within 6 months of study entry (as determined by SCID) - an active eating disorder or antisocial personality disorder - a history of a cognitive disorder or ≤28 on the Mini-Mental State Exam unless otherwise approved by the PI - pregnancy or lactation - chronic use of non-steroidal anti-inflammatory agents (NSAIDS) (excluding 81mg of aspirin), glucocorticoid containing medications - use of NSAIDS or oral glucocorticoids at any time during the study - any contraindication for MRI scanning - failure of more than 2 antidepressant trials in the current episode - Intolerance of bupropion or escitalopram - BMI >40 (to exclude severe obesity) - due to the high co-morbidity between anxiety disorders and depression, the study team plans to include patients with anxiety-related disorders excluding obsessive-compulsive disorder (OCD) if depression is the primary diagnosis. Patients with stable medical conditions and on medications for those conditions will not be excluded. Concomitant administration of up to 2 mg of clonazepam or its equivalent per day will be allowed, but not within 12 hours of study assessments. - sexually active participants are required to use medically approved birth control methods as defined in the Birth Control Method Form for the duration of the study |
Salir
Medidas de resultado primarias
1. Change in Targeted Ventromedial Prefrontal Cortex-Ventral Striatal (vmPFC-VS) Functional Connectivity (FC) [Baseline, Week 4, Week 8]
Medidas de resultado secundarias
1. Change in Effort-Expenditure for Rewards Task (EEfRT) Score [Baseline, Week 2, Week 4, Week 6, Week 8]
2. Change in Snaith-Hamilton Pleasure Scale (SHAPS-C) Score [Baseline, Week 2, Week 4, Week 6, Week 8]
3. Change in Motivation and Pleasure Scale-Self-Report (MAP-SR) Score [Baseline, Week 2, Week 4, Week 6, Week 8]
4. Change in Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) [Baseline, Week 2, Week 4, Week 6, Week 8]
