The purpose of this study is to determine if translocator protein total distribution volume (TSPO VT) is elevated in major depressive disorder that is not responding to medication and if adding minocycline can affect TSPO VT. Many remain treatment resistant with common antidepressant treatments and the investigators think it may be due to poor targeting of brain pathologies.
Name: Minocycline
Description: 50 mg and 100 mg capsule, oral administrationType: DrugMinocycline
Name: Placebo
Description: Lactose monohydrate in identical gel capsules to minocycline, oral administration.Type: DrugPlacebo
Name: Celecoxib
Description: 100 mg and 200 mg capsules, oral administration.Type: DrugCelecoxib
Description: TSPO VT will be measured using [18F]FEPPA positron emission tomography brain scans. Eligible MDE participants will be randomized to either minocycline or placebo. Following 8 weeks of either minocycline or placebo treatment, MDE participants will have a second PET scan .
Measure: Translocator total distribution volume (TSPO VT): Treatment Effect of Minocycline in MDE Subjects Time: Pre- and post-minocycline or placebo treatment= 8 weeks total between pretreatment and posttreatment scansDescription: Compare baseline TSPO VT prior to treatment between MDE group and healthy group
Measure: Translocator total distribution volume (TSPO VT): Difference between MDE and healthy subjects Time: Pre-treatment scan will take place up to 8 weeks from initial assessmentDescription: Change in HDRS score following minocycline vs. placebo treatment. Change in HDRS score following celecoxib treatment.
Measure: Change in Hamilton Depression Rating Scale Score Time: Pre- and post-minocycline treatment (8 weeks total between pre- and post-treatment). Pre- and post-celecoxib treatment (8 weeks total between pre- and post-treatment).Description: To assess verbal memory we will administer the Hopkins Verbal Learning Test-Revised to MDE participants before and after treatment.
Measure: Hopkins Verbal Learning Test-Revised Time: Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)Description: To assess visuospatial memory we will administer the Brief Visuospatial Memory Test-Revised to MDE participants before and after treatment.
Measure: Brief Visuospatial Memory Test-Revised Time: Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)Description: To assess psychomotor speed and attention we will administer the Comprehensive Trails Making Test to MDE participants before and after treatment.
Measure: Comprehensive Trails Making Test Time: Pre- and post-minocycline or placebo treatment.Description: The priority of the genetic sample is to analyze the alleles of polymorphism rs6971 which has an association with the affinity of most second generation TSPO ligands including [18F]FEPPA. The genetic sample will also be used to study sequences of genes that are believed to affect TSPO expression, inflammation, mood and conditions that may predispose to mood disorders.
Measure: Genetic sample Time: Phase 1-single sampleDescription: Analyses will include complete blood cell count (CBC), ESR, hepatic and renal function. Peripheral marker analyses will include proteins related to TSPO expression and inflammation. Plasma minocycline and celecoxib levels will be analyzed.
Measure: Blood samples (serum and plasma) Time: Pre- and post-minocycline or placebo treatment (8 weeks between measures). Pre- and post-celecoxib treatment (8 weeks between measures).Allocation: Randomized
Single Group Assignment
There is one SNP
The priority of the genetic sample is to analyze the alleles of polymorphism rs6971 which has an association with the affinity of most second generation TSPO ligands including [18F]FEPPA.