Clinical trial NCT03152409: Salicylic Augmentation in Depression
Official title: Salicylic Augmentation in Depression
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Depression
Depressive Disorder
Major Depressive Disorder
Treatment Resistant Depression
Keywords: Aspirin
Treatment
Salicylic acid
anti-inflammatory
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Columbia University
First posted: 2017-05-15
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized control trial with about half of all participants receiving placebo.
Primary purpose: TREATMENT

Brief summary: The investigators are doing this research study to find out if using aspirin along with antidepressant treatment can lessen symptoms of depression. This study also aims to find out if some people improve more from taking aspirin than others. The investigators also want to see if it is possible to predict which participants will do better based on a blood test.

Aspirin is approved by the U.S. Food and Drug Administration (FDA) as an over-the-counter pain medication. But, aspirin is not approved by the FDA to make antidepressant treatment better.

This research study will compare aspirin to placebo.

Detailed description: This study is a randomized, double-blind, placebo-control trial. The primary aims of this study are:

Aim 1: To evaluate the clinical effect of aspirin augmentation on depression.

Aim 2: To assess the inflammatory profile of the blood of the aspirin augmentation responders compared with the non-responders.

Aim 3: To evaluate whether immune gene expression patterns are associated with antidepressant response to aspirin.

Aim 4: To collect samples for later, more detailed immunologic characterization.

Eligibility criteria: Inclusion Criteria:

* Current diagnosis of major depressive disorder
* Hamilton Depression Rating Scale (HDRS) score of \>19
* Stable treatment regimen (no medication changes or changes in psychotherapy treatment in past 8 weeks, and no participation in stepped treatments, such as completion of a course of cognitive behavioral therapy, during the trial)
* Failed to remit with at least 1 antidepressant trial, or combination of 1 antidepressant and 1 augmentation agent
* Women of childbearing age must agree to use an approved method of contraception for the duration of the study

Exclusion Criteria:

* Active suicidal ideation
* History of manic episodes or psychosis
* Alcohol or substance use disorder up to one month prior to first testing session
* Comorbid neurologic condition affecting the central nervous system
* Comorbid autoimmune condition
* Uncorrected thyroid disease or a current abnormal thyroid-stimulating hormone (TSH)
* Active or recent (within the past month) infection (such as otitis, pneumonia, urinary tract infection); temperature \> 100.3 or white blood cell (WBC) count \> 11 K/microL will be considered evidence of active infection even in the absence of other symptoms
* History of GI bleed
* History of stroke
* History of a bleeding disorder
* Platelet count \< 150,000/mm3 on initial screening
* On a blood-thinning agent or taking NSAIDs daily
* Current use of oral steroids or other immunomodulating medications
* Salicylate sensitivity
* Pregnancy or breastfeeding

Primary outcomes:
measure: Change in Hamilton Depression Scale Score
timeFrame: 8 weeks
Secondary outcomes:
measure: Response of Inflammatory Biomarkers
timeFrame: 2 years
measure: Biomarker Association With Antidepressant Response
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Jessica Harder, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Philip NS, Carpenter LL, Tyrka AR, Price LH. Pharmacologic approaches to treatment resistant depression: a re-examination for the modern era. Expert Opin Pharmacother. 2010 Apr;11(5):709-22. doi: 10.1517/14656561003614781.
citation: Berk M, Dean O, Drexhage H, McNeil JJ, Moylan S, O'Neil A, Davey CG, Sanna L, Maes M. Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness. BMC Med. 2013 Mar 18;11:74. doi: 10.1186/1741-7015-11-74.
citation: Iyengar RL, Gandhi S, Aneja A, Thorpe K, Razzouk L, Greenberg J, Mosovich S, Farkouh ME. NSAIDs are associated with lower depression scores in patients with osteoarthritis. Am J Med. 2013 Nov;126(11):1017.e11-8. doi: 10.1016/j.amjmed.2013.02.037. Epub 2013 Aug 29.
citation: Muller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B, Spellmann I, Hetzel G, Maino K, Kleindienst N, Moller HJ, Arolt V, Riedel M. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry. 2006 Jul;11(7):680-4. doi: 10.1038/sj.mp.4001805. Epub 2006 Feb 21.
citation: Eyre HA, Air T, Proctor S, Rositano S, Baune BT. A critical review of the efficacy of non-steroidal anti-inflammatory drugs in depression. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Mar 3;57:11-6. doi: 10.1016/j.pnpbp.2014.10.003. Epub 2014 Oct 16.
citation: Gallagher PJ, Castro V, Fava M, Weilburg JB, Murphy SN, Gainer VS, Churchill SE, Kohane IS, Iosifescu DV, Smoller JW, Perlis RH. Antidepressant response in patients with major depression exposed to NSAIDs: a pharmacovigilance study. Am J Psychiatry. 2012 Oct;169(10):1065-72. doi: 10.1176/appi.ajp.2012.11091325.
citation: Akhondzadeh S, Jafari S, Raisi F, Nasehi AA, Ghoreishi A, Salehi B, Mohebbi-Rasa S, Raznahan M, Kamalipour A. Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial. Depress Anxiety. 2009;26(7):607-11. doi: 10.1002/da.20589.
citation: Abbasi SH, Hosseini F, Modabbernia A, Ashrafi M, Akhondzadeh S. Effect of celecoxib add-on treatment on symptoms and serum IL-6 concentrations in patients with major depressive disorder: randomized double-blind placebo-controlled study. J Affect Disord. 2012 Dec 10;141(2-3):308-14. doi: 10.1016/j.jad.2012.03.033. Epub 2012 Apr 18.