The effects of combined sertraline and aspirin therapy on depression severity among patients with major depressive disorder
A randomized clinical trial
Keywords:
Sertraline, Depression, AspirinAbstract
Background: Different studies have been conducted to find the best adjuvant therapies for depression management. There are controversies over the effects of aspirin as an adjuvant therapy for depression.
Objective: To determine the effects of combined sertraline and aspirin therapy on depression severity among patients with major depressive disorder.
Methods: This randomized clinical trial was conducted at Kargarnejad Psychiatric Hospital in Kashan, Isfahan, Iran, from September 1, 2016 to November 1, 2016. The study participants included 100 patients with major depressive disorder who were assigned to aspirin and placebo groups by the use of computer-generated random numbers. Patients in these groups respectively received sertraline-aspirin and sertraline-placebo for eight consecutive weeks. Patients were prescribed 80 milligrams of aspirin twice a day. Also, sertraline was administered at a dose of 50-200 milligrams daily. Beck Depression Inventory was employed for depression severity assessment at four time points, namely before, two, four, and eight weeks after the beginning of the intervention. Medication side effects were also assessed eight weeks after the beginning of the intervention. Data were analyzed by SPSS version 12.0, using Chi-square and the Independent-samples t-test (α=0.05).
Results: Both groups were matched in terms of age (p=0.46), gender (p=0.539), and depression severity (p=0.509, with mean score 33.5±4.1 vs. 32.8±5.9) at baseline. However, depression scores were reduced significantly four and eight weeks after initiation of therapy just in the sertraline-aspirin group (p<0.05).
Conclusion: As an adjuvant therapy, aspirin can reduce depression severity among patients with major depressive disorder. Yet, further studies are needed to prove the effectiveness of aspirin and other anti-inflammatory agents in reducing depression severity.
Trial registration: The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2016082829556N1.
Funding: The authors received financial support from Research Deputy of Kashan University of Medical Sciences, Kashan, Isfahan, Iran
References
Ferrari AJ, Charlson FJ, Norman RE, Patten SB, Freedman G, Murray CJ, et al. Burden of depressive
disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med.
; 10(11): e1001547. doi: 10.1371/journal.pmed.1001547. PMID: 24223526, PMCID: PMC3818162.
Ustun TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJ. Global burden of depressive disorders in
the year 2000. Br J Psychiatry. 2004; 184: 386-92. doi: 10.1192/bjp.184.5.386. PMID: 15123501.
Sadeghirad B, Haghdoost AA, Amin Esmaeili M, Ananloo ES, Ghaeli P, Rahimi-Movaghar A, et al.
Epidemiology of major depressive disorder in iran: a systematic review and meta-analysis. Int J Prev Med.
; 1(2): 81-91. PMID: 21566767, PMCID: PMC3075476.
Ferrari AJ, Somerville AJ, Baxter AJ, Norman R, Patten SB, Vos T, et al. Global variation in the
prevalence and incidence of major depressive disorder: a systematic review of the epidemiological
literature. Psychol Med. 2013; 43(3): 471-81. doi: 10.1017/S0033291712001511. PMID: 22831756.
Sadock BJ, Sadock VA, Ruiz P. Kaplan & Sadock's Synopsis of Psychiatry: Behavioral Sciences/clinical
Psychiatry. Lippincott Williams & Wilkins; 2014.
Association AP. Diagnostic and Statistical Manual of Mental Disorders (DSM-5): American Psychiatric
Publishing; 2013. doi: 10.1176/appi.books.9780890425596.
Greenberg PE, Fournier AA, Sisitsky T, Pike CT, Kessler RC. The economic burden of adults with major
depressive disorder in the United States (2005 and 2010). J Clin Psychiatry. 2015; 76(2): 155-62. doi:
4088/JCP.14m09298. PMID: 25742202.
Cipriani A, La Ferla T, Furukawa TA, Signoretti A, Nakagawa A, Churchill R, et al. Sertraline versus other
antidepressive agents for depression. Cochrane Database Syst Rev. 2009; (2): CD006117. doi:
1002/14651858.CD006117.pub2. PMID: 19370626. 9) Vahia VN, Sonavane S, Gandhi A, Vahia I. Suicide and depression. J Indian Med Assoc. 2000; 98(5): 232- 6. PMID: 11002621.
Kedzior KK, Laeber LT. A positive association between anxiety disorders and cannabis use or cannabis use
disorders in the general population--a meta-analysis of 31 studies. BMC Psychiatry. 2014; 14: 136. doi:
1186/1471-244X-14-136. PMID: 24884989, PMCID: PMC4032500.
Schreiber LR, Grant JE, Odlaug BL. Emotion regulation and impulsivity in young adults. J Psychiatr Res.
; 46(5): 651-8. doi: 10.1016/j.jpsychires.2012.02.005. PMID: 22385661, PMCID: PMC3334448.
Ono Y, Fujisawa D, Nakagawa A, Kikuchi T, Sado M. Cognitive therapy/cognitive behavior therapy for
depression. Seishin Shinkeigaku Zasshi. 2013; 115(5): 539-46. PMID: 23855232.
Parker G, Roy K, Eyers K. Cognitive behavior therapy for depression? Choose horses for courses. Am J
Psychiatry. 2003; 160(5): 825-34. doi: 10.1176/appi.ajp.160.5.825. PMID: 12727682.
Kanter JW, Baruch DE, Gaynor ST. Acceptance and commitment therapy and behavioral activation for the
treatment of depression: description and comparison. Behav Anal. 2006; 29(2): 161-85. doi:
1007/BF03392129. PMID: 22478462, PMCID: PMC2223147.
Harley R, Sprich S, Safren S, Jacobo M, Fava M. Adaptation of dialectical behavior therapy skills training
group for treatment-resistant depression. J Nerv Ment Dis. 2008; 196(2): 136-43. doi:
1097/NMD.0b013e318162aa3f. PMID: 18277222.
Smit A, Schene AH, Peeters FP, Spijker J. Tailored pharmacotherapy. Consultations about medication in a
care programme for depression. Tijdschr Psychiatr. 2016; 58(12): 881-5. PMID: 27976786.
Casey G. Antidepressants: their role in treating depression. Nurs N Z. 2013; 19(8): 20-4. PMID: 24279052.
Liu CS, Adibfar A, Herrmann N, Gallagher D, Lanctôt KL. Evidence for Inflammation-Associated
Depression. Curr Top Behav Neurosci. 2017; 31: 3-30. doi: 10.1007/7854_2016_2. PMID: 27221622.
Durmaz O. Rheumatoid Arthritis, Depressive Symptoms and Inflammation. Noro Psikiyatr Ars. 2014;
(2): 186. doi: 10.4274/npa.y7504. PMID: 28360624, PMCID: PMC5353099.
Alian S, Masoudzadeh A, Khoddad T, Dadashian A, Ali Mohammadpour R. Depression in hepatitis B and
C, and its correlation with hepatitis drugs consumption (interfron/lamivodin/ribaverin). Iran J Psychiatry
Behav Sci. 2013; 7(1): 24-9. PMID: 24644496, PMCID: PMC3939977.
Benros ME, Waltoft BL, Nordentoft M, Ostergaard SD, Eaton WW, Krogh J, et al. Autoimmune diseases
and severe infections as risk factors for mood disorders: a nationwide study. JAMA psychiatry. 2013;
(8): 812-20. doi: 10.1001/jamapsychiatry.2013.1111. PMID: 23760347.
Lotrich FE. Major depression during interferon-alpha treatment: vulnerability and prevention. Dialogues
Clin Neurosci. 2009; 11(4): 417-25. PMID: 20135899, PMCID: PMC3181938.
Prather AA, Vogelzangs N, Penninx BW. Sleep duration, insomnia, and markers of systemic inflammation:
results from the Netherlands Study of Depression and Anxiety (NESDA). J Psychiatr Res. 2015; 60: 95- 102. doi: 10.1016/j.jpsychires.2014.09.018. PMID: 25307717, PMCID: PMC4250403.
Vane JR, Botting RM. The mechanism of action of aspirin. Thromb Res. 2003; 110(5-6): 255-8. doi:
1016/S0049-3848(03)00379-7. PMID: 14592543.
Seibert K, Masferrer JL. Role of inducible cyclooxygenase (COX-2) in inflammation. Receptor. 1994; 4(1):
-23. PMID: 8038702.
Choi SH, Aid S, Bosetti F. The distinct roles of cyclooxygenase-1 and -2 in neuroinflammation:
implications for translational research. Trends Pharmacol Sci. 2009; 30(4): 174-81. doi:
1016/j.tips.2009.01.002. PMID: 19269697, PMCID: PMC3379810.
Asanuma M, Miyazaki I, Ogawa N. Neuroprotective effects of nonsteroidal anti-inflammatory drugs on
neurodegenerative diseases. Curr Pharm Des. 2004; 10(6): 695-700. doi: 10.2174/1381612043453072.
PMID: 14965332.
Kulmatycki KM, Jamali F. Drug disease interactions: role of inflammatory mediators in depression and
variability in antidepressant drug response. J Pharm Pharm Sci. 2006; 9(3): 292-306. PMID: 17207413.
Rainsford KD. Anti-inflammatory drugs in the 21st century. Subcell Biochem. 2007; 42: 3-27. doi:
1007/1-4020-5688-5_1. PMID: 17612044.
Nebhinani N. Sertraline-induced galactorrhea: case report and review of cases reported with other SSRIs.
Gen Hosp Psychiatry. 2013; 35(5): 576 e3-5. doi: 10.1016/j.genhosppsych.2012.10.010. PMID: 23260337.
Ghanizadeh A, Hedayati A. Augmentation of Citalopram with Aspirin for Treating Major Depressive
Disorder, a Double Blind Randomized Placebo Controlled Clinical Trial. Antiinflamm Antiallergy Agents
Med Chem. 2014; 13(2): 108-11. doi: 10.2174/1871523013666140804225608. PMID: 25091820.
Uher R, Carver S, Power RA, Mors O, Maier W, Rietschel M, et al. Non-steroidal anti-inflammatory drugs
and efficacy of antidepressants in major depressive disorder. Psychol Med. 2012; 42(10): 2027-35. doi:
1017/S0033291712000190. PMID: 22391106.
Kohler O, Petersen L, Mors O, Gasse C. Inflammation and depression: combined use of selective serotonin
reuptake inhibitors and NSAIDs or paracetamol and psychiatric outcomes. Brain Behav. 2015; 5(8):
e00338. doi: 10.1002/brb3.338. PMID: 26357585, PMCID: PMC4559013.
Vasegh S, Baradaran N. Using the Persian-language version of the Beck Depression Inventory-II (BDI-II- Persian) for the screening of depression in students. J Nerv Ment Dis. 2014; 202(10): 738-43. doi:
1097/NMD.0000000000000183. PMID: 25208346.
Sharifi V, Mohammad Assadi S, Mohammadi MR, Amini H, Kaviani H, Semnani Y, et al. Structured
Clinical Interview for DSM-IV (SCID): Persian translation and cultural adaptation. Iran J Psychiatry. 2007;
: 46-8.
Savitz J, Preskorn S, Teague TK, Drevets D, Yates W, Drevets W. Minocycline and aspirin in the treatment
of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2x2
clinical trial. BMJ Open. 2012; 2(1): e000643. doi: 10.1136/bmjopen-2011-000643. PMID: 22357572,
PMCID: PMC3289990.
Berk M, Woods RL, Nelson MR, Shah RC, Reid CM, Storey E, et al. ASPREE-D: Aspirin for the
prevention of depression in the elderly. Int Psychogeriatr. 2016; 28(10): 1741-8. doi:
1017/S104161021600079X. PMID: 27587328.
Wium-Andersen IK, Wium-Andersen MK, Jorgensen MB, Osler M. Anti-inflammatory treatment and risk
for depression after first-time stroke in a cohort of 147 487 Danish patients. J Psychiatry Neurosci. 2017;
(5): 320-30. doi: 10.1503/jpn160244. PMID: 28632121, PMCID: PMC5573574.
Brunello N, Alboni S, Capone G, Benatti C, Blom JM, Tascedda F, et al. Acetylsalicylic acid accelerates
the antidepressant effect of fluoxetine in the chronic escape deficit model of depression. Int Clin
Psychopharmacol. 2006; 21(4): 219-25. doi: 10.1097/00004850-200607000-00004. PMID: 16687993.
Almeida OP, Flicker L, Yeap BB, Alfonso H, McCaul K, Hankey GJ. Aspirin decreases the risk of
depression in older men with high plasma homocysteine. Transl Psychiatry. 2012; 2: e151. doi:
1038/tp.2012.79. PMID: 22872164, PMCID: PMC3432193.
Quinn AL, Dean OM, Davey CG, Kerr M, Harrigan SM, Cotton SM, et al. Youth Depression Alleviation- Augmentation with an anti-inflammatory agent (YoDA-A): protocol and rationale for a placebo-controlled
randomized trial of rosuvastatin and aspirin. Early Interv Psychiatry. 2015. doi: 10.1111/eip.12280. PMID:
Dantzer R. Cytokine-induced sickness behavior: where do we stand? Brain Behav Immun. 2001; 15(1): 7- 24. doi: 10.1006/brbi.2000.0613. PMID: 11259077.
Published
Issue
Section
License
Copyright (c) 2020 KNOWLEDGE KINGDOM PUBLISHING
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
