Clinical Role of Aspirin in Mood Disorders: A Systematic Review

Qin Xiang Ng, Krishnapriya Ramamoorthy, Wayren Loke, Matthew Wei Liang Lee, Wee Song Yeo, Donovan Yutong Lim, Vivekanandan Sivalingam, Qin Xiang Ng, Krishnapriya Ramamoorthy, Wayren Loke, Matthew Wei Liang Lee, Wee Song Yeo, Donovan Yutong Lim, Vivekanandan Sivalingam

Abstract

Worldwide, depression and bipolar disorder affect a large and growing number of people. However, current pharmacotherapy options remain limited. Despite adequate treatment, many patients continue to have subsyndromal symptoms, which predict relapse in bipolar illness and often result in functional impairments. Aspirin, a common nonsteroidal anti-inflammatory drug (NSAID), has purported beneficial effects on mood symptoms, showing protective effects against depression in early cohort studies. This systematic review thus aimed to investigate the role of aspirin in mood disorders. Using the keywords (aspirin or acetylsalicy* or asa) and (mood or depress* or bipolar or mania or suicid*), a comprehensive search of PubMed, EMBASE, Medline, PsycINFO, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), Clinicaltrials.gov and Google Scholar databases found 13,952 papers published in English between 1 January 1988 and 1 May 2019. A total of six clinical studies were reviewed. There were two randomized, placebo-controlled, double-blind trials and populations drawn from two main cohort studies (i.e., the Geelong Osteoporosis Study and the Osteoarthritis Initiative study). Using a random-effects model, the pooled hazard ratio of the three cohort studies was 0.624 (95% confidence interval: 0.0503 to 1.198, p = 0.033), supporting a reduced risk of depression with aspirin exposure. Overall, the dropout rates were low, and aspirin appears to be well-tolerated with minimal risk of affective switch. In terms of methodological quality, most studies had a generally low risk of bias. Low-dose aspirin (80 to 100 mg/day) is safe, well-tolerated and potentially efficacious for improving depressive symptoms in both unipolar and bipolar depression. Due to its ability to modulate neuroinflammation and central nervous system processes, aspirin may also have valuable neuroprotective and pro-cognitive effects that deserve further exploration. Further randomized, controlled trials involving the adjunctive use of aspirin should be encouraged to confirm its therapeutic benefits.

Keywords: anti-inflammatory; aspirin; bipolar; depression; mood disorder; psychiatry; systematic review.

Conflict of interest statement

The authors declare that there are no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram summarizing the studies identified during the literature search and the abstraction process.
Figure 2
Figure 2
Forest plot showing pooled hazard ratios for the effect of ASA exposure on incident depression.

References

    1. World Health Organization . Depression and Other Common Mental Disorders: Global Health Estimates. World Health Organization; Geneva, Switzerland: 2017.
    1. Whiteford H.A., Degenhardt L., Rehm J., Baxter A.J., Ferrari A.J., Erskine H.E., Charlson F.J., Norman R.E., Flaxman A.D., Johns N., et al. Global burden of disease attributable to mental and substance use disorders: Findings from the Global Burden of Disease Study 2010. Lancet. 2013;382:1575–1586. doi: 10.1016/S0140-6736(13)61611-6.
    1. Grande I., Berk M., Birmaher B., Vieta E. Bipolar disorder. Lancet. 2016;387:1561–1572. doi: 10.1016/S0140-6736(15)00241-X.
    1. Klein D.N., Santiago N.J. Dysthymia and chronic depression: Introduction, classification, risk factors, and course. J. Clin. Psychol. 2003;59:807–816. doi: 10.1002/jclp.10174.
    1. Jakobsen J.C., Katakam K.K., Schou A., Hellmuth S.G., Stallknecht S.E., Leth-Møller K., Iversen M., Banke M.B., Petersen I.J., Klingenberg S.L., et al. Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis. BMC Psychiatry. 2017;17:58.
    1. Khin N.A., Chen Y.F., Yang Y., Yang P., Laughren T.P. Exploratory analyses of efficacy data from major depressive disorder trials submitted to the US Food and Drug Administration in support of new drug applications. J. Clin. Psychiatry. 2011;72:464–472. doi: 10.4088/JCP.10m06191.
    1. Ng Q.X., Yeo W.S., Sivalingam V. Lithium-associated Renal Dysfunction: To Stop or Not to Stop? Bipolar Disord. 2019 doi: 10.1111/bdi.12853.
    1. Popovic D., Reinares M., Goikolea J.M., Bonnin C.M., Gonzalez-Pinto A., Vieta E. Polarity index of pharmacological agents used for maintenance treatment of bipolar disorder. Eur. Neuropsychopharmacol. 2012;22:339–346. doi: 10.1016/j.euroneuro.2011.09.008.
    1. Bauer M., Glenn T., Alda M., Grof P., Sagduyu K., Bauer R., Lewitzka U., Whybrow P.C. Comparison of pre-episode and pre-remission states using mood ratings from patients with bipolar disorder. Pharmacopsychiatry. 2011;44:S49–S53. doi: 10.1055/s-0031-1273765.
    1. Ogawa H., Nakayama M., Morimoto T., Uemura S., Kanauchi M., Doi N., Jinnouchi H., Sugiyama S., Saito Y. Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) Trial Investigators. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: A randomized controlled trial. JAMA. 2008;300:2134–2141. doi: 10.1001/jama.2008.623.
    1. Kalgutkar A.S., Crews B.C., Rowlinson S.W., Garner C., Seibert K., Marnett L.J. Aspirin-like molecules that covalently inactivate cyclooxygenase-2. Science. 1998;280:1268–1270. doi: 10.1126/science.280.5367.1268.
    1. Eller T., Vasar V., Shlik J., Maron E. Pro-inflammatory cytokines and treatment response to escitaloprsam in major depressive disorder. Prog. Neuro Psychopharmacol. Biol. Psychiatry. 2008;32:445–450. doi: 10.1016/j.pnpbp.2007.09.015.
    1. Kim Y.K., Jung H.G., Myint A.M., Kim H., Park S.H. Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder. J. Affect. Disord. 2007;104:91–95. doi: 10.1016/j.jad.2007.02.018.
    1. Pasco J.A., Jacka F.N., Williams L.J., Henry M.J., Nicholson G.C., Kotowicz M.A., Berk M. Clinical implications of the cytokine hypothesis of depression: The association between use of statins and aspirin and the risk of major depression. Psychother. Psychosom. 2010;79:323. doi: 10.1159/000319530.
    1. Higgins J.P., Altman D.G., Gøtzsche P.C., Jüni P., Moher D., Oxman A.D., Savović J., Schulz K.F., Weeks L., Sterne J.A. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. doi: 10.1136/bmj.d5928.
    1. Wells G.A. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Non Randomised Studies in Meta-Analyses. [(accessed on 29 June 2019)]; Available online: .
    1. Veronese N., Koyanagi A., Stubbs B., Solmi M., Fornaro M., Fernandes B.S., Muller C., Thompson T., Carvalho A.F., Maggi S. Aspirin and incident depressive symptoms: A longitudinal cohort study over 8 years. Int. J. Geriatr. Psychiatr. 2018;33:e193–e198. doi: 10.1002/gps.4767.
    1. Saroukhani S., Emami-Parsa M., Modabbernia A., Ashrafi M., Farokhnia M., Hajiaghaee R., Akhondzadeh S. Aspirin for treatment of lithium-associated sexual dysfunction in men: Randomized double-blind placebo-controlled study. Bipolar Disord. 2013;15:650–656. doi: 10.1111/bdi.12108.
    1. Savitz J.B., Teague T.K., Misaki M., Macaluso M., Wurfel B.E., Meyer M., Drevets D., Yates W., Gleason O., Drevets W.C., et al. Treatment of bipolar depression with minocycline and/or aspirin: An adaptive, 2 × 2 double-blind, randomized, placebo-controlled, phase IIA clinical trial. Transl. Psychiatry. 2018;8:27. doi: 10.1038/s41398-017-0073-7.
    1. Stolk P., Souverein P.C., Wilting I., Leufkens H.G., Klein D.F., Rapoport S.I., Heerdink E.R. Is aspirin useful in patients on lithium? A pharmacoepidemiological study related to bipolar disorder. Prostaglandins Leukot. Essent. Fat. Acids. 2010;82:9–14. doi: 10.1016/j.plefa.2009.10.007.
    1. Williams L.J., Pasco J.A., Mohebbi M., Jacka F.N., Stuart A.L., Venugopal K., O’Neil A., Berk M. Statin and aspirin use and the risk of mood disorders among men. Int. J. Neuropsychopharmacol. 2016;19 doi: 10.1093/ijnp/pyw008.
    1. Sidor M.M., MacQueen G.M. An update on antidepressant use in bipolar depression. Curr. Psychiatry Rep. 2012;14:696–704. doi: 10.1007/s11920-012-0323-6.
    1. Rao J.S., Harry G.J., Rapoport S.I., Kim H.W. Increased excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from bipolar disorder patients. Mol. Psychiatry. 2010;15:384. doi: 10.1038/mp.2009.47.
    1. Casolini P., Catalani A., Zuena A.R., Angelucci L. Inhibition of COX-2 reduces the age-dependent increase of hippocampal inflammatory markers, corticosterone secretion, and behavioral impairments in the rat. J. Neurosci. Res. 2002;68:337–343. doi: 10.1002/jnr.10192.
    1. Compton M.T., Nemeroff C.B. The treatment of bipolar depression. J. Clinic. Psychiatry. 2000;61:57–67.
    1. Nahman S., Belmaker R.H., Azab A.N. Effects of lithium on lipopolysaccharide-induced inflammation in rat primary glia cells. Innate Immun. 2012;18:447–458. doi: 10.1177/1753425911421512.
    1. Budni J., Feijó D.P., Batista-Silva H., Garcez M.L., Mina F., Belletini-Santos T., Krasilchik L.R., Luz A.P., Schiavo G.L., Quevedo J. Lithium and memantine improve spatial memory impairment and neuroinflammation induced by β-amyloid 1-42 oligomers in rats. Neurobiol. Learn. Mem. 2017;141:84–92. doi: 10.1016/j.nlm.2017.03.017.
    1. Hoozemans J.J., Veerhuis R., Janssen I., van Elk E.J., Rozemuller A.J., Eikelenboom P. The role of cyclo-oxygenase 1 and 2 activity in prostaglandin E2 secretion by cultured human adult microglia: Implications for Alzheimer’s disease. Brain Res. 2002;951:218–226. doi: 10.1016/S0006-8993(02)03164-5.
    1. Söderlund J., Olsson S.K., Samuelsson M., Walther-Jallow L., Johansson C., Erhardt S., Landén M., Engberg G. Elevation of cerebrospinal fluid interleukin-1β in bipolar disorder. J. Psychiatry Neurosci. JPN. 2011;36:114. doi: 10.1503/jpn.100080.
    1. Patel D., Roy A., Kundu M., Jana M., Luan C.H., Gonzalez F.J., Pahan K. Aspirin binds to PPARα to stimulate hippocampal plasticity and protect memory. Proc. Nat. Acad. Sci. USA. 2018;115:E7408–E7417. doi: 10.1073/pnas.1802021115.
    1. MacQueen G.M., Memedovich K.A. Cognitive dysfunction in major depression and bipolar disorder: A ssessment and treatment options. Psychiatry Clin. Neurosci. 2017;71:18–27. doi: 10.1111/pcn.12463.
    1. Chang C.W., Horng J.T., Hsu C.C., Chen J.M. Mean daily dosage of aspirin and the risk of incident Alzheimer’s dementia in patients with type 2 diabetes mellitus: A nationwide retrospective cohort study in Taiwan. J. Diabetes Res. 2016;2016 doi: 10.1155/2016/9027484.
    1. Lu Y., Ho C.S., McIntyre R.S., Wang W., Ho R.C. Effects of vortioxetine and fluoxetine on the level of Brain Derived Neurotrophic Factors (BDNF) in the hippocampus of chronic unpredictable mild stress-induced depressive rats. Brain Res. Bull. 2018;142:1–7. doi: 10.1016/j.brainresbull.2018.06.007.
    1. Giuliani F., Hader W., Yong1 V.W. Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction. J. Leukoc. Biol. 2005;78:135–143. doi: 10.1189/jlb.0804477.
    1. Rosenblat J.D., McIntyre R.S. Efficacy and tolerability of minocycline for depression: A systematic review and meta-analysis of clinical trials. J. Affect. Disord. 2018;227:219–225. doi: 10.1016/j.jad.2017.10.042.
    1. Vogt M.A., Mallien A.S., Pfeiffer N., Inta I., Gass P., Inta D. Minocycline does not evoke anxiolytic and antidepressant-like effects in C57BL/6 mice. Behav. Brain Res. 2016;301:96–101. doi: 10.1016/j.bbr.2015.12.015.
    1. Gao R., Li X. Risk assessment and aspirin use in Asian and Western populations. Vasc. Health Risk Manag. 2010;6:943.
    1. Jonker C., Comijs H.C., Smit J.H. Does aspirin or other NSAIDs reduce the risk of cognitive decline in elderly persons? Results from a population-based study. Neurobiol. Aging. 2003;24:583–588. doi: 10.1016/S0197-4580(02)00188-4.
    1. Saito Y., Okada S., Ogawa H., Soejima H., Sakuma M., Nakayama M., Doi N., Jinnouchi H., Waki M., Masuda I., et al. Low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus: 10-year follow-up of a randomized controlled trial. Circulation. 2017;135:659–670. doi: 10.1161/CIRCULATIONAHA.116.025760.

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