Exploring the Association Between Monoclonal Antibodies and Depression and Suicidal Ideation and Behavior: A VigiBase Study

Overview

Journal Drug Saf

Specialties Pharmacology
Toxicology

Date 2019 Jan 9

PMID 30617497

Citations 11

Authors

Lotte A Minnema

Thijs J Giezen

Patrick C Souverein

Toine C G Egberts

Hubert G M Leufkens

Helga Gardarsdottir

Affiliations

Soon will be listed here.

Abstract

Introduction: Several monoclonal antibodies (mAbs) have been linked to neuropsychiatric adverse effects in patients, including depression and suicidal ideation and behavior.

Objective: The aim of this study was to quantify and characterize spontaneously reported adverse drug reactions (ADRs) of depression and suicidal ideation and behavior related to mAb users, and to explore a possible association with their mechanism of action.

Methods: We included mAb ADRs that were reported in VigiBase, and identified those related to depression and suicidal ideation and behavior. Reporting odds ratios (RORs) were estimated for each mAb (bevacizumab as the reference) and according to their influence on the immune system (not directly targeting [reference], stimulating, or suppressing). Those suppressing the immune system were further divided into their intended indication (auto-immune diseases, cancer).

Results: Overall, 2,924,319 ADRs for 44 mAbs were included; 9455 ADRs were related to depression and 1770 were related to suicidal ideation and behavior. The association was strongest for natalizumab and belimumab, both for depression (ROR 5.7, 95% confidence interval [CI] 5.0-6.4; and ROR 5.1, 95% CI 4.2-6.2) and suicidal ideation and behavior (ROR 12.0, 95% CI 7.9-18.3; and ROR 20.2, 95% CI 12.4-33.0). Those suppressing the immune system showed higher ROR, i.e. 1.9 (95% CI 1.8-2.0) for depression and 3.6 (95% CI 3.0-4.4) for suicidal ideation and behavior. This finding was only seen for mAbs used for treating autoimmune diseases.

Conclusion: Depression and suicidal ideation and behavior are seen in patients using mAbs, particularly mAbs used for treating autoimmune diseases that suppress the immune system. For interpretation of these data, the indications for use and other characteristics require further consideration.

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References

Silverstein N, Huh J . Interleukin-17: Why the Worms Squirm. Immunity. 2017; 46(3):347-349. DOI: 10.1016/j.immuni.2017.03.007. View

Mumoli L, Ciriaco M, Gambardella A, Bombardiere G, Valentino P, Palleria C . A possible case of natalizumab-dependent suicide attempt: A brief review about drugs and suicide. J Pharmacol Pharmacother. 2013; 4(Suppl 1):S90-3. PMC: 3853678. DOI: 10.4103/0976-500X.120974. View

Zhang L, Fu T, Yin R, Zhang Q, Shen B . Prevalence of depression and anxiety in systemic lupus erythematosus: a systematic review and meta-analysis. BMC Psychiatry. 2017; 17(1):70. PMC: 5310017. DOI: 10.1186/s12888-017-1234-1. View

Roblin X, Oltean P, Heluwaert F, Bonaz B . Panic attack with suicide: an exceptional adverse effect of infliximab. Dig Dis Sci. 2006; 51(6):1056. DOI: 10.1007/s10620-006-8007-x. View

Chen C, Itakura E, Nelson G, Sheng M, Laurent P, Fenk L . IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses. Nature. 2017; 542(7639):43-48. PMC: 5503128. DOI: 10.1038/nature20818. View

Benros M, Waltoft B, Nordentoft M, Ostergaard S, Eaton W, Krogh J . Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study. JAMA Psychiatry. 2013; 70(8):812-20. DOI: 10.1001/jamapsychiatry.2013.1111. View

Nagesh O, Bastiampillai T, Fisher L, Mohan T . Cyclical suicidal ideation following natalizumab infusion for multiple sclerosis. Aust N Z J Psychiatry. 2015; 49(7):668-9. DOI: 10.1177/0004867415572414. View

Hoepner R, Faissner S, Salmen A, Gold R, Chan A . Efficacy and side effects of natalizumab therapy in patients with multiple sclerosis. J Cent Nerv Syst Dis. 2014; 6:41-9. PMC: 4011812. DOI: 10.4137/JCNSD.S14049. View

Pitman A, Suleman S, Hyde N, Hodgkiss A . Depression and anxiety in patients with cancer. BMJ. 2018; 361:k1415. DOI: 10.1136/bmj.k1415. View

10.

Wallace D, Navarra S, Petri M, Gallacher A, Thomas M, Furie R . Safety profile of belimumab: pooled data from placebo-controlled phase 2 and 3 studies in patients with systemic lupus erythematosus. Lupus. 2012; 22(2):144-54. DOI: 10.1177/0961203312469259. View

11.

Schmidt C . Suicidal thoughts end Amgen's blockbuster aspirations for psoriasis drug. Nat Biotechnol. 2015; 33(9):894-5. DOI: 10.1038/nbt0915-894b. View

12.

Neuendorf R, Harding A, Stello N, Hanes D, Wahbeh H . Depression and anxiety in patients with Inflammatory Bowel Disease: A systematic review. J Psychosom Res. 2016; 87:70-80. DOI: 10.1016/j.jpsychores.2016.06.001. View

13.

Hiles S, Baker A, de Malmanche T, Attia J . A meta-analysis of differences in IL-6 and IL-10 between people with and without depression: exploring the causes of heterogeneity. Brain Behav Immun. 2012; 26(7):1180-8. DOI: 10.1016/j.bbi.2012.06.001. View

14.

Choi G, Yim Y, Wong H, Kim S, Kim H, Kim S . The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. Science. 2016; 351(6276):933-9. PMC: 4782964. DOI: 10.1126/science.aad0314. View

15.

Bagley S, Sirota M, Chen R, Butte A, Altman R . Constraints on Biological Mechanism from Disease Comorbidity Using Electronic Medical Records and Database of Genetic Variants. PLoS Comput Biol. 2016; 12(4):e1004885. PMC: 4846031. DOI: 10.1371/journal.pcbi.1004885. View

16.

Haapakoski R, Mathieu J, Ebmeier K, Alenius H, Kivimaki M . Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder. Brain Behav Immun. 2015; 49:206-15. PMC: 4566946. DOI: 10.1016/j.bbi.2015.06.001. View

17.

Tonelli L . Neuroinflammation in suicide: too little may be just as bad as too much. Acta Psychiatr Scand. 2014; 131(4):242-3. PMC: 5717750. DOI: 10.1111/acps.12340. View

18.

Marrie R, Reingold S, Cohen J, Stuve O, Trojano M, Soelberg Sorensen P . The incidence and prevalence of psychiatric disorders in multiple sclerosis: a systematic review. Mult Scler. 2015; 21(3):305-17. PMC: 4429164. DOI: 10.1177/1352458514564487. View

19.

Banovac M, Candore G, Slattery J, Houyez F, Haerry D, Genov G . Patient Reporting in the EU: Analysis of EudraVigilance Data. Drug Saf. 2017; 40(7):629-645. DOI: 10.1007/s40264-017-0534-1. View

20.

Montastruc J, Sommet A, Bagheri H, Lapeyre-Mestre M . Benefits and strengths of the disproportionality analysis for identification of adverse drug reactions in a pharmacovigilance database. Br J Clin Pharmacol. 2011; 72(6):905-8. PMC: 3244636. DOI: 10.1111/j.1365-2125.2011.04037.x. View