INTRODUCTION: The use of antidepressants in bipolar disorder (BD) remains contentious, in part due to the risk of antidepressant-induced mania (AIM). However, there is no information on the architecture of mood regulation in patients who have experienced AIM. We compared the architecture of mood regulation in euthymic patients with and without a history of AIM. METHODS: Eighty-four euthymic participants were included. Participants rated their mood, anxiety and energy levels daily using an electronic (e-) visual analog scale, for a mean (SD) of 280.8(151.4) days. We analyzed their multivariate time series by computing each variable's auto-correlation, inter-variable cross-correlation, and composite multiscale entropy of mood, anxiety, and energy. Then, we compared the data features of participants with a history of AIM and those without AIM, using analysis of covariance, controlling for age, sex, and current treatment. RESULTS: Based on 18,103 daily observations, participants with AIM showed significantly stronger day-to-day auto-correlation and cross-correlation for mood, anxiety, and energy than those without AIM. The highest cross-correlation in participants with AIM was between mood and energy within the same day (median (IQR), 0.58 (0.27)). The strongest negative cross-correlation in participants with AIM was between mood and anxiety series within the same day (median (IQR), -0.52 (0.34)). CONCLUSION: Patients with a history of AIM have a different underlying mood architecture compared to those without AIM. Their mood, anxiety and energy stay the same from day-to-day; and their anxiety is negatively correlated with their mood.

Campbell Family Research Institute Centre for Addiction and Mental Health Toronto Ontario Canada

Department of Psychiatry Dalhousie University Halifax Nova Scotia Canada

Department of Psychiatry Temerty Faculty of Medicine University of Toronto Toronto Ontario Canada

National Institute of Mental Health Klecany Czech Republic

Zobrazit více v PubMed

American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders (DSM‐5 (R)). American Psychiatric Association Publishing; 2013.

Disease GBD, Injury I, Prevalence C. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990‐2017: a systematic analysis for the global burden of Disease study 2017. Lancet. 2018;392:1789‐1858. doi:10.1016/S0140-6736(18)32279-7 PubMed DOI PMC

Rihmer Z, Kiss K. Bipolar disorders and suicidal behaviour. Bipolar Disord. 2002;4(Suppl 1):21‐25. doi:10.1034/j.1399-5618.4.s1.3.x PubMed DOI

Simon GE, Hunkeler E, Fireman B, Lee JY, Savarino J. Risk of suicide attempt and suicide death in patients treated for bipolar disorder. Bipolar Disord. 2007;9:526‐530. doi:10.1111/j.1399-5618.2007.00408.x PubMed DOI

Judd LL, Akiskal HS, Schettler PJ, et al. A prospective investigation of the natural history of the long‐term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry. 2003;60:261‐269. doi:10.1001/archpsyc.60.3.261 PubMed DOI

Michalak EE, Murray G, Young AH, Lam RW. Burden of bipolar depression: impact of disorder and medications on quality of life. CNS Drugs. 2008;22:389‐406. doi:10.2165/00023210-200822050-00003 PubMed DOI

Goodwin GM, Haddad PM, Ferrier IN, et al. Evidence‐based guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2016;30:495‐553. doi:10.1177/0269881116636545 PubMed DOI PMC

Grunze H, Vieta E, Goodwin GM, et al. The world Federation of Societies of biological psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: acute and long‐term treatment of mixed states in bipolar disorder. World J Biol Psychiatry. 2018;19:2‐58. doi:10.1080/15622975.2017.1384850 PubMed DOI

Malhi GS, Bell E, Boyce P, et al. The 2020 Royal Australian and New Zealand college of psychiatrists clinical practice guidelines for mood disorders: bipolar disorder summary. Bipolar Disord. 2020;22:805‐821. doi:10.1111/bdi.13036 PubMed DOI

Yatham LN, Arumugham SS, Kesavan M, et al. Duration of adjunctive antidepressant maintenance in bipolar I depression. N Engl J Med. 2023;389:430‐440. doi:10.1056/NEJMoa2300184 PubMed DOI

Daray FM, Thommi SB, Ghaemi SN. The pharmacogenetics of antidepressant‐induced mania: a systematic review and meta‐analysis. Bipolar Disord. 2010;12:702‐706. doi:10.1111/j.1399-5618.2010.00864.x PubMed DOI

Ghaemi SN. Antidepressants in bipolar depression: the clinical debate. Aust N Z J Psychiatry. 2012;46:298‐301. doi:10.1177/0004867412441035 PubMed DOI

Ghaemi SN, Wingo AP, Filkowski MA, Baldessarini RJ. Long‐term antidepressant treatment in bipolar disorder: meta‐analyses of benefits and risks. Acta Psychiatr Scand. 2008;118:347‐356. doi:10.1111/j.1600-0447.2008.01257.x PubMed DOI PMC

Fornaro M, de Berardis D, Koshy A, et al. Prevalence and clinical features associated with bipolar disorder polypharmacy: a systematic review. Neuropsychiatr Dis Treat. 2016;12:719‐735. doi:10.2147/NDT.S100846 PubMed DOI PMC

Goldberg JF, Nassir Ghaemi S. Benefits and limitations of antidepressants and traditional mood stabilizers for treatment of bipolar depression. Bipolar Disord. 2005;7(Suppl 5):3‐12. doi:10.1111/j.1399-5618.2005.00251.x PubMed DOI

Liu B, Zhang Y, Fang H, Liu J, Liu T, Li L. Efficacy and safety of long‐term antidepressant treatment for bipolar disorders ‐ A meta‐analysis of randomized controlled trials. J Affect Disord. 2017;223:41‐48. doi:10.1016/j.jad.2017.07.023 PubMed DOI

Fornaro M, Anastasia A, Novello S, et al. Incidence, prevalence and clinical correlates of antidepressant‐emergent mania in bipolar depression: a systematic review and meta‐analysis. Bipolar Disord. 2018;20:195‐227. doi:10.1111/bdi.12612 PubMed DOI

Tohen M, Frank E, Bowden CL, et al. The International Society for Bipolar Disorders (ISBD) task force report on the nomenclature of course and outcome in bipolar disorders. Bipolar Disord. 2009;11:453‐473. doi:10.1111/j.1399-5618.2009.00726.x PubMed DOI

Alda M. The phenotypic spectra of bipolar disorder. Eur Neuropsychopharmacol. 2004;14(Suppl 2):94‐99. doi:10.1016/j.euroneuro.2004.03.006 PubMed DOI

Garnham J, Munro A, Slaney C, et al. Prophylactic treatment response in bipolar disorder: results of a naturalistic observation study. J Affect Disord. 2007;104:185‐190. doi:10.1016/j.jad.2007.03.003 PubMed DOI

Grof P, Alda M, Grof E, Fox D, Cameron P. The challenge of predicting response to stabilising lithium treatment. The importance of patient selection. Br J Psychiatry Suppl. 1993;21:16‐19. PubMed

Valenti M, Pacchiarotti I, Bonnín CM, et al. Risk factors for antidepressant‐related switch to mania. J Clin Psychiatry. 2012;73:e271‐e276. doi:10.4088/JCP.11m07166 PubMed DOI

Pacchiarotti I, Bond DJ, Baldessarini RJ, et al. The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders. Am J Psychiatry. 2013;170:1249‐1262. doi:10.1176/appi.ajp.2013.13020185 PubMed DOI PMC

Truman CJ, Goldberg JF, Ghaemi SN, et al. Self‐reported history of manic/hypomanic switch associated with antidepressant use: data from the systematic treatment enhancement program for bipolar disorder (STEP‐BD). J Clin Psychiatry. 2007;68:1472‐1479. doi:10.4088/jcp.v68n1002 PubMed DOI

Nohr AK, Forsingdal A, Moltke I, et al. Polygenic heterogeneity in antidepressant treatment and placebo response. Transl Psychiatry. 2022;12:456. doi:10.1038/s41398-022-02221-4 PubMed DOI PMC

Yatham LN, Kennedy SH, Parikh SV, et al. Canadian network for mood and anxiety treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20:97‐170. doi:10.1111/bdi.12609 PubMed DOI PMC

Baumer FM, Howe M, Gallelli K, Simeonova DI, Hallmayer J, Chang KD. A pilot study of antidepressant‐induced mania in pediatric bipolar disorder: characteristics, risk factors, and the serotonin transporter gene. Biol Psychiatry. 2006;60:1005‐1012. doi:10.1016/j.biopsych.2006.06.010 PubMed DOI

Ferreira Ade A, Neves FS, da Rocha FF, et al. The role of 5‐HTTLPR polymorphism in antidepressant‐associated mania in bipolar disorder. J Affect Disord. 2009;112:267‐272. doi:10.1016/j.jad.2008.04.012 PubMed DOI

Serretti A, Artioli P, Zanardi R, et al. Genetic features of antidepressant induced mania and hypo‐mania in bipolar disorder. Psychopharmacology. 2004;174:504‐511. doi:10.1007/s00213-004-1948-x PubMed DOI

Ingelman‐Sundberg M, Sim SC, Gomez A, Rodriguez‐Antona C. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther. 2007;116:496‐526. doi:10.1016/j.pharmthera.2007.09.004 PubMed DOI

Kozisek ME, Middlemas D, Bylund DB. Brain‐derived neurotrophic factor and its receptor tropomyosin‐related kinase B in the mechanism of action of antidepressant therapies. Pharmacol Ther. 2008;117:30‐51. doi:10.1016/j.pharmthera.2007.07.001 PubMed DOI

Biernacka JM, McElroy SL, Crow S, et al. Pharmacogenomics of antidepressant induced mania: a review and meta‐analysis of the serotonin transporter gene (5HTTLPR) association. J Affect Disord. 2012;136:e21‐e29. doi:10.1016/j.jad.2011.05.038 PubMed DOI

Melhuish Beaupre LM, Tiwari AK, Gonçalves VF, et al. Antidepressant‐associated mania in bipolar disorder: A review and meta‐analysis of potential clinical and genetic risk factors. J Clin Psychopharmacol. 2020;40:180‐185. PubMed

de Aguiar Ferreira A, Neves FS, Pimenta GJ, et al. The role of genetic variation of BDNF gene in antidepressant‐induced mania in bipolar disorder. Psychiatry Res. 2010;180:54‐56. doi:10.1016/j.psychres.2010.04.036 PubMed DOI

Ortiz A, Bradler K, Garnham J, Slaney C, MacLean S, Alda M. Corrigendum to nonlinear dynamics of mood regulation in unaffected first‐degree relatives of bipolar disorder patients [journal of affective disorders 243 (2019) 274‐279]. J Affect Disord. 2019;245:16. doi:10.1016/j.jad.2018.10.103 PubMed DOI

Ortiz A, Bradler K, Garnham J, Slaney C, Alda M. Nonlinear dynamics of mood regulation in bipolar disorder. Bipolar Disord. 2015;17:139‐149. doi:10.1111/bdi.12246 PubMed DOI

Abigail Ortiz MA. The perils of being too stable: mood regulation in bipolar disorder. J Psychiatry Neurosci. 2018;43:363‐365. PubMed PMC

Bonsall MB, Wallace‐Hadrill SM, Geddes JR, Goodwin GM, Holmes EA. Nonlinear time‐series approaches in characterizing mood stability and mood instability in bipolar disorder. Proc Biol Sci. 2012;279:916‐924. doi:10.1098/rspb.2011.1246 PubMed DOI PMC

Ortiz A, Bradler K, Mowete M, et al. The futility of long‐term predictions in bipolar disorder: mood fluctuations are the result of deterministic chaotic processes. Int J Bipolar Disord. 2021;9:30. doi:10.1186/s40345-021-00235-3 PubMed DOI PMC

Jelinek HF, Md Imam H, Al‐Aubaidy H, Khandoker AH. Association of cardiovascular risk using non‐linear heart rate variability measures with the framingham risk score in a rural population. Front Physiol. 2013;4:186. doi:10.3389/fphys.2013.00186 PubMed DOI PMC

Katerndahl D, Ferrer R, Best R, Wang CP. Dynamic patterns in mood among newly diagnosed patients with major depressive episode or panic disorder and normal controls. Prim Care Companion J Clin Psychiatry. 2007;9:183‐187. PubMed PMC

Pincus SM, Schmidt PJ, Palladino‐Negro P, Rubinow DR. Differentiation of women with premenstrual dysphoric disorder, recurrent brief depression, and healthy controls by daily mood rating dynamics. J Psychiatr Res. 2008;42:337‐347. doi:10.1016/j.jpsychires.2007.01.001 PubMed DOI

Chen F, Xu J, Gu F, Yu X, Meng X, Qiu Z. Dynamic process of information transmission complexity in human brains. Biol Cybern. 2000;83:355‐366. doi:10.1007/s004220000158 PubMed DOI

Pincus SM, Goldberger AL. Physiological time‐series analysis: what does regularity quantify? Am J Phys. 1999;266:643‐656. PubMed

Ortiz A, Park Y, Gonzalez‐Torres C, et al. Predictors of adherence to electronic self‐monitoring in patients with bipolar disorder: a contactless study using growth mixture models. Int J Bipolar Disord. 2023;11:18. doi:10.1186/s40345-023-00297-5 PubMed DOI PMC

Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978;133:429‐435. doi:10.1192/bjp.133.5.429 PubMed DOI

Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382‐389. PubMed

Ortiz A, Bradler K, Garnham J, Slaney C. Nonlinear dynamics of mood regulation in unaffected first‐degree relatives of bipolar disorder patients. J Affect Disord. 2019;243:274‐279. doi:10.1016/j.jad.2018.09.034 PubMed DOI

Folstein MF, Luria R. Reliability, validity, and clinical application of the visual analogue mood scale. Psychol Med. 1973;3:479‐486. doi:10.1017/s0033291700054283 PubMed DOI

Luria RE. The validity and reliability of the visual analogue mood scale. J Psychiatr Res. 1975;12:51‐57. doi:10.1016/0022-3956(75)90020-5 PubMed DOI

Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)‐a metadata‐driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377‐381. doi:10.1016/j.jbi.2008.08.010 PubMed DOI PMC

Harris PA, Taylor R, Minor BL, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform. 2019;95:103208. doi:10.1016/j.jbi.2019.103208 PubMed DOI PMC

Goldberg JF, Truman CJ. Antidepressant‐induced mania: an overview of current controversies. Bipolar Disord. 2003;5:407‐420. doi:10.1046/j.1399-5618.2003.00067.x PubMed DOI

MacKinnon JG. Approximate asymptotic distribution functions for unit‐root and cointegration tests. J Bus Econ Stat. 1994;12:167‐176. doi:10.2307/1391481 DOI

Halabi R, Mulsant BH, Alda M, et al. Not missing at random: missing data are associated with clinical status and trajectories in an electronic monitoring longitudinal study of bipolar disorder. J Psychiatr Res. 2024;174:326‐331. doi:10.1016/j.jpsychires.2024.04.036 PubMed DOI PMC

Murti DMP, Pujianto U, Wibawa AP, Akbar MI. In 2019 5th International Conference on Science in Information Technology (ICSITech). 83–88.

Harris RID. Testing for unit roots using the augmented dickey‐fuller test: some issues relating to the size, power and the lag structure of the test. Econ Lett. 1992;38:381‐386. doi:10.1016/0165-1765(92)90022-Q DOI

Wu S‐D, Wu C‐W, Lin S‐G, Lee K‐Y, Peng C‐K. Analysis of complex time series using refined composite multiscale entropy. Phys Lett A. 2014;378:1369‐1374. doi:10.1016/j.physleta.2014.03.034 DOI

Fisher RA. Breakthroughs in Statistics: Methodology and Distribution. Springer; 1970:66‐70.

Benjamini Y, Hochberg Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J R Stat Soc B Methodol. 1995;57:289‐300.

Viktorin A, Lichtenstein P, Thase ME, et al. The risk of switch to mania in patients with bipolar disorder during treatment with an antidepressant alone and in combination with a mood stabilizer. Am J Psychiatry. 2014;171:1067‐1073. doi:10.1176/appi.ajp.2014.13111501 PubMed DOI

Barbuti M, Menculini G, Verdolini N, et al. A systematic review of manic/hypomanic and depressive switches in patients with bipolar disorder in naturalistic settings: the role of antidepressant and antipsychotic drugs. Eur Neuropsychopharmacol. 2023;73:1‐15. doi:10.1016/j.euroneuro.2023.04.013 PubMed DOI