Bipolar Disorder: Analysis of Frequency and Structure of Affective Phases “with Mixed Features” in the Focus of Prognosis

Background: despite numerous scientific studies, the topic of affective-mixed states in individuals diagnosed with bipolar disorder (BD) remains unexplored to a full extent due to difficulties in diagnosis, lower referral rates for medical advice, compared to depressive episodes, difficulties in developing correct therapeutic tactics and prognosis. The aim was to study the frequency of occurrence and structure of affective-mixed episodes in patients diagnosed with bipolar disorder. Patients and Methods: a total of 165 patients who underwent inpatient treatment for the first time at the Department for the Study of Endogenous Mental Disorders and Affective States of Mental Health Research Centre in the period from 2013 to 2023 were examined using clinical, psychopathological and statistical methods. All patients included in the study had a clinically confirmed diagnosis of bipolar disorder. Results: based on the affective characteristics, four groups of affective phases were distinguished: manic with mixed features, purely manic, depressive with mixed manifestations, and depressive without mixed features. The frequency rates of episodes with mixed features varied significantly from compared types of affective disorders. Patients with affective-mixed episodes were characterized by an early age of onset, a younger age at first hospitalization, frequent hospitalizations, and a high suicidal risk compared with patients without mixed features. Conclusion: the analysis made allow us to deepen our understanding of the BD course, clinical characteristics, and to formulate a therapeutic strategy for this patient population. The results obtained suggest the formation of a trajectory for future research in the field of bipolar disorder, including the development of an accurate definition of characteristics in patients with affective-mixed phases in bipolar disorder.

1. Castle DJ. Bipolar mixed states: still mixed up? Curr Opin Psychiatry. 2014 Jan;27(1):38–42. doi: 10.1097/YCO.0000000000000029 PMID: 24270474.

2. Perugi G, Akiskal HS. Emerging concepts of mixed states: a longitudinal perspective. In: Marneros A., Goodwin FK, eds. Emerging Concepts of Mixed States: A Longitudinal Perspective. Cambridge: Cambridge University Press; 2005:45–60.

3. Vasilieva SN, Simutkin GG, Schastnyy ED, Lebedeva EV, Bokhan NA. Bipolar Disorder: Comorbidity with Other Mental Disorders. Psychiatry (Moscow) (Psikhiatriya). 2021;19(3):15–21. (In Russ.). doi: 10.30629/2618-6667-2021-19-3-15-21

4. Benazzi F. Reviewing the diagnostic validity and util ity of mixed depression (depressive mixed states). Eur Psychiatry. 2008 Jan;23(1):40–8. doi: 10.1016/j.eurpsy.2007.07.003 Epub 2007 Aug 30. PMID: 17764909.

5. Akiskal HS, Akiskal KK, Lancrenon S, Hantouche EG, Fraud JP, Gury C, Allilaire JF. Validating the bipolar spectrum in the French National EPIDEP Study: over view of the phenomenology and relative prevalence of its clinical prototypes. J Affect Disord. 2006 Dec; 96(3):197–205. doi: 10.1016/j.jad.2006.05.015 Epub 2006 Jul 7. PMID: 16824616.

6. Faedda GL, Marangoni C, Reginaldi D. Depressive mixed states: A reappraisal of Koukopoulos’ crite ria. J Affect Disord. 2015;176:18–23. doi: 10.1016/j. jad.2015.01.053 Epub 2015 Feb 4. PMID: 25687279.

7. Shim IH, Woo YS, Bahk WM. Prevalence rates and clinical implications of bipolar disorder “with mixed features” as dened by DSM-5. J Affect Dis ord. 2015;173:120–5. doi: 10.1016/j.jad.2014.10.061 Epub 2014 Nov 10. PMID: 25462405.

8. Avedisova AS, Vorob'ev RV. Typology of mixed depres sive states in bipolar affective disorder. S.S. Korsakov Journal of Neurology and Psychiatry. 2014;114(1):16 25. (In Russ.).

9. Yatham LN, Chakrabarty T, Bond DJ, Schaffer A, Beaulieu S, Parikh SV, McIntyre RS, Milev RV, Alda M, Vazquez G, Ravindran AV, Frey BN, Sharma V, Gold stein BI, Rej S, O’Donovan C, Tourjman V, Kozicky JM, Kauer-Sant’Anna M, Malhi G, Suppes T, Vieta E, Kap czinski F, Kanba S, Lam RW, Kennedy SH, Calabrese J, Berk M, Post R. /Canadian Network for Mood and Anx iety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) recommendations for the management of patients with bipolar disorder with mixed presentations. Bipolar Disord. 2021;23(8):767 788. doi: 10.1111/bdi.13135

10. Fico G, Anmella G, De Prisco M, Oliva V, Possidente C, Bracco L, Bort M, Fernandez-Plaza T, Giménez-Palo mo A, Vieta E, Murru A. The Mixed Tendency in Bipolar Disorder: An Operational Proposal for the Integra tion of Mixed Episodes in Predominant Polarity. J Clin Med. 2023;12(23):7398. doi: 10.3390/jcm12237398 PMID: 38068451; PMCID: PMC10707440.

11. Vieta E, Valentí M. Mixed states in DSM-5: impli cations for clinical care, education, and research. J Affect Disord. 2013;148(1):28–36. doi: 10.1016/j. jad.2013.03.007 Epub 2013 Apr 2. PMID: 23561484.

12. Swann AC, Lafer B, Perugi G, Frye MA, Bauer M, Bahk WM, Scott J, Ha K, Suppes T. Bipolar mixed states: an international society for bipolar disor ders task force report of symptom structure, course of illness, and diagnosis. Am J Psychiatry. 2013 Jan; 170(1):31–42. doi: 10.1176/appi.ajp.2012.12030301 PMID: 23223893.