ABSTRACT FROM: Miller S, Trisha S, Jim M, et al. Mixed depression in bipolar disorder: prevalence rate and clinical correlates during naturalistic follow-up in the stanley bipolar network. Am J Psychiat 2016;173:1015–23.
What is already known on this topic
It is well established that mixed features are a common presentation in bipolar disorder (BD).1 It is also previously reported that subthreshold depressive symptoms are common during hypomania and differentially affect female patients.2 Moreover, individuals with mixed features are more likely to present with greater illness complexity, higher rates of chronicity and non-recovery, as well as a less favourable course of illness.3
Methods of the study
A total of 907 patients with bipolar disorder (BD I n=680, BD II n=187, BD not otherwise specified n=18 or schizoaffective disorder-bipolar type n=22) who were participants in the Stanley Bipolar Network Study were included. Patients were seen monthly (14 310 visits from 1995 to 2012) and assessed prospectively with the Young Mania Rating Scale (YMRS) and the Inventory for Depressive Symptomatology-Clinician Rated Version (IDS-C). The definition of mixed depression was an IDS-C score ≥15 and a YMRS score greater than 2 and less than 12. In addition, a DSM-V-based definition of mixed depression was employed requiring ≥3 non-overlapping YMRS items concurrent with and IDS-C score ≥15.
What this paper adds
The primary outcome was the prevalence and phenomenology of mixed depression among patients with BD comparing a range of diagnostic threshold. The outcome was that mixed depression was observed in 14.9% of total visits and 43.5% of visits with depression.
Women were significantly more likely than men to experience subthreshold hypomania during visits with depression (40.7% vs 34.4%).
Employing the narrower DSM-V mixed features definition, mixed depression prevalence rates were 6.3% and 10.8% of visits.
Mixed depression differentially affects female patients.
Mixed depression affects bipolar I and bipolar II disorder equally.
Relaxing DSM-V criteria increases sensitivity for mixed features.
Limitations
Investigators proxied definition of mixed features.
Tertiary centres were sole participants (ie, four USA, three non-USA sites), raising questions of generalisability to other settings (eg, primary care).
Study was observational, and symptom duration and illness trajectory were not known.
What next in research
There is a pressing need to carefully evaluate the prevalence and clinical correlates of mixed features according to the DSM-V criteria. In addition, future phenomenological research should evaluate and compare measures of cognitive function to determine whether there are differences between those with and without mixed features. Finally, there is a paucity of interventional studies targeting DSM-V mixed features, clearly an unmet need.4 5 Additionally, there is a need to better characterise mixed features in adults with major depressive disorder.6 7
Do these results change your practices and why?
Yes. The results of this paper have encouraged me to systematically screen for and measure subthreshold hypomanic symptoms in all patients presenting with BDs or major depressive disorder. In addition, the finding that mixed features are associated with subsequent mixed presentations is an important topic for psychoeducation with patients around prognostication and vigilance for symptomatic recrudescence. The hazardous effect of mixed features invites the need for prioritising this phenomenology as a priority therapeutic target.
Footnotes
Competing interests: RM is on the advisory boards and receives speaker fees from Lundbeck, Pfizer, AstraZeneca, Elli-Lilly, JanssenOrtho, Purdue, Johnson & Johnson, Moksha8, Sunovion, Mitsubishi, Takeda, Forest, Otsuka, Bristol-Myers Squibb and Shire. He has received research grants from Lundbeck, JanssenOrtho, Shire, Purdue, AstraZeneca, Pfizer, Otsuka and Allergan.
Provenance and peer review: Commissioned; internally peer reviewed.
References
- 1. McIntyre RS, Soczynska JK, Liauw SS, et al. The association between childhood adversity and components of metabolic syndrome in adults with mood disorders: results from the international mood disorders collaborative project. Int J Psychiatry Med 2012;43:165–77. 10.2190/PM.43.2.e [DOI] [PubMed] [Google Scholar]
- 2. Suppes T, Mintz J, McElroy SL, et al. Mixed hypomania in 908 patients with bipolar disorder evaluated prospectively in the Stanley Foundation Bipolar Treatment Network: a sex-specific phenomenon. Arch Gen Psychiatry 2005;62:1089–96. 10.1001/archpsyc.62.10.1089 [DOI] [PubMed] [Google Scholar]
- 3. Swann AC, Lafer B, Perugi G, et al. Bipolar mixed states: an international society for bipolar disorders task force report of symptom structure, course of illness, and diagnosis. Am J Psychiatry 2013;170:31–42. 10.1176/appi.ajp.2012.12030301 [DOI] [PubMed] [Google Scholar]
- 4. McIntyre RS, Cucchiaro J, Pikalov A, et al. Lurasidone in the Treatment of Bipolar Depression With Mixed (Subsyndromal Hypomanic) Features. J Clin Psychiatry 2015:398–405. 10.4088/JCP.14m09410 [DOI] [PubMed] [Google Scholar]
- 5. McIntyre RS. Pharmacology and efficacy of asenapine for manic and mixed states in adults with bipolar disorder. Expert Rev Neurother 2010;10:645–9. 10.1586/ern.10.49 [DOI] [PubMed] [Google Scholar]
- 6. McIntyre RS. Mixed features and mixed states in psychiatry: from calculus to geometry. CNS Spectr 2017;22:116–7. 10.1017/S1092852916000559 [DOI] [PubMed] [Google Scholar]
- 7. Suppes T, Silva R, Mao Y, et al. P.2.b.013 lurasidone for the treatment of Major depressive disorder with mixed features: a randomised, double-blind, placebo-controlled 6 week trial. Eur Neuropsychopharmacol 2015;25:S391–2. 10.1016/S0924-977X(15)30513-7 [DOI] [Google Scholar]