Mixed state and suicide: Is the effect of mixed state on suicidal behavior more than the sum of its parts?

Abstract

Objective To assess whether suicidal behavior during mixed states exceeds that expected from the manic or depressive components alone. Methods This study included 429 participants with bipolar disorder from the National Institute of Mental Health Collaborative Depression Study (CDS). Mood and suicidal behavior were captured using the Longitudinal Interval Follow‐up Evaluation and the Schedule of Affective Disorders and Schizophrenia. Suicidal behavior during each mood state, relative to euthymia, was analyzed using Cox regression to allow for repeated events, with a frailty term to account for intra‐participant correlation. Mixed states were modeled as a depression‐by‐mania interaction. Results Individuals with a history of mixed states were at higher risk of suicidal behavior and spent more time depressed, compared to subjects with no such history. In bipolar I disorder, risk increased during episodes of mania (hazard ratio [HR]: 1.96, 95% confidence interval [CI]: 1.28‐2.99, P = .0019) and depression (HR: 5.49, 95% CI: 4.01‐7.51, P < .0001) and there was a less than additive effect of mixed states. In bipolar II disorder, risk was increased during episodes of depression (HR: 3.66, 95% CI: 2.51‐5.35, P < .0001) and there was no excess risk during mixed states beyond that attributable to the depressed component. Most of the excess risk (71%) among those with a history of mixed states was attributable to a depression predominant course of illness. Conclusions Individuals with mixed states are at high risk of suicidal behavior, largely due to more time spent depressed. Clinicians should aggressively treat depression to mitigate suicide risk for patients with or without mixed states.

<p>Development of the 12-item questionnaire for quantitative assessment of depressive mixed state (DMX-12)</p>

“…The disruptive emotion/behavior symptoms, featuring dysphoria, irritability, aggression, and risk-taking behavior, are much less frequently observed during MDEs than any other DMX-12 subscales (Figures 1 and 2), but are possibly helpful in distinguishing patients with DMX from those without DMX, by both Benazzi’s definition12,14,15 and DMX-56 criteria (Table 4). These symptoms have also been regarded as promoting factors for suicidal behavior,7,30,31 to which clinicians should pay the greatest attention in assessing and managing the suicidal risks of patients with DMX. Presumably, the disruptive emotion/behavior symptoms may be essential and core characteristics of DMX even when different categorical criteria are applied 7,8,16.…”

“…Contrary to our clinical impression, the overall severity of mixed symptoms assessed by total DMX-12 score was not directly associated with patients’ GAF (Table 3). Despite this negative result, clinicians should be warned that DMX symptoms often provoke risky behavior, including suicide attempts 7,30,31…”

Affective Temperaments and Clinical Course of Bipolar Disorder: An Exploratory Study of Differences among Patients with and without a History of Violent Suicide Attempts

“…Other potential mechanisms may be the presence of shared risk factors for suicidal behavior and psychotic symptoms, including traumatic early life experiences, especially physical and sexual abuse [45], as reported by a recent meta-analysis by Ng et al [50]. Therefore, mixed states, both with or without psychotic symptoms, are associated with an elevated risk of suicidal behavior, due to a greater proportion of time spent being depressed than patients without mixed episodes [51]. Furthermore, our study has outlined several clinical characteristics of violent suicide attempters.…”

Suicide Risk in Bipolar Disorder: A Brief Review

“…Family history of suicide acts and/or major mood disorders are also strong risk factors for suicide in subjects with BD. Some results also suggest that living in geographical locations where there are large differences in solar insolation between winter and summer (i.e., near the poles) may be associated with increased risks of attempted suicide in patients with BD-I [2,7,8,10,11,12,15,17,19,25,26,27,28,29,30,31,32,33,34].…”