To our knowledge, this is the first study to examine past, intake, and time-varying follow-up predictors of prospectively examined suicide attempts among youth with bipolar disorder. Even in the literature on adult bipolar disorder, data on near-term factors associated with prospective suicide risk are limited. Our findings provide further evidence of the substantial risk for suicidal behavior associated with early-onset bipolar disorder: 18% of youth with bipolar disorder made at least 1 clinically significant suicide attempt within 5 years of study intake, and 8% made multiple attempts. Attempt rates were similar among youth with bipolar I disorder, bipolar II disorder, and bipolar disorder not otherwise specified. The most potent past and intake factors predictive of a prospectively examined suicide attempt included severity of depressive episode at study intake and family history of depression. More weeks spent with threshold depression, substance use disorder, and mixed mood symptoms, as well as more weeks receiving outpatient psychosocial services in the preceding 8-week period, predicted greater likelihood of a prospective suicide attempt. Therefore, family history, severity of depressive episode at study intake, and near-term persistence of depression, mixed states, and substance use disorder independently contribute to the prediction of prospective suicidal behavior among youth with bipolar disorder.
The 18% rate of suicidal behavior over an average of 5 years of follow-up that we report is similar to that documented in other prospectively observed samples of youth with bipolar disorder. Strober and colleagues22
reported medically significant suicide attempts in 20% of adolescents with bipolar I disorder (mean age, 16 years) over a 5-year follow-up. Among community adolescents followed up for 4 years into young adulthood (age range, 19–23 years), Lewinsohn and colleagues43
reported that 5.9% of adolescents with bipolar I or II disorder and 6.3% of adolescents with subthreshold bipolar disorder attempted suicide. The mean age of the COBY sample at study intake was 12.6 years; thus, even followed up longitudinally over 5 years, many COBY youth have yet to pass through the highest risk period for new onset of suicidal behavior (age range, 16–18 years).44
We therefore expect greater rates of suicidal behavior as the sample ages into young adulthood.
Prior findings that more than 70% of suicide attempts among individuals with bipolar disorder occur during depressive episodes45
converge with the prominence of depression-related variables in the present study. First, severity of depressive episode at study intake predicted risk for suicidal behavior during follow-up in our sample. Depression at study intake has similarly been associated with prospective risk for suicidal behavior among adults with bipolar disorder.4,16
Family history of depression also emerged as a significant predictor of a prospective suicide attempt. Studies of adolescent suicide completers document the substantial contribution of parental depression to offspring suicide risk,46
even after accounting for the child’s depressive severity.47
It is possible that familial depression contributes to offspring suicide risk via multiple avenues, including decreased familial support and increased conflict.48
Finally, univariate analyses indicated that subjects who attempted suicide during follow-up were more likely to have past exposure to an antidepressant; this relationship was not significant in multivariate analysis. This finding may be linked to the knowledge that depressive severity is a potent risk factor for suicidality among youth.49
Thus, those COBY youth with more severe depressive presentations (and therefore also at greater risk of suicide) may have been more likely to be prescribed antidepressants. It is important to note that antidepressant use during follow-up was not temporally associated with increased suicide risk in this sample, further suggesting that the association is not causal. Similarly, in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study of adults with bipolar disorder,16
antidepressant exposure was not associated with prospectively examined new-onset suicidal ideation and behavior.
This analysis represents a novel contribution to the literature owing to our ability to identify factors in close temporal proximity (ie, within 8 weeks) to suicide attempts in this population. The identification of near-term risk factors holds importance for informing risk assessment and prevention efforts. We found that more weeks with threshold depression in the preceding 8 weeks was associated with a greater prospective suicide risk. Among adults with bipolar disorder in the STEP-BD study,16
the percentage of days that an individual was depressed during the year preceding study intake was associated with attempted and completed suicide during 2-year follow-up.2
As compared with the STEP-BD study,16
we analyzed prospective factors preceding suicidal behavior using a substantially narrower time frame (ie, 8 weeks); we may conclude with greater precision that depressive burden confers near-term risk.
Retrospective and cross-sectional data support an association between mixed mood states and suicide risk.21,50,51
In fact, some such studies indicate that suicide attempt rates among adults with bipolar disorder are highest (up to 70%) during mixed episodes.52,53
In a prospective study of adults with bipolar disorder, Valtonen et al10
documented a 37-fold elevated risk for a suicide attempt during mixed mood states. To our knowledge, this is the first report to document a proximal temporal association between prospectively examined mixed states and suicide risk among youth with bipolar disorder. We found that a greater amount of time spent with mixed symptoms in the preceding 8 weeks conferred a greater risk for a suicide attempt. Clinical risk assessment of youth with bipolar disorder should attend not only to severity but also to the pervasiveness of acute mixed symptoms.
An association between comorbid substance use disorder and suicide risk in bipolar disorder is well established,54
and the association appears to be particularly strong among younger patients.55
We found that more weeks with threshold substance use disorder in the preceding 8-week period was associated with a greater risk of suicide attempt. Substance use is hypothesized to increase the risk for attempted suicide both through the negative impact of substance use on mood disorder and by the increased risk of lethal suicidal behavior while under the influence.1
However, our data indicate low rates of intoxication (5%) during the suicidal act. Future studies may investigate the specific pathways underlying the association between substance use and suicide risk in pediatric bipolar disorder as a means of improving suicide prevention efforts.
We found greater outpatient psychosocial service use in the preceding 8-week period was associated with a greater risk for a subsequent suicide attempt. Greater amount of time in outpatient psychosocial treatment may reflect recognition on the part of the patient, family, and/or treatment providers that more resources were needed to manage the patient’s illness severity and/or safety. Thus, these youth may have been getting more treatment in response to greater clinical need. This finding also calls attention to the importance of imminent risk assessment among out-patient providers treating youth with bipolar disorder, referral to higher levels of care when warranted, and the need for suicide prevention efforts for this group.
There were limitations to our study. Prospective data on suicide attempts and other follow-up variables (eg, illness status) were gathered longitudinally in the COBY study and were assessed retrospectively at follow-up periods encompassing an average of 9 months. It is possible that conducting assessments more frequently during follow-up, possibly by using ecological momentary assessment methodology, would increase the reliability of the prospective data. Furthermore, it is possible that the 8-week time period that we used for prospective analyses may have been either too broad or too narrow to adequately capture factors associated with suicidal behavior. Future studies should also aim to expand on the association between significant life events and suicidal behavior in this population. In addition, we relied on patient and parent reports of suicidal behavior, and these reports were not corroborated with emergency and/or in-patient service records. The COBY participants were primarily recruited from clinical facilities and thus may not be representative of youth with bipolar disorder who have not sought treatment. Lastly, given that the COBY sample of participants is predominantly white, these findings may not be representative of cultural minority groups because studies identify culturally specific risk factors for suicidal behavior.56
In conclusion, these prospective data indicate pediatric bipolar disorder is associated with high rates of suicide attempts. These findings highlight the importance of suicide prevention strategies in youth with bipolar disorder, including frequent and thorough suicide risk assessment and safety planning. Clinicians treating youth with bipolar disorder should attend to intake depressive severity and to family history of depression when considering the prospective risk for suicidal behavior. Persistent depression, mixed presentations, and active substance use disorder may signal imminent suicide risk in youth with bipolar disorder. Risk assessment targeting these clinical factors for youth with bipolar disorder may help to identify those at highest risk and may contribute to the prevention of suicidal behavior in this population.