Risk of Suicidal Behavior With Antidepressants in Bipolar and Unipolar Disorders

Abstract

Objective To examine the risk ofsuicidal behavior (suicide attempts and deaths) associated with antidepressants in participants with bipolar I, bipolar n, and unipolar major depressive disorders. Design A 27-year longitudinal (1981-2008) observational study ofmood disorders (Research Diagnostic Criteria diagnoses based on Schedule Dr Afi:ctive Disorders and Schizophrenia and review ofmedical records) was used to evaluate antidepressants and risk Dr suicidal behavior. Mixed-efi:cts logistic regression models examined propensity Dr antidepressant exposure. Mixed-efi:cts swvival models that were matched on the propensity score examined exposure status as a risk factor for time until suicidal behavior. Setting Five US academic medical centers. Results Analyses of206 participants with bipolar I disorder revealed 2,010 exposure intervals (980 exposed to antidepressants; 1,030 unexposed); 139 participants with bipolar II disorder had 1 ,407 exposure intervals (694 exposed; 713 unexposed); and 361 participants with unipolar depressive disorder had 2, 745 exposure intervals (1,328 exposed; 1,417 unexposed). Propensity score analyses confinned that more severely ill participants were more likely to initiate antidepressant treatment. In mixed-elects swvival analyses, those with bipolar I disorder had a significant reduction in risk of suicidal behavior by 54% (HR = 0.46; 95% CI, 0.31-0.69; t = -3.74; P < .001) during periods of antidepressant exposure compared to propensity-matched unexposed intervals. Similarly, the risk was reduced by 35% (HR = 0.65; 95% CI, 0.43-0.99; t = −2.01; P = .045) in bipolar II disorder. By contrast, there was no evidence of an increased or decreased risk with antidepressant exposure in unipolar disorder. Condusions Based on obsetVational data adjusted Dr propensity to receive antidepressants, antidepressants may protect patients with bipolar disorders but not unipolar depressive disorder from suicidal behavior.

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

“…Suicidal behavior was broadly defined as a suicide completion or a suicide attempt of any degree of intent or medical lethality, in keeping with previous CDS analyses . A history of suicide attempts at intake into the study was captured using the Schedule of Affective Disorders and Schizophrenia (SADS) and suicide attempts and completions were ascertained over follow‐up using the LIFE, which characterizes suicide attempt based on both intent and medical lethality.…”

“…Medication use was not modeled due to the number of time‐varying covariates already modeled and prior publication of analyses designed specifically to look at the effects of medication and suicide in this sample; previous analyses of this cohort reveal that the majority of depressive episodes were medically managed with a mood stabilizer (approximately half) or a mood stabilizer plus an antidepressant (approximately one‐quarter) …”

The Safety, Tolerability and Risks Associated with the Use of Newer Generation Antidepressant Drugs: A Critical Review of the Literature

“…The emergence of suicidality and self-injurious behavior upon treatment with ADs represents one of the most debated and controversial risks associated with antidepressant use [176,177,178,179]. Since 2014, the US Food and Drug Administration (FDA) issued a black box warning regarding the risk of suicidality related to the use of antidepressants in children and adolescents [179].…”

Longitudinal studies: An essential component for complex psychiatric disorders

“…The long-term chronicity of the disorder was emphasized and in particular when the presence of depressive symptoms were prominent (Coryell et al, 1998). Risks and protective factors of suicide that includes long periods of time (>27 years) can be studied and evidence of a modest protective factor of exposure to antidepressants supports judicial use of antidepressants during the lifetime of the bipolar patient (Leon et al, 2014).…”