Risk of Suicidal Behavior With Antidepressants in Bipolar and Unipolar Disorders
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 07/2014; 75(7):720-727. DOI: 10.4088/JCP.13m08744
Objective: To examine the risk of suicidal behavior (suicide attempts and deaths) associated with antidepressants in participants with bipolar I, bipolar II, and unipolar major depressive disorders. Design: A 27-year longitudinal (1981-2008) observational study of mood disorders (Research Diagnostic Criteria diagnoses based on Schedule for Affective Disorders and Schizophrenia and review of medical records) was used to evaluate antidepressants and risk for suicidal behavior. Mixed-effects logistic regression models examined propensity for antidepressant exposure. Mixed-effects survival 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 of 206 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 confirmed that more severely ill participants were more likely to initiate antidepressant treatment. In mixed-effects survival 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. Conclusions: Based on observational data adjusted for propensity to receive antidepressants, antidepressants may protect patients with bipolar disorders but not unipolar depressive disorder from suicidal behavior.
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ABSTRACT: Bipolar disorder is associated with high mortality, and people with this disorder on average may die 10-20 years earlier than the general population. This excess and premature mortality continues to occur despite a large and expanding selection of treatment options dating back to lithium and now including anticonvulsants, antipsychotics, and evidence-based psychotherapies. This review summarizes recent findings on mortality in bipolar disorder, with an emphasis on the role of suicide (accounting for about 15 % of deaths in this population) and cardiovascular disease (accounting for about 35-40 % of deaths). Recent care models and treatments incorporating active outreach, integrated mental and physical health care, and an emphasis on patient self-management have shown promise in reducing excess mortality in this population.
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ABSTRACT: It is well known that concerning the prevalence of unipolar depression, females have almost double rates in comparison to males. However, this does not hold true concerning BD, for which similar rates between males and females are reported. There are some data suggesting that males might be over-represented in those diagnosed with a BD-I and females over-represented in those diagnosed with a BD-II disorder.
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ABSTRACT: Mortality rates, in particular due to suicide, are especially high in bipolar patients. This nationwide, registry-based study analyses the associations of medication use with hospitalization due to attempted suicides, deaths from suicide, and overall mortality across different psychotropic agents in bipolar patients. Altogether 826 bipolar patients hospitalized in Finland between 1996-2003 because of a suicide attempt were followed-up for a mean of 3.5 years. The relative risk of suicide attempts leading to hospitalization, completed suicide, and overall mortality during lithium vs. no-lithium, antipsychotic vs. no-antipsychotic, valproic acid vs. no-valproic acid, antidepressant vs. no-antidepressant and benzodiazepine vs. no-benzodiazepine treatment was measured. The use of valproic acid (RR=1.53, 95% CI: 1.26-1.85, p<0.001), antidepressants (RR=1.49, 95% CI: 1.23-1.8, p<0.001) and benzodiazepines (RR=1.49, 95% CI: 1.23-1.80, p<0.001) was associated with increased risk of attempted suicide. Lithium was associated with a (non-significantly) lower risk of suicide attempts, and with significantly decreased suicide mortality in univariate (RR=0.39, 95% CI: 0.17-0.93, p=0.03), Cox (HR=0.37, 95% CI: 0.16-0.88, p=0.02) and marginal structural models (HR=0.31, 95% CI: 0.12-0.79, p=0.02). Moreover, lithium was related to decreased all-cause mortality by 49% (marginal structural models). Only high-risk bipolar patients hospitalized after a suicide attempt were studied. Diagnosis was not based on standardized diagnostic interviews; treatment regimens were uncontrolled. Maintenance therapy with lithium, but not with other medications, is linked to decreased suicide and all-cause mortality in high-risk bipolar patients. Lithium should be considered for suicide prevention in high-risk bipolar patients. Copyright © 2015 Elsevier B.V. All rights reserved.
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