Bipolar pharmacotherapy and suicidal behavior. Part I: Lithium, divalproex and carbamazepine

Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, United States.
Journal of Affective Disorders (Impact Factor: 3.38). 12/2007; 103(1-3):5-11. DOI: 10.1016/j.jad.2007.05.019
Source: PubMed


The anti-suicidal benefit of lithium on suicidal behavior in bipolar disorder is well-established. Data are mixed on the effects of divalproex and carbamazepine.
Retrospective chart review study of 405 veterans with bipolar disorder followed for a mean of 3 years, with month by month review of clinical progress notes, and systematic assessment of current pharmacotherapy and suicide completion, attempt or hospitalization for suicidality. Comparison of suicide event rates (events/100 patient years) between mood stabilizers and during-vs-after discontinuation of mood stabilizers, with linear regression analysis for influence of potential confounding variables, and robust bootstrap confirmation analysis.
No completed suicides occurred during or after discontinuation of monotherapy. Rates of non-lethal suicidal behavior were similar during lithium (2.49), divalproex (4.67) and carbamazepine (3.80) monotherapies. There was a sixteen fold greater, highly statistically significant non-lethal suicidal event rate after discontinuation compared with during mood stabilizer monotherapy (55.89 vs. 3.48 events/100 patient years; Chi2=13.95; df=1; p<0.0002). On compared with off treatment differences were similar for the three different agents.
Treatments were uncontrolled in this naturalistic setting, and data were analyzed retrospectively.
Lithium and the anticonvulsants may show similar benefits in protecting bipolar patients from non-lethal suicidal behavior when careful analysis of clinical data is done to confirm medication adherence/non-adherence. Findings in this study were similar to those of a previous study that applied the same methodology in a private practice setting.

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    • "El tratamiento con litio continuado se defi nió por el hecho de adquirir litio en dos o más ocasiones y ello se asoció a una reducción de 0,44 veces en el riesgo de suicidio en ambos sexos. Yerevanian et al 42-44 (2007) han completado recientemente un estudio retrospectivo de 405 pacientes con trastornos bipolares, con una media de seguimiento de 3 años, en el que se examinó el efecto benefi cioso antisuicidio de los estabilizadores del estado de ánimo. Esos autores indicaron una tasa de episodios de conducta suicida (episodios/100 años-paciente) 16 veces superior tras la interrupción del tratamiento en comparación con la observada durante la monoterapia con un estabilizador del estado de ánimo (55,89 frente a 3,48). "
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    ABSTRACT: Bipolar disorder is associated with high risk for suicidal behavior. Lack of adherence to treatment is one factor that may be partly responsible for this common complication. We searched MEDLINE with the combination of the key words “compliance” or “adherence” with “suicide” and “bipolar”, limited to English language papers published between 1990 and July 2008.We evaluate the existent literature studying the influence of treatment adherence on suicidality among these patients. Our findings show a limited number of studies addressing this issue, mostly conducted with patients enrolled in lithium clinics. Results suggest an association between non-adherence and an increased risk of suicidal behavior among bipolar patients. Whether non-adherence leads to increase risk of suicidality due to specific properties of interventions such as lithium treatment or simply is secondary to mood stabilization is still an open question.
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    ABSTRACT: Suicide, which is both a stereotypic yet highly individualized act, is a common endpoint for many patients with severe psychiatric illness. The mood disorders (depression and bipolar manic-depression) are by far the most common psychiatric conditions associated with suicide. At least 25% to 50% of patients with bipolar disorder also attempt suicide at least once. With the exception of lithium--which is the most demonstrably effective treatment against suicide-remarkably little is known about specific contributions of mood-altering treatments to minimizing mortality rates in persons with major mood disorders in general and bipolar depression in particular. Suicide is usually a manifestation of severe psychiatric distress that is often associated with a diagnosable and treatable form of depression or other mental illness. In a clinical setting, an assessment of suicidal risk must precede any attempt to treat psychiatric illness.
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    ABSTRACT: Antipsychotics, particularly second generation agents, are widely used in bipolar disorder, but their effect on suicidal behavior in this population has not been systematically studied. Retrospective chart review of 405 veterans with bipolar disorder followed for a mean of three years, with month-by-month systematic assessment of current pharmacotherapy and suicide completion, attempt or hospitalization for suicidality. Comparison of rates of suicidal events during mood stabilizer monotherapy, antipsychotic monotherapy, and combination of mood stabilizer and antipsychotic. Non-lethal suicide event rates were 9.4 times greater (chi2=28.29, p<.0001) during antipsychotic monotherapy and 3.5 times greater during mood stabilizer+antipsychotic (chi2=15.13, p=0.0001) than during mood stabilizer monotherapy. Antipsychotics may have been prescribed because patients were at greater risk of suicidal behavior. First and second generation antipsychotics were not distinguished. Treatment of bipolar patients with antipsychotics is associated with an increase in non-lethal suicidal behavior. Thus, use of antipsychotics for bipolar patients requires careful monitoring for suicidal behavior. Further studies are urgently needed to better characterize this relationship.
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