Article

Bipolar pharmacotherapy and suicidal behavior Part 2. The impact of antidepressants

Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles 16111 Plummer Street, North Hills, CA 91343, United States.
Journal of Affective Disorders (Impact Factor: 3.38). 12/2007; 103(1-3):13-21. DOI: 10.1016/j.jad.2007.05.017
Source: PubMed

ABSTRACT

Antidepressant-induced mania and cycle acceleration is a potential risk in bipolar patients. Another serious risk of antidepressants, that of increasing suicidal behavior, has been identified in some affectively ill populations. However, there is a dearth of knowledge about the effects of antidepressants on suicidal behavior specifically in bipolar patients.
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. Chi-squared comparison of (log) rates of suicidal events during mood stabilizer monotherapy, antidepressant monotherapy, and combination of mood stabilizer and antidepressant.
Suicidal behavior event rates (per 100 patient years) were greatest during treatment with antidepressant monotherapy (25.92), least during mood stabilizer monotherapy (3.48), and intermediate during mood stabilizer + antidepressant combination treatment (9.75). These differences were statistically significant.
In a clinical setting, antidepressants may have been prescribed because patients were deemed at greater risk of suicidality.
During treatment with antidepressants (even when coupled with mood stabilizers), patients with bipolar disorder have significantly higher rates of non-lethal suicidal behavior compared to those on mood stabilizers without antidepressants, and thus require careful monitoring.

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    • "There has also been recent interest in the pharmacogenomics of treatment emergent suicidality associated with antidepressants (Perlis et al., 2007). These concerns are perhaps even more relevant in bipolar disorder as recent data suggests differential suicidal behavior events in bipolar disorder patients managed by antidepressant monotherapy (25.92/100 patient years) in comparison to mood stabilizer monotherapy (3.48), and combination antidepressant/mood stabilizer (9.75) (Yerevanian et al., 2007). There has been recent speculation that antidepressant treatment emergent induction of suicidality in bipolar disorder may be a marker for mixed manic conversion (McElroy et al., 2006), which further underscores the importance of rigorous phenotyping to ascertain this specific risk of manic, mixed, or mixed with suicidal ideation induction. "
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    ABSTRACT: Polymorphisms in SNCA, MAPT and LRRK2 genes have recently been confirmed as risk factors for Parkinson's disease (PD), although with small individual attributable risk. Here we investigated the association of PD with interactions between variants of these genes. As part of a previous study of PD susceptibility genes 119 SNCA, MAPT, and LRRK2 haplotype tagging single nucleotide polymorphisms (SNPs) and two variable number tandem repeats (VNTRs) were genotyped in 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Twenty-six of these SNPs were selected for SNP-SNP (or SNP-VNTR or VNTR-VNTR) interaction analysis (256 interaction pairs). Case-control analyses were performed to study association of pairwise SNP interactions with PD susceptibility. Out of the 256 interaction pairs investigated, 10 had uncorrected p-values <0.05. These represented six SNCA-LRRK2 pairs, three SNCA-MAPT pairs, and one MAPT-LRRK2 pair. However, none of these pairwise interactions were significant after correction for multiple testing. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not reveal any significant interactions after accounting for multiple testing. This study provides no statistically significant evidence of gene-gene interaction effects for the three confirmed genetic susceptibility loci for PD. However, this does not exclude the possibility that other genomic loci or environmental risk factors interact with these genes.
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    • "There has also been recent interest in the pharmacogenomics of treatment emergent suicidality associated with antidepressants (Perlis et al., 2007). These concerns are perhaps even more relevant in bipolar disorder as recent data suggests differential suicidal behavior events in bipolar disorder patients managed by antidepressant monotherapy (25.92/100 patient years) in comparison to mood stabilizer monotherapy (3.48), and combination antidepressant/mood stabilizer (9.75) (Yerevanian et al., 2007). There has been recent speculation that antidepressant treatment emergent induction of suicidality in bipolar disorder may be a marker for mixed manic conversion (McElroy et al., 2006), which further underscores the importance of rigorous phenotyping to ascertain this specific risk of manic, mixed, or mixed with suicidal ideation induction. "
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    ABSTRACT: Antidepressants can trigger a rapid mood switch from depression to mania. Identifying genetic risk factors associated with antidepressant induced mania (AIM) may enable individualized treatment strategies for bipolar depression. This review and meta-analysis evaluates the evidence for association between the serotonin transporter gene promoter polymorphism (5HTTLPR) and AIM. Medline up to November 2009 was searched for key words bipolar, antidepressant, serotonin transporter, SLC6A4, switch, and mania. Five studies have evaluated the SLC6A4 promoter polymorphism and AIM in adults (total N=340 AIM+ cases, N=543 AIM- controls). Although a random effects meta-analysis showed weak evidence of association of the S allele with AIM+ status, a test of heterogeneity indicated significant differences in estimated genetic effects between studies. A similar weak association was observed in a meta-analysis based on a subset of three studies that excluded patients on mood stabilizers; however the result was again not statistically significant. Few pharmacogenomic studies of antidepressant treatment of bipolar disorder have been published. The completed studies were underpowered and often lacked important phenotypic information regarding potential confounders such as concurrent use of mood stabilizers or rapid cycling. There is insufficient published data to confirm an association between 5HTTLPR and antidepressant induced mania. Pharmacogenomic studies of antidepressant induced mania have high potential clinical impact provided future studies are of adequate sample size and include rigorously assessed patient characteristics (e.g. ancestry, rapid cycling, concurrent mood stabilization, and length of antidepressant exposure).
    Full-text · Article · Jun 2011 · Journal of Affective Disorders

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