Bipolar pharmacotherapy and suicidal behavior Part 2. The impact of antidepressants.
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.
- SourceAvailable from: Rafael Fernández
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ABSTRACT: The potential role of psychopharmacology in suicide prevention is often minimised. This may to some extent reflect that few medication trials have specifically focussed on prevention of suicidal behaviour--indeed this outcome is often not reported in trials. However, there is reasonably strong evidence that lithium may reduce risk of suicide, the postulated mechanism being a specific effect on aggression. Evidence is lacking with regard to any protective effect of other mood stabilizers. Clozapine may reduce suicidal behaviour in patients with schizophrenia, with reduction of affective symptoms being a possible explanation. The role of antidepressants in relation to suicide risk is highly controversial, especially in children and adolescents. It is unclear whether minor tranquillizers or hypnotics can assist in suicide prevention, although they can reduce the anxiety symptoms that may occur during initial treatment with SSRI antidepressants. It is also uncertain whether psychopharmacology has a role in preventing suicidal behaviour in people with personality disorders. Despite the limitations of the evidence we contend that suicide risk should be an important factor in deciding when and what to prescribe.Epidemiologia e psichiatria sociale 09/2009; 18(3):172-8. DOI:10.1017/S1121189X00000427 · 3.16 Impact Factor
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ABSTRACT: The glutamate receptor 6 (GluR6 or GRIK2, one of the kainate receptors) gene resides in a genetic linkage region (6q21) associated with bipolar disorder (BPD), but its function in affective regulation is unknown. Compared with wild-type (WT) and GluR5 knockout (KO) mice, GluR6 KO mice were more active in multiple tests and super responsive to amphetamine. In a battery of specific tests, GluR6 KO mice also exhibited less anxious or more risk-taking type behavior and less despair-type manifestations, and they also had more aggressive displays. Chronic treatment with lithium, a classic antimanic mood stabilizer, reduced hyperactivity, aggressive displays and some risk-taking type behavior in GluR6 KO mice. Hippocampal and prefrontal cortical membrane levels of GluR5 and KA-2 receptors were decreased in GluR6 KO mice, and chronic lithium treatment did not affect these decreases. The membrane levels of other glutamatergic receptors were not significantly altered by GluR6 ablation or chronic lithium treatment. Together, these biochemical and behavioral results suggest a unique role for GluR6 in controlling abnormalities related to the behavioral symptoms of mania, such as hyperactivity or psychomotor agitation, aggressiveness, driven or increased goal-directed pursuits, risk taking and supersensitivity to psychostimulants. Whether GluR6 perturbation is involved in the mood elevation or thought disturbance of mania and the cyclicity of BPD are unknown. The molecular mechanism underlying the behavioral effects of lithium in GluR6 KO mice remains to be elucidated.Molecular Psychiatry 04/2008; 13(9):858-72. DOI:10.1038/mp.2008.20 · 15.15 Impact Factor