Relationship Between Antiepileptic Drugs and Suicide Attempts in Patients With Bipolar Disorder

Center for Health Statistics, University of Illinois at Chicago, Chicago, IL 60614, USA.
Archives of general psychiatry (Impact Factor: 14.48). 12/2009; 66(12):1354-60. DOI: 10.1001/archgenpsychiatry.2009.159
Source: PubMed


On January 31, 2008, the Food and Drug Administration issued an alert regarding increased risk of suicidal thoughts and behavior related to use of antiepileptic drugs (AEDs). On July 10, 2008, a Food and Drug Administration scientific advisory committee voted that, yes, there was a significant positive association between AEDs and suicidality but voted against placing a black box warning on AEDs for suicidality.
To determine if AEDs increase the risk of suicide attempt in patients with bipolar disorder.
A pharmacoepidemiologic study in which suicide attempt rates were compared before and after treatment and with a medication-free control group. Analyses were restricted to AED and lithium monotherapy.
We used the PharMetrics medical claims database to study the relationship between the 11 AEDs identified in the FDA alert, and lithium, to suicide attempts.
Suicide attempts. Patients A cohort of 47 918 patients with bipolar disorder with a minimum 1-year window of information before and after the index date of their illness.
Overall, there was no significant difference in suicide attempt rates for patients treated with an AED (13 per 1000 person-years [PY]) vs patients not treated with an AED or lithium (13 per 1000 PY). In AED-treated subjects, the rate of suicide attempts was significantly higher before treatment (72 per 1000 PY) than after (13 per 1000 PY). In patients receiving no concomitant treatment with an antidepressant, other AED, or antipsychotic, AEDs were significantly protective relative to no pharmacologic treatment (3 per 1000 vs 15 per 1000 PY).
Despite Food and Drug Administration reports regarding increased risk of suicidality associated with AED treatment, the current study reveals that, as a class, AEDs do not increase risk of suicide attempts in patients with bipolar disorder relative to patients not treated with an AED or lithium. Use of AEDs reduces suicide attempt rates both relative to patients not receiving any psychotropic medication and relative to their pretreatment levels.

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Available from: J. John Mann, Aug 11, 2014
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    • "), and others being opposed (Gibbons and others 2009; VanCott and others 2010). "
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    ABSTRACT: Introduction: This report from the World Psychiatric Association Section on Pharmacopsychiatry examines the possible relationship of antiepileptic drugs with suicide-related clinical features and behaviors in patients with epilepsy. Materials and methods: A systematic review of the MEDLINE search returned 1039 papers, of which only 8 were considered relevant. A critical analysis of the Food and Drug Administration (FDA) report on the increase risk for patients under antiepileptics to manifest suicidality is also included in this report. Results: The analysis of these studies revealed that the data are not supportive of the presence of a "class effect" on suicide-related behavior; on the contrary, there are some data suggesting such an effect concerning treatment with topiramate, lamotrigine, and levetiracetam for which further research is needed. Discussion: For the majority of people with epilepsy, anticonvulsant treatment is necessary and its failure for any reason is expected to have deleterious consequences. Therefore, clinicians should inform patients and their families of this increased risk of suicidal ideation and behavior, but should not overemphasize the issue. Specific subgroups of patients with epilepsy might be at a higher risk, and deserve closer monitoring and follow-up. Future research with antiepileptics should specifically focus on depression and suicidal thoughts.
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    • "Since the release of the warning, a number of observational studies have investigated the association between AEDs and suicidality [6] [7] [8] [9] [10] [11]. These results have been conflicting with some studies reporting an increased risk of suicidality [6] [7] [8] [9] while others reporting no increased risk [10] [11]. "
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    ABSTRACT: In January 2008, the Food and Drug Administration (FDA) communicated concerns and, in May 2009, issued a warning about an increased risk of suicidality for all antiepileptic drugs (AEDs). This research evaluated the association between the FDA suicidality communications and the AED prescription claims among members with epilepsy and/or psychiatric disorder. A longitudinal interrupted time-series design was utilized to evaluate Oklahoma Medicaid claims data from January 2006 through December 2009. The study included 9289 continuously eligible members with prevalent diagnoses of epilepsy and/or psychiatric disorder and at least one AED prescription claim. Trends, expressed as monthly changes in the log odds of AED prescription claims, were compared across three time periods: before (January 2006 to January 2008), during (February 2008 to May 2009), and after (June 2009 to December 2009) the FDA warning. Before the FDA warning period, a significant upward trend of AED prescription claims of 0.01% per month (99% CI: 0.008% to 0.013%, p<0.0001) was estimated. In comparison to the prewarning period, no significant change in trend was detected during (-20.0%, 99% CI: -70.0% to 30.0%, p=0.34) or after (80.0%, 99% CI: -20.0% to 200.0%, p=0.03) the FDA warning period. After stratification, no diagnostic group (i.e., epilepsy alone, epilepsy and comorbid psychiatric disorder, and psychiatric disorder alone) experienced a significant change in trend during the entire study period (p>0.01). During the time period considered, the FDA AED-related suicidality warning does not appear to have significantly affected prescription claims of AED medications for the study population.
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    • "Moreover, literature data on this issue are conflicting. Other investigators[14] found opposite results: None increase the risk of suicide attempts in patients with bipolar disorder treated with AEDs compared to patients treated without AEDs, but a reduction of suicide attempt rates in patient with AEDs was observed. The question whether the FDA alert was a fire or a false alarm is still unsolved. "
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