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: 13.75). 12/2009; 66(12):1354-60. DOI: 10.1001/archgenpsychiatry.2009.159
Source: PubMed

ABSTRACT 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: Abstract Introduction This Report from the WPA Section on Pharmacopsychiatry examines the possible relationship of antiepileptic drugs with suicide-related clinical features and behaviours in patients with epilepsy. Material and methods A systematic review of the MEDLINE search returned 1039 papers, of which only 8 were considered relevant. A critical analysis of the 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 behaviour; 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 sub-groups 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.
    International Journal of Psychiatry in Clinical Practice 12/2014; DOI:10.3109/13651501.2014.1000930 · 1.31 Impact Factor
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    • "As a result, the US Food and Drug Administration issued a warning on antiepileptic drugs highlighting the increased risk of suicide and suicidal thoughts in 2008. However, a number of reports had also suggested that antiepileptic drugs are not associated with suicidality [2] [3] [4] [5] [6]. In 2012, the task force of the Commission on Neuropsychobiology of the International League Against Epilepsy had collected opinions and recommended cautious use of antiepileptic drugs with investigation for suicidal risk and, if necessary, referring for psychiatric consultation, but concluded the actual suicidal risk is yet to be established [7]. "
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    ABSTRACT: New antiepileptic drugs have been known to increase the risk of suicide. Among them, levitracetam is a widely used antiepileptic drug approved as a monotherapy treatment for partial seizures or as an adjunctive therapy for partial, myoclonic and generalized tonic-clonic seizures. It has been reported that the incidence of suicidal ideation during treatment with levitracetam was about 0.5-0.7%, but an explanation regarding a mechanism by which it causes suicidality is lacking. We made a multifaceted approach using the Hamilton depression rating score (HDRS), the Hamilton anxiety rating score (HARS), the Beck Hopelessness Scale (BHS), the Barratt Impulsiveness Scale (BIS), the Beck Scale for Suicidal ideation(BSS) daily and the Sheehan Suicidality Tracking Scale (SSTS) weekly in a patient taking levitracetam who acutely developed suicidal ideation after starting the medication. Suicidal ideation disappeared within 5 days of levitracetam discontinuation. We found decreasing HDRS and BHS socres were correlated with BSS, SSTS scores. On the other hand, HARS and BIS did not change from their baselines. Our findings suggest that suicidality induced by an antiepileptic drug may be related to depression rather than anxiety and impulsiveness.
    General hospital psychiatry 01/2013; 36(3). DOI:10.1016/j.genhosppsych.2013.12.002 · 2.90 Impact Factor
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    • "In addition, suicidal prevalence must also be taken in the context of treatment with AEDs. Although there is conflicting literature, the majority of recent articles support a potential increased relative risk for suicidal ideation and behaviors when AEDs are used to treat epilepsy, psychiatric disorders, and/or other conditions (presumptively pain syndromes); further, the literature suggests that this increased risk may be AED selective [26] [27] [28] [29] [30] [31] [32] [33] [34] [35]. The variances in literature-reported prevalence of psychiatric disorders in PWE represent methodological flaws (especially lack of established diagnostic criteria, controls, and standardized psychometric instruments) and sample populations: comparative prevalence rates between underdeveloped (poor-resource) countries and developed (industrialized) countries may be strongly impacted by the increased treatment gap in underdeveloped countries with concomitant increased seizure frequency and chronic active epilepsy ; specific cultures in which epilepsy and/or psychiatric disorders are stigmatized may have disproportionate prevalence rates; population-based studies compared with community-based samples , representing general and specialist practices, have a lower prevalence; tertiary centers or specific populations (refractory epilepsy, mesial temporal sclerosis, or postsurgical PWE) have a higher prevalence [7,23,36–43]. "
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    ABSTRACT: The clinical interface between psychiatry and neurology is epilepsy; the pharmacological expression of this interface is antiepileptic drugs (AEDs), as they are used to treat both epilepsy and psychiatric disorders, especially bipolar disorders. The prevalence of psychiatric comorbidity and the risk of suicidal behavior/ideation/suicide are markedly increased in patients with epilepsy (PWE). Though AEDs receive initial indications for the treatment of epilepsy, currently the majority of AEDs are used to treat pain and psychiatric disorders. Thus in selecting the appropriate AEDs for treatment of PWE, consideration should be given to which AEDs best treat the epileptic disorder and the psychiatric comorbidity. This review is an overview of 21 AEDs in which negative psychotropic properties, approved indications in psychiatry, off-label studied uses in psychiatry, and principal uses in psychiatry are presented with literature review. A total of 40 psychiatric uses have been identified. Of the 21 AEDs reviewed, only 5 have U.S. Food and Drug Administration and/or European Medicines Agency psychiatric approval for limited uses; the majority of AEDs are used off-label. Many of these off-label uses are based on case reports, open-label studies, and poorly controlled or small-sample-size studies. In some instances, off-label use persists in the face of negative pivotal trials. Further placebo-controlled (augmentation and monotherapy) parallel-arm research with active comparators is required in the complex field of AED treatment of psychiatric disorders to minimize the treatment gap not only for PWE with psychiatric disorders, but also for psychiatric patients who would benefit from properly studied AEDs while minimizing adverse effects.
    Epilepsy & Behavior 05/2011; 21(1):1-11. DOI:10.1016/j.yebeh.2011.03.011 · 2.06 Impact Factor
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