Antiepileptic drugs and suicide-related outcomes in bipolar disorder: A descriptive review of published data

Abstract

Introduction:In January 2008 the US Food and Drug Administration issued a warning to healthcare professionals about the potential for an increased risk of suicidal thinking and behavior associated with antiepileptic drugs (AEDs). Given that AEDs are important for treating bipolar disorder (BD), a better understanding of suicide-related events is necessary.Methods:A PubMed search was performed using the following search terms: anticonvulsant OR valpro* OR carbamazepine OR lamotrigine OR oxcarbazepine OR topiramate AND bipolar AND suicid*. The objective was to identify published investigations reporting rate and/or risk data of suicide-related outcomes in BD patients treated with AED monotherapy.Results:The search identified 323 reviewable citations, with 13 of these studies (4.0%) being reviewed. Valproate was studied most often, and lithium treatment was frequently used as a reference group. Carbamazepine and lamotrigine had small treatment exposure durations. Suicide attempts and suicide deaths were studied the most; a few trials investigated suicidal thinking and/or hospitalizations for suicidal behavior. Suicide attempt rates occurred in the following order: no treatment > carbamazepine > valproate > lithium, while suicide death rates were: no treatment > valproate > lithium > carbamazepine. For valproate, the risk of suicide attempts and suicide death appeared higher than lithium, but lower than no treatment.Discussion:Investigating suicide-related events for AEDs in BD is difficult; more data are necessary for valproate, carbamazepine, and lamotrigine. An improved understanding of AED treatment and suicide-related events in BD may help pharmacists become more effective at supporting their patients with BD.

Relative toxicity of mood stabilisers and antipsychotics: case fatality and fatal toxicity associated with self-poisoning

“…While people with bipolar disorder have an elevated risk of taking prescribed drugs in overdose, [23] it is also important to recognise that risks of both suicide and non-fatal self-poisoning are elevated in people with epilepsy [8, 24]. Although antiepileptic drugs in general may not lead to higher rates of suicidal behaviour, carbamazepine has been found to be associated with increased levels of suicide attempts compared to other anti-epileptics [25] and carbamazepine is related to a higher risk of suicide attempts in bipolar disorder [26]. Carbamazepine also interacts with other drugs, which may increase its toxicity [27].…”

Suicide Risk in Bipolar Disorder: A Brief Review

“…On the other hand, the concern of the FDA about the potential for an increased risk of suicidality associated with anticonvulsants seems not to be applicable to patients with BD (i.e., in this population the use of these agents is not associated with increased levels of suicidality). According to our current knowledge, in regard to suicide prevention lithium is superior than these agents [2,8,15,41,43,44].…”

Trends in Prescriptions of Lithium and Other Medications for Patients with Bipolar Disorder in Office-based Practices in the United States: 1996-2015

“…Gitlin, 2018; Lindstrom, Lindstrom, Nilsson, & Hoistad, 2017; Weisler, Cutler, Ballenger, Post, & Ketter, 2006). However, anticonvulsants and antipsychotics may be less effective than lithium in preventing the recurrence of mood episodes or in reducing the overall risk of suicide (Caley, Perriello, & Golden, 2018; Kessing, Sondergard, Kvist, & Andersen, 2005). In addition, the appropriate clinical use of antidepressants in BPD remains uncertain (M. J.…”