Despite government warnings about an increased risk of suicidal thoughts and actions while taking antiepileptic drugs, these medications do not appear to be associated with increased risk of suicide attempts in individuals with bipolar disorder, and may have a possible protective effect, according to a report in the December issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
Antiepileptic drugs are life-saving for those with seizure disorders and are also used to treat many other conditions, including mood disorders and nerve pain, the authors write as background information in the article. The 11 antiepileptic drugs include gabapentin, pregabalin, topiramate and carbamazepine. "On Jan. 31, 2008, the Food and Drug Administration issued an alert regarding increased risk of suicidal thoughts and behavior related to use of antiepileptic drugs," the authors write. "On July 10, 2008, a Food and Drug Administration scientific advisory committee voted that, yes, there was a significant positive association between antiepileptic drugs and suicidality but voted against placing a black box warning on antiepileptic drugs for suicidality."
Individuals with bipolar disorder -- often treated with antiepileptic drugs -- have a higher risk of attempted and completed suicide than the general population. "That makes this a population of interest in detecting the effect on suicide risk of antiepileptic drugs compared with a no-treatment control group," the authors write. Robert D. Gibbons, Ph.D., of the University of Illinois at Chicago, and colleagues studied a cohort of 47,918 patients with bipolar disorder who had at least one year of data before and after their diagnosis in a national database of medical claims.
A total of 13,385 patients received one of 11 antiepileptic drugs and 25,432 received neither antiepileptic medications nor lithium. After treatment, those taking antiepileptic medication had similar rates of suicide attempts (13 per 1,000 patients per year) as those taking lithium (18 per 1,000 patients per year) or those who did not receive treatment (13 per 1,000 patients per year).
Among those taking antiepileptic drugs, the rate of suicide attempt was significantly lower after treatment (13 per 1,000 patients per year) than before treatment (72 per 1,000 patients per year). In patients who were not receiving treatment with another antiepileptic, an antidepressant or an antipsychotic medication, taking any antiepileptic mediation appeared protective against suicide attempts relative to no pharmacologic treatment (three per 1,000 suicide attempts per patient per year vs. 15 per 1,000 per patient per year).
"Our analysis also reveals that there is a selection effect, in that the pretreatment suicide attempt rate is five times higher than the rate in untreated patients," the authors write. "If pretreatment suicide attempt rates reflect the severity of illness, it is the more severely impaired patients who receive treatment with an antiepileptic drug or lithium. Nevertheless, the post-treatment suicide attempt rate is significantly reduced relative to their elevated pretreatment levels to the level found at or below patients not receiving treatment. This finding suggests a possible protective effect of antiepileptic drug treatment on suicidality."
This study was supported by grants from the National Institute of Mental Health and a grant from the Agency for Healthcare Research and Quality.
- Robert D. Gibbons; Kwan Hur; C. Hendricks Brown; J. John Mann. Relationship Between Antiepileptic Drugs and Suicide Attempts in Patients With Bipolar Disorder. Arch Gen Psychiatry, 2009; 66 (12): 1354-1360 [link]
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