by Joye C. Anestis
Ok, prepare yourself for this one...the article was hard for me to get through, making it even harder to translate into non-scientific jargon. Medical journals, as opposed to psychology journals, like to make things difficult.
Bipolar disorder is a difficult illness to live with. Among the many difficulties faced by those with this illness is usually a lifetime of medication management. Psychotherapy has been shown to be a useful adjunct to pharmacotherapy, but pharmacological treatment is considered the front-line for bipolar disorder. The most common is lithium, but some alternative medications have been identified as useful in managing bipolar disorder. Specifically, antiepileptic medications are commonly prescribed (on a side note, antiepileptic meds are also commonly prescribed for borderline personality disorder). As you can guess from their name, this class of drugs was originally developed to control seizures in individuals with epilepsy but they also have mood stabilizing effects.
Recently, the Food & Drug Administration (FDA) has questioned the safety of these drugs in regard to suicidality. They conducted a meta-analysis of placebo-controlled trials of 11 antiepileptic drugs (AEDs) - importantly, this meta-analysis examined AED use for any reason, not just psychiatric ones. Results revealed that 0.43% of those treated with AEDs reported suicidal behavior or ideation compared to 0.22% of patients in placebo groups. On January 31, 2008, the FDA issued an alert to healthcare providers about an increase risk for suicidal behavior and ideation with AEDs, and on July 10, 2008, the FDA's scientific advisory committee voted that there was a significant association between suicide and AEDs but voted against a black box warning similar to the one found on antidepressant labels(click here for the FDAs webpage on this topic).
Obviously, increased risk of suicide is always concerning, especially when the risk concerns a population already at elevated risk of suicidality. Without treatment, an estimated 10 per 1000 individuals with bipolar disorder complete suicide annually and 40 per 1000 attempt suicide (Baldessarini et al., 2006). Risk of completed suicide and suicide attempt in bipolar disorder are 100-fold and 10-fold higher, respectively, than the risk of the general population. So it's important to determine if AEDs specifically affect suicide risk in bipolar disorder...it would be troubling to discover that the primary treatment for an illness made those taking it less safe!
A new study by Gibbons, Hur, Brown, & Mann (2009) in Archives of General Psychiatry investigated this very topic and attempted to correct some of the methodological problems found in the FDAs study and other studies on this topic. Gibbons et al. obtained data from a large database of longitudinal medical claims data, representing over 47 million people. All individuals with a diagnosis of bipolar disorder who were enrolled in the same healthcare plan for 1 year before and after the index diagnosis data were included (i.e., they included everyone with the diagnoses continuous data pre- and post-treatment data). 47,918 patient met these criteria, and 1,226 of them had at least one suicide attempt. Analyses were restricted to AED monotherapy, which they defined as taking only 1 of the 11 AEDs in the year following diagnosis and not taking lithium. Other psychiatric medications were included as covariates in the analyses, including concomitant antidepressant, other antiepileptic, antipsychotic use or lithium monotherapy - meaning they could statistically remove the effects from these other treatments in order to examine findings for just the AEDs. For comparison groups, the researchers identified a group of patients who received none of the 11 AEDs or lithium in the year following diagnosis and a group of patients who received no central nervous system (CNS) medication.
Interestingly, the results explicitly contradict the FDA warnings. Gibbons et al. did a lot of complicated analyses, and I've reported just the primary ones below. Please refer back to the original article for more details. But overall they found:
- After treatment, there was no significant difference in suicide attempt rates for those treated with an AED and those received no AED or lithium.
- When each individual AED was examined, similar findings appeared with 2 exceptions, topiramate and carbamazepine, which had significantly greater post-treatment risk than no treatment.
- A small but significant increase was found with lithium compared with no treatment. Overall, AEDs were associated with lower suicide attempts than lithium.
- When they did within-subjects comparisons, rate of suicide attempt was significantly greater prior to any AED treatment than after. Similar reductions were found for the individual AEDs and lithium, except for topiramate and carbamazepine. Also, interestingly, the pretreatment suicide attempt rate was significantly higher for the group that ultimately received an AED than the no-treatment suicide attempt rate, indicating the the AED group was potentially more impaired prior to treatment.
- Suicide attempt rate for patients not treated with any CNS drug was significantly higher than those who received an AED only.
- Sensitivity analyses revealed that these effects were maintained for the duration of treatment. They were also found when looking at single attempters and multiple attempters.
So, in sum, it appears that AEDs are not associated with increased suicide attempt risk in folks with bipolar disorder. Certainly, a number of limitations exist in the present study, including the use of medical claims data which likely underreport suicide attempts, no information on completed suicides (just attempts), no data on intensity of treatment, lack of random assignment to treatment, reliance on diagnoses from the database and not from structured interviews, no consideration of treatment adherence, and the fact that patients could have had a concomitant illness (such as epilepsy) for which the AED was prescribed. Despite all of this, it is remarkable that the AED group had such higher rates of suicide attempts prior to treatment and still achieved lower rates post-treatment, compared to the control groups. Hopefully, the FDA will consider these findings, and any future data that may emerge on this topic, as they issue warnings.
For more information on suicide and bipolar disorder, check out our online bookstore.