The U.S. Food and Drug Administration requires a class warning of increased suicidality risk on all antiseizure medications based on clinical trials completed prior to 2008 that found epilepsy patients had a higher suicidality risk with these medicines than with placebo, researchers note in JAMA Neurology.
The current analysis examined data from phase 2 and 3 studies for five medications approved since 2008 to determine if these drugs also have an increased risk of suicidality.
Researchers examined data from 17 randomized clinical trials with a total of 5,996 patients, including 4,000 who received one of the five newer antiseizure medications - which all currently carry the class warning - and 1,996 who received a placebo.
Overall, there was no increased risk of suicidal ideation with the antiseizure medications versus placebo (overall risk ratio 0.75), nor any increased risk of suicide attempts (ORR 0.75). The analysis also found no increased risk of suicidal ideation or attempted suicide with any of the five medications examined individually.
"The newer antiseizure medications do not deserve to have the class warning of increased suicidality that they currently have," said lead study author Dr. Pavel Klein of the Mid-Atlantic Epilepsy and Sleep Center in Bethesda, Maryland.
"Going forward, each new antiseizure medication should be evaluated individually for suicidality risk, and a suicidality warning should only be applied to the drug if there is a clear evidence for increased suicidality with that particular drug, rather than because it belongs to a class of drugs, such as antiseizure medications," Dr. Klein said by email.
Suicidal ideation occurred among 12 (0.30%) patients on antiseizure medications and 7 (0.35%) patients on placebo, the analysis found.
Three patients on antiseizure medications attempted suicide, while none on placebo did.
Dr. Klein and other study authors have financial ties to several companies that sell antiseizure medications.
One limitation of the study is its small size, another is the lack of standardized suicidality questionnaires in the included studies done before 2011.
In addition, patients with a history of suicidality and uncontrolled psychiatric conditions were excluded from studies used in the current analysis, meaning results would not be generalizable to patients at high risk for suicidality.
Because patients in the current study were at low risk for suicidality, it is not surprising that the analysis didn't identify an increased risk of suicidality associated with antiseizure medications, said Dr. Jakob Christensen of the department of neurology at Aarhus University Hospital in Denmark. Dr. Christensen, who wasn't involved in the study, has financial ties to companies that make antiseizure medications.
"The risk of suicidality is low in persons with treatment refractory epilepsy who did not have suicidal ideation at time of start of treatment," Dr. Christensen said by email. "However, the study does not address the risk in high-risk patients with suicidal ideation."
Even so, the risks associated with untreated epilepsy are high, and antiseizure medications shouldn't be avoided - even in patients who do have psychiatric disorders - Dr. Christensen said.
However, clinicians should assess patients on antiseizure medications for mood disorders, said Mary Jo Pugh of the University of Utah School of Medicine and the VA Salt Lake City Healthcare system.
"Because suicidality is more common among people with epilepsy, clinicians should also evaluate the possibility of suicidality," Pugh, who wasn't involved in the study, said by email. "There is no indication that antiseizure medications should be avoided in patients with a history of depression or suicidal ideation; in fact, data suggests that by controlling seizures, mood improves."
SOURCE: https://bit.ly/3Cce0xZ JAMA Neurology, online August 2, 2021.
By Lisa Rapaport
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