HEALTH NEWS

Study Title:

Neurontin and Suicide Risk

Study Abstract

Context In 2008, the US Food and Drug Administration mandated warning labeling for anticonvulsant medications regarding the increased risk of suicidal thoughts and behaviors. The decision was based on a meta-analysis not sufficiently large to investigate individual drugs.

Objective To evaluate the risk of suicidal acts and combined suicidal acts or violent death associated with individual anticonvulsants.

Design A cohort study of the risk of suicidal acts and combined suicidal acts or violent death in patients beginning use of anticonvulsant medications compared with patients initiating a reference anticonvulsant drug.

Setting and Patients Patients 15 years and older from the HealthCore Integrated Research Database (HIRD) who began taking an anticonvulsant between July 2001 and December 2006.

Main Outcome Measures Cox proportional hazards models and propensity score–matched analyses were used to evaluate risk of attempted or completed suicide and combined suicidal acts or violent death, controlling for psychiatric comorbidities and other risk factors, among individual anticonvulsants compared with topiramate and secondarily carbamazepine.

Results The study identified 26 completed suicides, 801 attempted suicides, and 41 violent deaths in 297 620 new episodes of treatment with an anticonvulsant (overall median follow-up, 60 days). The incidence of the composite outcomes of completed suicides, attempted suicides, and violent deaths for anticonvulsants used in at least 100 treatment episodes ranged from 6.2 per 1000 person-years for primidone to 34.3 per 1000 person-years for oxcarbazepine. The risk of suicidal acts was increased for gabapentin (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.11-1.80), lamotrigine (HR, 1.84; 95% CI, 1.43-2.37), oxcarbazepine (HR, 2.07; 95% CI, 1.52-2.80), tiagabine (HR, 2.41; 95% CI, 1.65-3.52), and valproate (HR, 1.65; 95% CI, 1.25-2.19), compared with topiramate. The analyses including violent death produced similar results. Gabapentin users had increased risk in subgroups of younger and older patients, patients with mood disorders, and patients with epilepsy or seizure when compared with carbamazepine.

Conclusion This exploratory analysis suggests that the use of gabapentin, lamotrigine, oxcarbazepine, and tiagabine, compared with the use of topiramate, may be associated with an increased risk of suicidal acts or violent deaths.

From press release:

An analysis of prescription and clinical claims data suggests that the use of certain anticonvulsant medications may be associated with an increased risk of suicide, attempted suicide or violent death, according to a study in the April 14 issue of JAMA.

Anticonvulsant medications are a primary therapeutic approach for patients with epilepsy, but labeled indications also include bipolar disorder, mania, neuralgia (sudden occurrences of short, sharp pains along a nerve), migraine and neuropathic pain. "The wide range of indications and common use of anticonvulsants in patients with or without psychiatric comorbidities make their safety an issue of great relevance," the authors write. "In 2008, the U.S. Food and Drug Administration mandated warning labeling for anticonvulsant medications regarding the increased risk of suicidal thoughts and behaviors. The decision was based on a meta-analysis not sufficiently large to investigate individual drugs."

Elisabetta Patorno, M.D., M.P.H., of Brigham and Women's Hospital and Harvard Medical School, Boston, and colleagues evaluated whether there was an increased risk of attempted or completed suicide, and combined suicidal acts or violent death associated with a range of individual anticonvulsant medications and within patient subgroups. The researchers analyzed data for 14 states from the HealthCore Integrated Research Database (includes information on filled prescriptions and clinical encounters) for patients 15 years and older who began taking an anticonvulsant between July 2001 and December 2006.

The study identified 827 suicidal acts (801 attempted suicides and 26 completed suicides) and an additional 41 violent deaths (868 combined suicidal acts or violent deaths) in 297,620 new episodes of treatment with an anticonvulsant. The researchers found that the risk of suicidal acts was increased for gabapentin, lamotrigine, oxcarbazepine, tiagabine, and valproate, compared with topiramate. "The analyses including violent death produced similar results. Gabapentin users had increased risk in subgroups of younger and older patients, patients with mood disorders, and patients with epilepsy or seizure when compared with carbamazepine," the authors write

Study Information

Elisabetta Patorno, MD, MPH; Rhonda L. Bohn, MPH, ScD; Peter M. Wahl, MLA, MS; Jerry Avorn, MD; Amanda R. Patrick, MS; Jun Liu, MD, MS; Sebastian Schneeweiss, MD, ScD .
Anticonvulsant Medications and the Risk of Suicide, Attempted Suicide, or Violent Death
JAMA
2010 April
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston.