Epilepsy drugs including the widely used carbamazepine, gabapentin, Pregabalin, levetiracetam, topiramate can lead to suicide among patients using them, warned USFDA.
US FDA now requires that all manufacturers of anti-epileptic to include a warning in their labeling and develop a Medication Guide to be provided to patients prescribed these drugs to inform them of the risks of suicidal thoughts or actions.
US FDA has completed its analysis of reports of suicidality (suicidal behavior or thoughts) from placebo-controlled clinical trials of drugs used to treat epilepsy, psychiatric disorders, and other conditions.
The risk of suicidal thoughts or behavior was generally consistent among the eleven drugs analyzed and was observed in patients who were treated for epilepsy, psychiatric disorders, and other conditions.
The relative risk for suicidal thoughts or behavior was higher in the clinical trials for epilepsy compared to trials for psychiatric or other conditions.
The increased risk was observed as early as one week after starting antiepileptic drug treatment and throughout the observed duration of treatment.
However, the absolute risk differences were similar in the clinical trials for epilepsy and psychiatric indications.
The increased risk of suicidal thoughts or behavior was generally consistent among the eleven drugs — Carbamazepine (Carbatrol, Equetro, Tegretol, Tegretol XR); Divalproex sodium (Depakote, Depakote ER); Felbamate (Felbatol); Gabapentin (Neurontin); Lamotrigine (Lamictal); Levetiracetam (Keppra); Oxcarbazepine (Trileptal); Pregabalin (Lyrica); Tiagabine (Gabitril); Topiramate (Topamax) and Zonisamide (Zonegran) — with varying mechanisms of action and across a range of indications.
US FDA suggested that the increased suicide risk applies to all antiepileptic drugs used for any indication.
US FDA’s pooled analyses of 199 clinical trials of eleven antiepileptic drugs used as mono- and adjunctive therapies showed that patients who were randomized to receive one of the antiepileptic drugs had almost twice the risk of suicidal behavior or ideation (0.43%) compared to patients randomized to receive placebo (0.24%).
This increase in the risk of suicidal thoughts or behavior represents the occurrence of approximately one additional case of suicidal thinking or behavior for every 530 patients treated with an antiepileptic drug.
All patients who are currently taking or starting on any antiepileptic drug for any indication should be monitored for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression, US FDA said.
However, US FDA made it clear that it did not advice health care professionals to discontinue prescribing anti-epileptic drugs.
All patients treated with antiepileptic drugs should be monitored for the emergence or worsening of depression, suicidal behaviors and other unusual changes in behavior. Symptoms such as anxiety, agitation, aggression, hostility, mania and insomnia may be precursors to emerging suicidality.
US FDA alerted patients that medicines that have been prescribed should not be stopped or changed without first talking with the healthcare professional responsible for care. Stopping these medicines suddenly can cause serious problems.
Health care workers and patients should pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences.
they should be aware of common warning signs that might be a signal for risk of suicidal behavior. Some of these are: talking or thinking about wanting to hurt one’s self or end one’s life; becoming preoccupied with death and dying; becoming depressed or having depression get worse; withdrawing from friends and family; giving away prized possessions etc.
FDA has completed its review and analysis of data from 199 placebo-controlled clinical studies for the incidence of suicidal behavior (completed suicides, suicide attempts and preparatory acts) and suicidal ideation. These studies examined the effectiveness of eleven different antiepileptic drugs used as mono- and adjunctive therapies in epilepsy, psychiatric disorders (e.g., bipolar disorder, depression and anxiety) and other conditions (e.g., migraine and neuropathic pain syndromes) and included a total of 43,892 patients ages five and older (27,863 in drug treatment groups and 16,029 in placebo groups).
Patients randomized to receive one of the antiepileptic drugs had almost twice the risk of suicidal thinking or behavior compared to patients randomized to a placebo group (adjusted relative risk 1.8, 95% CI: 1.2, 2.7). The estimated incidence of suicidal behavior or suicidal ideation in the 27,863 antiepileptic drug treated patients was 0.43% compared to 0.24% for the 16,029 placebo treated patients. This increase in the risk of suicidal thoughts or behavior represents the occurrence of approximately one additional case of suicidal thinking or behavior for every 530 patients treated with an antiepileptic drug.
The approved anti-epileptic drugs affected by these safety label changes are Carbatrol, Celontin, Depakene, Depakote ER, Depakote sprinkles, Depakote tablets, Dilantin, Equetro, Felbatol, Gabitril, Keppra, Keppra XR, Klonopin, Lamictal, Lyrica, Mysoline, Neurontin, Peganone, Stavzor, Tegretol, Tegretol XR, Topamax, Tranxene, Tridione, Trileptal, Zarontin, Zonegran, and generics.