Antiepileptic drugs (AEDs, also known as anticonvulsant medications) have a prominent role in the treatment of several types of chronic pain, particularly relating to neuropathy and fibromyalgia. Yet, there have been strong concerns about suicide risks associated with these medications and a new review article examines the relatively weak evidence behind this apprehension.
The recent research on suicidality and AEDs and discuss implications for the treatment of neuropathic pain and fibromyalgia. According to background information in their article, gabapentin and pregabalin are recommended as first-line treatments for various neuropathic conditions, while carbamazepine and oxcarbazepine are commonly used in trigeminal neuralgia, and other AEDs are considered second- or third-line treatments for neuropathic pain. Additionally, pregabalin is recommended for fibromyalgia, and topiramate and valproic acid are considered first-line treatments for migraine prophylaxis.
Given the major role of AEDs in pain management, it is important to consider findings regarding these medications and suicidality, which includes both suicidal ideation and actual suicidal behavior. Furthermore, the researchers note that chronic pain it is also associated with suicidality, and as many as 50% of patients with chronic pain have comorbid depression, which is a well-established risk factor for suicide.
Three articles were discovered as demonstrating increased suicidality risks of AEDs:
- The first article was a large meta-analysis conducted by the FDA that focused on 199 placebo-controlled trials of 11 AEDs and included a total of nearly 44,000 patients. Approximately half of the patients had epilepsy or psychiatric disorders (52%), and the remainder were classified as having “other” conditions, including obesity, insomnia, migraine, and various pain disorders. Based on adjusted risk estimates, 0.43% of patients in the AED groups had suicidal ideation or behavior vs. 0.24% in the placebo groups. The FDA concluded that AEDs appeared to increase the risk of suicidality regardless of treatment indication, specific AED, or mechanism of action, and that increased risk was observed as early as one week after treatment initiation and continued for at least 24 weeks. The odds ratio for increased suicidality risk in the “other” group in the FDA meta-analysis, which included patients with various pain conditions, was a moderate 1.87 (95% Confidence Interval, 0.81-4.76), but this was not statistically significant. Patients in this group were taking divalproex, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, topiramate, or zonisamide.
- A Danish study assessed 6,780 suicides compared with a cohort of 169,725 treatments-naïve patients. The cohort population consisted of patients with epilepsy, psychiatric disorders, and those taking opioids, presumably for chronic pain. The authors concluded that valproate, lamotrigine, clonazepam, and phenobarbital may increase the risk of suicide shortly after treatment initiation.
- A third investigation, using a medical claims database, was an observational study of 297,620 patients treated for various neurologic and psychiatric conditions. Suicidal acts and violent death were compared in patients beginning AEDs and those taking topiramate, the reference AED. Various statistical analyses demonstrated that several AEDs, including gabapentin, increased the risk of suicidal acts. Of particular interest, nearly 17% of the gabapentin group were being treated for neuropathic pain; whereas, less than 1% were treated for epilepsy.
The risk of suicidality can be evaluated in patients initiating AED therapy for pain and periodically thereafter, the authors suggest. This would be especially appropriate in those with evidence of past or current suicidality, past or present mood disorders, and other risk factors for suicidality, including treatment with antidepressant medications in individuals under the age of 25.
by
Dr.Akshaya Srikanth,
Pharm.D India
Good work................
ReplyDelete