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PubMed Clinical Q&A [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2008-2013.

PubMed Clinical Q&A [Internet].

Comparing Antiepileptics for Bipolar Disorder, Migraines, Fibromyalgia, and Chronic Pain

Laura Dean, MD.

National Center of Biotechnology Information (NCBI)

Created: October 1, 2010.

Antiepileptic drugs first became available in the 1960s when they were used to treat seizure disorders. It is not known exactly how they work, but they are thought to depress abnormal firing of neurons in the central nervous system.

Antiepileptics have since been used to treat other disorders, including bipolar disorder, migraines, fibromyalgia, and chronic pain. Often, antiepileptics are taken in combination with other drugs to try to further improve symptoms that have not been effectively managed by prior treatments.

The "Drug Class Review on Antiepileptic Drugs for Indications Other Than Epilepsy" compares the safety and effectiveness of 13 drugs. A summary of the findings is below.

How do antiepileptics compare in treating bipolar disorder?

For manic or mixed episodes:

  • Acute treatment: Symptoms are improved by carbamazepine (immediate and extended release forms) and valproate.
  • Maintenance: Lamotrigine, immediate-release carbamazepine and valproate have been found to reduce the risk of relapse.
  • Evidence is either lacking or does not the support the use of other antiepileptics. [details]

For bipolar depression:

How do antiepileptics compare in treating fibromyalgia?

For the treatment of fibromyalgia:

  • Acute treatment: Compared to placebo, both pregabalin and gabapentin have been found to significantly increase patients’ chances of experiencing at least a 30% or greater reduction in pain. Whereas, only pregabalin, at doses of 450-600 mg, has significantly increased patients’ chances of experiencing at least a 50% or greater reduction in pain. For example, at a maximum dose of 600mg, 30% of patients taking pregabalin had a 50% or greater reduction in pain compared to only 15% with placebo (NNT=7).
  • Maintenance: Pregabalin is the only antiepileptic drug with evidence of significantly prolonging time to loss of therapeutic response compared to placebo (34 days vs. 7 days, P<0.001). [details]

How do antiepileptics compare in preventing migraines?

The following antiepileptics, compared to placebo, have been found to reduce the frequency of migraine attacks by at least 50%: carbamazepine, gabapentin, topiramate and valproate. [details]

How do antiepileptics compare in relieving chronic pain?

When added to ongoing treatment with analgesics or antidepressants, patients taking either gabapentin or tiagabine had similar reductions in pain scores after 3 months (-2.3 points vs. -1.2 points on an 11-point scale). But, improvements in sleep ratings were significantly greater for tiagabine.

Although topiramate has not been directly compared to any other antiepileptic drug in a head-to-head trial, it has at least been found to be superior to placebo in improving pain. [details]

How do antiepileptics compare in safety?

Suicide risk: Lamotrigine and topiramate increase the risk of suicide relative to placebo. Compared to lithium, both valproate and carbamazepine have been found to increase the risk of suicide attempts resulting in hospitalization. Evidence is lacking for other antiepileptics. [details]

Fractures: Compared to no use of an antiepileptic drug, risk of fracture at any site is significantly increased in patients taking carbamazepine, oxcarbazepine, and valproate. Whereas, for lamotrigine, phenytoin, tiagabine, and topiramate, the increase in risk is not significant. [details]

Birth defects: Compared to the general population, the risk of birth defects is doubled from exposure to older antiepileptics during the first trimester of pregnancy (risk of 4-10%). Data are too limited for the newer antiepileptics, gabapentin, levetiraetam, and topiramate, to draw conclusions about risk of birth defects. [details]

Serious skin reactions: Evidence suggests that short-term risk of serious skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis is similarly high for carbamazepine and phenytoin. [details]

Agranulocytosis: Carbamazepine and valproate have both been associated with significant increases in the risk of agranulocytosis, which is a rare but dangerous sudden drop in white blood cell count. [details]

Do patient factors such as age or gender influence the effectiveness and harms of antiepileptics?

In bipolar disorder:

  • Valproate: treatment response was not found to be associated with age, sex and ethnicity. But patients experiencing mixed episodes may respond better than those experiencing manic episodes.
  • Lamotrigine: age does not appear to affect relapse of mood disorders. However, the response to lamotrigine may be better in males who have had fewer trials of taking the drug compared with those who have had many (the difference was not significant in females).
  • Gabapentin: treatment response appears to be better in younger patients with a lower baseline weight.
  • Carbamazepine: patients experiencing manic episodes may respond better to carbamazepine than those experiencing mixed episodes.

In patients with fibromyalgia, pregabalin improves pain relief regardless of the presence of depression and anxiety.

There is insufficient evidence to assess the impact of patient factors on treatment for chronic pain and migraines. [details]

Drugs included in this review

Generic NameTrade Names
CarbamazepineTegretol
Carbatrol
Equetro
Divalproex sodiumDepakote
Epival
EthotoinPeganone
GabapentinNeurontin
LamotrigineLamictal
LevetiracetamKeppra
OxcarbazepineTrileptal
PhenytoinDilantin
PregabalinLyrica
TiagabineGabitril
TopiramateTopamax
ValproateDepakene
Depacon
ZonisamideZonegran

Further information

Image th-antiepi.jpgThis PubMed Clinical Q&A was reviewed by Kimberly Peterson, MS.

For the full report and evidence tables, please see:
McDonagh M, Peterson K, Lee N, et al. Drug Class Review: Antiepileptic Drugs for Indications Other Than Epilepsy: Final Report Update 2 [Internet]. Portland (OR): Oregon Health & Science University; 2008 Oct. Available at: http://www.ncbi.nlm.nih.gov/books/NBK10371/.