Comparison of Levetiracetam and sodium Valproate in migraine prophylaxis

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SCIENCE
Comparison of Levetiracetam and sodium Valproate in migraine prophylaxis
Key Take-Away: 
  • New drug levetiracetam shows comparable efficacy to currently used drugs such as valproate in migraine prophylaxis

  • Levetiracetam significantly reduces headache frequency in patients with migraine

Migraine is a common neurological disorder. It is categorized as migraine with aura (classic migraine) and migraine without aura (common migraine). Pharmacological treatment of migraine consists of prophylactic (preventive) treatment and symptomatic (abortive) treatment.

ABSTRACT: 
Background: 

Migraine is a common neurological disorder. It is categorized as migraine with aura (classic migraine) and migraine without aura (common migraine). Pharmacological treatment of migraine consists of prophylactic (preventive) treatment and symptomatic (abortive) treatment.

The symptomatic therapy of migraine ranges from simple analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen to triptans or the less commonly used dihydroergotamine. Frequent, severe, disabling and long-lasting migraine attacks require prophylaxis. The prophylactic therapy in both migraine without aura and migraine with aura consists of beta-blockers, calcium-channel blockers, partial serotonin agonists, tricyclic agents and antiepileptic agents such as gabapentin, valproate and topiramate.

Levetiracetam, a broad spectrum anti-epileptic used in many seizure types in children and adults with an excellent tolerability profile, have also been used in migraine prophylaxis.

Studies have shown that levetiracetam has been effective in prophylactic treatment of migraine in elderly and adult patients. It has also been shown to be promising in refractory chronic migraine and for migraine with aura with high frequency of attacks.

  • Rationale behind research

While all these drugs are effective in prophylactic treatment of migraine but newer drugs also emerged to be effective and also shown to be promising effect in refractory chronic migraine and for migraine with aura with high frequency of attacks

Objective

To assess the efficacy and tolerability of levetiracetam in adult migraine prophylaxis compared to valproate and placebo.

Methods: 

  • Study outcomes
  • Treatment efficacy was assessed as a more than 50% decrease in headache frequency (per month attacks) in the last visit (after 6 months).

  • Measure of treatment outcome because all patients with a 50% decrease in attack frequency considered this as an improvement in their quality of life.

  • Time-points

    • Efficacy : Baseline, 1, 3 and 6 months

Results: 

  • Outcome:

  • In levetiracetam group, 17 (63.0%) patients experienced a more than 50% decrease in headache frequency, while this efficacy number was 21 (65.6%) for valproate group and 4 (15.4%) for placebo group.

  • The difference was not statistically significant between levetiracetam and valproate, while it was significant when comparing either levetiracetam or valproate to placebo.

  • Twenty-three patients (85.2%) reported no side effects on levetiracetam, while this figure was 22 (68.8%) in VPT group. The most frequent side effects in LEV group were somnolence and dizziness, mild irritability, hostility, moodiness, and hyperactive behavior.

   

 Figure 1: Number of headache attacks before and 6 months after  treatment

Conclusion: 

Compared to placebo, levetiracetam offers improvement in headache frequency in patients with migraine. The efficacy of levetiracetam in migraine prophylaxis is comparable to currently used standard drugs such as valproate. In this study, we observed after 6 months, both levetiracetam and valproate significantly reduced attacks frequency, compared to placebo (which was inefficient in this regard).

They also significantly increased the number of patients with a successful outcome (more than 50% decrease in monthly attacks), compared to placebo. However, not all antiepileptic drugs are useful in clinical practice for the prophylaxis of migraine. Also, an approximate 85% of patients fully tolerated levetiracetam during the treatment course. According to Linde et al., review showed that efficacy of antiepileptic drugs other than gabapentin, pregabalin, topiramate and valproate in the prophylaxis of episodic migraine among adults. However, they observed that in some trials, levetiracetam was significantly superior to placebo in reducing headache frequency, a finding supported by two other studies.

Ann Indian Acad Neurol. 2015 Jan-Mar; 18(1): 45–48
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