Vigabatrin for refractory complex partial seizures

Short answer: vigabatrin is approved as an add-on medicine for refractory complex partial seizures in adults and children 2 years and older. It is not a first-line treatment.^1,2 In the dose-finding trial, about half of people taking 3,000 mg a day had their seizures cut by at least half. Because of the risk of permanent vision loss, the label advises stopping it if it has not clearly helped within 3 months.^1,3

Complex partial seizures are a type of focal seizure. "Refractory" means they have not been controlled by other seizure medicines, also called drug-resistant. This page covers what the evidence shows for vigabatrin in this group. The treating neurologist weighs the benefit against the vision risk for each person.

What the label says

Vigabatrin tablets and powder for oral solution are approved as adjunctive (add-on) treatment for refractory complex partial seizures from age 2. They are not meant as a first-line medicine.^1,2 The ready-to-use liquid is not labeled for these seizures; it is labeled only for infantile spasms in babies 1 month to 2 years old.⁴

All vigabatrin products carry a boxed warning for permanent vision loss and are only available through the Vigabatrin REMS program.⁴ See vision loss and REMS.

How well it works

The dose-finding trial

A trial gave 174 people with uncontrolled complex partial seizures either placebo or vigabatrin at 1,000, 3,000 or 6,000 mg a day, on top of their usual medicines. The share of people whose seizures fell by at least half was:³

• Vigabatrin, daily dose
• Placebo

Placebo

7%

1,000 mg a day

24%

3,000 mg a day

51%

6,000 mg a day

54%

174 people with uncontrolled complex partial seizures, added to their usual medicines.

Show as a table

Group	Measure	Value
Dose-finding trial: people with at least 50% fewer seizures	Placebo	7%
Dose-finding trial: people with at least 50% fewer seizures	1,000 mg a day	24%
Dose-finding trial: people with at least 50% fewer seizures	3,000 mg a day	51%
Dose-finding trial: people with at least 50% fewer seizures	6,000 mg a day	54%

The highest dose worked no better than 3,000 mg and more people dropped out on it.³ That is why the label's recommended adult dose is 3,000 mg a day.¹

The Cochrane review

A 2020 Cochrane review pooled 11 trials with 756 people aged 10 to 64 with drug-resistant focal epilepsy.⁵

• People on vigabatrin were about 2.6 times as likely as those on placebo to have their seizures cut by at least half (risk ratio 2.60). The authors rated the certainty of this evidence as low.
• People on vigabatrin were also more likely to stop treatment (risk ratio 2.86).
• Dizziness, fatigue and drowsiness were more common, and depression was about three times as common (risk ratio 3.28).
• The authors say the results should not be applied to children under 10, because the trials did not include them.⁵

Compared with carbamazepine as a first medicine

In a trial of 459 people with newly diagnosed epilepsy, vigabatrin was less effective than carbamazepine at preventing seizures, though it was better tolerated. Weight gain (11% vs 5%) and psychiatric symptoms (25% vs 15%) were more common with vigabatrin. The authors did not recommend it as a first-line treatment.⁶

Dosing in brief

• Adults and children 17 and older: start at 500 mg twice a day, increase by 500 mg a day each week, up to the recommended 1,500 mg twice a day (3,000 mg a day).¹
• Children 2 to 16 years: the dose depends on weight. For example, a child of 10 to 15 kg starts at 350 mg a day and moves to 1,050 mg a day; a child of over 25 to 60 kg starts at 500 mg a day and moves to 2,000 mg a day. Children over 60 kg take adult doses.¹
• Kidney function: doses are lowered when kidney function is reduced, because vigabatrin leaves the body through the kidneys.^1,7

See dosage for the full tables and a calculator.

When to stop

The label advises withdrawing vigabatrin if it has not given a substantial benefit within 3 months.¹ It should not be stopped suddenly. The dose is tapered under the prescriber's direction.⁴

Side effects and vision in adults

Vision loss is the main concern with long-term use. Based on adult studies, the label says 30% or more of patients can be affected, and severe cases can leave tunnel vision.¹ A review of 32 studies found visual field loss in about 52% of exposed adults, and risk rose with total dose.⁸ In 147 adults treated for a median of nearly 8 years, 59% had vigabatrin-related field loss.⁹ Eye checks are required at baseline, at least every 3 months on treatment, and 3 to 6 months after stopping.⁴

Other common effects in adults include drowsiness, dizziness, headache and fatigue. Depression and psychosis were reported more often than with placebo.¹⁰ The brain MRI changes seen in some infants were not seen more often in children or adults treated for complex partial seizures.¹¹ See side effects.

Which form to use

For refractory complex partial seizures, the labeled forms are:

• Tablets: 500 mg film-coated tablets with a score line.¹ See tablets.
• Powder for oral solution: 500 mg packets mixed with water before each dose. The tablet and the oral solution are bioequivalent, meaning they deliver the same amount of drug to the body.¹ See powder sachets.

Many children's doses, such as 175 mg twice a day, cannot be made from whole or half 500 mg tablets, so children are often given the powder.¹ The ready-to-use liquid is not labeled for this use.⁴ See liquid vs powder for how the forms differ.