As of 2003, vigabatrin is approved in Mexico for the treatment of epilepsy that is not satisfactorily controlled by conventional therapy (adjunctive or monotherapy) or in recently diagnosed patients who have not tried other agents (monotherapy).
Fechtner et al found in an eight week study that vigabatrin was effective in the treatment of cocaine and/or methamphetamine dependence. Twenty-eight subjects were enrolled; only twenty stayed after the escalation phase and out of those, only eighteen completed the study and follow-up. Out of those, sixteen subjects tested negative for cocaine and methamphetamine during the last six weeks. No ocular adverse effects were noted.
In November of 2001, a team of scientists lead by Peter Zwanzger of the University of Munich reported that vigabatrin reduced cholecystokinin tetrapeptide-induced symptoms of panic disorder, in addition to elevated cortisol and ACTH levels, in healthy volunteers.
In 1994, Feucht and Brantner-Inthaler reported that vigabatrin reduced seizures by 50-100% in 85% of children with Lennox-Gastaut syndrome who had poor results with a valproate.
In 1984, a double-blind crossover-study of six Huntington's disease patients—five of them on antipsychotics—reported that vigabatrin did little, if anything, to improve hyperkinetic movements, the ability to carry out daily activities, or normalize motor function.
Mechanism of action
Vigabatrin is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the catabolism of GABA, which increases the level of GABA in the synapses.
Vigabatrin is a racemic compound, and its [S]-enantiomer is pharmacologically active.,
Some patients develop psychosis during the course of vigabatrin therapy, which is more common in adults than in children. This can happen even in patients with no prior history of psychosis. Other rare CNS side effects include anxiety, emotional lability, irritability, tremor, abnormal gait, and speech disorder.
Abdominal pain (1.6%), constipation (1.4%), vomiting (1.4%), and nausea (1.4%). Dyspepsia and increased appetite occurred in less than 1% of subjects in clinical trials.
Body as a Whole
Fatigue (9.2%), weight gain (5.0%), asthenia (1.1%).
A teratology study conducted in rabbits found that a dose of 150mg/kg/day caused cleft palate in 2% of pups and a dose of 200 mg/kg/day caused it in 9%. This may be due to a decrease in methionine levels, according to a study published in March of 2001. In 2005, a study conducted at the University of Catania was published stating that rats whose mothers had consumed 250-1000 mg/kg/day had poorer performance in the water maze and open-field tasks, rats in the 750-mg group were underweight at birth and did not catch up to the control group, and rats in the 1000 mg group did not survive pregnancy.
There is no controlled teratology data in humans to date.
In 2003, vigabatrin was shown by Frisén and Malmgren to cause irreversible diffuse atrophy of the retinal nerve fiber layer in a retrospective study of 25 patients. This has the most effect on the outer area (as opposed to the macular, or central area) of the retina.
A study published in 2002 found that vigabatrin causes a statistically significant increase in plasma clearance of carbamazepine.
In 1984, Drs Rimmer and Richens at the University of Wales reported that administering vigabatrin with phenytoin lowered the serum phenytoin concentration in patients with treatment-resistant epilepsy. The concentration of phenytoin falls to 23% within five weeks, according to an experiment published in 1989 by the same two scientists that tried and failed to elucidate the mechanism behind this interaction.
With most drugs, elimination half-life is a useful predictor of dosing schedules and the time needed to reach steady state concentrations. In the case of vigabatrin, however, it has been found that the half-life of biologic activity is far longer than the elimination half-life.
For vigabatrin, there is no range of target concentrations because researchers found no difference between the serum concentration levels of responders and those of non-responders. Instead, the duration of action is believed to be more a function of the GABA-T resynthesis rate; levels of GABA-T do not usually return to their normal state until six days after stopping the medication.
Vigabatrin is sold as Sabril® in Canada, Mexico,
and the United Kingdom. The brand name in Denmark is Sabrilex®.
References and end notes
^ abcdefghi Long, Phillip W. "Vigabatrin." Internet Mental Health. 1995-2003.
^ Fechtner, Robert D.; Albert S. Khouri, Emilia Figueroa, Marina Ramirez, MD; Martha Federico, Stephen L. Dewey, Jonathan D. Brodie (September 2006). "Short-term Treatment of Cocaine and/or Methamphetamine Abuse With Vigabatrin: Ocular Safety Pilot Results". Archives of Ophthalmology124 (9): 1257–62. PubMed. Retrieved on 2007-10-20.
^ Zwanzger P, Baghai TC, Schuele C, Strohle A, Padberg F, Kathmann N, Schwarz M, Moller HJ, Rupprecht R (2001). "Vigabatrin decreases cholecystokinin-tetrapeptide (CCK-4) induced panic in healthy volunteers". Neuropsychopharmacology25 (5): 699–703. PubMed.
^ Feucht M, Brantner-Inthaler S (1994). "Gamma-vinyl-GABA (vigabatrin) in the therapy of Lennox-Gastaut syndrome: an open study" (PDF). Epilepsia35 (5): 993–8. PubMed. Retrieved on 2006-05-25.
^ Sheean, G.; Schramm T, Anderson DS, Eadie MJ. (1992). "Vigabatrin--plasma enantiomer concentrations and clinical effects". Clinical and Experimental Neurology29: 107-16. PubMed.
^ ab Gram L, Larsson OM, Johnsen A, Schousboe A (1989). "Experimental studies of the influence of vigabatrin on the GABA system". British Journal of Clinical Pharmacology27 (Suppl 1): 13S-17S. PMID 2757904.
^ Sander JW, Hart YM (1990). "Vigabatrin and behaviour disturbance". Lancet335 (8680): 57. PubMed.
^ Chiaretti A, Castorina M, Tortorolo L, Piastra M, Polidori G (1994). "[Acute psychosis and vigabatrin in childhood]". La Pediatria Medica e Chirurgica : Medical and surgical pediatrics16 (5): 489-90. [Article in Italian] PMID 7885961
^ Sander JW, Hart YM, Trimble MR, Shorvon SD (1991). "Vigabatrin and psychosis". Journal of Neurology, Neurosurgery, and Psychiatry54 (5): 435-9. PubMed.
^ Abdulrazzaq YM, Padmanabhan R, Bastaki SM, Ibrahim A, Bener A (2001). "Placental transfer of vigabatrin (gamma-vinyl GABA) and its effect on concentration of amino acids in the embryo of TO mice". Teratology63 (3): 127-33. PubMed.
^ Lombardo SA, Leanza G, Meli C, Lombardo ME, Mazzone L, Vincenti I, Cioni M (2005). "Maternal exposure to the antiepileptic drug vigabatrin affects postnatal development in the rat". Neurological Sciences26 (2): 89-94. PubMed.
^ Frisén L, Malmgren K (2003). "Characterization of vigabatrin-associated optic atrophy". Acta Ophthalmologica Scandinavica81 (5): 466-73. PubMed.
^ Buncic JR, Westall CA, Panton CM, Munn JR, MacKeen LD, Logan WJ (2004). "Characteristic retinal atrophy with secondary "inverse" optic atrophy identifies vigabatrin toxicity in children". Ophthalmology111 (10): 1935-42. PubMed.
^ Sanchez-Alcaraz, Agustín; Quintana MB, Lopez E, Rodriguez I, Llopis P (2002). "Effect of vigabatrin on the pharmacokinetics of carbamazepine". Journal of Clinical Pharmacology and Therapeutics27 (6): 427-30. PubMed.
^ Rimmer EM, Richens A (1984). "Double-blind study of gamma-vinyl GABA in patients with refractory epilepsy". Lancet1 (8370): 189-90. PubMed.
^ Rimmer EM, Richens A (1989). "Interaction between vigabatrin and phenytoin". British Journal of Clinical Pharmacology27 (Suppl 1): 27S-33S. PubMed.
^ Lindberger M, Luhr O, Johannessen SI, Larsson S, Tomson T (2003). "Serum concentrations and effects of gabapentin and vigabatrin: observations from a dose titration study". Therapeutic Drug Monitoring25 (4): 457-62. PMID 12883229.