Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Vigabatrin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMedDate not supplied

Pharmacokinetics and metabolism of vigabatrin following a single oral dose of [14C]vigabatrin in healthy male volunteers.

14C-labeled vigabatrin (50 microCi), an antiepileptic drug, was administered to six healthy male volunteers as a single oral dose containing 1500 mg of vigabatrin to determine the disposition profile of 14C and parent drug, and to investigate the metabolism of vigabatrin in humans. Vigabatrin was well tolerated by all subjects. There were no clinically important changes in any clinical laboratory parameter. Plasma concentration profiles of both 14C and vigabatrin exhibited biexponential decay. AUC, Cmax, Tmax, and terminal phase t1/2, for 14C were consistently greater than vigabatrin (248.2 vs. 176.0 micrograms-hr/ml; 48.8 vs. 42.8 micrograms/ml; 0.7 vs. 0.6 hr; and 9.5 vs. 7.7 hr, respectively). Mean renal clearance, oral clearance, and volume of distribution for 14C was consistently lower than vigabatrin (1.20 vs. 1.45 ml/min/kg; 1.26 vs. 1.77 ml/min/kg; and 1.01 vs. 1.18 liters/kg, respectively). The mean percentage of recovery of 14C in urine was higher than vigabatrin (95.4 vs. 82.0%). The mean percentage of recovery of 14C in feces was 1.0%. Concentration ratios of 14C showed that vigabatrin distributes into red blood cells at a concentration of 30-80% of that in plasma. The concentration of vigabatrin in saliva was approximately 10% of that in the plasma. The main radioactive component eliminated in the urine was vigabatrin. Two minor urinary metabolites (< 5% of total dose) of vigabatrin were detected using liquid scintillation counting of HPLC eluant fractions. One urinary metabolite was identified by thermospray-LC/MS as the lactam metabolite of vigabatrin.

Administration, Oral↗
PubMed1994

Vigabatrin in uncontrolled seizures: Belgian clinical experience. The Belgian Vigabatrin Evaluation Group.

The antiepileptic activity of vigabatrin has been established in several double-blind, placebo-controlled, clinical trials. The purpose of this study was to evaluate the efficacy and tolerability of this new antiepileptic drug in normal clinical practice rather than in controlled studies. A total of 102 patients (46 females and 56 males, ranging in age from 1 to 62 years) with previously uncontrolled seizures were treated with vigabatrin (0.5-4 g/day) as add-on medication, on an individual patient basis by 39 neurologists, for a mean duration of 235 days (range 30-520 days). Efficacy of vigabatrin was assessed after 3 months of therapy. Sixty-five patients (63.7%) showed a > 50% decrease in seizure frequency, and 12 patients (11.7%) became seizure-free. Thirty-one patients (29.4%) experienced a < 50% decrease or no change in seizure frequency, and 6 patients (5.9%) had an increase in seizure frequency. Adverse events, nearly all of mild severity, were reported in 27 patients (26.5%). These data are remarkably similar to previous placebo-controlled studies and support that vigabatrin is beneficial to a significant number of patients with previously uncontrolled seizures.

Adolescent↗
PubMed1992

Single-blind, placebo-controlled multicenter trial of vigabatrin in the treatment of epilepsy. The Italian Study Group on Vigabatrin.

A single-blind, placebo-controlled multicenter trial of vigabatrin was carried out in 101 epileptic patients (mostly with partial seizures) refractory to conventional therapy. The study design included four consecutive periods: (i) an observation phase (run-in), (ii) a placebo period, (iii) fixed-dosage add-on vigabatrin (2 g/day) and (iv) dose titration (up to a maximum of 4 g/day) to optimize clinical response. Each period lasted 8 weeks, except for the titration phase, which could be extended to 16 weeks. 90 patients completed the trial. Eleven dropped out, one patient developing absence status and 4 cases showing an increased seizure frequency. In the patients completing the trial, the median number of seizures/month decreased from 16 (inter-quartile range 8-34) during placebo to 5 (2-10) during the last 8 weeks on vigabatrin (p < 0.0001). Both partial and generalized tonic clonic (mostly secondary) seizures were significantly reduced. A greater than 50% reduction in seizure frequency (compared to placebo) was observed in 60 patients. Sedation and weight gain were the most frequently reported adverse events.

Adolescent↗
PubMed1992

Effects of single and multiple increasing doses of vigabatrin on brain GABA metabolism and correlation with vigabatrin plasma concentration.

UNLABELLED: The effects of increasing (50-1600 mg/kg/day) doses of vigabatrin (GVG) both as single doses and after 8 or 28 days of treatment have been studied in 19 groups of 10 adult Wistar rats. The parameters studied were brain gamma-aminobutyric acid-transaminase (GABA-T) activity, GABA concentration and L-glutamate decarboxylase (GAD) activity. Single increasing doses of GVG progressively inhibited GABA-T activity, but a residual activity of about 40% was observed with the highest doses. GABA concentration increased in a dose-dependent manner but a ceiling was not reached. GAD activity was slightly inhibited at low doses and stimulated at high ones. When treatment was continued for 8 days, more marked effects of GVG on GABA-T and GABA, a more severe toxicity and higher GVG plasma concentrations were observed. GAD was inhibited instead of stimulated by high GVG doses. After 28 days of treatment the effects of GVG on GABA-T and GABA were similar to those after 8 days. However, toxic effects decreased and lower GVG plasma concentrations were found. IN CONCLUSION: (a) the more marked brain GABAergic effects observed after 8 days of treatment with GVG may explain the greater anticonvulsant effects observed by others in animals, and (b) GVG plasma concentrations correlate well with changes in brain GABA-T and GABA, and may partly explain changes in the effects of GVG related to the length of treatment.

4-Aminobutyrate Transaminase↗
PubMed1995

Vigabatrin in unsatisfactory controlled epilepsies. Swiss Vigabatrin Study Group.

One hundred and twenty-seven patients with uncontrolled epilepsy have been treated in an open add-on study with vigabatrin with a mean follow up of ten months. Mean duration of epilepsy prior to treatment was seven-teen years. Patients with partial seizures, with and without secondary generalisation responded best with 44% achieving a greater than 50% reduction in seizure frequency. Adverse events were primarily CNS related and reversible, two patients were withdrawn because of somnolence and eight because of behavioral disturbances. Reduction of concomittant AEDs was difficult in this population with chronic epilepsy.

Adolescent↗
PubMed1992

Vigabatrin. Clinical pharmacokinetics.

Vigabatrin is a structural analogue of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). It is supplied as a racemic mixture, with the S(+) enantiomer possessing pharmacological activity. [R,S]-Vigabatrin plasma concentrations can be estimated using high-performance liquid chromatographic methods. Only gas chromatography-mass spectrometry methods allow quantification of the S(+) and R(-) enantiomers. Vigabatrin was rapidly absorbed reaching peak concentrations within 1 to 2h. Area under plasma concentration-time curves indicated dose-linear pharmacokinetics. There was no effect of food on the absorption of vigabatrin. The absorption characteristics of the enantiomers were similar to those of the [R,S]-vigabatrin. No chiral inversion was detected after administration of the pure S(+) enantiomer. Vigabatrin is not protein bound. The apparent volume of distribution of [R,S]-vigabatrin was approximately 0.8 L/kg. Despite the lack of protein binding, cerebrospinal concentrations of the [R,S]-vigabatrin were only 10% of the plasma concentration 6h after a single oral dose. The half-life of [R,S]-vigabatrin was between 5.3 and 7.4h, the half-life of the enantiomers were 7.5 and 8.1h for the S(+) and the R(-) forms, respectively. The major route of elimination was renal excretion; urinary recovery of the [R,S]-vigabatrin was close to 70%. Pharmacokinetic studies in epileptic children did not show any significant effect of maturation on the disposition of the S(+) enantiomer: the half-life and the renal clearance were similar to adult values. Data suggest a lower bioavailability in children. In adults with epilepsy, the half-life of the [R,S]-vigabatrin ranged from 4.2 and 5.6h, similar to that measured in healthy adults. In elderly nonepileptic volunteers the pharmacokinetics of the enantiomers of vigabatrin showed delayed absorption, a major increase in peak concentration and a prolonged half-life. These changes were attributed to decreased renal clearance of vigabatrin. A nonlinear relationship between renal clearance and creatinine clearance was suggested. Vigabatrin caused a 20% fall in plasma phenytoin concentrations, the mechanism of which has not been elucidated. There were no other interactions with most concurrently administered anticonvulsants. The usual dosage of vigabatrin as add-on treatment in adults is 2 to 4g daily. Higher dosages up to 80 mg/kg daily were required in children. A dosage adjustment was recommended in any patient with decreased renal clearance. Although anticonvulsant effects were clearly related to dosage, monitoring of plasma concentrations of vigabatrin as a guide to dosage is unlikely to be of as much value as with other antiepileptic drugs. The action of the drug long outlasts its presence in plasma.

Administration, Oral↗
PubMed1995

Vigabatrin vs carbamazepine monotherapy in patients with newly diagnosed epilepsy. A randomized, controlled study.

OBJECTIVE: To evaluate the efficacy, safety, and cognitive effects of initial vigabatrin monotherapy compared with initial carbamazepine monotherapy in patients with newly diagnosed epilepsy. DESIGN: Open, randomized, controlled design. Follow-up period of 12 months. SETTING: University hospital with an epilepsy center. PATIENTS: A total of 100 patients, aged 15 to 64 years, classified as suffering from partial seizures and/or generalized tonic-clonic seizures were randomized to either vigabatrin or carbamazepine monotherapy. Fifty-nine patients with a single epileptic seizure and no antiepileptic drug treatment served as a control population for objective safety measures. OUTCOME MEASURES: To evaluate the comparative efficacy and toxicity of vigabatrin and carbamazepine, the drug success rate (ie, the proportion of patients continuing successful treatment with the randomly assigned drug) after 12 months of steady-state treatment was used. To evaluate the safety of the drugs in addition to reported side effects, visual evoked potential recordings and neuropsychological evaluation were performed during follow-up. RESULTS: During the 12-month follow-up period, 60% of patients receiving vigabatrin and carbamazepine were treated successfully. Vigabatrin caused fewer side effects that required discontinuation of therapy. However, vigabatrin had to be discontinuated more often owing to lack of efficacy, and fewer of the successfully treated patients receiving vigabatrin achieved total freedom from seizures. Vigabatrin had no detrimental effects on cognitive functions. Retrieval from both episodic and semantic memory and flexibility of mental processing improved significantly in patients successfully treated with vigabatrin. CONCLUSION: Vigabatrin seems to be an effective and safe antiepileptic drug as primary monotherapy for epilepsy with fewer cognitive side effects than carbamazepine.

Adult↗
PubMed1991

Vigabatrin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy and disorders of motor control.

Vigabatrin was specifically designed to enhance gamma-aminobutyric acid (GABA) function in the CNS. By increasing brain concentrations of this inhibitory neurotransmitter the drug appears to decrease propagation of abnormal hypersynchronous discharges, thereby reducing seizure activity. At this stage in its development, clinical experience with vigabatrin is limited primarily to patients with refractory seizure disorders. In this difficult-to-treat population, 'add-on' therapy with vigabatrin greater than or equal to 2 g/day has shown impressive efficacy, reducing seizure frequency by greater than or equal to 50% in approximately half of patients. Clinical efficacy does seem to vary with seizure type with the best response reported in adults with complex partial seizures with or without generalisation and in children with cryptogenic partial epilepsy or symptomatic infantile spasm. Vigabatrin appears to have a negative effect on absences and myoclonic seizures. Some disorders of motor control may also be amenable to enhanced GABAergic function. In the small number of patients with tardive dyskinesia treated to date, vigabatrin produced mild to moderate improvement in hyperkinetic symptom scores but Parkinsonism or schizophrenic symptoms occasionally worsened. The best response was reported in a study of patients who had been withdrawn from neuroleptic therapy. In a small but well-controlled comparative trial, vigabatrin was as effective as baclofen in reducing spasm and improving some parameters of spasticity in patients with spinal cord lesions or multiple sclerosis. Most adverse reactions to vigabatrin are mild and transient with central nervous system (CNS) changes being reported most frequently. Of particular note, serial evoked potential studies and the few available histology reports have not found evidence of intramyelinic oedema during therapeutic use, as was reported in rats and dogs on chronic high-dose treatment. Thus, vigabatrin is a promising new anticonvulsant drug. Current evidence supports a trial of this agent as adjunctive therapy in patients with refractory seizure disorders, and future investigation of vigabatrin monotherapy and its efficacy relative to established agents is awaited with interest. Wider experience should help to clarify which patients - by seizure type and concurrent CNS pathology - are likely to benefit from vigabatrin and ongoing monitoring should further clarify the potential detrimental effects, if any, of long term use. In the meantime, it is a welcome addition in the difficult setting of resistant epilepsy.

4-Aminobutyrate Transaminase↗
PubMed1994

Effects of vigabatrin on partial seizures and cognitive function.

Forty five patients with refractory partial seizures were studied in a prospective, randomised, placebo controlled, add on, parallel group, double blind trial of the new antiepileptic drug vigabatrin (1.5 g twice daily) followed by open treatment. Seizure frequency was monitored throughout an eight week baseline, 20 weeks double blind, and up to 18 months of open vigabatrin treatment. Cognitive function, including measures of memory and concentration, mood, and behaviour were assessed at baseline and again during the 20th week of treatment. Vigabatrin was associated with a significant reduction in a measure of motor speed and overall score on a design learning test in the first 20 weeks of treatment. In comparison with the baseline period, vigabatrin treatment was associated with a significant reduction in median complex partial seizure frequency four to 12 and 12 to 20 weeks after commencing vigabatrin (-66% and -69% in the vigabatrin group, +50% and +25% in the placebo group). Ten of 20 patients on vigabatrin and four of 23 on placebo showed a > 50% reduction in complex partial seizure frequency in the last eight weeks of double blind treatment. At least 60% of responders had maintained the response to vigabatrin when assessed during the open phase of the trial at 44 weeks. Two patients discontinued vigabatrin because of depression, which resolved on drug withdrawal.

Adolescent↗
PubMed1993

Plasma vigabatrin enantiomer ratios in adults and children.

The new anticonvulsant vigabatrin (gamma-vinyl-gamma-aminobutyric acid) is normally supplied as a racemate, but its anticonvulsant effect is thought to reside in its [S]-enantiomer only. The plasma concentration ratio of the [R] to [S] enantiomers appears to remain constant across the vigabatrin dosage interval in adult volunteers, and in the present study this has also proved to be the case in 12 chronically treated adult epileptic patients. However, in 8 epileptic children chronically treated with other anticonvulsants and given add-on vigabatrin therapy because of failure to control seizures, plasma [R]:[S]-vigabatrin ratios changed across the drug dosage interval, the [R]-vigabatrin levels tending to be relatively higher soon after intake, and to fall more rapidly than the [S]-vigabatrin concentrations over the next few hours (mean half-lives 2.52 +/- SD 0.49 and 6.53 +/- SD 6.62 hours). The reason for the shorter half-life of [R]-vigabatrin in children remains to be elucidated, but it appears that measurement of racemic vigabatrin plasma concentrations in children, though not in adults, may lead to somewhat misleading conclusions as regards the amount of the circulating anticonvulsant [S]-vigabatrin.

Aged↗
PubMed1990

Administration of vigabatrin (gamma-vinyl-gamma-aminobutyric acid) affects the levels of both inhibitory and excitatory amino acids in rat cerebrospinal fluid.

The effect of vigabatrin (gamma-vinyl-gamma-aminobutyric acid), a new anticonvulsant drug, on the transmitter amino acids in rat cisternal CSF was studied. CSF was collected through a permanently implanted polyethylene cannula from freely moving rats at 5, 24, 48, and 96 h after administration of 1,000 mg/kg of vigabatrin. The free gamma-aminobutyric acid (GABA) level was elevated maximally (13.5-fold; p less than 0.01) at 24 h after injection. The homocarnosine (GABA-histidine) level also was increased (123%; p less than 0.01) at 24 h after injection, and its concentration remained at the same level for the next 3 days. Glycine and taurine concentrations had increased [31% (p less than 0.05) and 63% (p less than 0.01), respectively] at 5 h after injection. It is interesting that the levels of glutamate and aspartate increased [330% (p less than 0.05) and 421% (p less than 0.01), respectively] at 96 h after injection, the time when the free GABA level had returned to the baseline concentration and the vigabatrin level was 3% of the maximal concentration. The present study indicates that a single dose of vigabatrin in rats elevates levels of both the inhibitory and excitatory amino acids in CSF. However, the temporal profile of observed changes in relation to vigabatrin injection shows that neither the long-lasting elevation of GABA content nor the increase in glutamate and aspartate levels correlates with the level of vigabatrin in CSF. These findings suggest that the excitatory mechanisms are also augmented following acute administration of vigabatrin, especially when the content of GABA had decreased to the baseline level and the level of vigabatrin was low.

Amino Acids↗
PubMed1995

Vigabatrin: effect on brain GABA levels measured by nuclear magnetic resonance spectroscopy.

Vigabatrin is undoubtedly one of the most exciting anti-epilepsy drugs in use today. Many open and controlled clinical trials have confirmed that it is particularly effective in controlling partial epileptic seizures with or without secondary generalization. Vigabatrin acts to increase GABA levels in the presynaptic nerve terminal by inhibiting the activity of GABA-transaminase. There is no direct correlation between the blood or brain concentration of vigabatrin and its clinical effect, so monitoring vigabatrin levels is not predictive of patient response. However, it is possible to relate the activity of vigabatrin to levels of GABA in the brain, measured by nuclear magnetic resonance spectroscopy (NMRS). NMRS studies show that following administration of vigabatrin, brain concentrations of GABA rise to about 2-3 times their baseline values. This 'extra' GABA is held within the nerve terminal, and is only released during synaptic transmission. Although there appears to be a clear dose-response relationship up to 3 g/day, it is not well documented if higher doses result in proportionately higher brain GABA levels. This finding seems to support the results of clinical studies suggesting that the optimal dose of vigabatrin may be 3 g/day. There is also some evidence for a correlation between the concentration of GABA in the brain and the clinical outcome. Continuing investigations using NMRS aim to confirm these preliminary findings, and to determine the time course and extent of changes in brain GABA levels after vigabatrin administration.

Anticonvulsants↗
PubMed1992

Vigabatrin--plasma enantiomer concentrations and clinical effects.

Plasma concentrations of the [R]- and [S]- enantiomers of the new anticonvulsant vigabatrin were measured by an enantiospecific gas-liquid chromatographic assay in a group of therapy-resistant epileptic patients in whom racemic vigabatrin was added to their existing antiepileptic drug regimens. The peak plasma concentrations of the biologically active [S]-enantiomer of vigabatrin were correlated with those of the [R]-enantiomer, with drug dose, seizure frequency and change in score on various tests of psychological function administered prior to and when the subjects were under steady-state conditions following vigabatrin therapy. Plasma [S]-vigabatrin concentrations correlated with drug dose, [R]-vigabatrin concentration and change in score of certain psychological tests reflecting verbal memory, recall and speed of information processing. No definite pharmacokinetic interactions were detected, though plasma phenobarbitone concentrations tended to fall during vigabatrin administration. There were too few data to assess the relation between [S]-vigabatrin concentrations and seizure frequency.

Adolescent↗
PubMedDate not supplied

[New drugs in the treatment of childhood epilepsy: vigabatrin (study of 61 subjects)].

This study was conducted to determine the efficacy of vigabatrin in children with epilepsy. Sixty-one children with various types of severe epilepsy were studied. In 12 children vigabatrin was introduced as monotherapy, while in 49 it was added to other antiepileptic drugs. Following the introduction of vigabatrin, 17 patients became seizure free, and 19 responded with a greater than 50% reduction in seizure frequency. The following types of epilepsy responded favorably to treatment (in order of decreasing efficacy): West syndrome, especially if secondary to Tuberous Sclerosis; cryptogenic and symptomatic partial epilepsy; Lennox-Gastaut syndrome, and other symptomatic generalized epilepsy. Optimal responses were found with vigabatrin doses of 30 to 50 mg/kg/day. Forty-one responders continued on vigabatrin, with generally good efficacy. Vigabatrin tolerability was good; in only 6 children was treatment discontinued because of side-effects such as somnolence, irritability, weight gain, and cutaneous rash. This study shows that vigabatrin is effective in the treatment of refractory epilepsy, especially in West syndrome secondary to Tuberous Sclerosis, partial epilepsy, and Lennox-Gastaut syndrome. Further studies are needed to analyze the increased frequency of seizures and the appearance of new seizure types associated with vigabatrin treatment.

4-Aminobutyrate Transaminase↗
PubMed1991

The effect of subchronic administration of vigabatrin on learning and memory in nonepileptic rats.

The present experiments investigated whether subchronic administration of vigabatrin, a GABA-mimetic drug, affects the performance of normal rats in the behavioural tasks assessing learning and memory. The effects of vigabatrin [50-200 mg/kg (IP)/day] administration on the acquisition and retention of water maze and passive avoidance task were studied. According to the results of three experiments, vigabatrin treatment did not markedly impair the acquisition or retention of water maze task. Furthermore, vigabatrin-treated rats were not inferior to saline-treated rats in reversal learning of water maze task. On the other hand, vigabatrin treatment slightly increased the speed of swimming in rats. The administration of vigabatrin did not affect the performance (training latency, number of training trials, testing latency) of rats in the passive avoidance task. According to these results, the effects of vigabatrin, a new antiepileptic drug, on the performance of nonepileptic rats were modest in behavioural tasks used to assess learning and memory.

Amino Acids↗
PubMed1989

Experimental studies of the influence of vigabatrin on the GABA system.

1. Studies of the influence of clinically relevant concentrations of vigabatrin on GABA-transaminase and on the release of endogenous GABA were performed in selectively cultured astrocytes and neurons. In addition, the two stereoisomers of vigabatrin were investigated separately. 2. The results indicated a preferential inhibition of neuronal GABA-transaminase by vigabatrin. 3. Only the (S)-form of vigabatrin seems to inhibit GABA-transaminase. This finding corresponds to observations in epileptic animals that the (R)-form exhibits no anticonvulsant effect. 4. Resynthesis of GABA-transaminase, following withdrawal of vigabatrin showed that maximum enzyme activity was obtained within 6 days. This finding corresponds to the persistent effect after withdrawal of the drug in patients, observed in clinical trials. 5. At a concentration of 25 microM, vigabatrin caused a significant increase in the release of endogenous GABA from cultured GABAergic neurons. Although no data on brain levels of the drugs are currently available, judging from vigabatrin blood concentrations in man and from information of brain levels in animals, following chronic treatment, it is conceivable that a sufficiently high concentration of the drug in human brain is obtained to augment GABA release.

4-Aminobutyrate Transaminase↗
PubMed1992

Pharmacology of vigabatrin.

Vigabatrin (gamma-vinyl GABA) is a relatively new antiepileptic drug. Vigabatrin increases the concentration of gamma-aminobutyric acid (GABA) in the brain by inhibiting the major GABA metabolizing enzyme, GABA transaminase. Controlled clinical trials have demonstrated an excellent antiepileptic effect of vigabatrin, especially in the treatment of partial epilepsies. Long-term evaluations have shown no signs of tolerance development. Vigabatrin decreases the plasma concentration of phenytoin during concomitant therapy, the only drug with which an interaction seems to occur. In general, vigabatrin is well tolerated. Psychotic reactions occur in 3-6% of patients. Other frequent side effects are sedation and weight increase. Chronic vigabatrin intoxication in animals caused development of intramyelinic oedema, appearing as microvacuoles in brain white matter. No microvacuolation has been observed in humans, even after long-term treatment. Vigabatrin seems a very valuable new antiepileptic drug.

4-Aminobutyrate Transaminase↗
PubMed1991

Vigabatrin and psychosis.

We report a series of 14 cases of psychosis occurring in patients with severe intractable epilepsy, following the prescription of vigabatrin, a new antiepileptic drug. Nine patients had no previous history of psychosis. In eight patients the psychosis occurred following a change in the habitual pattern of seizure activity; in four it developed after a period of seizure freedom followed by a cluster of seizures, and in the other four patients an alternating psychosis was observed. In five patients there was no clear relationship to seizure pattern. Another patient developed psychosis after taking an overdose of between eight and 12 g of vigabatrin. A further three patients, who developed psychosis following vigabatrin withdrawal, were not included in this series. The mean dose at onset of the psychosis (excluding the patient who took an overdose) was 2580 mg, and the period from initiation of therapy to the onset of psychosis varied from five days to 32 weeks (and occurred 24 hours after the overdose of vigabatrin). In all cases the psychosis resolved, but necessitated the withdrawal of vigabatrin, except in the single patient who took the overdose. The mechanism of this behaviour change is unclear, but in some instances may reflect vigabatrin's powerful anti-epileptic action. This is clearly not the case for all patients. Vigabatrin should be started with caution in patients with severe epilepsy, particularly in the presence of a previous history of psychosis, and such patients should be carefully monitored.

4-Aminobutyrate Transaminase↗