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Journal of Neurology, Neurosurgery, and Psychiatry 1991;54:435-439 435 Vigabatrin and psychosis J W A S Sander, Y M Hart, M R Trimble, S D Shorvon Abstract The side effect profile of vigabatrin is not We report a series of 14 cases of dissimilar to other anticonvulsants, especially psychosis occurring in patients with in the early phases of treatment, and to date severe intractable epilepsy, following the no particular long term hazards have been prescription of vigabatrin, a new anti- identified. Reversible intra-myelinic oedema epileptic drug. Nine patients had no has been described in early toxicity studies in previous history of psychosis. In eight experimental animals. This was seen in patients the psychosis occurred follow- rodents and beagles, but has not been seen in ing a change in the habitual pattern of primates or humans.""3 seizure activity; in four it developed Behavioural changes associated with the after a period of seizure freedom fol- initiation of vigabatrin therapy have been lowed by a cluster of seizures, and in the reported. Behaviour has been variously other four patients an alternating documented as being improved'4 or psychosis was observed. In five patients deteriorating."5 In investigations, however, there was no clear relationship to seizure using standardised and validated rating scales, pattern. Another patient developed evidence for a consistent effect on affective psychosis after taking an overdose of symptoms is lacking.'6 between eight and 12 g of vigabatrin. A More severe behavioural problems repor- further three patients, who developed ted, sufficient in some cases to lead to with- psychosis following vigabatrin with- drawal of the drug, include severe agitation7 18 drawal, were not included in this series. and psychosis.'920 We report here a series of The mean dose at onset of the psychosis 14 cases of psychosis which occurred follow- (excluding the patient who took an over- ing the prescription of vigabatrin, some of dose) was 2580 mg, and the period from which were noted during a clinical trial of the initiation of therapy to the onset of drug reported elsewhere.21 22 psychosis varied from five days to 32 weeks (and occurred 24 hours after the overdose of vigabatrin). In all cases Patients and methods the psychosis resolved, but necessitated During the past four years, we have treated the withdrawal of vigabatrin, except in approximately 210 patients with vigabatrin the single patient who took the overdose. (GVG), either during the course of a clinical The mechanism of this behaviour change trial of vigabatrin, or during the prescription of is unclear, but in some instances may the drug to patients (mostly on compassionate reflect vigabatrin's powerful anti-epilep- grounds) from the specialist clinics of the tic action. This is clearly not the case for National Hospitals for Neurology and Neuro- all patients. Vigabatrin should be started surgery, including the National Hospital- with caution in patients with severe Chalfont Centre for Epilepsy. We identified 14 epilepsy, particularly in the presence of patients who became psychotic after the pres- a previous history of psychosis, and such cription of the drug. None of the patients was patients should be carefully monitored. psychotic at the time of starting vigabatrin, INSEG-Institute of although five had a history of previous psy- Neurology, National chosis. Here we have documented the relevant Hospital for Neurology, London Vigabatrin, a new anti-epileptic drug, is an clinical details of their epilepsy and the psy- and the National irreversible inhibitor of gamma-aminobutyric choses, and other demographic and clinical Society for Epilepsy information on sex, seizure type, classification Research Group, acid aminotransferase (GABA-T), the main Gerrards Cross catabolic enzyme of the cerebral inhibitory and frequency, dose of vigabatrin, IQ, past J W A S Sander Y M Hart neurotransmitter GABA. It leads to a rise in psychiatric history and concomitant medica- M R Trimble GABA concentrations in cerebrospinal fluid tions. Psychoses were regarded as paranoid or S D Shorvon and in the brainl" which is believed to be the schizophrenia-like if the patients presented Correspondence to: basis of its anti-epileptic action. The efficacy with an incongruent mood, hallucinations or Dr Sander, National Hospital, Chalfont of vigabatrin as a new anti-epileptic drug has delusions in the setting of clear consciousness, Centre for Epilepsy, been established in controlled studies and it and many of these had Schneiderian first-rank Gerrards Cross, Buckinghamshire SL9 ORJ, has been shown to reduce partial and general- symptoms. The term "organic psychosis" was UK ised tonic-clonic seizures.''0 Vigabatrin has used when there was clear evidence of altera- Received 18 May 1990 recently been registered in the United King- tion of consciousness in association with the and in revised form 15 August 1990. dom for use as an anti-epileptic drug in psychotic phenomena. No statistical methods Accepted 30 August 1990 refractory epilepsy. have been applied to the data. 436 Sander, Hart, Trimble, Shorvon Table Clinical details of patients Seizure Neurological No Age Sex Aetiology Age of onset classification examination EEG 01 39 M Cryptog 12 yrs B C Ataxia Right front-temp focus 02 22 F Cryptog 8 yrs D G* Normal Diffuse 03 21 M Cryptog 11 yrs B C Normal Bi-temp foci 04 26 F Symptom 9yrs A B C Left sided focal Right occip pariet. focus 05 20 M Symptom 2 yrs D C* Normal Diffuse with R emphasis 06 28 F Symptom 2 yrs B Normal Bi-temp foci 07 21 F Cryptog 3 yrs B C Normal Multifocal 08 29 M Symptom 20 yrs D G* Right sided focal Slow spike and waves 09 34 M Symptom 15 yrs B C Normal Multifocal 10 31 M Cryptog 12 yrs B C Normal Bi-temp foci 11 23 F Symptom 5 yrs B C Normal Multifocal, left temp seizure recorded 12 40 M Cryptog 6 yrs A B C Normal Bi-temp foci 13 25 F Cryptog 11 yrs G M* Normal General spike and waves, right sided onset 14 32 F Cryptog 12 yrs B C Normal Bi-tenp foci Key: Seizure classification: A = simple partial seizure; B = complex partial seizure; C = secondary generalised seizures; D = atonic seizures; G = gen. tonic clonic; M = myoclonic seizures; * = atypical absences. Results within five days and in most within 48 hours of The data from the 14 cases are shown in the the cluster). The clinical diagnosis in three was table. The mean age of the patients was 28, and of a schizophrenic psychosis with auditory and half were female. All patients had severe refrac- visual hallucinations and religious delusions. tory epilepsy, identifiable causes being present The fourth developed a twilight state with in six. With regard to the seizure type, nine had visual hallucinations and delusions. In this partial seizures with secondary generalisation, pattern, in all patients the period of seizure one had complex partial seizures only and the freedom was unusually long, and some four remaining cases had a generalised seizure patients' notes contained comments such as disorder. Eleven patients had a normal neuro- "this is the longest ever free of attacks", logical examination and the CT scan was identifying the change of pattern. In one case normal in 11 patients. EEG recordings were obtained after the seizure Eight patients were on anti-epileptic drug cluster when the patient was psychotic. The (AED) monotherapy at the initiation of GVG, record had normalised in contrast to recordings five were taking two concomitant AEDs and the taken in the pre-treatment, pre-psychotic state remaining patient was taking three con- (fig 1). In patients 3 and 9, the psychosis comitant AEDs. The commonest concomitant resolved on halving the dose of vigabatrin, only AED was carbamazepine (n = 11) followed by to recur after a period of five weeks to four phenytoin (n = 5). EEG data revealed that five months without a seizure cluster, necessitating patients had bilateral temporal changes, one complete withdrawal of the drug. had a right fronto-temporal focus, and one had In the other pattern (pattern 2), the patients a right occipito-parietal focus. Three patients became seizure free, and developed the psy- had multifocal abnormalities in their EEG, and chosis some time after the onset of the seizure in one of these seizures originating in the left remission. The time elapsing varied from ten temporal region were recorded on telemetry. days to six weeks. This pattern was seen in four The remaining four patients had generalised cases (patients 6, 7, 11 and 14). Three of these abnormalities; in one, however, seizure record- patients had a schizophrenic-like psychosis, ing showed initial ictal electrographic activity and the fourth had an organic psychosis. EEG widely over the right hemisphere. records in two patients with pattern 2 show Nine patients had no previous history of some evidence of forced normalisation23 24 (one psychosis, although two of these patients had a example is shown in fig 2). This is the change long history of behavioural disorders and one from a patient's usual abnormal interictal had a previous diagnosis of anorexia nervosa. EEG, during the non-psychotic state, to a Two patients had had an earlier psychotic normal or near normal EEG during the episode when clobazam was prescribed and the psychosis. remaining three patients had an earlier history It is worth noting that two of these patients of interictal psychosis not associated with had had an earlier psychotic episode when their seizures or drugs. seizures were treated and remitted in a similar The pattern of seizures in eight of these way. Both (patients 6 and 11) were then pres- patients was of particular interest, with four cribed clobazam, although at the time patient patients falling into each of two readily identi- 11 also had phenytoin toxicity. Patient 14 had a fiable patterns. In the first (pattern 1), patients previous history of interictal psychosis not (3, 8, 9, and 10) became seizure free fairly soon, clearly relatedto her seizure pattern. Patients 1, or virtually so, following the introduction of 2, 4, 5 and 13 developed psychiatric distur- vigabatrin, only to develop a cluster of seizures, bances after initiation of vigabatrin with no following which the psychosis erupted (in all clear relation to seizure pattern. Patient 1 had a Vigabatrin and psychosis 437 Full Concom Initial therapy Dose of CT IQ AEDs Past Psychiatric history Psychiatric diagnosis to episode Pattern GVG Normal 80 CBZ Organic psychosis Organic psychosis 2 weeks n/a 2-0 g SVP CZP Normal 82 CBZ Behav disturbances Schiz like psychosis 3 weeks n/a 2-5 g Right temp lesion 117 CBZ Nil Schiz like psychosis 12 weeks Type 1 4-0 g DPH Normal 87 CBZ Nil Schiz like psychosis 6 weeks n/a 20 g Normal 61 CBZ Behav disturbances Paranoid state 3 weeks n/a 30g Normal 93 CBZ Similar episode on COZ Schiz like psychosis 4 weeks Type 2 3-0 g Normal 92 DPH Anorexia nervosa Organic psychosis 2 weeks Type 2 2-0 g Normal 96 CBZ Nil Schiz like psychosis 5 weeks Type 1 30 g DPH Normal 118 DPH Nil Schiz-manic 32 weeks Type 1 40 g PRM Normal 122 CBZ Nil Twilight state/Org psychosis 5 weeks Type 1 40 g DPH Occip lesion 80 CBZ Similar episode on COZ Schiz like psychosis 4 weeks Type 2 15g Normal 94 CBZ Nil Organic psychosis 1 day after GVG n/a ?8-12 g SVP overdose Normal 87 CBZ Psychosis Schiz like psychosis 5 days n/a 0-5 g Mild atrophy 88 PRM Schiz like psychosis Schiz like psychosis 6 weeks Type 2 20g Anti-Epileptic Drugs (AEDs): CBZ = carbamazepine; COZ = clobazam; CZP = clonazepam; DPH = phenytoin; GVG = vigabatrin; PRM = primidone; SVP = sodium valproate. previous history of recurrent psychosis, and here 14 patients who developed a psychosis developed a florid organic psychosis two weeks after starting vigabatrin. Although isolated after the start of vigabatrin. Patient 2 developed cases of psychosis have been noted as a possible an organic psychosis after starting vigabatrin. side effect of this drug in clinical trials'9 20 to date She had ceased to have generalised attacks, there has been no attempt at documenting such although atypical absences continued unabated cases from the clinical and EEG viewpoint. at an increased rate. She had diffuse abnor- Psychosis in these patients in association mality on EEG. Patient 4 developed psychotic with GVG has followed a cluster of seizures symptoms after being seizure free for 17 days, (post-ictal psychosis-pattern 1), a period of six weeks after starting the drug, but had had seizure freedom (altemating psychosis- previous episodes in which she had been pattem 2), withdrawal of anti-epileptic drugs, seizure free for up to three months without drug overdose, or in some cases occurred psychiatric disorder. She had, however, been independently of all these factors. having almost daily seizures in the period In pattern 1 (4 cases), patients had suppres- immediately before starting vigabatrin. Patient sion of their seizures following drug initiation, 5 developed a paranoid state three weeks after and then suddenly had a burst or cluster of starting vigabatrin. His seizure pattern was seizures (representing a change in pattem) unchanged. Patient 13 became psychotic five which was followed by the psychosis. Psychotic days after starting vigabatrin, during which episodes were short lasting, and resolved with time she had continued to have atypical reduction or withdrawal of the vigabatrin. In absences. the two patients who had the dose reduced, Patient 12 developed a psychotic episode however, there was a subsequent recurrence of lasting 36 hours after having taken an overdose the psychosis (without a seizure cluster), neces- of between eight and 12 g of vigabatrin during sitating the complete withdrawal of the drug. post-ictal confusion. The mean dose of In pattem 2 (4 cases), an altemating psychosis vigabatrin at the onset of psychosis was 2500 occurred with EEG evidence in two (patients 6 mg (excluding patient 12) with a range of 500 and 14) of forced normalisation (fig 2). The mg to 4000 mg. All patients made a full remaining six cases did not fit clearly into either recovery, and in all but one patient (patient 12) ofthese two patterns. Two of these patients had vigabatrin has now been stopped. Three had a previous history of psychosis, however, patients (1, 6 and 14) required neuroleptic and a third developed psychosis after an over- drugs. dose of vigabatrin. In addition to these 14 cases, We have also noted the development of three further patients were seen who developed psychosis within days of the withdrawal of psychosis on withdrawal of vigabatrin. vigabatrin in a further three of our patients not The literature on post-ictal psychosis is documented above; two of these patients were limited, and such states, while being common admitted to hospitals other than our own. in practice, are not well documented. In the largest series, that of Levin,25 clinical features Discussion similar to our cases in pattern 1 were noted, and It is well recognised that patients with chronic it was reported that the onset could be up to epilepsy may present with interictal psychosis seven days after the seizures. Two or more or episodic psychosis related to drug therapy. attacks usually preceded the psychosis. In the Nevertheless, since the advent of GVG, we more recent series of Logsdaile and Toone,26 have noted an increased incidence of such clusters were again a frequent herald to the cases, to an extent which is not associated with psychosis, and there was often a lucid interval any of the major anti-epileptic drugs nor other of several (up to six) days before the psychosis drugs on clinical trial in our unit. We report appeared. 438 Sander, Hart, Trimble, Shorvon such attacks could last several weeks, and they U could be provoked by anticonvulsant therapies. FP2-F8 Further, the psychoses could be relieved by ECT, or a spontaneous seizure, and the EEG F8-T4 would revert to its previous abnormal state. T4-T6 _ Although the term forced normalisation may not have been well chosen, similar events have T6-02 now been well documented.27 In many settings, FP1 -F7 confirmation of the EEG changes is not pos- sible, and Tellenbach' introduced the term F7 -T3 .,1 .... ..... alternating psychosis as a clinical expression of the alternation between seizures or psychosis as T3-TS A seen in these cases. In his earlier work Landolt TS-01 tended to emphasise a relationship to temporal lobe epilepsy and partial seizures, although he FP2- F4 later noted cases in association with generalised F4-C4 w seizure disorders. TL.e possibility that anticonvulsant drugs C4-P4 A played a role in the development of these states was earlier raised by Gibbs' in trials with P4-02 phenacetylurea (phenurone), and in Landolt's FP1 -F3 studies, particular attention was drawn to the succinimides. Wolf27 30 has reinforced this sug- F3-C3 gestion, noting especially a link between gen- C3-P3 eralised seizures, alternating psychoses and ethosuximide. In his studies valproic acid was P3-01 not associated in the same way, although other authors have described cases of forced normal- isation on this anticonvulsant.3' Wolf specu- lates that disturbed sleep is an early manifesta- tion of the ethosuximide induced alternating psychosis, this drug sometimes provoking FP2-F8 arousal.27 0 It is of interest that of the anti- F8-T4 convulsants tested using Critical Flicker Fusion (CFF), a measure of cortical arousal, all T4-T6 decrease values, with the exception of viga- T6-02 batrin,32 and clobazam.33 It is the more remark- able therefore that two of our cases had FP1 -F7 previous episodes of alternating psychosis F7-T3 while on clobazam with similar clinical features. Although the influence of etho- T3-TS suximide on CFF is untested, these ideas are in TS-01 keeping with the views of Wolf. The relationship between GABA and psy- FP2-F4 chosis is unclear. At first sight a GABA agonist may be expected to be antipsychotic. GABA F4-C4 levels in schizophrenic brain material and in C4-P4 CSF are probably normal,34 3 and theoretically a GABA agonist should antagonise dopamine P4-02 release. Certainly the acute rise in CSF FP1 - F3 homovanillic acid (HVA) noted on treatment with vigabatrin is similar to that seen with F3-C3 typical neuroleptics.3 In contrast, the known C3-P3 GABA pathways from limbic forebrain areas such as the nucleus accumbens to ventral P3-01 -__-_--_ pallidum and the ventral tegmental area sug- Figure 1 showing EEG recordings ofpatient 9 (A, interictal, before vigabatr-in, B, gest possible associations between vigabatrin, during the psychotic episode), demonstrating the marked improvement in the EEG GABA and anatomical pathways thought to be during the psychotic phase. involved in the pathogenesis of the psychoses.36 Further work in this area is urgently required. The second pattern is also well re-corded in Vigabatrin is a potent anti-epileptic drug, the literature. Of interest in our serie.s is that in and in our experience2l 22 and that of others,>'0 two cases the EEG showed marked improve- has been highly effective in controlling seizures ment during the psychotic phase compared in some patients. All our patients had severe with previous EEGs. Landolt2324 c,oined the epilepsy and had been prescribed vigabatrin phrase "forced normalisation" whten he re- only after conventional anti-epileptic treat- ported a group of patients who developed ment had failed. The role of vigabatrin in the psychosis with epilepsy, and noted t]hat during development of psychosis in these patients may these episodes, seizures abated arad patho- be due to a number of factors. In the cases logical EEGs normalised. He pointe d out that exhibiting patterns 1 and 2, the psychosis may Vigabatrin and psychosis 439 Gamma-vinyl-GABA (4-amino-hex-5-enoic-acid), a new selective inhibitor of GABA-T: effects on brain GABA metabolism in mice. JNeurochem 1977;29:797-802. FP2-F8 2 Schechter PJ, Hanke NF, GroveJ, Huebert N, Sjoerdsma A. Biochemical and clinical effects of gamma-vinyl-GABA in patients with epilepsy. Neurology 1984;34:182-6. F8-T4 3 Ben-Menachem E, Persson LI, Schechter PJ. Effects of single doses of vigabatrin on CSF concentrations of T4 - T6 GABA, homocarnosine, homovanillic acid and 5- hydroxyindolacetic acid in patients with complex partial T6-02 epilepsy. Epilepsy Res 1988;2:96-101. 4 Gram L, Larsson OM, Johnsen A, Schousboe A. Experi- mental studies of the influence of vigabatrin on the Gaba FP1 - F7 system. Br J Clin Pharmac 1989;27:13S-7S. 5 Rimmer EM, Richens A. Double-blind study of gamma- F7-T3 vinyl-GABA in patients with refractory epilepsy. Lancet 1984;i:189-90. T3-TS 6 Gram L, Klosterkov P, Dam M. Gamma-vinyl-GABA: a double-blind, placebo-controlled trial in partial epilepsy. TS -01 _t Ann Neurol 1985;17:262-6. 7 Loiseau P, Hardenberg JP, Pestre M, Guyot M, Schechter FP2-F4 PJ, Tell GP. Double-blind, placebo-controlled study of vigabatrin in drug resistant epilepsy. Epilepsia 1986;27: 115-20. F4-C4 8 Tartara A, Manni R, Galimnberti CA, Herdenberg J, Orwin J, Perucca E. Vigabatrin in the treatment of epilepsy: a double-blind, placebo-controlled study. Epilepsia 1986; C4-P4 27:717-23. 9 Tassinari CA, Michelucci R, Ambrosetto G, Salvi F. P4-02 Double-blind study of vigabatrin in the treatment of drug- resistant epilepsy. Arch Neurol 1987;44:907-10. FP1 -F3 10 Mumford JP, Dam M. Meta-analysis of European placebo controlled studies of vigabatrin in drug resistant epilepsy. F3-C3 BrJ Clin Pharmac 1989;27:101-7S. 11 Butler WH, Ford GP, Newberne JW. A study of the effects of C3 -P3 _ vigabatrin on the central nervous system and retina of rats. Toxicol Pathol 1987;15:143-8. 12 Pederson B, Hojgaard K, Dam M. Vigabatrin: no micro- P3-01 vacuoles in human brain. Epilepsy Res 1987;1:74-6. 13 Anon. Vigabatrin (editorial). Lancet 1989;i:532-3. 14 Chauvel T, Vignal JP, Trottier S, Beaumont D. Long term follow up of vigabatrin treated patients with partial seizures. Abstracts: 18th Epilepsy International Congress; New FP2-F8 Delhi, India, 1989:140. 15 Birbeck KA, Ossetin J, Ring HA, Farr I, Heller A, Reynolds F8-T4 EH. Vigabatrin and mood. Abstracts: 18th Epilepsy Inter- T4-T6 national Congress; New Delhi, India, 1989:78. 16 McGuire A, Duncan JS, Trimble MR. Effects of vigabatrin T6-02 in cognitive function and mood, when used as an add-on FP1 - F7 therapy in patients with intractable epilepsy. Epilepsia 1990 (in press). F7-T3 17 Livingston JH, Beaumont D, Arzimanoglou A, Aicardi J. T3-TS Vigabatrin in the treatment of epilepsy in children. Br J TS-01 Clin Pharmac 1989;27:109-12S. 18 Luna D, Dulac 0, Pajot N, Beaumont D. Vigabatrin in the FP2-F4 treatment of childhood epilepsies: A single-blind placebo F4-C4- controlled study. Epilepsia 1989;30:430-7. 19 Faedda MR, Iani C, Paris L, Fusco L, Manfredi M, Ash- C4-P4 Rogers G, Mumford JP. Clinical results of vigabatrin P4-02 treatment in patients with refractory epilepsy. Abstracts: FP1 -F3 17th Epilepsy International Congress; Jerusalem, Israel, 1987:59. F3-C3 20 Ben-Menachem E, Persson L, Mumford J. Long-term C3-P3 evaluation of once daily vigabatrin in drug-resistant partial epilepsy. Epilepsy Res 1990;5:240-6. P3-01 21 Sander JWAS, Hart YM. Vigabatrin and behaviour distur- bances. Lancet 1990;i:57. Figure 2 showing EEG recordings of patient 6 (A, before vigabatrin, B, during the 22 Sander JWAS, Trevisol-Bittencourt PC, Hart YM, psychotic episode), shows features similar to that of figure 1. Shorvon SD. Evaluation of vigabatrin as an add-on drug in the management of severe epilepsy. J Neurol Neurosurg Psychiatry 1990;53:1008-10. result from an alteration in seizure activity. 23 Landolt H. Some clinical EEG correlations in epileptic Furthermore, it is common clinical experience psychoses. Electroencephalogr Clin Neuro 1953;5:121. 24 Landolt H. Serial EEG investigations during psychotic that epileptic psychosis is more frequent in episodes in epileptic patients and during schizophrenic patients with severe epilepsy; all patients in this attacks. In: Lorenz de Haas AM, ed. Lectures on Epilepsy. Amsterdam: Elsevier, 1958:91-133. series had a severe and intractable seizure 25 Levin S. Epileptic clouded states. JNerv Men Dis 1952;116: disorder and over one third had a previous 215-25. 26 Logsdaile S, Toone B. Post-ictal psychoses. Brit J Psychiat history of psychosis. Whatever the mechanism 1988;152:246-52. 27 Wolf P. Forced Normalisation. In: Trimble MR, Bolwig T, of the psychosis, and the relationship between eds. Aspects of Epilepsy and Psychiatry. Chichester: J this and the prescription of vigabatrin, we Wiley, 1986:101-15. 28 Tellenbach H. Epilepsie als Anfallsfeiden und als Psychose. would urge caution when starting vigabatrin, Nervenartz 1965;36:190-202. particularly in patients with a previous history 29 Gibbs FA. Ictal and non-ictal psychiatric disorders in of psychosis or with severe chronic epilepsy. temporal lobe epilepsy. J Nerv Men Dis 1951; 1 13:522-8. 30 Wolf P. Forced Normalisation. In: Smith DB, Treiman D, Other behaviour disturbances were also seen in Trimble MR, eds. Neurobehavioural Problems in Epilepsy: Scientific basis, Insights and Hypotheses. New York: Raven some of our patients, including agitation, con- Press, 1991:127-42. fusion, hyperactivity, stupor and depression 31 Pakalnis A, Drake ME, Kuruvilla J, Blake K. Forced Normalisation. Arch Neurol 1988;44:289-92. and certainly in our series and others, be- 32 Morrow JI, Richens A, Gisselbrecht D, Mumford J. A long haviour changes were the most common im- term placebo controlled study of vigabatrin in resistant portant side effect of this anti-epileptic drug. epilepsy with reference to dose and toxicity evaluation. Abstract: 18th Epilepsy International Congress; New We are very grateful for the support of Merrell-Dow in our Delhi, India, 1989:26. studies on vigabatrin. We are also grateful for the support of the 33 Hindmarsh I. The psychopharmacology of clobazam. RSM National Society for Epilepsy, Sir Jules Thorn Charitable Trust, Int Congress and Symposium Series, 74. London: RSM, 1985:3-10. the Action Research for Crippling Diseases, and the Brain 34 Von Kammen DP, Sternberg DE, Harle TA, Walters RN, Research Trust. We thank Dr David Fish for his helpful Bunney WE. SCF levels of GABA in schizophrenia. Arch comments on the EEGs of our patients. Gen Psychiat 1982;39:91-7. 35 Cross AJ, Crow TJ, Owen F. GABA in the brain in schizophrenia. Lancet 1979;i:560-1. 36 Trimble MR. Biological Psychiatry. Chichester: J Wiley, 1 Jung MJ, Lippert B, Metcalf BW, Bohlen P, Schechter PJ. 1988.
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