The following MEDLINE items were compiled by SilverPlatter and are presented with their generous cooperation and permission. (See SilverPlatter's Worldwide Library for bibliographic search information.)Record 1 of 13 in MEDLINE EXPRESS (R) 1999/01-1999/06
TITLE: A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group.
AUTHOR(S): Calabrese-JR; Bowden-CL; Sachs-GS; Ascher-JA; Monaghan-E; Rudd-GD
ADDRESS OF AUTHOR: Case Western Reserve University, Cleveland, Ohio, USA.
SOURCE (BIBLIOGRAPHIC CITATION): J-Clin-Psychiatry. 1999 Feb; 60(2): 79-88
INTERNATIONAL STANDARD SERIAL NUMBER: 0160-6689
PUBLICATION YEAR: 1999
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: BACKGROUND: More treatment options for bipolar depression are needed. Currently available antidepressants may increase the risk of mania and rapid cycling, and mood stabilizers appear to be less effective in treating depression than mania. Preliminary data suggest that lamotrigine, an established antiepileptic drug, may be effective for both the depression and mania associated with bipolar disorder. This is the first controlled multicenter study evaluating lamotrigine monotherapy in the treatment of bipolar I depression. METHODS: Outpatients with bipolar I disorder experiencing a major depressive episode (DSM-IV, N = 195) received lamotrigine (50 or 200 mg/day) or placebo as monotherapy for 7 weeks. Psychiatric evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), Mania Rating Scale, and the Clinical Global Impressions scale for Severity (CGI-S) and Improvement (CGI-I) were completed at each weekly visit. RESULTS: Lamotrigine 200 mg/day demonstrated significant antidepressant efficacy on the 17-item HAM-D, HAM-D Item 1, MADRS, CGI-S, and CGI-I compared with placebo. Improvements were seen as early as week 3. Lamotrigine 50 mg/day also demonstrated efficacy compared with placebo on several measures. The proportions of patients exhibiting a response on CGI-I were 51%, 41%, and 26% for lamotrigine 200 mg/day, lamotrigine 50 mg/day, and placebo groups, respectively. Adverse events and other safety results were similar across treatment groups, except for a higher rate of headache in the lamotrigine groups. CONCLUSION: Lamotrigine monotherapy is an effective and well-tolerated treatment for bipolar depression.
MINOR MESH HEADINGS: Adult-; Aged-; Anticonvulsants-adverse-effects; Bipolar-Disorder-psychology; Depressive-Disorder-drug-therapy; Depressive-Disorder-psychology; Dose-Response-Relationship,-Drug; Double-Blind-Method; Drug-Administration-Schedule; Middle-Age; Patient-Compliance; Placebos-; Psychiatric-Status-Rating-Scales; Severity-of-Illness-Index; Treatment-Outcome; Triazines-adverse-effects
MAJOR MeSH HEADINGS: *Ambulatory-Care; *Anticonvulsants-therapeutic-use; *Bipolar-Disorder-drug-therapy; *Triazines-therapeutic-use
CHECKTAGS: Female; Human; Male; Support,-Non-U.S.-Gov't
PUBLICATION TYPE: CLINICAL-TRIAL; JOURNAL-ARTICLE; MULTICENTER-STUDY; RANDOMIZED-CONTROLLED-TRIAL
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 0; 84057-84-1
NAME OF SUBSTANCE: Anticonvulsants; Placebos; Triazines; lamotrigine
MEDLINE ACCESSION NUMBER: 1999182124
UPDATE CODE: 199905
Record 2 of 13 in MEDLINE EXPRESS (R) 1996-1998
TITLE: [The assessment of lamotrigine effectiveness in patients with drug-resistant epilepsy]
ORIGINAL TITLE: Ocena skutecznosci lamotryginy u pacjentow z lekooporna padaczka.
AUTHOR(S): Malowidzka-Serwinska-M
ADDRESS OF AUTHOR: Kliniki Neurologicznej CSK WAM, Warszawie.
SOURCE (BIBLIOGRAPHIC CITATION): Neurol-Neurochir-Pol. 1998 Mar-Apr; 32(2): 285-93
INTERNATIONAL STANDARD SERIAL NUMBER: 0028-3843
PUBLICATION YEAR: 1998
LANGUAGE OF ARTICLE: POLISH; NON-ENGLISH
COUNTRY OF PUBLICATION: POLAND
ABSTRACT: The aim of the study was to evaluate the efficacy of lamotrigine (LTG, Lamictal) in patients with long-lasting epilepsy. The group of 11 patients, 4F, 7M aged 16-45 years, mean 31.3 years was included in the study. Complex partial seizures and complex partial with sec. generalization ones occurred in 5 patients, only simple and complex partial seizures in 4 and in 2 cases we observed primary generalized nonconvulsive seizures. The mean seizure frequency was 20/month before LTG treatment. The mean duration of epilepsy was 20 years. Monotherapy with carbamazepine was used in 2 patients, 9 took 2 antiepileptic drugs. The time of investigation and treatment was 4 months with 3 control visits. During LTG treatment the number of conventional antiepileptic drugs was reduced in 7 patients. The dose of the basic antiepileptic drug was not changed. We evaluated how LTG had influenced the frequency, severity and duration of seizures, patients' mental state and adverse events appearance. Good result of treatment--seizure frequency reduction at least 50%--was observed in 5 patients (45.5%), moderate--seizure frequency reduction below 50%--in 1 patient (9%), bad result--no change in seizure frequency or its increase--in 5 cases (45.5%). In 5 patients the drug influenced positively seizure severity and duration. Beneficial psychotropic effect of the drug was found in 2 patients with mental disturbances. Adverse effects occurred in 3 patients. They were vertigo and ataxia in 1 patient, drowsiness in 1 case and dyspeptic symptoms in 1 patient. Adverse events were mild and transient in 2 patients. In 1 patient with vertigo and ataxia they resulted in the drug being discontinued after 3 month treatment. On the whole lamotrigine shows a positive influence on the frequency, severity and duration of seizures in some patients with therapy resistant epilepsy. The drug is well tolerated and seems to have positive psychotropic effects.
MINOR MESH HEADINGS: Adolescence-; Adult-; Drug-Resistance; English-Abstract; Middle-Age; Severity-of-Illness-Index
MAJOR MeSH HEADINGS: *Anticonvulsants-therapeutic-use; *Carbamazepine-therapeutic-use; *Epilepsy,-Complex-Partial-drug-therapy; *Triazines-therapeutic-use
CHECKTAGS: English-Abstract; Female; Human; Male
PUBLICATION TYPE: CLINICAL-TRIAL; JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 298-46-4; 84057-84-1
NAME OF SUBSTANCE: Anticonvulsants; Triazines; Carbamazepine; lamotrigine
MEDLINE ACCESSION NUMBER: 1998433257
UPDATE CODE: 199901
Record 3 of 13 in MEDLINE EXPRESS (R) 1996-1998
TITLE: [Combined therapy with lamotrigine++ in primary generalized epilepsy in adult patients]
ORIGINAL TITLE: Terapia wspomagana lamotrigina w padaczce z napadami pierwotnie uogolnionymi u osob doroslych.
AUTHOR(S): Wender-M; Pruchnik-Wolinska-D
ADDRESS OF AUTHOR: Katedry i Kliniki Neurologii AM, Poznaniu.
SOURCE (BIBLIOGRAPHIC CITATION): Neurol-Neurochir-Pol. 1998 Jan-Feb; 32(1): 23-9
INTERNATIONAL STANDARD SERIAL NUMBER: 0028-3843
PUBLICATION YEAR: 1998
LANGUAGE OF ARTICLE: POLISH; NON-ENGLISH
COUNTRY OF PUBLICATION: POLAND
ABSTRACT: An attempt is presented to use Lamictal (lamotrigine) produced by GlaxoWellcome in 30 patients with primary generalized epilepsy, already taking one of antiepileptic drugs, but refractory to this treatment. The patients were treated with carbamazepine (Amizepin) 600-1200 mg daily or with sodium valproate (Depakine) 1200-1600 mg daily. In the course of add-on therapy patients were receiving in first 4 weeks increasing doses of Lamictal starting from 50 mg or 25 mg (patients treated with sodium valproate). Maintenance dose of lamotrigine was 200 mg daily in two divided doses. The results of first three months of the treatment were generally positive. Half the patients experienced a reduction in seizure count by more than a half, what testify the Lamictal is a valuable medication in the treatment of primary generalized epilepsy. The observed side effects had transitory character.
MINOR MESH HEADINGS: Adult-; Carbamazepine-therapeutic-use; Drug-Therapy,-Combination; English-Abstract; Middle-Age; Treatment-Outcome; Valproic-Acid-therapeutic-use
MAJOR MeSH HEADINGS: *Anticonvulsants-therapeutic-use; *Epilepsy,-Generalized-drug-therapy; *Triazines-therapeutic-use
CHECKTAGS: English-Abstract; Female; Human; Male
PUBLICATION TYPE: JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 298-46-4; 84057-84-1; 99-66-1
NAME OF SUBSTANCE: Anticonvulsants; Triazines; Carbamazepine; lamotrigine; Valproic-Acid
MEDLINE ACCESSION NUMBER: 1998294836
UPDATE CODE: 199810
Record 4 of 13 in MEDLINE EXPRESS (R) 1996-1998
TITLE: [Comparative assessment of treatment efficacy with lamotrigine (Lamictal) together with valproate and/or carbamazepine in patients with refractory epilepsy]
ORIGINAL TITLE: Ocena porownawcza skutecznosci leczenia skojarzonego lekoopornej padaczki lamotrygina (Lamictal) z leczeniem walproinianem i/lub karbamazepina.
AUTHOR(S): Wierzba-W; Wajgt-A
ADDRESS OF AUTHOR: I Katedry i Kliniki Neurologii Sl.A.M. w Katowicach.
SOURCE (BIBLIOGRAPHIC CITATION): Neurol-Neurochir-Pol. 1997 Nov-Dec; 31(6): 1133-46
INTERNATIONAL STANDARD SERIAL NUMBER: 0028-3843
PUBLICATION YEAR: 1997
LANGUAGE OF ARTICLE: POLISH; NON-ENGLISH
COUNTRY OF PUBLICATION: POLAND
ABSTRACT: For the study 17 patients aged 26-55 years were qualified after ineffective treatment with carbamazepine and/or valproate for simple partial, complex partial or secondary generalized seizures. The criterion of resistance to treatment was the occurrence of four or more seizures monthly. The treatment with lamotrigine was successful in 9 (52%) cases, with reduction of seizures by at least 50%. In 2 cases the seizure activity in EEG became normal. In 8 cases the addition of lamotrigine was ineffective and the drug was discontinued (in one case due to allergic rash and in one the cause was toxic hepatocellular damage).
MINOR MESH HEADINGS: Adult-; English-Abstract; Middle-Age
MAJOR MeSH HEADINGS: *Anticonvulsants-therapeutic-use; *Carbamazepine-therapeutic-use; *Epilepsy,-Generalized-drug-therapy; *Triazines-therapeutic-use; *Valproic-Acid-therapeutic-use
CHECKTAGS: Comparative-Study; English-Abstract; Female; Human; Male
PUBLICATION TYPE: CLINICAL-TRIAL; JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 298-46-4; 84057-84-1; 99-66-1
NAME OF SUBSTANCE: Anticonvulsants; Triazines; Carbamazepine; lamotrigine; Valproic-Acid
MEDLINE ACCESSION NUMBER: 1998253525
UPDATE CODE: 199809
Record 5 of 13 in MEDLINE EXPRESS (R) 1996-1998
TITLE: [Lamotrigine (Lamictal)]
ORIGINAL TITLE: La lamotrigine (Lamictal).
AUTHOR(S): Scheen-AJ
ADDRESS OF AUTHOR: Departement de Medecine, Universite de Liege.
SOURCE (BIBLIOGRAPHIC CITATION): Rev-Med-Liege. 1997 Nov; 52(11): 738-40
INTERNATIONAL STANDARD SERIAL NUMBER: 0035-3663
PUBLICATION YEAR: 1997
LANGUAGE OF ARTICLE: FRENCH; NON-ENGLISH
COUNTRY OF PUBLICATION: BELGIUM
MINOR MESH HEADINGS: Anticonvulsants-administration-and-dosage; Anticonvulsants-adverse-effects; Anticonvulsants-chemistry; Anticonvulsants-pharmacology; Anticonvulsants-therapeutic-use; Brain-drug-effects; Child-; Child,-Preschool; Drug-Combinations; Drug-Eruptions-etiology; Epilepsy-drug-therapy; Epilepsy,-Generalized-drug-therapy; Epilepsy,-Partial-drug-therapy; Excitatory-Amino-Acid-Antagonists-administration-and-dosage; Excitatory-Amino-Acid-Antagonists-adverse-effects; Excitatory-Amino-Acid-Antagonists-chemistry; Excitatory-Amino-Acid-Antagonists-pharmacology; Excitatory-Amino-Acid-Antagonists-therapeutic-use; Sodium-Channels-antagonists-and-inhibitors; Triazenes-antagonists-and-inhibitors; Triazines-administration-and-dosage; Triazines-adverse-effects; Triazines-chemistry; Triazines-pharmacology; Valproic-Acid-administration-and-dosage; Valproic-Acid-therapeutic-use
MAJOR MeSH HEADINGS: *Triazines-therapeutic-use
CHECKTAGS: Human
PUBLICATION TYPE: JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 0; 0; 0; 0; 84057-84-1; 99-66-1
NAME OF SUBSTANCE: Anticonvulsants; Drug-Combinations; Excitatory-Amino-Acid-Antagonists; Sodium-Channels; Triazenes; Triazines; lamotrigine; Valproic-Acid
MEDLINE ACCESSION NUMBER: 1998097004
UPDATE CODE: 199804
Record 6 of 13 in MEDLINE EXPRESS (R) 1996-1998
TITLE: Lamotrigine (lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo controlled crossover trial.
AUTHOR(S): Zakrzewska-JM; Chaudhry-Z; Nurmikko-TJ; Patton-DW; Mullens-EL
ADDRESS OF AUTHOR: Department of Oral Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, UK.
SOURCE (BIBLIOGRAPHIC CITATION): Pain. 1997 Nov; 73(2): 223-30
INTERNATIONAL STANDARD SERIAL NUMBER: 0304-3959
PUBLICATION YEAR: 1997
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: NETHERLANDS
ABSTRACT: Lamotrigine is a chemically novel antiepileptic drug which has not been adequately assessed for its antineuralgic properties. It was used in a double-blind placebo controlled crossover trial in 14 patients with refractory trigeminal neuralgia. Patients continued to take a steady dose of carbamazepine or phenytoin throughout the trial over a 31-day period. Each arm of the trial lasted 2 weeks with an intervening 3-day washout period. The maintenance dose of lamotrigine was 400 mg. Lamotrigine was superior to placebo (P = 0.011) based on analysis of a composite efficacy index which compared the numbers of patients assigned greater efficacy on lamotrigine with those assigned greater efficacy on placebo. Efficacy for one treatment over another was determined according to a hierarchy of: (i) use of escape medication; (ii) total pain scores; or (iii) global evaluations. Eleven of the 13 patients eligible for inclusion in the composite efficacy index showed better efficacy on lamotrigine compared with placebo. Global evaluations further suggested that patients did better on lamotrigine than placebo (P = 0.025). The adverse reactions with both lamotrigine and placebo were predominantly dose-dependent effects on the central nervous system. A 14th patient withdrew from the study due to severe pain during the placebo arm of the trial. It would appear that lamotrigine has antineuralgic properties.
MINOR MESH HEADINGS: Adult-; Aged-; Cross-Over-Studies; Double-Blind-Method; Middle-Age; Prognosis-
MAJOR MeSH HEADINGS: *Analgesics-therapeutic-use; *Triazines-therapeutic-use; *Trigeminal-Neuralgia-drug-therapy
CHECKTAGS: Female; Human; Male; Support,-Non-U.S.-Gov't
PUBLICATION TYPE: CLINICAL-TRIAL; JOURNAL-ARTICLE; RANDOMIZED-CONTROLLED-TRIAL
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 84057-84-1
NAME OF SUBSTANCE: Analgesics; Triazines; lamotrigine
MEDLINE ACCESSION NUMBER: 1998075991
UPDATE CODE: 199804
Record 7 of 13 in MEDLINE EXPRESS (R) 1996-1998
TITLE: Lamotrigine for generalized seizures associated with the Lennox-Gastaut syndrome. Lamictal Lennox-Gastaut Study Group [published erratum appears in N Engl J Med 1998 Sep 17;339(12):851-2]
AUTHOR(S): Motte-J; Trevathan-E; Arvidsson-JF; Barrera-MN; Mullens-EL; Manasco-P
ADDRESS OF AUTHOR: American Memorial Hospital, Hopital d'Enfants, Reims, France.
SOURCE (BIBLIOGRAPHIC CITATION): N-Engl-J-Med. 1997 Dec 18; 337(25): 1807-12
INTERNATIONAL STANDARD SERIAL NUMBER: 0028-4793
PUBLICATION YEAR: 1997
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: BACKGROUND: The Lennox-Gastaut syndrome, a severe form of epilepsy that usually begins in early childhood, is difficult to treat. Dose-related drug toxicity is common. METHODS: We conducted a double-blind, placebo-controlled trial of the antiepileptic drug lamotrigine in patients with the Lennox-Gastaut syndrome. Eligible patients had more than one type of predominantly generalized seizure, including tonic-clonic, atonic, tonic, and major myoclonic, and had seizures on average at least every other day. After a 4-week base-line period in which all participants received placebo, we randomly assigned 169 patients (age range, 3 to 25 years) to 16 weeks of lamotrigine (n= 79) or placebo (n=90) in addition to their other antiepileptic drugs. RESULTS: The median frequency of all major seizures changed from base-line levels of 16.4 and 13.5 per week in the lamotrigine and placebo groups, respectively, to 9.9 and 14.2 per week after 16 weeks of treatment (P=0.002). Thirty-three percent of the patients in the lamotrigine group and 16 percent of those in the placebo group had a reduction of at least 50 percent in the frequency of seizures (P= 0.01). There were no significant differences between groups in the incidence of adverse events, except for colds or viral illnesses, which was more common in the lamotrigine group (P=0.05). CONCLUSIONS: Lamotrigine was an effective and well-tolerated treatment for seizures associated with the Lennox-Gastaut syndrome.
MINOR MESH HEADINGS: Adolescence-; Adult-; Anticonvulsants-adverse-effects; Child-; Child,-Preschool; Double-Blind-Method; Mental-Retardation; Seizures-drug-therapy; Syndrome-; Treatment-Outcome; Triazines-adverse-effects
MAJOR MeSH HEADINGS: *Anticonvulsants-therapeutic-use; *Epilepsy-drug-therapy; *Triazines-therapeutic-use
CHECKTAGS: Female; Human; Male; Support,-Non-U.S.-Gov't
PUBLICATION TYPE: CLINICAL-TRIAL; CONTROLLED-CLINICAL-TRIAL; JOURNAL-ARTICLE; MULTICENTER-STUDY
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 84057-84-1
NAME OF SUBSTANCE: Anticonvulsants; Triazines; lamotrigine
MEDLINE ACCESSION NUMBER: 1998051155
UPDATE CODE: 199802
SUBSET: AIM
Record 8 of 13 in MEDLINE EXPRESS (R) 1996-1998
TITLE: Lamotrigine analysis in plasma by gas chromatography-mass spectrometry after conversion to a tert.-butyldimethylsilyl derivative.
AUTHOR(S): Dasgupta-A; Hart-AP
ADDRESS OF AUTHOR: Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque 87106, USA.
SOURCE (BIBLIOGRAPHIC CITATION): J-Chromatogr-B-Biomed-Sci-Appl. 1997 May 23; 693(1): 101-7
PUBLICATION YEAR: 1997
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: NETHERLANDS
ABSTRACT: Lamotrigine (lamictal) is a new anticonvulsant drug recently approved by the FDA for clinical use. Therapeutic monitoring of lamotrigine is useful for patient management (therapeutic range 1-4 microg/ml). Here we describe a gas chromatography-mass spectrometric identification and quantitation of lamotrigine after extraction from human serum and derivatization. Lamotrigine was extracted from alkaline serum with chloroform and derivatized with N-methyl-N-(tert.-butyldimethysilyl) trifluoroacetamide containing 2% tert.-butyldimethylchlorosilane. Oxazepam-d5 was used as an internal standard. The tert.-butyldimethylsilyl derivative of lamotrigine showed distinct molecular ions at m/z 483 and 485 as well as other peaks at m/z 426, 370 and 334 for unambiguous identification. The base peak was observed at m/z 199. Similarly, the tert.-butyldimethysilyl derivative of oxazepam-d5 showed molecular ions at m/z 519 and 521 along with other characteristic peaks at m/z 462, 376 and 318. For the analysis of lamotrigine, the mass spectrometer was operated in the selective ion monitoring mode. The within-run and between-run precisions were 4.3% (mean=3.01, S.D.=0.13 microg/ml) and 5.1% (mean=2.93, S.D.=0.15 microg/ml), respectively at a serum lamotrigine concentration of 3.0 microg/ml. The within-run and between-run precisions were 8.2% (mean=0.49, S.D.=0.04 microg/ml) and 10.6% (mean=0.47, S.D.=0.05 microg/ml), respectively at a serum lamotrigine concentration of 0.5 microg/ml. The assay was linear for serum lamotrigine concentrations of 0.5-20 microg/ml. The detection limit was 0.25 microg/ml. The assay was free from interferences from common tricyclic antidepressants, benzodiazepines, other common anticonvulsants, salicylate and acetaminophen.
MINOR MESH HEADINGS: Anticonvulsants-therapeutic-use; Mass-Fragmentography; Sensitivity-and-Specificity; Triazines-therapeutic-use
MAJOR MeSH HEADINGS: *Anticonvulsants-blood; *Indicators-and-Reagents; *Silanes-; *Triazines-blood
CHECKTAGS: Human
PUBLICATION TYPE: JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 0; 0; 0; 84057-84-1
NAME OF SUBSTANCE: tert-butyldimethylsilane; Anticonvulsants; Indicators-and-Reagents; Silanes; Triazines; lamotrigine
MEDLINE ACCESSION NUMBER: 1997343996
UPDATE CODE: 199710
Record 9 of 13 in MEDLINE EXPRESS (R) 1996-1998
TITLE: A rapid cost-effective high-performance liquid chromatographic (HPLC) assay of serum lamotrigine after liquid-liquid extraction and using HPLC conditions routinely used for analysis of barbiturates.
AUTHOR(S): Hart-AP; Mazarr-Proo-S; Blackwell-W; Dasgupta-A
ADDRESS OF AUTHOR: Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, USA.
SOURCE (BIBLIOGRAPHIC CITATION): Ther-Drug-Monit. 1997 Aug; 19(4): 431-5
INTERNATIONAL STANDARD SERIAL NUMBER: 0163-4356
PUBLICATION YEAR: 1997
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Lamotrigine (lamictal) is a new anticonvulsant drug approved by the FDA for clinical use. Therapeutic monitoring of lamotrigine is useful for patient management and avoidance of toxicity. The suggested therapeutic range is 1 to 4 micrograms/ml. The authors describe a simple high-performance liquid chromatographic (HPLC) method for analysis of lamotrigine from serum. Serum (0.5 ml) was alkalinized with borate buffer (pH 9.8). Lamotrigine and the internal standard thiopental were extracted with 10 ml of chloroform. After evaporation of the extract, the residue was reconstituted in the mobile phase (prepared by mixing 750 ml of potassium dihydrogen phosphate, 550 ml of deionized water, 430 ml of methanol, and 100 microliters of triethylamine as an ion pairing reagent) and injected into an LC-18 column (15 cm x 4.6 mm). The authors use this HPLC system routinely in their laboratory for the analysis of barbiturates. They demonstrated that the same system can be used for the analysis of lamotrigine. The within-run and between-run precisions of the lamotrigine assay were 1.63% (mean = 3.05, SD = 0.05 microgram/ml, n = 6) and 3.7% (mean = 2.97 micrograms/ml, SD = 0.11, n = 8). The assay was linear for serum lamotrigine concentrations of 0.5 microgram/ml to 20 micrograms/ml with a detection limit of 0.5 microgram/ml. The authors observed excellent correlation between serum lamotrigine concentrations measured by their assay and a reference laboratory in six patients receiving lamotrigine. Their assay is free from interferences from common tricyclic antidepressants, benzodiazepines, other common anticonvulsants, salicylate, and acetaminophen.
MINOR MESH HEADINGS: Barbiturates-analysis; Chromatography,-High-Pressure-Liquid-economics; Cost-Benefit-Analysis; Drug-Monitoring-economics
MAJOR MeSH HEADINGS: *Anticonvulsants-blood; *Chromatography,-High-Pressure-Liquid-methods; *Drug-Monitoring-methods; *Triazines-blood
CHECKTAGS: Human
PUBLICATION TYPE: JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 0; 84057-84-1
NAME OF SUBSTANCE: Anticonvulsants; Barbiturates; Triazines; lamotrigine
MEDLINE ACCESSION NUMBER: 1997408866
UPDATE CODE: 199712
Record 10 of 13 in MEDLINE EXPRESS (R) 1996-1998
TITLE: Toxic epidermal necrolysis after treatment with lamotrigine (Lamictal).
AUTHOR(S): Fogh-K; Mai-J
ADDRESS OF AUTHOR: Department of Dermatology, Aarhus University Hospital, Denmark.
SOURCE (BIBLIOGRAPHIC CITATION): Seizure. 1997 Feb; 6(1): 63-5
INTERNATIONAL STANDARD SERIAL NUMBER: 1059-1311
PUBLICATION YEAR: 1997
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
MINOR MESH HEADINGS: Adult-; Anticonvulsants-administration-and-dosage; Biopsy-; Dose-Response-Relationship,-Drug; Electroencephalography-drug-effects; Epidermal-Necrolysis,-Toxic-pathology; Skin-drug-effects; Skin-pathology; Triazines-administration-and-dosage
MAJOR MeSH HEADINGS: *Anticonvulsants-adverse-effects; *Epidermal-Necrolysis,-Toxic-etiology; *Epilepsy,-Myoclonic-drug-therapy; *Triazines-adverse-effects
CHECKTAGS: Case-Report; Female; Human
PUBLICATION TYPE: JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 84057-84-1
NAME OF SUBSTANCE: Anticonvulsants; Triazines; lamotrigine
MEDLINE ACCESSION NUMBER: 1997215473
UPDATE CODE: 199708
Record 11 of 13 in MEDLINE EXPRESS (R) 1996-1998
TITLE: Long-term safety and efficacy of lamotrigine (Lamictal) in paediatric patients with epilepsy.
AUTHOR(S): Besag-FM; Dulac-O; Alving-J; Mullens-EL
ADDRESS OF AUTHOR: Hopital St Vincent de Paul, Paris, France.
SOURCE (BIBLIOGRAPHIC CITATION): Seizure. 1997 Feb; 6(1): 51-6
INTERNATIONAL STANDARD SERIAL NUMBER: 1059-1311
PUBLICATION YEAR: 1997
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: This study was initiated to evaluate the long-term safety, tolerability and effect on seizure control of lamotrigine (Lamictal) in paediatric patients with epilepsy. A total of 155 children (aged 2-19 years) with treatment-resistant epilepsy received add-on therapy or monotherapy lamotrigine for up to four years. Patients had already experienced benefit from lamotrigine treatment in an open one-year study before entering this open continuation study of up to three additional years of treatment. Overall, including both these studies, patients were treated with lamotrigine for 53-221 weeks, representing 417.9 patient-years of experience. The physician's global assessment of seizure control compared to the three-month period before lamotrigine treatment, indicated that seizure control was generally maintained during long-term lamotrigine treatment for up to four years. For 19 patients, the investigator recorded a subjective improvement in behaviour, alertness, seizure severity, quality of life and mobility with lamotrigine treatment, sometimes independent of seizure control. In total, 34 patients received lamotrigine monotherapy; 22 of these were maintained on lamotrigine monotherapy for at least one year. Lamotrigine was well tolerated. The majority of adverse experiences were classified by the physician as being mild in intensity and only six patients (4%) withdrew from the study due to adverse experiences.
MINOR MESH HEADINGS: Adolescence-; Anticonvulsants-therapeutic-use; Child-; Child,-Preschool; Dose-Response-Relationship,-Drug; Drug-Administration-Schedule; Drug-Therapy,-Combination; Electroencephalography-drug-effects; Epilepsy-diagnosis; Long-Term-Care; Product-Surveillance,-Postmarketing; Treatment-Outcome; Triazines-therapeutic-use
MAJOR MeSH HEADINGS: *Anticonvulsants-adverse-effects; *Epilepsy-drug-therapy; *Triazines-adverse-effects
CHECKTAGS: Female; Human; Male
PUBLICATION TYPE: JOURNAL-ARTICLE; MULTICENTER-STUDY
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 84057-84-1
NAME OF SUBSTANCE: Anticonvulsants; Triazines; lamotrigine
MEDLINE ACCESSION NUMBER: 1997215471
UPDATE CODE: 199708
Record 12 of 13 in MEDLINE EXPRESS (R) 1996-1998
TITLE: Controlled trial of lamotrigine (Lamictal) for treatment-resistant partial seizures.
AUTHOR(S): Boas-J; Dam-M; Friis-ML; Kristensen-O; Pedersen-B; Gallagher-J
ADDRESS OF AUTHOR: Glostrup Hospital, Copenhagen, Denmark.
SOURCE (BIBLIOGRAPHIC CITATION): Acta-Neurol-Scand. 1996 Oct; 94(4): 247-52
INTERNATIONAL STANDARD SERIAL NUMBER: 0001-6314
PUBLICATION YEAR: 1996
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: DENMARK
ABSTRACT: The antiepileptic effect of lamotrigine (Lamictal) was assessed in a double-blind, placebo-controlled, crossover trial in 56 adult patients with refractory partial seizures. Lamotrigine or placebo was added to the patients' existing antiepileptic drugs (AEDs). The dose of lamotrigine varied from 75 to 400 mg daily. Thirty-eight patients completed the trial and 7 withdrew because of adverse experiences. There was a statistically significant reduction in seizure counts on lamotrigine compared with placebo for total seizures (30.3% reduction, 95% CI 8.4%, 47.0%), complex partial seizures (29.2% reduction, 95% CI 3.8%, 47.9%) and secondary generalised seizures (37.9%, CI 18.9%, 52.4%). The analysis of total seizure days showed a similar significant reduction during lamotrigine treatment for the same seizure categories. There was no statistically significant difference in reporting of adverse events between lamotrigine and placebo except for dizziness which was reported more frequently on lamotrigine than on placebo. There were no differences in abnormal haematological or biochemical findings between lamotrigine and placebo, and lamotrigine had no effect on plasma concentrations of concomitant AEDs.
MINOR MESH HEADINGS: Adolescence-; Adult-; Anticonvulsants-administration-and-dosage; Anticonvulsants-blood; Cross-Over-Studies; Double-Blind-Method; Middle-Age; Placebos-; Triazines-administration-and-dosage; Triazines-blood; Valproic-Acid-blood; Valproic-Acid-therapeutic-use
MAJOR MeSH HEADINGS: *Anticonvulsants-therapeutic-use; *Epilepsy,-Complex-Partial-drug-therapy; *Triazines-therapeutic-use
CHECKTAGS: Comparative-Study; Human
PUBLICATION TYPE: CLINICAL-TRIAL; JOURNAL-ARTICLE; MULTICENTER-STUDY; RANDOMIZED-CONTROLLED-TRIAL
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 0; 84057-84-1; 99-66-1
NAME OF SUBSTANCE: Anticonvulsants; Placebos; Triazines; lamotrigine; Valproic-Acid
MEDLINE ACCESSION NUMBER: 1997091869
UPDATE CODE: 199705
Record 13 of 13 in MEDLINE EXPRESS (R) 1996-1998
TITLE: Lamotrigine inhibits Ca2+ currents in cortical neurons: functional implications.
AUTHOR(S): Stefani-A; Spadoni-F; Siniscalchi-A; Bernardi-G
ADDRESS OF AUTHOR: Dipartimento Sanita Pubblica, Universita di Tor Vergata, Rome, Italy.
SOURCE (BIBLIOGRAPHIC CITATION): Eur-J-Pharmacol. 1996 Jun 20; 307(1): 113-6
INTERNATIONAL STANDARD SERIAL NUMBER: 0014-2999
PUBLICATION YEAR: 1996
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: NETHERLANDS
ABSTRACT: In pyramidal cortical cells, high-voltage-activated Ca2+ currents affect seizure propagation and the release of excitatory amino acids at the corticostriatal axon terminals. The new antiepileptic drug lamotrigine (Lamictal) produced a large and dose-dependent inhibition of high-voltage-activated Ca2+ currents (IC50 = 12.3 microM) in rat cortical neurons. This action was not blocked by the dihydropyridine receptor antagonist nifedipine; instead, the response was blocked by the concomitant application of the N-type Ca2+ channel blocker, omega-conotoxin GVIA (1-3 microM) and the P-type Ca2+ channel blocker, omega-agatoxin-IVA (20-100 nM). These findings demonstrate that lamotrigine, at therapeutic doses, is capable of modulating the Ca2+ conductances involved in excitatory amino acid release in the corticostriatal pathway, partially explaining lamotrigine usefulness in the therapy of epilepsy as well as in the treatment of excitatory amino acid-induced neurotoxicity.
MINOR MESH HEADINGS: Cells,-Cultured; Membrane-Potentials-drug-effects; Nifedipine-pharmacology; Pyramidal-Cells-cytology; Rats-
MAJOR MeSH HEADINGS: *Anticonvulsants-pharmacology; *Calcium-Channel-Blockers-pharmacology; *Calcium-Channels-physiology; *Neurons-drug-effects; *Neurons-physiology; *Pyramidal-Cells-drug-effects; *Pyramidal-Cells-physiology; *Triazines-pharmacology
CHECKTAGS: Animal
PUBLICATION TYPE: JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 0; 0; 21829-25-4; 84057-84-1
NAME OF SUBSTANCE: Anticonvulsants; Calcium-Channel-Blockers; Calcium-Channels; Triazines; Nifedipine; lamotrigine
MEDLINE ACCESSION NUMBER: 1996427796
UPDATE CODE: 199702