Lamictal

Lamictal-lamotrigine. The following studies goes along with the chatter on the net of many people singing the praises of lamictal helping them where other medications have not in trying to get their chemistry straight, especially for bipolar disorder. Lamictal has helped many with their depression. I couldn't take it because it produced swollen gums

From GlaxoSmithkline news release

New study show Lamictal effective for maintenance treatment of bipolar I disorder

Research Triangle Park, NC, April 14, 2003 - Results of a landmark study published in the April issue of Archives of General Psychiatry show that Lamictalâ (lamotrigine), was effective in delaying the relapse/recurrence of any mood episode in bipolar I patients who had recently experienced and been treated for an acute manic or hypomanic episode. The study results, from one of the longest and largest trials ever conducted in bipolar disorder, point to the therapeutic effects of Lamictal in the maintenance treatment of bipolar I disorder.

online discount pharmacy for cheap medications

This 18-month study assessed the safety and efficacy of Lamictal and lithium compared to placebo in delaying the relapse/recurrence of any mood episode (depression, mania, hypomania, mixed states) in adult patients (18 and older) with bipolar I disorder. Of 349 patients who met screening criteria and entered the open-label phase, 175 met stabilization criteria and were randomized to double blind maintenance treatment. Lamictal was superior to placebo at prolonging the time to intervention for any mood episode. The most commonly reported side effects during the double-blind phase of this study were headache, infection, influenza, somnolence, insomnia, nausea, diarrhea and rash.

"These groundbreaking results indicate that Lamictal is a significant advance in the treatment of bipolar disorder," said Charles Bowden, M.D., chairman of the Department of Psychiatry, University of Texas Health Science Center, and lead author of this study. "Bipolar disorder historically has been difficult to treat. New treatments approved within the last 25 years for use in bipolar disorder are only indicated for mania."

online discount Canadian pharmacy deep discounts

Joseph R. Calabrese, M.D., director of the Mood Disorders Center at the University Hospitals of Cleveland and professor of psychiatry at the Case Western University School of Medicine, who was also a study author, said, "Bipolar studies conducted over the past 25 years have almost always focused on the short-term treatment of bipolar mania, but these data suggest that Lamictal is a mood stabilizer with long-term efficacy in bipolar depression."

About Lamictal
Lamictal is available in over 90 countries and has been used by an estimated 5 million patients worldwide.

Lamictal has been available in the U.S. since 1994 and currently is indicated as adjunctive therapy for partial seizures in adults and pediatric patients (ł2 years of age). Lamictal is also indicated as adjunctive therapy for the generalized seizures of Lennox-Gastaut syndrome in adult and pediatric patients (ł2 years of age). Lamictal is indicated for conversion to monotherapy in adults with partial seizures who are receiving treatment with a single enzyme-inducing antiepileptic drug.

The safety and effectiveness of Lamictal have not been established 1) as initial monotherapy, 2) for conversion to monotherapy from non-enzyme-inducing anti epileptic drugs (e.g. valproate), or 3) for simultaneous conversion to monotherapy from 2 or more concomitant AEDs). Safety and effectiveness in patients below the age of 16 other than those with partial seizures and the generalized seizures of Lennox-Gastaut syndrome have not been established.

In a prospectively followed cohort of 1,983 pediatric patients taking adjunctive Lamictal, there was one rash-related death. In worldwide post-marketing experience, rare cases of toxic epidermal necrolysis (TEN) and/or rash-related death have been reported, but their numbers are too few to permit a precise estimate of the rate. Lamictal ordinarily should be discontinued at the first signs of rash, unless the rash is clearly not drug-related.

The risk of nonserious rash is increased when the recommended initial dose and/or the rate of dose escalation of Lamictal is exceeded. There are suggestions, yet to be proven, that the risk of severe, potentially life- threatening rash may be increased by 1) coadministration of Lamictal with valproic acid; 2) exceeding the recommended initial dose of Lamictal; or 3) exceeding the recommended dose escalation of Lamictal. However, cases have been reported in the absence of these factors. Therefore, it is important that the dosing recommendations be followed closely. For more information on Lamictal, log on to www.lamictal.com.

GlaxoSmithKline, one of the world's leading research-based pharmaceutical and healthcare companies, is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

For more information contact
Ramona DuBose GlaxoSmithKline 919-483-2839

Updated April 15, 2003 Š 2001-2003 GlaxoSmithKline - All Rights Reserved
Legal Notices - Privacy Statement _______________________________________________ GlaxoSmithKline Announced Today the U.S. Food and Drug Administration's (FDA) approval of Lamictal 06-23-2003

FDA Approval A Major Milestone for Many with Common Mental Illness

RESEARCH TRIANGLE PARK - GlaxoSmithKline announced today the U.S. Food and Drug Administration's (FDA) approval of Lamictal(R) (lamotrigine) tablets for the long-term maintenance treatment of Bipolar I Disorder. Specifically, the FDA approved Lamictal for the maintenance treatment of adults with Bipolar I Disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy. Additionally, the FDA has noted that findings for Lamictal maintenance treatment were more robust in bipolar depression. Maintenance treatment of bipolar depression is one of the most significant medical needs in the treatment of this devastating illness. The effectiveness of Lamictal in the acute treatment of mood episodes has not been established. Lamictal is the first FDA-approved therapy since Lithium for maintenance treatment of bipolar I disorder.

Bipolar disorder, a serious, chronic illness marked by disabling mood swings from high (manic) to low (depressed) states,(1) is one of the most common mental illnesses in the United States. Recent research suggests bipolar symptoms may affect three times as many people -- nearly eight million American adults (or one in 30 people) -- as previously believed.(2) A recent study in patients with bipolar disorder showed that the total time spent depressed exceeded time spent manic by a factor of three, indicating that the depressive phases of bipolar illness were more problematic and treatment-resistant.(3) Most attempted and completed suicides occur during the depressive or mixed phases. "The finding that Lamictal possesses long-term efficacy in the treatment of bipolar disorder is extremely important," said Joseph R. Calabrese, M.D., Director of the Mood Disorders Center, University Hospitals of Cleveland and professor of psychiatry, Case Western University School of Medicine. "The last time the FDA approved a long-term treatment for bipolar disorder was lithium in the 1970s. In addition, the results are more robust for depression, the phase of illness in which patients spend the majority of their time."

The FDA's approval of Lamictal was based on the results of two landmark, randomized, placebo-controlled 18-month studies, which evaluated adult patients who were either currently or recently manic or depressed. Combined, these studies represent the largest, prospectively defined, placebo-controlled maintenance data set in bipolar disorder (1,305 patients). Following the open- label phase, patients who reached stabilization criteria entered the randomized phase. Findings from these studies show Lamictal significantly delays the time to intervention for mood episodes (depression, mania, hypomania, and mixed episodes) in patients with bipolar I disorder. Intervention was defined as additional pharmacotherapy or electroconvulsive therapy (ECT) for a mood episode or one that was emerging. Specifically, in recently depressed patients, the median days to intervention were 200 for Lamictal and 93 for placebo, which represents 115% more intervention-free days. Similarly, in recently manic or hypomanic patients, the median days to intervention was 141 for Lamictal and 85 for placebo, which represents 66 percent more intervention-free days. The combined analysis for the two studies revealed a statistically significant benefit for Lamictal over placebo in delaying the time to occurrence of both depression and mania, although the finding was more robust for depression. Lamictal was associated with a favorable tolerability profile in these studies.

The most common (=5% and numerically >placebo) side effects associated with Lamictal in the randomized phase of these studies were: nausea (14%) insomnia (10%) somnolence (9%) back pain (8%) fatigue (8%) rhinitis (7%) non-serious rash, (7%), abdominal pain (6%) dry mouth (6%), constipation (5%), vomiting (5%), exacerbation of cough (5%) pharyngitis (5%). Adverse events that occurred in =5% and were numerically more common in patients during the dose escalation phase of these trials, when patients may have been receiving concomitant psychotropic medications, compared to the monotherapy phase were: headache (25%), rash (11%), dizziness (10%), diarrhea (8%), dream abnormality (6%) and pruritus (6%).

Serious rashes requiring hospitalization and discontinuation of treatment have been reported in association with the use of Lamictal. For further important safety information on serious rash, see "About Lamictal" section below and accompanying prescribing information.

"Combined, these studies are unique in that they not only included bipolar patients who were recently manic but also others who were recently depressed, which is reflective of how bipolar patients present in the clinic," said Robert Leadbetter, M.D., Senior Director of Psychiatry, clinical Development and Medical Affairs at GlaxoSmithKline. "Going into these studies, our goal was to extend stability by delaying the time to occurrence of mood episodes and we are excited by the results achieved by patients on Lamictal, compared to those on placebo."

About Bipolar Disorder

Bipolar I disorder is characterized by the occurrence of one or more manic or mixed episodes and often individuals also have had one or more major depressive episodes; in bipolar II disorder, a person experiences one or more major depressive episodes and hypomania (a milder form of mania with less severe symptoms). If manic and depressive symptoms overlap for a period of time, it is called a "mixed" episode.

Although there is no cure for bipolar disorder, the revised APA treatment guidelines stressed that treatment can significantly improve symptoms associated with the illness.(4) One of the most serious risks of bipolar disorder is suicide, which is associated most often with the depressive phase.(5)

Suicide completion rates may be as high as 10-15 percent of patients with bipolar I disorder(6) making it one of the most serious and deadly psychiatric illnesses. Additionally, researchers estimate that more than 40 percent of individuals with bipolar disorder have problems with alcohol or drugs during their illness.(7) When left untreated, bipolar disorder can worsen and patients can experience a greater frequency of events. For more information on bipolar I disorder, visit www.bipolar.com.

About Lamictal

Lamictal is available in over 90 countries and has been used by an estimated 5 million patients worldwide.

Lamictal has been available in the U.S. since 1994 and also is indicated as adjunctive therapy for partial seizures in adults and pediatric patients ((2 years of age). Lamictal is also indicated as adjunctive therapy for the generalized seizures of Lennox-Gastaut syndrome in adult and pediatric patients ((2 years of age). Lamictal is indicated for conversion to monotherapy in adults with partial seizures who are receiving treatment with a single enzyme-inducing antiepileptic drug.

Serious rashes requiring hospitalization and discontinuation of treatment have been reported in association with the use of Lamictal. The incidence of these rashes, which have included Stevens-Johnson Syndrome, is approximately 0.8 percent (8/1,000) in pediatric patients under the age of 16 years receiving Lamictal as adjunctive therapy for epilepsy, and 0.3 percent (3/1,000) in adults on adjunctive therapy for epilepsy. In clinical trials of bipolar and other mood disorders, the rate of serious rash was 0.08 percent (0.8/1,000) in adult patients receiving Lamictal as initial monotherapy and 0.13 percent (1.3/1,000) in adult patients receiving Lamictal as adjunctive therapy.

In a prospectively followed cohort of 1,983 pediatric patients taking adjunctive Lamictal, there was one rash-related death. In worldwide post- marketing experience, rare cases of toxic epidermal necrolysis (TEN) and/or rash-related death have been reported, but their numbers are too few to permit a precise estimate of the rate. Lamictal ordinarily should be discontinued at the first signs of rash, unless the rash is clearly not drug-related.

GlaxoSmithKline, one of the world's leading research-based pharmaceutical and health care companies, is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

For prescribing information, contact Ramona DuBose at (919) 483-2839 or Danielle Brown at (212) 213-7416 or at danielle.brown@mslpr.com.

(1) American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. (2) Hirschfeld RMA, Calabrese JR, Weissman MM, et al., Screening for Bipolar Disorder in the Community. J Clin Psychiatry, January 2003; 64(1): 53-59. (3) Post, et al. "Presentations of Depression in Bipolar Illness." Clinical Neuroscience Research; 2 (2002); 142-157. (4) Hirschfeld RMA, et al. "Practice Guideline for the Treatment of Patients with Bipolar Disorder (Revision)." American Journal of Psychiatry. 2002; 159:4. (5) Tondo L, Baldessarini RJ. "Reduced Suicide Risk during Lithium Maintenance Treatment." Journal of Clinical Psychiatry 2000; 61 (suppl 9) 97-104. (6) Baldessarini RJ, et al. "Effects of Lithium Treatment and its Discontinuation on Suicidal Behavior in Bipolar Manic-Depressive Disorders." Journal of Clinical Psychiatry 1999; 60 (suppl 2) 77-84. (7) Regier DA, et al. "Comorbidity of Mental Disorders with Alcohol and other Drug Abuse: Results from the Epidemiologic Catchment Area (ECA) Study." JAMA 1990; 264:2511-2518

Br J Pharmacol. 2004 Mar 22 [Epub ahead of print] : Effect of acute and chronic lamotrigine on basal and stimulated extracellular 5-hydroxytryptamine and dopamine in the hippocampus of the freely moving rat.
Ahmad S, Fowler LJ, Whitton PS
We have studied the effects of acute and chronic treatment with the anticonvulsant lamotrigine (LTG) on basal and stimulated extracellular 5-hydroxytryptamine (5-HT), dopamine (DA) and their metabolites in the hippocampus of freely moving rats using in vivo microdialysis. Acute LTG (10 and 20 mg kg(-1)) decreased extracellular 5-HT, but had no effect on its metabolite 5-hydroxyindoleacetic acid (5-HIAA). Dialysate DA was also decreased by LTG as were its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). When transmitter release was stimulated by either 50 micro M veratridine or 100 mM K(+), marked increases in the release of both transmitters occurred, but LTG was entirely without effect on this. In chronic experiments, rats were dialysed after 2, 4, 7, 14 and 21 days of LTG treatment (5 mg kg(-1), twice daily). During this period a progressively different response to the drug was seen. After 2 days, basal extracellular 5-HT was significantly greater in treated rats than control rats. This effect persisted up to 14 days, but by 21 days 5-HT levels had returned to control values. 5-HIAA levels were unaltered and there was no effect of LTG on veratridine or K(+) stimulated 5-HT release. Similarly, DA concentrations significantly increased after 2-7 days of LTG treatment, but returned and remained at basal values thereafter. During the treatment period LTG had no effect on extracellular DOPAC, but HVA followed a similar pattern to its parent transmitter. As with 5-HT, at no time point did LTG have any effect on stimulated DA release. These neurochemical findings observed in these experiments are considered in relation to the use of LTG in bipolar disorder.

J Clin Psychiatry 2003 May;64 Suppl 5:18-24 : Rationale for using lithium in combination with other mood stabilizers in the management of bipolar disorder.
Goodwin FK.
Psychopharmacology Research Center, George Washington University Medical Center, Washington, D.C.
Bipolar disorder is a complex illness, and no single agent has been proven in randomized, placebo-controlled trials to effectively prevent and/or control all aspects of the illness-acute mania, rapid cycling, and breakthrough depression. However, for the most important issue, prophylaxis of episodes, lithium has more evidence of efficacy than any other agent. Like lithium, typical antipsychotics, carbamazepine, divalproex, and the atypical antipsychotic olanzapine are effective in the treatment of mania. Carbamazepine, divalproex, and olanzapine seem effective in preventing manic episodes but, like lithium, are less effective in preventing depression. Few trials have been conducted in the more difficult-to-treat characteristics of bipolar disorder, specifically, rapid cycling and break-through depression. For patients with rapid cycling, carbamazepine or divalproex therapy may improve symptoms, but only lamotrigine has been shown to reduce cycling, mostly in the bipolar II group, in a randomized, placebo-controlled study. For the treatment of depressive episodes, lithium and olanzapine have shown modest efficacy in controlled trials, and among the mood stabilizers, lamotrigine has the most robust effect. Because manic symptoms may respond best to one agent and depressive symptoms to another, combination therapy may be the optimal treatment for many patients with bipolar disorder. For example, lithium augmentation may improve overall response rates to treatment with carbamazepine or divalproex, and the lithium-lamotrigine combination should provide effective prevention of both mania and depression. Also, each mood stabilizer may be given at lower doses when given in combination, resulting in a reduced side effect burden and improved compliance.

Brain Inj. 2003 Aug;17(8):715-22. : Beneficial behavioural effects of lamotrigine in traumatic brain injury.
Pachet A, Friesen S, Winkelaar D, Gray S.
Brain Injury Rehabilitation Provincial Program, Alberta Hospital Ponoka, Alberta Mental Health Board, Alberta, Canada.
apachet@networc.com
Anti-convulsant medications have been employed to treat behavioural disorders resulting from traumatic brain injury (TBI). However, there is a paucity of literature investigating the use of lamotrigine to treat aggression and agitation in patients with TBI. In a single case study design, the present study examined the effectiveness of lamotrigine to treat aggressive and agitated behaviour in a 40-year-old male who sustained a severe TBI. A substantial decrease in problematic behaviours and a significant improvement in neurobehavioural functioning were observed after lamotrigine treatment. This case study provides some support for the use of lamotrigine to treat aggression and agitation in patients with a TBI. Further research is needed to examine the relationship between lamotrigine and functional outcome after TBI

Eur Neuropsychopharmacol. 2003 Aug;13 Suppl 2:S57-66. : Latest maintenance data on lamotrigine in bipolar disorder.
Calabrese JR, Vieta E, Shelton MD.
Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Cleveland, OH, USA.
Joseph.Calabrese@uhhs.com
1: Eur Neuropsychopharmacol. 2003 Aug;13 Suppl 2:S57-66. Related Articles, Links Latest maintenance data on lamotrigine in bipolar disorder. Calabrese JR, Vieta E, Shelton MD. Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Cleveland, OH, USA. Joseph.Calabrese@uhhs.com Two 18-month, randomised, double-blind trials have compared lamotrigine, lithium, and placebo as maintenance treatment in a total of 1315 recently manic or depressed patients with bipolar I disorder. Individual and combined analyses of these studies showed that both lamotrigine and lithium significantly prolonged the time to intervention for any mood episode compared with placebo. Lamotrigine was primarily effective against depression and lithium was primarily effective against mania. There was no evidence that lamotrigine induced mania/hypomania/mixed states, caused episode acceleration, or destabilised the overall course of illness. Lamotrigine was well tolerated, with a placebo-like adverse-event profile. In summary, lamotrigine is an effective and well-tolerated maintenance treatment for bipolar I disorder, providing a spectrum of efficacy complementary to that of lithium.

J Child Neurol. 2003 Jul;18(7):479-80. : Unusual side effects of lamotrigine therapy.
Das KB, Harris C, Smyth DP, Cross JH.
Neurosciences Unit, Institute of Child Health (University College London) and Great Ormond Street Hospital for Children NHS Trust, London, England.
An 8-year-old boy developed tremor, unsteadiness, chorea, and eye movement abnormalities on starting lamotrigine for myoclonic jerks. Investigations for a neurodegenerative disorder were negative. Symptoms and signs resolved on stopping lamotrigine. He was well and asymptomatic on follow-up after 4 years. Another 7-year-old boy who started on lamotrigine for suspected absence seizures developed abnormalities of eye movement with associated cognitive decline, which also resolved on discontinuing the medication. Eye movement abnormalities, involuntary movements, and behavioral changes appear to be unusual side effects of lamotrigine therapy.

Ned Tijdschr Geneeskd. 2003 Jun 7;147(23):1128-31. : [Toxic epidermal necrolysis due to lamotrigine]
[Article in Dutch]
Beerhorst K, Renier WO.
Rijnstate Ziekenhuis, afd. Neurologie, Arnhem.

A 10-year-old girl developed a progressive rash and high fever more than a month after the start of lamotrigine as add-on medication for therapy-resistant epilepsy. A skin biopsy indicated toxic epidermal necrolysis (Lyell syndrome). Because her situation deteriorated and the lesions of the skin and mucosa progressed, she was transferred to a specialised centre for burn patients. Despite maximal supportive treatment, she died 3 weeks after the first skin lesions. Even with a low initial dosage of lamotrigine followed by a slow increase, a fatal toxic epidermal necrolysis is still possible. This should be kept in mind, especially in case of concurrent administration of valproic acid.

Acta Neurol Belg. 2003 Jun;103(2):95-8. : Suspected lamotrigine-induced toxic epidermal necrolysis.
Sogut A, Yilmaz A, Kilinc M, Sogut AG, Demiralay E, Uzar H.
Baskent University Faculty of Medicine, Neurology Department.
Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare, life treating cutaneous reactions. Most cases of toxic epidermal necrolysis are drug induced. The drugs with the highest estimated incidence include co-trimoxazloe (trimethoprim-sulfamethoxazole), sulfadoxine-pyrethamine, and carbamazepine. Among other drugs, the reported reaction rates are relatively low for lamotrigine and sulbactam-ampicillin. We describe a patient who developed toxic epidermal necrolysis after either administration of lamotrigine or of ampicillin.

Bipolar Disord. 2003 Jun;5(3):203-16. : Alternatives to lithium and divalproex in the maintenance treatment of bipolar disorder.
Gnanadesikan M, Freeman MP, Gelenberg AJ.
Department of Psychiatry, University of Arizona, Tuscon 85724, USA.
OBJECTIVES: The role of lithium carbonate in the maintenance treatment of bipolar disorder is well established. Unfortunately, many patients fail to respond adequately to this agent or are unable to tolerate its adverse effects. Divalproex has become a commonly used alternative to lithium, but it also is ineffective or poorly tolerated in many patients. This article attempts to review the available data on maintenance therapy in bipolar disorder with a variety of anticonvulsants and antipsychotics (both conventional and novel), with reference to relevant studies in acute mania and bipolar depression as well. METHODS: Evidence on maintenance therapy and relevant acute-phase data were collected using MEDLINE database searches. RESULTS: Data on maintenance therapy with agents other than lithium and divalproex are sparse, and often derived from open, uncontrolled studies. Implications and flaws of available data are discussed. CONCLUSIONS: Other than lithium, there are few robust double-blind data to support the use of a variety of agents in the maintenance phase. However, uncontrolled data suggest that a number of agents merit further study.

Actas Esp Psiquiatr 2003 May;31(3):149-155: [Up-date in the treatment of rapid cycling and other refractory bipolar disorders]
[Article in Spanish]
Fernandez I, De Frutos M, Lujan E, Ortiz Del Romero J.

Introduction: Up-date in the treatment of rapid cycling and other resistant bipolar disorders. Methods: A Medline research of the literature was performed in several databases as Pub-Med, Cochrane and Embasse, from 1998 to December 2001. We have also reviewed bibliography supplied by different laboratories and several monographies. Results: 30 articles were selected: 11 reviews, 17 openlabeled studies and 2 articles on general recommendations. From the 17 open-labaled studies, 10 were on topiramate (25 to 400 mg/day) as a coadjuvant of another stabilizer. Improvement ranged from 40 to 70%; 4 adding gabapentin to the previous treatment, at the dosage of 60 to 5,600 mg/day, 27 and 92% showed improvement; 1 with mexiletine (200 to 1,200 mg/day) in which 46% were full responders, 15% partial responders and 38 % had no response, 100% response in manic or mixed and 38 % in depressed patients; and 2 with lamotrigine (50 to 500 mg/day) in which 52 to 80 % showed improvement. With risperidone at the dosage of 2-3 mg/day as coadjuvant, improvement was seen in 62 %. Olanzapine had direct short-term antimanic effects, with 49 % improvement in single drug therapy and 57 % as coadjuvant. Conclusions: More double-blind studies are necessary to assess efficacy in monotherapy or as coadjuvants, in short-term or even in monotherapy, and to compare the different treatments with each other as well as with the conventional treatment. The authors agree in pointing out the efficacy of gabapentin and topiramate associated to another stabilizer, and also of lamotrigine in depressed phases. Actas Esp Psiquiatr 2003;31(3):149-155

Psychosomatics 2003 Jun;44(3):204-8: Effect of lamotrigine on mood and cognition in patients receiving chronic exogenous corticosteroids.
Brown ES, Frol A, Bobadilla L, Nejtek VA, Perantie DC, Dhillon H.
Received April 18, 2002.

Mood changes, cognitive deficits, and psychosis have been reported during corticosteroid therapy. However, minimal data are available on the treatment of these side effects. This pilot study examined the effect of 12 weeks of open-label lamotrigine treatment (dose: mean=340 mg/day, SD=65) on mood and cognition in five patients receiving prescription corticosteroids continuously for at least 6 months before study entry. The participants showed significant improvement in cognition with lamotrigine. Two subjects who met criteria for a current major depressive episode at baseline had baseline-to-exit reductions in scores on the Hamilton Depression Rating Scale of more than 20 points. These pilot data suggest that lamotrigine may be associated with improved mood and performance on cognitive tasks in steroid-treated patients. Larger controlled trials are needed to confirm these preliminary findings.

Neurology 2003 May 13;60(9):1508-14 : Lamotrigine for HIV-associated painful sensory neuropathies: A placebo-controlled trial.
Simpson DM, McArthur JC, Olney R, Clifford D, So Y, Ross D, Baird BJ, Barrett P, Hammer AE.
Mount Sinai School of Medicine (Dr. Simpson), New York, NY.
OBJECTIVE: To evaluate the efficacy and tolerability of lamotrigine (LTG) for the treatment of pain in HIV-associated sensory neuropathies. METHODS: In a randomized, double-blind study, patients with HIV-associated distal sensory polyneuropathy (DSP) received LTG or placebo during a 7-week dose escalation phase followed by a 4-week maintenance phase. Randomization was stratified according to whether or not patients were currently using neurotoxic antiretroviral therapy (ART). RESULTS: The number of patients randomized was 92 (62 LTG, 30 placebo) in the stratum receiving neurotoxic ART and 135 (88 LTG, 47 placebo) in the stratum not receiving neurotoxic ART. Mean change from baseline in Gracely Pain Scale score for average pain was not different between LTG and placebo at the end of the maintenance phase in either stratum, but the slope of the change in Gracely Pain Scale score for average pain reflected greater improvement with LTG than with placebo in the stratum receiving neurotoxic ART (p = 0.004), as did the mean change from baseline scores on the Visual Analogue Scale for Pain Intensity and the McGill Pain Assessment Scale and patient and clinician ratings of global impression of change in pain (p J Clin Psychiatry 2003 May;64 Suppl 5:53-61 : Selecting effective long-term treatment for bipolar patients: monotherapy and combinations.
Grof P.
Department of Psychiatry, University of Ottawa Royal Ottawa Hospital, Ottawa, Ontario, Canada.
This article explores the roles of monotherapy and drug combinations in finding effective long-term treatment for individual patients with bipolar disorder. While current practice relies heavily on combinations, many bipolar patients can be successfully stabilized if the initial monotherapy is carefully selected according to the patient's clinical characteristics. The data show that (1) unequivocal responders to long-term monotherapies such as lithium, lamotrigine, or atypical neuroleptics each have a very different clinical profile, including clinical presentation and course, comorbidity, and, in particular, family history and (2) bipolar patients who respond very well to a long-term monotherapy have often completely failed on other monotherapies. Combinations appear indicated particularly in bipolar patients who are treatment-resistant to monotherapy, do not tolerate it well, or have not yet exhibited the clinical characteristics needed to choose an effective monotherapy.

Ann Pharmacother 1999 Oct;33(10):1037-42 : Factors influencing the incidence of lamotrigine-related skin rash.
Wong IC, Mawer GE, Sander JW.
Department of Pharmacy Practice, School of Pharmacy, University of Bradford, UK. i.c.k.wong@bradford.ac.uk
OBJECTIVE: To determine the incidences of serious and nonserious lamotrigine-related rash, determine the risk factors for lamotrigine-related rash, and evaluate the impact on the incidence of rash of the manufacturer's recommendation to reduce the starting dose of lamotrigine. METHODS: This was a retrospective case record survey at five tertiary referral epilepsy centers in the UK. The risk factors for lamotrigine-related rash were identified by logistic regression. The independent factors tested were gender, age, epilepsy type, concurrent medication, and starting dose of lamotrigine. The incidences of rash before and after the recommendation of reduction in starting dose were compared by chi2 analysis. RESULTS: A total of 1050 patients were included. The incidences of serious and nonserious rash were 1.1% (95% CI 0.5% to 1.8%) and 7% (95% CI 5.5% to 8.6%), respectively. Females were at higher risk of developing rash than were males, with a relative risk of 1.8 (95% CI 1.2 to 2.8). The starting dose of lamotrigine was reduced in response to the manufacturer's recommendation, and there was a significant reduction (p = 0.045) in the incidence of serious rash, from 1.5% (12/805) to 0% (0/245). However, there was no reduction in the overall incidence of lamotrigine-related rash, with 63/805 (8%) before and 23/245 (9%) after the recommendation. CONCLUSIONS: Failure to detect a reduction in the incidence of lamotrigine-related rash since the new (reduced) recommended starting dose of lamotrigine may arise from failure to reduce the starting dose below a critical threshold level, incomplete compliance with current recommendations, or insufficient sample size. The results of this and other studies show that the starting dose of lamotrigine is a significant factor affecting the incidence of rash; furthermore, this study also shows that significant reduction in the incidence of serious rash can be achieved by reducing the starting dose. Therefore, clinicians should not deviate from the recommendations.

Pharmacol Biochem Behav 2003 Feb;74(3):565-71 : Coadministration of gabapentin or MK-801 with lamotrigine slows tolerance to its anticonvulsant effects on kindled seizures.
Zhang ZJ, Russell S, Obeng K, Postma T, Obrocea G, Weiss SR, Post RM.
Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, 20814, Bethesda, MD, USA
The development of tolerance to therapeutic effects of antiepileptic drugs can be a problem in the treatment of epilepsy, bipolar disorder, and pain syndromes. In the present study, acute treatment with the new antiepileptic drug lamotrigine (LTG, 15 mg/kg) markedly suppressed seizure stage and seizure duration in amygdala-kindled rats; but this antiseizure effect was rapidly lost following 4-8 days of repeated treatment. When gabapentin (GBP, 20 mg/kg) was coadministered with LTG, the ability of LTG to suppress seizure stage, seizure duration, and after-discharge (AD) duration was markedly extended. In addition, GBP coadministration with LTG decreased the number of animals that developed LTG-related running fits (Stage 6 seizures) and lengthened the number of days required to develop running fits or complete tolerance. Neither acute nor repeated treatment with MK-801 (0.3 mg/kg), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, had effects on kindled seizures. However, cotreatment with MK-801 markedly extended the anticonvulsant effects of LTG on the three seizure indices and reduced running fits. These data indicate that cotreatment with either GBP or MK-801 slows tolerance development to the anticonvulsant effects of LTG on kindled seizures. Therapeutic implications of the present study remain to be explored.

CNS Drugs 2003;17(1):9-25 : Bipolar depression: management options.
Malhi GS, Mitchell PB, Salim S.
School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.
Bipolar depression is the predominant abnormal mood state in bipolar disorder. However, despite the key pertinence of this phase of the condition, the focus of research and indeed of clinical interest in the management of bipolar disorder has been mainly on mania. Bipolar depression has been largely neglected, and early studies often failed to distinguish depression due to major unipolar depression from that due to bipolar disorder. Consequently, many treatments used in the management of major depression have been adopted for use in bipolar depression without any robust evidence of efficacy. The selective serotonin reuptake inhibitors (SSRIs), bupropion, tricyclic antidepressants and monoamine oxidase inhibitors are all effective antidepressants in the management of bipolar depression. They are all associated with a small risk of antidepressant-induced mood instability. The mood stabilisers lithium, carbamazepine and valproate semisodium (divalproex sodium) all appear to have modest acute antidepressant properties. Among these, lithium is supported by the strongest data, but the use of lithium in the treatment of bipolar depression as a monotherapeutic agent is limited by its slow onset of action. Recently, there has been a growing body of evidence suggesting that lamotrigine may have particular effectiveness in both the acute and prophylactic management of bipolar depression. Clinical management of bipolar depression involves various combinations of antidepressants and mood stabilisers and is partly determined by the context in which the depressive episode occurs. In general, 'de novo' and 'breakthrough' (where the patient is already receiving medication) bipolar depression may be successfully managed by initiating mood stabiliser monotherapy, to which an antidepressant or second mood stabiliser may be added at a later date, if necessary. Breakthrough episodes of bipolar depression occurring in patients receiving combination therapy (two mood stabilisers or a mood stabiliser plus an antidepressant) require either switching of ongoing medications or further augmentation. If this fails, then novel strategies or ECT should be considered. Bipolar depression is a disabling illness and the predominant mood state for the vast majority of those with bipolar disorder. It therefore warrants prompt management once suitably diagnosed, especially as it is associated with a considerable risk of suicide and in the majority of instances is eminently treatable.

Am J Clin Dermatol 2003;4(1):21-30 : Adverse cutaneous reactions to mood stabilizers.
Warnock JK, Morris DW.
University of Oklahoma Health Sciences Center, Tulsa, Oklahoma, USA.
Of all the psychotropic medications currently available, the mood-stabilizing agents have the highest incidence of severe and life-threatening adverse cutaneous drug reactions (ACDRs). An exanthematous eruption in a patient treated with a mood-stabilizing agent should be viewed as possibly being the initial symptom of a severe and life-threatening ACDR, such as a hypersensitivity reaction, Stevens-Johnson syndrome, or toxic epidermal necrolysis. The combination of mood-stabilizing agents may increase the risk of such reactions. The mood-stabilizing agents addressed in this article are carbamazepine, lithium carbonate, valproic acid, topiramate, lamotrigine, gabapentin, and oxcarbazepine. Prior to the initiation of a mood stabilizer, the potential benefits, risks, and adverse effects should be communicated to the patient. If possible, slow dose escalation should be attempted by the physician. Patients should also be advised to seek medical attention if they suspect a drug-induced skin reaction. If the physician suspects a severe ACDR, the offending agent should be removed immediately.

CNS Drugs 2003;17(1):9-25 : Bipolar depression: management options
. Malhi GS, Mitchell PB, Salim S.
School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.
Bipolar depression is the predominant abnormal mood state in bipolar disorder. However, despite the key pertinence of this phase of the condition, the focus of research and indeed of clinical interest in the management of bipolar disorder has been mainly on mania. Bipolar depression has been largely neglected, and early studies often failed to distinguish depression due to major unipolar depression from that due to bipolar disorder. Consequently, many treatments used in the management of major depression have been adopted for use in bipolar depression without any robust evidence of efficacy. The selective serotonin reuptake inhibitors (SSRIs), bupropion, tricyclic antidepressants and monoamine oxidase inhibitors are all effective antidepressants in the management of bipolar depression. They are all associated with a small risk of antidepressant-induced mood instability. The mood stabilisers lithium, carbamazepine and valproate semisodium (divalproex sodium) all appear to have modest acute antidepressant properties. Among these, lithium is supported by the strongest data, but the use of lithium in the treatment of bipolar depression as a monotherapeutic agent is limited by its slow onset of action. Recently, there has been a growing body of evidence suggesting that lamotrigine may have particular effectiveness in both the acute and prophylactic management of bipolar depression. Clinical management of bipolar depression involves various combinations of antidepressants and mood stabilisers and is partly determined by the context in which the depressive episode occurs. In general, 'de novo' and 'breakthrough' (where the patient is already receiving medication) bipolar depression may be successfully managed by initiating mood stabiliser monotherapy, to which an antidepressant or second mood stabiliser may be added at a later date, if necessary. Breakthrough episodes of bipolar depression occurring in patients receiving combination therapy (two mood stabilisers or a mood stabiliser plus an antidepressant) require either switching of ongoing medications or further augmentation. If this fails, then novel strategies or ECT should be considered. Bipolar depression is a disabling illness and the predominant mood state for the vast majority of those with bipolar disorder. It therefore warrants prompt management once suitably diagnosed, especially as it is associated with a considerable risk of suicide and in the majority of instances is eminently treatable.

Acta Anaesthesiol Scand 2002 Nov;46(10):1261-4 : Lamotrigine monotherapy for control of neuralgia after nerve section.
Sandner-Kiesling A, Rumpold Seitlinger G, Dorn C, Koch H, Schwarz G.
Department of Anesthesiology & Intensive Care Medicine and Plastic & Reconstructive Surgery, Karl Franzens-University, Graz, Austria.
BACKGROUND: We present six patients treated only with the new-generation anticonvulsant lamotrigine to define its sole effect on neuralgia after nerve section. METHODS: Previous surgical or pharmacological attempts failed to relieve this neuropathic pain in our patients. Before initiation of lamotrigine therapy, patients reported spontaneous and touch-evoked shooting pain followed by periods of burning pain. No breakthrough medication was needed during the maintenance phase of 1-23 months. Data were acquired by a pain diary on a weekly basis. RESULTS: With 75-300 mg of lamotrigine per day, the burning and shooting pain intensity was relieved by 33-100%. Most obviously, the attack frequency of the shooting pain was reduced by 80-100%. No adverse effects were observed. CONCLUSION: We conclude that lamotrigine may be beneficial in the treatment of neuralgia after nerve section following the failure of previous pharmacological or surgical attempts.

Mutat Res 2003 Jan 10;534(1-2):197-9 : Valproic acid and lamotrigine treatment during pregnancy. The risk of chromosomal abnormality.
Ozkinay F, Cogulu O, Gunduz C, Yilmaz D, Kultursay N.
Department of Paediatrics, Faculty of Medicine, Ege University, Izmir, Turkey
A baby born to an epileptic mother had dysmorphological features associated with 47,XXX karyotype. The mother had been treated with valproic acid (1800mg per day) and lamotrigine (100mg per day) throughout pregnancy. Dysmorphological features detected in baby were intrauterine growth retardation, hypertelorism, flattened nasal bridge, low set malformed auriculas, micrognathia, very small an bow-shaped mouth with thin upper lip, cleft palate, arachnodactyly, camptodactyly, secundum atrial septal defect, bilateral hammer toes and decreased creases on the soles. At 6 months old she showed motor retardation. The molecular analysis of parents revealed that extra X chromosome was inherited from the mother. In this case whether the dysmorphological features and 47,XXX karyotype were caused by lamotrigine and valproic acid treatment during pregnancy or coincidence is in question.

Epilepsia 2002 Oct;43(10):1161-7 : Preliminary results on pregnancy outcomes in women using lamotrigine.
Tennis P, Eldridge RR; International Lamotrigine Pregnancy Registry Scientific Advisory Committee.
Worldwide Epidemiology Department,
GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA.
PST49347@gsk.com
PURPOSE: In 1992, the International Lamotrigine Pregnancy Registry was initiated to enroll prospectively and to monitor pregnancies exposed to lamotrigine (LTG) for the occurrence of major birth defects. This study presents results as of September 2001 on 168 outcomes exposed to LTG monotherapy and 166 outcomes after pregnancies exposed to LTG polytherapy during the first trimester. METHODS: LTG pregnancy exposures are voluntarily reported to the registry by health care providers before they are aware of each pregnancy outcome. Pregnancy-outcome ascertainment is obtained through subsequent follow-up with the reporting health care provider, and each reported birth defect is reviewed by an expert pediatrician. The percentage with major birth defects in pregnancies with known birth defect status was calculated for LTG monotherapy and for polytherapy stratified by trimester of exposure. RESULTS: The registry identified 334 first-trimester LTG pregnancy outcomes exposed to LTG monotherapy or polytherapy during the first trimester and involving either a live birth with or without a major birth defect or an abortion with a major birth defect. After exposure to LTG monotherapy, the percentage with major birth defects exposed to LTG monotherapy was three (1.8%) of 168 [95% confidence interval (CI), 0.5-5.5%]. There were five (10%) major birth defects observed in 50 outcomes after LTG polytherapy involving valproic acid (VPA; 95% CI, 3.7-22.6%) during the first trimester. The observed proportion of major defects after LTG polytherapy without VPA during the first trimester was five (4.3%) of 116 (95% CI, 1.6-10.3%). No specific patterns of major birth defects in any subgroup or within the registry as a whole were observed. CONCLUSIONS: The sample sizes for individual regimens are too small to rule out small increases in frequency of all major birth defects or even large increases in frequency of rare major birth defects. However, the percentage of outcomes with major birth defects after LTG monotherapy in this study and in another similar pregnancy registry in the United Kingdom did not differ from that reported in the recent literature for women with epilepsy receiving antiepileptic drug monotherapy (4%). The frequency of major malformations after exposures of LTG-VPA is higher than that after the LTG monotherapy or LTG polytherapy regimens without VPA. Although there are published data on frequency of major malformations after VPA exposures in pregnancy, between-study differences in methods and source populations and the wide confidence intervals around the estimate for LTG and VPA limit the utility of comparison with such data, and no conclusions are made at this time about this combination. The continued registration of exposed pregnancies to an exposure registry as early as possible in the pregnancy before any knowledge of the outcome, and before any prenatal testing, will enhance the power of such data.

Neurology 2002 Sep 10;59(5 Suppl 2):S14-7 : Use of anticonvulsants for treatment of neuropathic pain.
Backonja MM.
Emerging evidence from animal models of neuropathic pain suggests that many pathophysiologic and biochemical changes occur in the peripheral and central nervous system. Similarities between the pathophysiologic phenomena observed in some epilepsy models and in neuropathic pain models justify the use of anticonvulsants in the symptomatic management of neuropathic pain. Positive results from laboratory and clinical trials further support such use. Carbamazepine was the first of this class of drugs to be studied in clinical trials and has been longest in use for treatment of neuropathic pain. Clinical trial data support its use in treating trigeminal neuralgia, but data for treatment of painful diabetic neuropathy are less convincing. Use of newer anticonvulsants has marked a new era in the treatment of neuropathic pain. Gabapentin has demonstrated efficacy, specifically in painful diabetic neuropathy and postherpetic neuralgia. Lamotrigine has been reported to be effective in relieving pain from trigeminal neuralgia refractory to other treatments, HIV neuropathy, and central post-stroke pain. Results from clinical trials of phenytoin are equivocal. Zonisamide's mechanisms of action suggest that it would be effective in controlling neuropathic pain symptoms. Other anticonvulsants, including lorazepam, valproate, topiramate, and tiagabine, have also been under investigation. Anecdotal experience provides support for studies with oxcarbazepine and levetiracetam for treating neuropathic pain. Evidence supporting the efficacy of anticonvulsants in treatment of such pain is evolving. Additional clinical trials should provide information that will better define their role in neuropathic pain

Epilepsia 2002 Sep;43(9):993-1000 Related Articles, Links Gabapentin versus lamotrigine monotherapy: a double-blind comparison in newly diagnosed epilepsy.
CONCLUSIONS: GBP and LTG monotherapy were similarly effective and well tolerated in patients with newly diagnosed epilepsy.

Lamotrigine in the treatment of bipolar disorder.
Lamotrigine has undergone a remarkable series of systematic studies since 1994 that now establish it as an efficacious, well-tolerated treatment in bipolar disorder. Its efficacy principally addresses both acute and maintenance phase benefits on depressive symptomatology. These benefits have been demonstrated in placebo-controlled studies, rapid cycling patients, bipolar I and II patients and monotherapy as well as in combination therapy, although this has been less well studied. The drug is exceptionally well-tolerated in long-term treatment, although initial dosing requires gradual dosage escalation to avoid the risk of inducing serious rashes with features within the spectrum of Stevens-Johnson syndrome. Administration with valproate requires a slower dosage titration, whereas, as with many drugs, administration with carbamazepine requires a more rapid dosage increase. In contrast to marketed antidepressants, lamotrigine appears not to induce manic or hypo-manic episodes, nor to increase cycling frequency. This combination of properties makes it a first-choice treatment for acute bipolar depression and continuation treatment, especially, but not limited to, prophylaxis against recurrent depression and depressive symptoms. Lamotrigine appears not to have acute antimanic properties. A small number of studies suggest a broader spectrum of efficacy, including in some axis I disorders that are comorbidly associated with bipolar disorder.

Lamotrigine as an augmentation agent in treatment-resistant depression.
ACKGROUND: The anticonvulsant lamotrigine has been reported to be efficacious and well tolerated as monotherapy in the treatment of bipolar patients as well as in treatment-refractory bipolar disorder. However, there is a paucity of research on the use of lamotrigine as an augmentation agent in treatment-refractory unipolar major depressive disorder. METHOD: This study was a retrospective chart review on the efficacy of lamotrigine augmentation in 37 individuals diagnosed with chronic or recurrent major depressive disorder (DSM-IV) who had failed to respond adequately to at least 2 previous trials of antidepressants. Thirty-one patients who were on lamotrigine treatment for at least 6 weeks (6 discontinued prematurely due to adverse events) took a mean dose of 112.90 mg/day for a mean of 41.80 weeks. The primary efficacy parameter for this study was the Clinical Global Impressions scale, which was retrospectively applied. In addition, these data were supplemented by an analysis of prospectively rated Global Assessment of Functioning scores. RESULTS: On the basis of intent-to-treat analysis, response rates were as follows: 40.5% (15/37) much improved or very much improved, 21.6% (8/37) mildly improved, and 37.8% (14/37) unchanged. The percentage of patients who were rated much or very much improved and completed 6 weeks on the drug was 48.4% (15/31). No differences were found in the doses of lamotrigine given to responders and nonresponders. CONCLUSION: Analyses revealed that lamotrigine treatment was most effective for patients who had been depressed for shorter periods of time and had failed fewer previous trials of antidepressants. Data also suggested a trend toward increased response for patients with comorbid anxiety disorders and/or chronic pain syndromes.

Third generation anticonvulsants in bipolar disorder: a review of efficacy and summary of clinical recommendations.
BACKGROUND: To review the literature on efficacy of third generation anticonvulsants for treatment of bipolar disorder and provide clinical recommendations. METHOD: Open and controlled studies, case reports, and case series on the efficacy of lamotrigine, gabapentin, topiramate, tiagabine, and zonisamide were located through electronic searches of several databases, by manual search of proceedings of international meetings, and through contacting authors of recent reports. RESULTS: Lamotrigine is the best studied anticonvulsant and has efficacy in acute bipolar depression and in longer term treatment of bipolar depression as well as rapid-cycling bipolar II disorder but not in acute mania. Open reports suggest usefulness of gabapentin as an adjunct in bipolar disorder, but double-blind trials failed to confirm efficacy in acute mania and treatment-resistant rapid-cycling bipolar disorder. Topiramate is reported to be effective in acute mania and rapid-cycling bipolar disorder in several open studies, but methodological problems in a double-blind study led to a failed study in acute mania. However, topiramate may lead to weight loss in some patients. Zonisamide deserves further investigation, but tiagabine does not appear to be useful in acute mania. CONCLUSION: Lamotrigine clearly fills an unmet need in treating bipolar depression and rapid-cycling bipolar disorder. Other third generation anticonvulsants with the exception of tiagabine offer promise but require confirmation of their efficacy from double-blind studies

Lamotrigine as adjunct to paroxetine in acute depression: a placebo-controlled, double-blind study.
BACKGROUND: Mood stabilizers appear to be more potent in treating mania than depression. The anticonvulsant lamotrigine has been shown to be effective for bipolar depression. This study examines putative antidepressive properties of lamotrigine in a mainly unipolar routine clinical patient population. METHOD: Forty patients with a depressive episode (DSM-IV criteria) requiring psychiatric intervention received lamotrigine or placebo using a fixed dose escalation scheme with a target dose of 200 mg/day for 9 weeks. Additionally, all patients were treated with paroxetine. Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impressions scale (CGI) ratings were used to monitor therapeutic efficacy. RESULTS: Adjunctive treatment with lamotrigine did not result in a significant difference in HAM-D total score at the endpoint of the study when compared with paroxetine alone. However, lamotrigine demonstrated significant efficacy on core depressive symptoms as reflected by HAM-D items 1 (depressed mood; p = .0019), 2 (guilt feelings; p = .0011), and 7 (work and interest; p = .049) and the CGI-Severity of Illness scale (p < .0001). Patients receiving lamotrigine had fewer days on treatment with benzodiazepines and fewer withdrawals for treatment failure. Lamotrigine appeared to accelerate the onset of action of the antidepressant. Two patients on lamotrigine treatment developed neutropenia, and 1 developed a benign rash. There was no detectable pharmacokinetic interaction between lamotrigine and paroxetine. CONCLUSION: Lamotrigine might have antidepressive properties in unipolar patients and may accelerate onset of action when given in combination with typical antidepressants.

Bipolar disorders and the effectiveness of novel anticonvulsants.
The discovery that valproic acid is helpful in the management of patients with rapid-cycling bipolar disorder led to an explosion of research culminating in the third-generation anticonvulsants. Refractory depressive phases are frequent in bipolar disorders. No studies to date have shown that gabapentin is effective in bipolar mania or hypomania. Lamotrigine may have a role in treating bipolar depressive episodes, but it is not a particularly effective antimanic agent. Topiramate has shown encouraging results in both depressed and manic bipolar patients, and it may also promote weight loss. The new anticonvulsants are promising agents for the treatment of bipolar disorders, but they are heterogeneous with regard to their efficacy, target symptoms, and adverse event profiles.

1: Acta Anaesthesiol Scand 2002 Nov;46(10):1261-4 : Lamotrigine monotherapy for control of neuralgia after nerve section.
Sandner-Kiesling A, Rumpold Seitlinger G, Dorn C, Koch H, Schwarz G.
Department of Anesthesiology & Intensive Care Medicine and Plastic & Reconstructive Surgery,
Karl Franzens-University, Graz, Austria.
BACKGROUND: We present six patients treated only with the new-generation anticonvulsant lamotrigine to define its sole effect on neuralgia after nerve section. METHODS: Previous surgical or pharmacological attempts failed to relieve this neuropathic pain in our patients. Before initiation of lamotrigine therapy, patients reported spontaneous and touch-evoked shooting pain followed by periods of burning pain. No breakthrough medication was needed during the maintenance phase of 1-23 months. Data were acquired by a pain diary on a weekly basis. RESULTS: With 75-300 mg of lamotrigine per day, the burning and shooting pain intensity was relieved by 33-100%. Most obviously, the attack frequency of the shooting pain was reduced by 80-100%. No adverse effects were observed. CONCLUSION: We conclude that lamotrigine may be beneficial in the treatment of neuralgia after nerve section following the failure of previous pharmacological or surgical attempts

Neurology 2002 Sep 10;59(5 Suppl 2):S14-7 : Use of anticonvulsants for treatment of neuropathic pain.
Backonja MM.
Department of Neurology, University of Wisconsin Hospital and Clinics, Room H6/574,
600 Highland Avenue, Madison, WI 53792-5132, USA.
backonja@neurology.wisc.edu
Emerging evidence from animal models of neuropathic pain suggests that many pathophysiologic and biochemical changes occur in the peripheral and central nervous system. Similarities between the pathophysiologic phenomena observed in some epilepsy models and in neuropathic pain models justify the use of anticonvulsants in the symptomatic management of neuropathic pain. Positive results from laboratory and clinical trials further support such use. Carbamazepine was the first of this class of drugs to be studied in clinical trials and has been longest in use for treatment of neuropathic pain. Clinical trial data support its use in treating trigeminal neuralgia, but data for treatment of painful diabetic neuropathy are less convincing. Use of newer anticonvulsants has marked a new era in the treatment of neuropathic pain. Gabapentin has demonstrated efficacy, specifically in painful diabetic neuropathy and postherpetic neuralgia. Lamotrigine has been reported to be effective in relieving pain from trigeminal neuralgia refractory to other treatments, HIV neuropathy, and central post-stroke pain. Results from clinical trials of phenytoin are equivocal. Zonisamide's mechanisms of action suggest that it would be effective in controlling neuropathic pain symptoms. Other anticonvulsants, including lorazepam, valproate, topiramate, and tiagabine, have also been under investigation. Anecdotal experience provides support for studies with oxcarbazepine and levetiracetam for treating neuropathic pain. Evidence supporting the efficacy of anticonvulsants in treatment of such pain is evolving. Additional clinical trials should provide information that will better define their role in neuropathic pain.