Does comorbid bipolar disorder increase neuropsychological impairment in children and adolescents with ADHD?

OBJECTIVE: To assess differences in executive functioning between children and adolescents with attention-deficit/hyperactivity disorder (ADHD) comorbid or not with bipolar disorder (BD), and to study the neuropsychological profile of subjects with the comorbidity in a clinical sample from a developing country. METHOD: Case-control study comparing 23 participants with BD + ADHD and 85 ADHD-only subjects aged 6 to 17 years old. Both groups were drug-free. Executive function domains were assessed with the Stroop Test, the Wisconsin Card Sorting Test, and the Continuous Performance Test II. RESULTS: The group with juvenile BD + ADHD showed a significantly worse performance on the Stroop task, including time in color (p = 0.002), time in color-word (p < 0.001), interference, number or errors in color and color-word (p = 0.001), and number of errors in word cards (p = 0.028). No between-group differences were found in other tests. CONCLUSIONS: Our findings suggest that ADHD-only and ADHD + BD do not show differences in inhibitory control and set-shifting domains. However, children and adolescents with BD and comorbid ADHD show greater impairment in processing speed and interference control. This suggests a potentially higher impairment in the dorsolateral prefrontal cortex and may be a potential neuropsychological signature of juvenile BD comorbid with ADHD.

Does comorbid bipolar disorder increase neuropsychological impairment in children and adolescents with ADHD?

Objective: To assess differences in executive functioning between children and adolescents with attention-deficit/hyperactivity disorder (ADHD) comorbid or not with bipolar disorder (BD), and to study the neuropsychological profile of subjects with the comorbidity in a clinical sample from a developing country. Method: Case-control study comparing 23 participants with BD + ADHD and 85 ADHD-only subjects aged 6 to 17 years old. Both groups were drug-free. Executive function domains were assessed with the Stroop Test, the Wisconsin Card Sorting Test, and the Continuous Performance Test II. Results: The group with juvenile BD + ADHD showed a significantly worse performance on the Stroop task, including time in color (p = 0.002), time in color-word (p < 0.001), interference, number or errors in color and color-word (p = 0.001), and number of errors in word cards (p = 0.028). No between-group differences were found in other tests. Conclusions: Our findings suggest that ADHD-only and ADHD + BD do not show differences in inhibitory control and set-shifting domains. However, children and adolescents with BD and comorbid ADHD show greater impairment in processing speed and interference control. This suggests a potentially higher impairment in the dorsolateral prefrontal cortex and may be a potential neuropsychological signature of juvenile BD comorbid with ADHD. .

The Val66Met polymorphism at the BDNF gene does not influence Wisconsin Card Sorting Test results in children and adolescents with bipolar disorder.

OBJECTIVES: To assess the role of the Val66Met polymorphism at the brain-derived neurotrophic factor (BDNF) gene on the performance of children and adolescents with bipolar disorder [juvenile bipolar disorder (JBD)] on the Wisconsin Card Sorting Test (WCST). METHODS: Children and adolescents were assessed by the K-SADS-PL and a clinical evaluation for BD and comorbid conditions. Manic and depressive symptoms were assessed with the Young Mania Rating Scale and the Children Depression Rating Scale - Reviewed. The Val66Met polymorphism at the BDNF was genotyped from a blood sample. Patients' IQ and executive functions were assessed by a standard cognitive flexibility test (WCST). RESULTS: Fifty-three subjects were included in the study. No significant difference was observed between the Val/Val and Val/Met+Met/Met groups on any WCST scores in the MANCOVA (F48,5 = .76; p = .59; Perseverative Errors, p = .66; Nonperseverative Errors, p = .58; Categories Completed, p = .34; Attempts to Reach First Category, p=.64; and Percentage of Conceptual Level Responses, p = .99). CONCLUSIONS: Our findings from this sample of children and adolescents with BD do not replicate results from studies of adults and suggest the existence of differences in the neurobiology of this disorder across the life cycle. Investigations of larger samples are necessary to confirm these data.

The Val66Met polymorphism at the BDNF gene does not influence Wisconsin Card Sorting Test results in children and adolescents with bipolar disorder

OBJECTIVES: To assess the role of the Val66Met polymorphism at the brain-derived neurotrophic factor (BDNF) gene on the performance of children and adolescents with bipolar disorder [juvenile bipolar disorder (JBD)] on the Wisconsin Card Sorting Test (WCST). METHODS: Children and adolescents were assessed by the K-SADS-PL and a clinical evaluation for BD and comorbid conditions. Manic and depressive symptoms were assessed with the Young Mania Rating Scale and the Children Depression Rating Scale - Reviewed. The Val66Met polymorphism at the BDNF was genotyped from a blood sample. Patients' IQ and executive functions were assessed by a standard cognitive flexibility test (WCST). RESULTS: Fifty-three subjects were included in the study. No significant difference was observed between the Val/Val and Val/Met+Met/Met groups on any WCST scores in the MANCOVA (F48,5 = .76; p = .59; Perseverative Errors, p = .66; Nonperseverative Errors, p = .58; Categories Completed, p = .34; Attempts to Reach First Category, p=.64; and Percentage of Conceptual Level Responses, p = .99). CONCLUSIONS: Our findings from this sample of children and adolescents with BD do not replicate results from studies of adults and suggest the existence of differences in the neurobiology of this disorder across the life cycle. Investigations of larger samples are necessary to confirm these data.

An open-label trial of risperidone in children and adolescents with severe mood dysregulation.

OBJECTIVE: The diagnosis and treatment of youth with severe nonepisodic irritability and hyperarousal, a syndrome defined as severe mood dysregulation (SMD), has been the focus of increasing concern and debate among clinicians and researchers. Our main objective was to assess the effectiveness of risperidone for youths with SMD. METHODS: An 8-week open label trial with risperidone was conducted. We extensively assessed 97 subjects with semistructured and clinical interviews and enrolled 21 patients in the study. Risperidone was titrated from 0.5 to 3 mg/day in the first 2 weeks. Evaluations were performed at baseline and weeks 2, 4, 6, and 8. Clinical outcome measures were (1) Aberrant Behavior Checklist-Irritability Subscale, (2) Clinical Global Impressions, and (3) severity of co-morbid conditions. RESULTS: We found a significant reduction of the Aberrant Behavior Checklist-Irritability scores during the trial after risperidone use (p < 0.001). The scores at week 2 (mean = 12.03; standard error [SE] = 2.94), week 4 (mean = 15.48; SE = 2.93), week 6 (mean = 12.29; SE = 2.86), and week 8 (mean = 11.28; SE = 3.06) were significantly reduced compared with the baseline mean score (mean = 25.89; SE = 2.76) (p < 0.001). We also found an improvement in attention-deficit/hyperactivity disorder, depression, and global functioning (p < 0.001). CONCLUSION: Risperidone was effective in reducing irritability in SMD youth. To the best of our knowledge, this is the first psychopharmacological trial in this group of patients with positive results. Further randomized, controlled studies are needed.

Are family variables associated with ADHD, inattentive type? A case-control study in schools.

Attention-deficit/hyperactivity disorder (ADHD) seems to be associated with significant psychosocial adversity. However, few studies assessed the role of environmental, social and interpersonal factors specifically in ADHD, inattentive type (ADHD-I). Thus, this study aims to investigate whether family environment risk factors are associated with ADHD-I. In a case-control study, we assessed a non-referred sample of 100 children and adolescents with ADHD-I and 100 non-ADHD controls (6-18 years old). They were systematically evaluated through structured diagnostic interviews. The following family adversity measures were used: Rutter's family adversity index (marital discord, low social class, large family size, paternal criminality, maternal mental disorder), Family Environment Scale (FES) (subscores of cohesion, expressiveness and conflict) and Family Relationship Index (FRI) (based on the subscores above). After adjusting for confounding factors (social phobia and maternal history of ADHD), the odds ratio (OR) for ADHD-I increased as the number of Rutter's indicators increased. Families of children with lower FES cohesion subscores presented higher OR for ADHD-I (OR 1.24; 95% confidence interval 1.05-1.45). Lower levels of FRI, a general index of family relationship, were also related to higher risk of ADHD-I (OR 1.11; 95% confidence interval 1.03-1.21). Our findings suggest that family adversity (in general), low family cohesion and low FRI (in particular) are associated with an increase in the risk for ADHD-I. However, the cross-sectional nature of the study limits our ability to infer causality.

Methylphenidate combined with aripiprazole in children and adolescents with bipolar disorder and attention-deficit/hyperactivity disorder: a randomized crossover trial.

In clinical samples, juvenile bipolar disorder (JBPD) is frequently accompanied by co-morbid attention-deficit/hyperactivity disorder (ADHD). Clinical trials assessing combined psychopharmacological interventions in this population are scarce, and methylphenidate (MPH) may worsen manic symptoms. We conducted a randomized crossover trial with MPH and placebo (2 weeks each) combined with aripiprazole in children and adolescents (n = 16; 8-17 years old) with JBPD and ADHD who had a significant response in manic symptoms with aripiprazole but still presented clinically significant symptoms of ADHD. ADHD, manic, and depressive symptoms were assessed by means of standard scales. Fourteen out of the 16 subjects completed the trial. No significant differences between the effects of methylphenidate and placebo were detected in ADHD (F(1, 43.22) = 0.00; p = 0.97) or manic (F(1, 40.19) = 0.93; p = 0.34) symptoms. Significant improvement in depressive symptoms was observed in the MPH group (F(1,19.03) = 7.75; p = 0.01) according to a secondary self-reported outcome measure. One patient using aripiprazole and MPH discontinued the trial due to the onset of a severe mixed episode. No other significant adverse events were observed. Although MPH did not worsen manic symptoms, it was not more effective than placebo in improving ADHD symptoms in children and adolescents with JBPD co-morbid with ADHD stabilized with aripiprazole. Further investigations are warranted. This study is registered at www.clinicaltrials.gov under the identifier NCT00305370.

Aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder: a pilot randomized clinical trial.

OBJECTIVE: To assess response to treatment with aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder (ADHD). METHOD: Children and adolescents were extensively assessed according to DSM-IV criteria for bipolar disorder comorbid with ADHD (n = 710). Those with this comorbidity who were acutely manic or in mixed states were randomly assigned in a 6-week double-blind, placebo-controlled trial to aripiprazole (n = 18) or placebo (n = 25). Primary outcome measures were assessed weekly and included the Young Mania Rating Scale; the Swanson, Nolan, and Pelham Scale-Version IV; and weight. Secondary outcome measures were the Clinical Global Impressions-Severity of Illness scale, the Child Mania Rating Scale-Parental Version (CMRS-P), the Children's Depression Rating Scale-Revised, the Kutcher Adolescent Depression Scale, and adverse events. The trial was conducted at the Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil, from January 2005 to November 2007. RESULTS: The group receiving aripiprazole showed a significantly greater reduction in YMRS scores (P = .02, effect size [ES] = 0.80), CMRS-P scores (P = .02; ES = 0.54), and CGI-S scores (P = .04; ES = 0.28) from baseline to endpoint than the placebo group. In addition, higher rates of response (P = .02) and remission (P = .01) were found for the aripiprazole group. No significant between-group differences were found in weight, ADHD symptoms, and depressive symptoms. Adverse events significantly more frequent in the aripiprazole group were somnolence and sialorrhea. CONCLUSION: Aripiprazole was effective in reducing manic symptoms and improving global functioning without promoting severe adverse events or weight gain. No significant treatment effect in ADHD symptoms was observed. Studies are needed to assess psychopharmacologic interventions for improving ADHD symptoms in juvenile bipolar disorder comorbid with ADHD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00116259.

Aripiprazole in juvenile bipolar disorder comorbid with attention-deficit/hyperactivity disorder: an open clinical trial.

INTRODUCTION: Juvenile bipolar disorder (JBD) is a highly impairing chronic mental health condition that affects children and adolescents' overall functioning. Comorbidity with attention-deficit/hyperactivity disorder (ADHD) is extremely prevalent and may determine worse response to treatment. Few investigations have addressed the use of recent atypical antipsychotics in JBD, although several guidelines suggest their use. METHODS: We conducted a 6-week open trial with aripiprazole in 10 children and adolescents with JBD comorbid with ADHD to assess impact on mania and ADHD symptoms, respectively, by means of the Young Mania Rating Scale and the Swanson, Nolan and Pelham Scale, as well as on global functioning (Clinical Global Impressions-Severity), and adverse events. RESULTS: Significant improvement in global functioning scores (F=3.17, P=.01, effect size=0.55), manic symptoms (F=5.63, P<.01; ES=0.93), and ADHD symptoms (t=3.42, P<.01;ES=1.05) were detected. Although an overall positive tolerability was reported, significant weight gain (F=3.07, P=.05) was observed. CONCLUSION: Aripiprazole was effective in improving mania and ADHD symptoms, but neither JBD nor ADHD symptom remission was observed in most of the cases. Randomized placebo-controlled trials for JBD and ADHD are needed.

Topiramate in adolescents with juvenile bipolar disorder presenting weight gain due to atypical antipsychotics or mood stabilizers: an open clinical trial.

BACKGROUND: Many children and adolescents with bipolar disorder (BD) do not adhere to the pharmacological treatment due to weight gain. This investigation aims to describe response, side effects, and weight changes in a sample of youths with BPD while receiving topiramate for 11 weeks during the treatment maintenance phase. METHODS: Ten consecutive outpatients with BPD (11-17 years) using a single mood stabilizer and/or an antipsychotic presenting weight gain over 5% of their baseline weight were enrolled in this 11-week protocol. Their medication was switched to topiramate during the first 4 weeks. The Young Mania Rating Scale (Y-MRS) was the main outcome measure to assess response to the treatment in a weekly basis. Side effects and weight were also assessed weekly. RESULTS: In repeated-measure analysis of variance (ANOVA), we found a significant reduction in both the YMRS scores (F = 10.21; p ,0.01) and in weight (F = 8.04; p ,0.01) during the trial. CONCLUSIONS: These initial findings suggesting antimanic effects for topiramate during the treatment maintenance phase associated with weight reductions indicate the need of randomized clinical trials assessing this clinical relevant issue.

An open-label trial of escitalopram in children and adolescents with social anxiety disorder.

Social anxiety disorder (SAD) is a highly prevalent and disabling disorder in children and adolescents. This study was designed to evaluate the efficacy and safety of a highly potent and selective serotonin reuptake inhibitor, escitalopram, in the treatment of SAD in children and adolescents. Twenty outpatients with a primary diagnosis of SAD were treated in a 12-week open trial with escitalopram. The primary outcome variable was the change from baseline to end point in Clinical Global Impression-Improvement scale (CGI-I). Secondary efficacy measures included the CGI-Severity scale (CGI-S), the Social Phobia and Anxiety Inventory for Children (SPAI-C), the Screen for Child and Anxiety Related Emotional Disorders (SCARED)-Child and Parent version, and The Youth Quality of Life Instrument-Research Version (Y-QOL-R). On the CGI-I scale, 13 of 20 patients (65%) had a score < or =2, meaning response to treatment. All symptomatic and quality of life measures showed improvements from baseline to week 12, with large effect sizes ranging from 0.9 to 1.9 (all p < 0.001). Escitalopram was generally well-tolerated. These results suggest that escitalopram may be an effective and safe treatment for pediatric SAD. Future double-blind, placebo-controlled, randomized clinical trials are warranted.

Psicoterapia baseada em evidências em crianças e adolescentes / Evidence-based psychotherapies for children and adolescents

CONTEXTO: O termo tratamentos baseados em evidências refere-se a intervenções que possuem evidência de eficácia em pesquisas empíricas. Tratamentos psicológicos baseados em evidências têm sido identificados como um objetivo principal nos Estados Unidos, e, atualmente, há uma clara orientação em direção à sua indicação para os transtornos psiquiátricos mais prevalentes. OBJETIVO: Revisar a efetividade de intervenções psicossociais para as principais formas clínicas dos transtornos mentais na infância e adolescência, e os desafios para a pesquisa em tratamentos baseados em evidência. MÉTODOS: Revisão bibliográfica do banco de dados Medline, de 1985 a 2005, e revisão de artigos encontrados em capítulos de livros e artigos de revisão. RESULTADOS: Psicoterapias com suporte empírico em depressão, ansiedade, transtornos do comportamento disruptivo e transtorno de déficit de atenção/hiperatividade. CONCLUSÃO: Houve um progresso importante na pesquisa em psicoterapia na infância e adolescência, que se reflete na quantidade de estudos e na identificação de tratamentos baseados em evidências. O desafio atual engloba a generalização de tais achados para a prática clínica.

BACKGROUND: Evidence-based treatments refer to interventions that have empirical research on their behalf. Evidence-based psychological therapy have been identified as a national goal in United States, and there is now clear guidance regarding referral for major mental health conditions. OBJECTIVE: Review the effectiveness of psychosocial interventions for all major forms of mental health problems in childhood and adolescence, and the challenges to research Evidence-Based treatments. METHODS: Computerized search of Medline database from 1985 to 2005 and review bibliographies of book chapters and review articles. RESULTS: We present empirically based psychological treatments for depression, anxiety, disruptive behavior disorder, attention deficit hyperactivity and autism. CONCLUSION: Considerable progress has been made in child and adolescent psychotherapy research, as reflected in the quantity of studies and the identification of evidence-based treatments. The actual challenge include generalization to clinical practice.

Tratamento do transtorno de ansiedade social em crianças e adolescentes / Treatment of social anxiety disorder in children and adolescents

CONTEXTO: Transtorno de ansiedade social é um transtorno incapacitante e altamente prevalente em crianças e adolescentes ao longo da vida, de acordo com os critérios do DSM-IV, variando de 0,7 por cento a 3,5 por cento. Se não tratado, pode interferir no funcionamento emocional, social e escolar. OBJETIVOS: Avaliar a evidência atual para a eficácia e efetividade de intervenções farmacológicas e psicoterápicas no tratamento do transtorno de ansiedade social na infância e na adolescência. MÉTODOS: Pesquisas foram realizadas por meio do PubMed, Lilacs, PsycINFO e Cochrane Library até agosto de 2006 usando os termos "social anxiety disorder" OR "social phobia" AND "child*" AND "adolesc*". RESULTADOS: Várias modalidades de tratamento, incluindo tratamentos psicoterápicos e farmacológicos, têm sido propostas para o tratamento desse transtorno. Terapia cognitivo-comportamental e farmacoterapia, principalmente com inibidores seletivos da recaptação de serotonina, são o tratamento de escolha para o transtorno de ansiedade social nessa idade. CONCLUSÕES: Embora vários tratamentos tenham sido propostos, estudos adicionais são necessários para melhorar os desfechos em crianças e adolescentes afetados com transtorno de ansiedade social.

BACKGROUND: Social anxiety disorder is a debilitating, highly prevalent disorder in children and adolescents with lifetime prevalence rates, according to DSM-IV criteria, ranging from 0.7 percent to 3.5 percent. If left untreated, it can interfere with emotional, social, and school functioning. OBJECTIVE: To evaluate the current evidence for efficacy and effectiveness of pharmacological and psychotherapeutic interventions in the treatment of social anxiety disorder in children and adolescents. METHODS: Searches were undertaken through PubMed, Lilacs, PsycINFO and Cochrane Library until august 2006, using the terms "social anxiety disorder" OR "social phobia" AND "child*" AND "adolesc*". RESULTS: Several treatment modalities, including psychotherapeutic and pharmacological treatments have been proposed for the treatment of this disorder. Cognitive-behavioral therapy and pharmacotherapy, mainly with selective serotonin reuptake inhibitors, are the treatments of choice for social anxiety disorder in this age. CONCLUSION: Although several treatments have been proposed, further studies are necessary to improve outcomes in affected children and adolescents with social anxiety disorder.

Uso de psicofármacos na lactação: revisão e proposta de manejo / Use of psychotropic drugs in breastðfeeding: review and management proposal

No período pós-parto, há alto risco de ocorrência de transtornos psiquiátricos, principalmente transtornos de humor, e em especial em mulheres com história de episódios anteriores. Entre 5 por cento e 20 por cento das mulheres terão depressão nos primeiros seis meses após o parto, e 1 por cento a 2 por cento terão psicose pós-parto. A vulnerabilidade para início ou recorrência desses transtornos aumenta a possibilidade de que seja necessário o uso de psicofármacos. A maioria destes é excretada no leite materno, mas há grande variabilidade na quantidade de droga recebida pelo lactente. Entretanto, com exceção de relatos de caso e algumas séries de casos, há poucos dados em relação a sua segurança na lactação. Os autores fizeram uma avaliação dos estudos disponíveis e revisaram o conhecimento atual sobre o uso de psicofármacos na lactação e as conseqüências para o desenvolvimento da criança. Diretrizes para o manejo da lactação em mães tratadas com essas drogas são apresentadas, ressaltando-se que cada caso necessita ser avaliado individualmente, através de análise da relação risco/benefício. Por fim, os autores apresentam recomendações específicas para o manejo psicofarmacológico de cada transtorno psiquiátrico em mães que amamentam

Mania e gravidez: implicações para o tratamento farmacológico e proposta de manejo / Mania and pregnancy: issues related to pharmacologic treatment and management proposal

O tratamento de doenças psiquiátricas na gravidez é complexo, implicando decisões clínicas difíceis, sem contar-se com dados da literatura que embasem aplamente estas decisões. O transtorno afetivo bipolar é comum em mulheres em idade fértil, e há alto risco de ocorrência de manifestações clínicas na gravidez e no período pós-parto. Os autores revisam o conhecimento atual sobre o uso de psicotrópicos para episódio maníaco na gravidez e o efeito no desenvolvimento fetal e da criança. Enfatizam que, hoje, o uso de psicotrópicos na gravidez é apropriado em muitas situações clínicas, mas nenhuma decisão é completamente isenta de risco. Também apresentam uma proposta de manejo da doença em relação ao uso de psicotrópicos na gravidez, para pacientes com transtorno bipolar, e para aquelas que desejam engravidar.

Granulomatose de Wegener: aspectos clínicos e terapêuticos / Wegener's granulomatosis: clinical aspects and therapeutics

A granulomatose de Wegener constitui-se em uma vasculite granulomatosa necrosante que acomete vários sistemas orgânicos, notadamente o trato respiratório e os rins. Possui etiologia desconhecida, provavelmente relacionada à hipersensibilidade a antígenos inalados causadores de infecçäo. Estes agentes parecem estimular a produçäo de auto-anticorpos contra antígenos no citoplasma de neutrófilos. Clinicamente, surge em torno da quarta e quinta décadas, através de um quadro de sinusite associado a sintomas constitucionais como febre, fadiga e mal-estar geral. Este quadro inespecífico dificulta o diagnóstico precoce, possibilitando o desenvolvimento de doença disseminada. A clínica do órgäo acometido, associada à presença do anticorpo antineutrofílico citoplasmático (c-ANCA) e os achados anatomopatológicos confirmam o diagnóstico de doença ativa. O tratamento é feito através da associaçäo de corticóides e ciclofosfamida, o que possibilita o controle da doença a curto e médio prazo. As recidivas säo ainda freqüentes, podendo ocorrer em até 20 anos após o início do tratamento.

Lamotrigina: indicações terapêuticas e efeitos adversos / Lamotrigine: therapeutic use and sideðeffects

A Lamotrigina (LTG), um feniltriazino, é um anticonvulsante novo que vem sendo utilizado com sucesso na clínica, como terapia coadjuvante no tratamento de crises convulsivas parciais, de ausência e generalizadas secundárias. Possui açäo inibitória na liberaçäo de aminoácidos excitatórios, sendo rápida e completamente absorvida por via oral, com moderada afinidade por proteínas plasmáticas, apresentando metabolismo hepático, com predominante excreçäo renal dos metabólitos. Seus efeitos indesejáveis säo menos freqüentes em relaçäo aos demais anticonvulsivantes, sendo o rash cutâneo e o mais relatado. A LTG, por näo ser metabolizada pelo citocromo Pð450, näo estabelece interações com hormônios esteróides e anticoagulantes, porém necessita de ajuste de doses quando utilizada concomitantemente com Ácido Valpróico

Lamotrigina: indicacoes terapeuticas e efeitos adversos

A Lamotrigina (LTG), um feniltriazino, e um anticonvulsivante novo que vem sendo utilizado com sucesso na clinica, como terapia coadjuvante no tratamento de crises convulsivas parciais, de ausencia e generalizadas secundarias. Possui acao inibitoria na liberacao de aminoacidos excitatorios, sendo rapida e completamente absorvida por via oral, com moderada afinidade por proteinas plasmaticas, apresentando metabolismo hepatico, com predominante excrecao renal dos metabolitos. Seus efeitos indesejaveis sao menos frequentes em relacao aos demais anticonvulsivantes, sendo o rash cutaneo o mais relatado. A LTG, por nao ser metabolizada pelo citocromo P-450, nao estabelece interacoes com hormonios esteroides e anticoagulantes, porem necessita de ajuste de doses quando utilizada concomitantemente com Acido Valproico.