topiramate and Bipolar-Disorder

Substance use disorders (SUDs), including those for alcohol, stimulants, tobacco, opioids and cannabis, in patients with bipolar disorder are a major clinical and public health problem, and are present in the majority of these patients. Nonetheless, the development of effective pharmacological treatments for co-occurring SUDs in bipolar illness have not been well-developed and may be an important practical reason for the reduced effectiveness of these medications in community practice.. We conducted a systematic review of the literature (PubMed, Medline, Google Scholar), and identified N = 29 clinical studies, which evaluated both mental health and SUD outcomes in patients with co-occurring bipolar disorders and SUDs.. Our findings suggest the potential of valproate sodium and lamotrigine as preferred pharmacological agents for the treatment of co-occurring psychiatric and substance use outcomes in these patients. However, many of the reviewed studies are of open-label designs and of modest sample sizes.. Thus, given the gaps in our knowledge, recommendations for treatment of this common and important co-morbidity are preliminary. Accordingly, the conduct of larger, randomized controlled trials for this co-morbidity is clearly needed.

Topics: Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Comorbidity; Humans; Lamotrigine; Lithium Compounds; Quetiapine Fumarate; Substance-Related Disorders; Topiramate; Valproic Acid

Capgras delusion (CD) has multiple etiologies including neurodegenerative disorders and can be associated with violent behavior. CD is a common complication of Alzheimer dementia (AD); however, CD with violent behavior is uncommon in AD. We report escalating violent behavior by a patient with advanced AD and CD who presented to the emergency department (ED) and required admission to an academic medical center.. Case analysis with PubMed literature review.. A 75-year-old male with a 13-year history of progressive AD, asymptomatic bipolar disorder, chronic kidney disease, hypertension, hyperlipidemia, and benign prostatic hypertrophy presented to the ED with recurrent/escalating violence toward his wife, whom he considered an impostor. His psychotropic regimen included potentially inappropriate medications (PIMs) for geriatric/AD patients-topiramate/amitriptyline/chlordiazepoxide/olanzapine-that are associated with delirium, cognitive decline, dementia, and mortality. Renal dosing for topiramate, reduction in PIMs/anticholinergic burden, and substituting haloperidol for olanzapine resolved his violent behavior and CD.. CD in AD is a risk factor for violent behavior. As the geriatric population in the United States grows, CD in patients with AD may present more frequently in the ED, requiring proper treatment. Pharmacovigilance is necessary to minimize PIMs in geriatric/AD patients. Clinicians and other caregivers require further education to appropriately address CD in AD.

Topics: Aged; Aggression; Alzheimer Disease; Amitriptyline; Anticonvulsants; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Capgras Syndrome; Chlordiazepoxide; Fructose; Haloperidol; Humans; Hypnotics and Sedatives; Male; Olanzapine; Potentially Inappropriate Medication List; Renal Insufficiency, Chronic; Topiramate; Violence

Our aim was to evaluate the efficacy and tolerability of anticonvulsant agents for the treatment of acute bipolar mania and ascertain if their effects on mania are a "class" effect. We conducted a systematic review of randomized controlled trials (RCTs) with placebo or active comparator, in acute bipolar mania in order to summarize available data on anticonvulsant treatment of mania/mixed episodes. We searched (PubMed/MEDLINE) with the combination of the words "acute mania" and "clinical trials" with each one of the following words: "anticonvulsants/antiepileptics,""valproic/valproate/divalproex,""carbamazepine,""oxcarbazepine,""lamotrigine,""gabapentin,""topiramate,""phenytoin,""zonisamide,""retigabine,""pregabalin,""tiagabine,""levetiracetam,""licarbazepine,""felbamate," and "vigabatrin." Original articles were found until November 1, 2008. Data from 35 randomized clinical trials suggested that not all anticonvulsants are efficacious for the treatment of acute mania. Valproate showed greater efficacy in reducing manic symptoms, with response rates around 50% compared to a placebo effect of 20-30%. It appears to have a more robust antimanic effect than lithium in rapid cycling and mixed episodes. As valproate, the antimanic effects of carbamazepine have been demonstrated. Evidences did not support the efficacy of the gabapentin, topiramate as well as lamotrigine as monotherapy in acute mania and mixed episodes. Oxcarbazepine data are inconclusive and data regarding other anticonvulsants are not available. Anticonvulsants are not a class when treating mania. While valproate and carbamazepine are significantly more effective than placebo, gabapentin, topiramate, and lamotrigine are not. However, some anticonvulsants may be efficacious in treating some psychiatric comorbidities that are commonly associated to bipolar illness.

Topics: Amines; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Carbamazepine; Cyclohexanecarboxylic Acids; Drug Interactions; Drug Therapy, Combination; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Lithium Compounds; Oxcarbazepine; Randomized Controlled Trials as Topic; Topiramate; Triazines; Valproic Acid

To compare antipsychotic and mood stabilizer (MS) efficacy and tolerability in youth and adults with bipolar mania.. Medline/PubMed search for studies including: (i) youth (< 18 years) or adults (> or = 18 years); (ii) bipolar I disorder; (iii) double-blind, randomized, placebo-controlled trial (DB-RPCT); (iv) < or = 12 weeks of treatment; and (v) calculable effect sizes (ES) and/or numbers needed to treat/harm (NNT/NNH) +/- 95% confidence intervals (CI). Non-overlapping 95% CIs determined significant group differences.. We identified nine DB-RPCTs in youth (n = 1,609), 5 evaluating second-generation antipsychotics (SGAs) (n = 1,140) and 4 evaluating MSs (n = 469). We also identified 23 DB-RPCTs in adults (n = 6,501), 14 including SGAs (n = 3,297), 5 using haloperidol as an active comparator (n = 580), and 11 including MSs (n = 2,581). Young Mania Rating Scale scores improved significantly more with SGAs than MSs in youth (ES = 0.65, CI: 0.53-0.78 versus 0.24, CI: 0.06-0.41) and adults (ES = 0.48, CI: 0.41-0.55 versus 0.24, CI: 0.17-0.31). After excluding topiramate studies, SGAs had larger ES than MSs only in youth (ES = 0.65, CI: 0.53-0.78 versus 0.20, CI: 0.02-0.39), but not adults (ES = 0.48, CI: 0.41-0.55 versus 0.46, CI: 0.37-0.55). However, in adults SGAs had significantly larger ES regarding Clinical Global Impressions scores than MSs, even without topiramate (ES = 0.75, CI: 0.68-0.82 versus 0.24, CI: 0.07-0.41). Rates of response, remission, and discontinuation due to any reason compared to placebo were similar between medication and age groups, except for more favorable NNTs for remission with SGAs than MSs in adults after excluding topiramate. SGAs caused more weight gain than MSs in youth (ES = 0.53, CI: 0.41-0.66 versus 0.10, CI: -0.12-0.33), but not in adults (ES = 0.13, CI: 0.05-0.22 versus 0.00, CI: -0.08-0.08). However, results were heterogeneous and not significant in either age group after excluding topiramate. Nevertheless, SGA-related weight gain was significantly greater in youth than adults. In youth, SGA-related somnolence was greater than with MSs (NNH = 4.7, CI: 3.9-6.0 versus 9.5, CI: 6.3-23.5), and more likely than in adults (NNH = 7.1, CI: 6.1-8.8). Conversely, youth experienced less akathisia with SGAs than adults (NNH = 20.4, CI: 14.1-36.5 versus 10.2, CI: 8.1-13.7), likely due to lower doses/slower titration.. In treating mania, potentially greater short-term efficacy compared to placebo with SGAs versus MS needs to be balanced against increased adverse events, especially in youth.

Topics: Adolescent; Adult; Age Factors; Akathisia, Drug-Induced; Anti-Obesity Agents; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Child; Confidence Intervals; Double-Blind Method; Female; Fructose; Haloperidol; Humans; Male; Randomized Controlled Trials as Topic; Time Factors; Topiramate; Treatment Outcome; Weight Gain; Weight Loss

Although lithium has been used therapeutically to treat patients with bipolar disorder for over 50 years, its mechanism of action, as well as that of other drugs used to treat bipolar disorder, is not agreed upon. In the present paper, I review studies in unanaesthetized rats using a neuropharmacological approach, combined with kinetic, biochemical and molecular biology techniques, demonstrating that chronic administration of three commonly used mood stabilizers (lithium, valproic acid and carbamazepine), at therapeutically relevant doses, selectively target the brain arachidonic acid cascade. Upon chronic administration, lithium and carbamazepine decrease the binding activity of activator protein-2 and, in turn, the transcription, translation and activity of its arachidonic acid-selective calcium-dependent phospholipase A(2) gene product, whereas chronic valproic acid non-competitively inhibits long-chain acyl-CoA synthetase. The net overlapping effects of the three mood stabilizers are decreased turnover of arachidonic acid, but not of docosahexaenoic acid, in rat brain phospholipids, as well as decreased brain cyclo-oxygenase-2 and prostaglandin E(2). As an extension of this theory, drugs that are thought to induce switching to mania, especially when administered during bipolar depression (fluoxetine and imipramine), up-regulate enzymes of the arachidonic acid cascade and turnover of arachidonic acid in rat brain phospholipids. Future basic and clinical studies on the arachidonic acid hypothesis of bipolar disorder are warranted.

Topics: Animals; Anticonvulsants; Antidepressive Agents; Arachidonic Acid; Bipolar Disorder; Brain; Carbamazepine; Fructose; Humans; Lamotrigine; Lithium Compounds; Molecular Structure; Signal Transduction; Topiramate; Triazines; Valproic Acid

Bipolar disorder is a common recurrent illness with high levels of chronicity. Treatment resistance persists despite the use of established medications, such as lithium and valproate. New medications are required for the treatment of refractory cases. Retrospective and open-label trials have suggested that the anticonvulsant topiramate may be efficacious in bipolar disorder. There is a need to clarify the evidence available in the form of randomised controlled trials for its use in bipolar disorder.. To review the evidence for the efficacy and acceptability of topiramate in the treatment of acute mood episodes in bipolar disorder.. The Cochrane Collaboration Depression, Anxiety and Neurosis (CCDAN) group search strategy was used. The following databases were searched:The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), September 2003;The Cochrane Controlled Clinical Trials Register (CCCTR), September 2003;EMBASE (1980 to December 2003);MEDLINE (1966 to December 2003);LILACS;PsycLIT;Psyndex.Reference lists of relevant papers and major textbooks of mood disorder. Handsearches (specialist journals and conference proceedings). Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials.. Randomised controlled trials which compared topiramate with placebo or with active agents in the treatment of any acute mood episodes in bipolar disorder. Participants were patients with bipolar disorder and were males and females of all ages.. Data extraction and methodological quality assessment were performed independently by two reviewers. For analysis, relative risk was used for binary efficacy outcomes and the weighted mean difference or standardised mean difference was used for continuously distributed outcomes.. One randomised controlled trial met the inclusion criteria for the review, a comparison between topiramate and bupropion sustained release (SR) in the adjunctive treatment of depressed patients with bipolar disorder. However, the trial had several limitations in methodology and in the description of data. Its data regarding efficacy required clarification before it could be analysed according to the protocol of this systematic review. From the limited data available, topiramate had efficacy similar to bupropion SR in the adjunctive treatment of bipolar depression. Both groups of subjects suffered a high drop-out rate. There was no significant difference between the topiramate and the bupropion treated groups in those dropping out for any reason (relative risk 1.60, 95% confidence interval 0.65 to 3.96). There was no significant difference in those withdrawing from the study due to adverse effects (relative risk 1.50, 95% confidence interval 0.51 to 4.43). Although the data on weight loss were not analysed formally, weight loss was marked in the topiramate treated group. Several unpublished trials have been identified and data from these trials may be included in future reviews.. There is insufficient evidence on which to base any recommendations regarding the use of topiramate in any phase of bipolar illness, either in monotherapy or as an adjunctive treatment.

Topics: Affective Disorders, Psychotic; Antimanic Agents; Bipolar Disorder; Bupropion; Depressive Disorder; Fructose; Humans; Randomized Controlled Trials as Topic; Topiramate

To review the scientific evidence examining the comorbidity among eating disorders and bipolar disorder (BD).. We reviewed all published English-language studies addressing the comorbidity of anorexia nervosa, bulimia, bulimia nervosa, and binge eating disorder in patients with BD and studies of comorbidity of BD in patients with eating disorders. In addition, we discuss the pharmacologic treatment implications from reviewed studies of agents used in BD and eating disorders.. Community and clinical population studies of the lifetime prevalence rates of eating disorders in patients with BD, and of BD in patients with eating disorders, particularly when subthreshold and spectrum manifestations of these disorders are included, indicate high rates of comorbidity among these illnesses.. Pharmacologic treatment approaches to patients with BD and a co-occurring eating disorder require examination of the possible adverse effects of the treatment of each syndrome on the other and attempts to manage both syndromes with agents that might be beneficial to both.

Topics: Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Comorbidity; Disruptive, Impulse Control, and Conduct Disorders; Feeding and Eating Disorders; Fructose; Humans; Isoxazoles; Topiramate; Zonisamide

Topics: Amines; Anticonvulsants; Bipolar Disorder; Carbamazepine; Cyclohexanecarboxylic Acids; Depressive Disorder; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Nurse's Role; Oxcarbazepine; Patient Selection; Safety; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Zonisamide

Bipolar disorder is defined as a mood disorder. It is characterized by alteration in mood, from elation and/or irritability to depression. The prevalence of this disorder in children and adolescents is 1%, and it disrupts the lives of children and adolescents. The treatment of bipolar disorder includes mood stabilizers. In contrast to the extensive literature in adult bipolar disorder, controlled studies of lithium and anticonvulsants in the management of mood disorders in childhood are scarce. This review summarizes recent clinical pharmacologic studies of mood stabilizers, including lithium and anticonvulsants in the management of bipolar disorder in children and adolescents who suffer from this syndrome. In addition, the authors review new anticonvulsants such as lamotrigine, gabapentin and topiramate as mood stabilizers.

Topics: Adolescent; Adult; Amines; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Child; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Lithium; Topiramate; Triazines

The anticonvulsants valproate and carbamazepine have efficacy in treating acute mania, but their efficacy in treating acute bipolar depression and preventing mood episodes remains uncertain. Despite this, and given their utility and widespread use, both are widely accepted as standard treatments for bipolar disorder. All the newer anticonvulsants that have become available during the last decade have been or are being assessed to determine their efficacy in the treatment of various phases of bipolar disorder. Among the newer anticonvulsants, some appear to have efficacy in treating core bipolar symptoms, while others have efficacy in treating psychiatric comorbidity such as substance abuse or an anxiety disorder. Lamotrigine is the most widely studied and is effective in treating and preventing bipolar depression, and it is the only anticonvulsant approved by the U.S. Food and Drug Administration as a maintenance treatment for bipolar disorder. Other newer anticonvulsants, levetiracetam, oxcarbazepine, phenytoin, and zonisamide offer promise, but further studies are required before they can be recommended for routine use to treat bipolar disorder. Gabapentin and topiramate do not appear to have efficacy in treating acute mania, but their utility in bipolar depression and prevention of mood episodes has not been studied in double-blind trials. Pregabalin has utility in treating generalized anxiety disorder, but it has not been studied in bipolar disorder. Given the success of lamotrigine in treating bipolar disorder, further double-blind controlled trials of the newer anticonvulsants in treating bipolar disorder are warranted. This article summarizes current evidence from trials of anticonvulsants in bipolar disorder and makes recommendations for their clinical use.

Topics: Acetates; Amines; Anticonvulsants; Bipolar Disorder; Carbamazepine; Cyclohexanecarboxylic Acids; Depressive Disorder; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Phenytoin; Piracetam; Pregabalin; Tiagabine; Topiramate; Treatment Outcome; Triazines; Zonisamide

The need for long-term management of bipolar disorder is evident. Bipolar patients spend more time depressed than manic; however, few agents used for maintenance therapy of bipolar disorder have demonstrated good efficacy in delaying relapse into depression. This article provides a comprehensive review of open-label and randomized, controlled studies examining prophylactic efficacy in bipolar disorder, especially bipolar depression. Lithium, considered the gold standard for bipolar disorder maintenance therapy may be more effective in delaying manic relapse than in delaying depressive relapse. Evidence for the efficacy of divalproex and carbamazepine in delaying depressive relapse is yet to be fully elucidated. Lamotrigine has demonstrated efficacy in delaying time to depressive relapse. Unpublished studies show olanzapine's efficacy in preventing manic recurrence, while its efficacy in preventing depressive recurrence is yet to be proven. As patients with bipolar disorder are prone to experiencing depressive episodes, more attention needs to be focused on preventing depressive relapse. To date, three agents--lithium, lamotrigine, and olanzapine--have been shown to have prophylactic benefits in treating this highly recurrent disorder.

Topics: Amines; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Carbamazepine; Chronic Disease; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Lithium Carbonate; Randomized Controlled Trials as Topic; Time; Topiramate; Triazines; Valproic Acid

A growing number of anticonvulsant drugs are receiving attention as possible mood stabilizers. This attention is based mainly on the assumption that the antimanic efficacy of anticonvulsants makes them suitable as mood stabilizers. However, their antidepressant properties have received less scrutiny. In this review, current evidence concerning the acute and prophylactic efficacy of divalproex, carbamazepine, gabapentin, lamotrigine, and topiramate in bipolar depression is evaluated. Clinical outcome data are considered, together with limitations of existing studies and the concept of unmet clinical needs. Findings in placebo-controlled trials suggest an acute and prophylactic antidepressant effect with lamotrigine monotherapy and more modest antidepressant benefits with other agents administered as monotherapies. Results of published studies are considered with respect to the conceptualization of mood stabilization as arising from antimanic and antidepressant efficacy in bipolar disorder.

Topics: Acetates; Affect; Amines; Anticonvulsants; Antidepressive Agents; Bipolar Disorder; Carbamazepine; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Lithium; Topiramate; Triazines; Valproic Acid

Topics: Acetates; Affect; Amines; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Lithium Compounds; Nipecotic Acids; Olanzapine; Oxcarbazepine; Pirenzepine; Tiagabine; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Zonisamide

Pharmacotherapeutic management of bipolar disorder has advanced considerably since the introduction of lithium therapy nearly 50 years ago. The sizable percentage of patients who do not respond adequately to lithium and/or are intolerant to its side effects has served as an impetus for identifying alternative pharmacotherapeutic agents. Recent advances in the understanding of the neurotransmitter systems and their receptors as it applies to treatment of bipolar disorder has, in part, led to progress in delineating applications of anticonvulsant/antiepileptic drugs (AEDs) in this area. Although the efficacy of many drugs has been evaluated in patients with this disorder, medication tolerability and adherence issues related to unfavorable side effect profiles are substantial impediments to the development of novel pharmacotherapies. The potential for excessive weight gain as a side effect of certain psychopharmacologic agents remains a concern to both clinicians and patients.. English-language literature from 1985-2001 in MEDLINE was searched for the terms bipolar disorder, anticonvulsant, antiepileptic, lithium, antipsychotic, weight, and compliance. This article reviewed current therapeutic options for bipolar disorder, including newer AEDs and atypical antipsychotic drugs, with emphasis on the issue of weight gain and possible approaches to minimizing this risk.. Certain newer AEDs are characterized by more favorable safety and tolerability profiles that include weight loss as a desirable side effect. Because bipolar disorder is associated with unacceptably high rates of relapse, recurrence, and morbidity, the concept of pharmacotherapeutic efficacy logically not only includes symptom relief but also necessarily encompasses issues related to regimen tolerability and adherence.. There is a need for guidelines to help physicians carefully formulate and individualize management plans to reach safe, effective, and cost-efficient patient outcomes. Monitoring the weight of patients with bipolar disorder and educating them regarding this issue should be standard components of any treatment plan.

Topics: Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Clinical Protocols; Female; Fructose; Humans; Lithium; Obesity; Patient Compliance; Patient Education as Topic; Topiramate; Treatment Outcome; Weight Gain; Weight Loss

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.. Evidence on maintenance therapy and relevant acute-phase data were collected using MEDLINE database searches.. 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.. 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.

Topics: Acetates; Amines; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Calcium Channel Blockers; Carbamazepine; Clozapine; Cyclohexanecarboxylic Acids; Dibenzothiazepines; Donepezil; Fatty Acids, Omega-3; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Indans; Lamotrigine; Lithium Carbonate; Olanzapine; Piperazines; Piperidines; Pirenzepine; Quetiapine Fumarate; Risperidone; Thiazoles; Topiramate; Treatment Outcome; Triazines; Valproic Acid

To evaluate the efficiency of topiramate (TPM), an antiepileptic medication (AEM) which possesses multiple mechanisms of action and good pharmacokinetics, in the different types of childhood epilepsy and to make an appraisal of its value in migraines, bipolar disorder, eating disorders and neuropathic pain, according to studies that have been published. To do so, we have made use of an analysis of the literature, together with a multi centre study conducted in Spain and personal casuistry.. We consider the percentage of seizure free patients and of patients who responded (reduction of 50% or above in the frequency of the seizures) in childhood epilepsy, partial epilepsy, generalized tonic clonic seizures, absence seizures, tonic seizures, patients with diverse types of seizures, juvenile myoclonic epilepsy, Lennox Gastaut syndrome, falling sickness and GTCS, West s syndrome and Dravet s syndrome. With monotherapy, in partial epilepsy, between 39 and 54% of patients treated were seizure free. TPM has also proved to be efficient in experiments with animals, as a neuroprotector, and in clinical trials, in type I bipolar disorder, eating disorders, neuropathic pain and migraine.. TPM is an AEM offering a wide therapeutic spectrum that has proved to be efficient in clinical trials, expansion phases and observational studies, as an associated drug in partial epilepsy, generalized epilepsy, Lennox Gastaut syndrome, West s syndrome and Dravet s syndrome. It has proved to be more efficient in monotherapy, in partial epilepsy, as a first line AEM. TPM has also proved to be useful in mood disorders, eating disorders, neuropathic pain and tremor in observational studies, although this efficiency has not been backed up by clinical trials. In migraine and in clinical trials TPM has shown its efficiency. Its neuroprotective effect opens up new therapeutic perspectives.

Topics: Animals; Anticonvulsants; Bipolar Disorder; Clinical Trials as Topic; Drug Interactions; Epilepsy; Feeding and Eating Disorders; Fructose; Humans; Migraine Disorders; Multicenter Studies as Topic; Neuroprotective Agents; Pain; Spain; Topiramate

Lithium alone or in combination with other psychotherapeutic drugs has long been the gold standard of management for bipolar disorder (BD). Recognition of its limitations in the acute and chronic management of BD has led to the development of alternative therapies. One such approach involves the use of antiepileptic drugs (AEDs). The AED topiramate is currently being studied in the efficacy and management of BD. Topiramate has mechanisms in common with other AEDs, including sodium channel-blocking activity and enhancement of cerebral GABA concentrations. Open-label trials have evaluated topiramate at mean daily doses of 100 to 300 mg in various BD subtypes, including acute mania, depression, rapid-cycling, mixed states, and BD refractory to other medications. Results from these trials suggest topiramate may be efficacious in BD subtypes, particularly in rapid-cycling patients and those refractory to conventional treatment. Its side effect profile appears benign when used as monotherapy or in combination with other mood stabilizers. Placebo-controlled, double-blind studies are warranted to evaluate topiramate further in BD.

Topics: Affect; Anticonvulsants; Bipolar Disorder; Body Weight; Clinical Trials as Topic; Drug Resistance; Drug Therapy, Combination; Drug Tolerance; Fructose; Humans; Topiramate; Treatment Outcome

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.

Topics: Acetates; Amines; Anticonvulsants; Bipolar Disorder; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Randomized Controlled Trials as Topic; Topiramate; Triazines

To review the literature on efficacy of third generation anticonvulsants for treatment of bipolar disorder and provide clinical recommendations.. 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.. 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.. 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.

Topics: Acetates; Amines; Anticonvulsants; Bipolar Disorder; Cyclohexanecarboxylic Acids; Double-Blind Method; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Nipecotic Acids; Placebos; Tiagabine; Topiramate; Treatment Outcome; Triazines; Zonisamide

Antiepileptic drugs (AEDS) are used regularly in the treatment of patients with bipolar disorders. Carbamazepine and valproic acid (sodium valproate) are effective as antimanic treatments, and the success of these medications has prompted investigation of other AEDs as possible treatments in patients with mood disorders. Lamotrigine appears to be the most promising of the newer AEDs with respect to effects in mood disorders. Current evidence suggests efficacy of this drug both as monotherapy and as an adjunctive agent in bipolar depression, and studies are underway to clarify its efficacy in mood stabilisation and rapid cycling, as currently available data are equivocal. Use of gabapentin is not as well supported in the literature, although data from open trials using it as an adjunctive agent suggest that it may be helpful in patients with bipolar depression. There have been some open trials and case reports supporting the use of topiramate as an adjunctive agent for the treatment of mania; however, data from controlled trials are not yet available. Further controlled trials of lamotrigine, gabapentin or topiramate as monotherapy and adjunctive treatment are needed to clarify their potential roles in the treatment of patients with mood disorders.

Topics: Acetates; Amines; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Topiramate; Treatment Outcome; Triazines

Treatments other than lithium have recently emerged as equally important in the management of bipolar disorder. The spectrum of efficacy of newer treatments differs from lithium and among the novel drug treatments valproate, generally used as the better tolerated divalproex form, principally benefits manic symptomatology both acutely and in prophylaxis. Atypical antipsychotic drugs have demonstrated efficacy in reducing acute manic symptoms. No controlled evidence of efficacy in prophylaxis has been published. Lamotrigine has demonstrated efficacy in both acute bipolar depression and maintenance efficacy in rapid cycling bipolar patients, especially those patients with bipolar II disorder, which is principally manifested as depression. Randomised, double-blind, placebo- controlled studies provide good evidence that regimens of risperidone or olanzapine in combination with lithium or valproate provide greater improvement in acute mania than the mood stabilisers alone. Similarly, valproate combined with antipsychotics provided greater improvement in mania than antipsychotic medication alone and resulted in lower dosage of the antipsychotic medication. A positive but unclear placebo-controlled study of omega-3 fatty acids added to lithium in bipolar disorder needs confirmation in standard clinical trial paradigms. Several other drugs that were reported as beneficial in various facets of bipolar disorder in open trials have not differed from placebo when studied in randomised, placebo-controlled trials.

Topics: Acetates; Amines; Bipolar Disorder; Carbamazepine; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Fatty Acids, Omega-3; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Topiramate; Triazines; Valproic Acid

The increasing use of anticonvulsant drugs in psychiatry has prompted greater awareness of their effects on a range of psychiatric domains, including cognition. Older versus newer antiepileptic drugs have been reported to either worsen or enhance cognitive performance in clinical populations, and the extent to which cognitive disturbances may reflect iatrogenic factors versus psychopathology is subject to debate. We review current information about the role of anticonvulsants in cognition, with particular emphasis on newer compounds (such as lamotrigine, gabapentin, and topiramate), the cognitive dimensions of affective illness, and the clinical approach to evaluating cognition in psychiatric patients taking anticonvulsant drugs over time.

Topics: Acetates; Amines; Anticonvulsants; Bipolar Disorder; Carbamazepine; Cognition Disorders; Cyclohexanecarboxylic Acids; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Mood Disorders; Topiramate; Triazines; Valproic Acid

Bipolar affective disorder is a life-long condition with profound effects on sufferers' social and occupational life. Despite efficacy in clinical trials and in some groups of patients, lithium's effectiveness in clinical practice is hampered by its side effect profile and limited concordance. Alternative and adjunctive treatments to lithium in bipolar disorder have been sought and the anticonvulsants carbamazepine and valproate show promise. Despite these advances, treatment resistance persists. Lamotrigine, a new anticonvulsant, is increasingly used in treatment-resistant cases under specialist supervision. Further pharmacological and non-pharmacological strategies for bipolar prophylaxis are currently under investigation. These developments are the focus of this review.

Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Carbamazepine; Electroconvulsive Therapy; Electromagnetic Fields; Fructose; Humans; Lamotrigine; Lithium; Nipecotic Acids; Psychotherapy; Suicide Prevention; Thyroxine; Tiagabine; Topiramate; Triazines; Valproic Acid

Topiramate, a structurally novel anticonvulsant, is being evaluated for other neurological conditions such as migraine, neuropathic pain, and essential tremor, and also for psychiatric conditions such as bipolar disorder, bulimia, post-traumatic stress disorder, and schizoaffective disorder, in addition to obesity. This article will focus on the use of topiramate for bipolar disorder.. The pharmacological profile of topiramate is compared to other established and putative mood stabilizers, and a rationale for its use in bipolar disorder is presented. Data from open clinical trials of topiramate for depression, mania, and rapid-cycling bipolar disorder are summarized. Preliminary data from one pilot dose-finding, double-blind, random-assignment, placebo-controlled, 3-week parallel group study of two doses of topiramate for acute bipolar I mania is reported. Safety data regarding topiramate was reviewed. Finally, the potential place of this agent in bipolar illness is considered.. The pharmacological advantages for topiramate are low protein binding, minimal hepatic metabolism and mainly unchanged renal excretion, a 24-h half-life, and minimal drug interactions. Open clinical studies suggest a 50-65% response for refractory bipolar mania, and a 40-56% response for refractory bipolar depression in mainly add-on treatment. Open clinical studies of topiramate for rapid-cycling subjects and those for comorbid bulimia, substance abuse, post-traumatic stress, migraine, and obesity report effectiveness. The primary efficacy endpoint data (change from baseline Y-MRS total scores) of the placebo-controlled, random assignment parallel group phase II dose-finding study were not statistically significant. However, once the antidepressant-associated manias (28 of the sample, of 97 subjects) were excluded from the controlled study, the post-hoc analyses indicated the higher dose (512 mg/day) topiramate treatment group showed a statistically significant reduction in endpoint Y-MRS change scores as compared to placebo (p < 0.03). Adverse effects of topiramate in bipolar subjects include attention, concentration and memory problems, fatigue, sedation, transient paraesthesias, nausea, and anorexia. Some subjects experience word-finding difficulty. Weight loss may be seen in several topiramate-treated subjects with bipolar disorder.. Topiramate appears to show promise as an addition to the agents available to treat bipolar disorder. More definitive controlled data on the efficacy of topiramate in the acute and continuation phases as well as for the prophylaxis either as monotherapy or as combination treatment of bipolar disorder are ongoing, and the results are awaited.

Topics: Acetates; Acute Disease; Amines; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Carbamazepine; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Lithium; Randomized Controlled Trials as Topic; Topiramate; Triazines; Valproic Acid

Bipolar disorder is a recurrent and relapsing mood disorder characterized by cycles of depression and mania. This article addresses the treatment of patients with bipolar mania, which remains one of the most difficult challenges facing clinicians. Patients require safe and effective therapeutic approaches for acute episodes of mania and depression, as well as chronic prophylaxis against future episodes. Monotherapeutic approaches are rarely effective, and combination approaches are associated with an increased risk of adverse events. Lithium is the only agent currently approved for the treatment of both acute episodes of mania and maintenance therapy; however, it is associated with a relatively poor response rate, high relapse rate, and less-than-optimal side effect profile. Other recent approaches have included several anticonvulsant agents, as well as conventional and atypical antipsychotic agents.

Topics: Acetates; Amines; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Clozapine; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Electroconvulsive Therapy; Electromagnetic Phenomena; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Lithium; Olanzapine; Pirenzepine; Risperidone; Topiramate; Treatment Outcome; Triazines; Valproic Acid

This clinical trials review is derived from the presentations made at the Third International Conference on Bipolar Disorder, held June 17-19, 1999 in Pittsburgh, PA, published as abstracts in Bipolar Disorders: An International Journal of Psychiatry and Neurosciences, Edited by Jair C. Soares, and Samuel Gershon. In this review, abstracts reporting on the efficacy of "third generation" anti-epileptic agents, including topiramate, lamotrigine, diphenylhydantoin, gabapentin, and the new generation antipsychotic agent, olanzapine in treating bipolar disorders are reviewed.

Topics: Acetates; Amines; Anticonvulsants; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Olanzapine; Phenytoin; Pirenzepine; Topiramate; Treatment Outcome; Triazines

Topics: Acetates; Amines; Anticonvulsants; Bipolar Disorder; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Lithium; Mood Disorders; Topiramate; Treatment Outcome; Treatment Refusal; Triazines

Topiramate is effective for alcohol use disorders (AUDs) among non-psychiatric patients. We examined topiramate for treating comorbid AUDs in bipolar disorder (BD).. Twelve participants were randomized to topiramate or placebo for 12 weeks.. The topiramate group, with two out of five participants (40%) completing treatment, experienced less improvement in drinking patterns than the placebo group, with five out of seven participants (71%) completing treatment.. Topiramate did not improve drinking behavior and was not well-tolerated. This study failed to recruit adequately. Problems surrounding high attrition, a small study sample, and missing data preclude interpretation of study findings.. This is the first randomized, placebo-controlled trial of topiramate for AUDs in BD.

Topics: Alcohol Drinking; Alcohol-Related Disorders; Bipolar Disorder; Diagnosis, Dual (Psychiatry); Double-Blind Method; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Neuroprotective Agents; Topiramate; Treatment Outcome

The aim of this study was to explore the probable prophylactic effects and evaluate different doses of topiramate on body weight in patients treated with olanzapine.. This was a 12 week, double-blind, placebo-controlled clinical trial (Iranian Clinical Trial Registration Code: 201402085280N15) to assess the preventative effects and estimate the optimal dosage of topiramate in drug-induced weight gain. Sixty eight patients aged 18 to 60 that were hospitalized and treated with olanzapine between 2009-2011due to the onset of an acute episode of schizophrenia or a manic episode of bipolar I disorder were selected in Mashhad, the second largest city in the northeast of Iran. Patients were randomly assigned to 4 groups, including 1- placebo; 2- 50 mg/day; 3- 100 mg/day; and 4- 200 mg/day topiramate. Two psychiatrists assigned participants to an intervention group and followed up the treatment process. Raters weighed patients at baseline and also at weeks 1, 2, 4, 6, 8, and 12, respectively. Waist and wrist circumferences were measured at baseline and weeks 4, 8, and 12. Body weight, BMI, wrist, and waist circumference changes were outcome measures of the study. Collected data were analyzed by ANOVA, post hoc Tukey test, Kruskal-Wallis, Mann-Whitney U, and Cohen's d with SPSS version 14. A p-value of less than 0.05 was considered significant.. All outcome measures were significantly less than the placebo group compared to the topiramate groups at the end of the fourth week and continued to twelfth week. Nevertheless, there was no statistically significant difference in the measures of any of the topiramate groups with each other at any interval.. All doses of 50, 100, and 200mg were shown effective in preventing olanzapine-related obesity in schizophrenic and/or bipolar patients.

Topics: Adolescent; Adult; Anticonvulsants; Bipolar Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Psychometrics; Schizophrenia; Topiramate; Treatment Outcome; Weight Gain; Young Adult

It has not been examined trialed whether obsessive compulsive symptoms in patients with bipolar disorder respond to topiramate as an adjuvant treatment.. This 4-month double-blind placebo-controlled randomized clinical trial examined the efficacy and safety of augmentation with topiramat for treating the patients with bipolar disorder, manic phase type-I, and obsessive compulsive disorder symptoms. Both groups received lithium+olanzapine+clonazepam. However, one group received topiramate and the other group placebo as adjuvant medications. Yale Brown obsessive compulsive behavior scale was used to assess the outcome. Adverse effects were also recorded.. A total of 32 patients completed this trial. The mean score decreased from 24.2(4.8) to 17.6(8.7) in the topiramate group (P<0.003) and from 20.9(2.9) to 9.6(3.5) in the placebo group during this trial (P<0.0001). Additionally, 9(52.9%) out of 17 patients in the topiramate group and 2(12.5%) out of 16 patients in the placebo group showed more than 34% decline in YBOC score (x2=6.0, df=1, P<0.01). No serious adverse effects were detected.. The limitations of the present study were its small sample size and the fact that it was conducted in a single center.. The combination of lithium+olanzapine+clonazepam decreased the symptoms of obsessive compulsive disorder in the patients with bipolar disorder type I. However, topiramate had a more significant effect than placebo on improvement of the patients with bipolar disorder and obsessive compulsive symptoms. This combination seems to be without serious adverse effects.

Topics: Adult; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Clonazepam; Double-Blind Method; Drug Therapy, Combination; Female; Fructose; Humans; Lithium Compounds; Male; Middle Aged; Neuroprotective Agents; Obsessive-Compulsive Disorder; Olanzapine; Selective Serotonin Reuptake Inhibitors; Topiramate; Treatment Outcome

The aim of this study was to test the efficacy and safety of olanzapine + topiramate versus olanzapine monotherapy in the treatment of bipolar disorder (BPD) and treatment-attendant weight gain in children and adolescents.. Subjects (N = 40) were outpatients of both sexes, 6-17 years of age, with a Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) diagnosis of BPD (manic, hypomanic, or mixed) and Young Mania Rating Scale (YMRS) total score of >15 treated over 8-week periods in two partially concurrent open-label trials with olanzapine (n = 17) or olanzapine + topiramate (n = 23).. Subjects in both groups experienced a statistically significant reduction in YMRS scores after 8-week, open-label treatment with olanzapine (baseline YMRS = 26.7 +/- 9.5; end-point YMRS = 18.2 +/- 12.5, p = 0.04) and olanzapine +topiramate (baseline YMRS = 31.3 +/- 7.9; end-point YMRS = 20.4 +/- 11.4, p = 0.04). There was no difference in response between the two groups based on YMRS or Clinical Global Impressions-Improvement (CGI-I) scores. Adverse events were few and mild and similar between the two groups, with the exception of weight gain. The weight gain in the olanzapine group was 5.3 +/- 2.1 kg and the weight gain in the olanzapine + topiramate group was statistically significantly lower, 2.6 +/- 3.6 kg.. Augmentation of olanzapine with topiramate resulted in a reduced weight gain over the course of an 8-week, open-label trial when compared with olanzapine treatment alone, but did not lead to greater reduction in symptoms of mania.

Topics: Adolescent; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Drug Therapy, Combination; Female; Fructose; Humans; Male; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Topiramate; Weight Gain

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.. 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.. 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.. 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.

Topics: Adolescent; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Body Mass Index; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fructose; Humans; Male; Psychiatric Status Rating Scales; Topiramate; Treatment Outcome; Weight Gain

To examine efficacy and tolerability of topiramate as an adjunctive treatment for overweight refractory bipolar patients.. Patients (n=30) with Bipolar I or II, were provided with an open label treatment with topiramate as an add-on therapy. All patients deemed refractory to at least one mood stabilizer, were overweight, and were treated with topiramate as an adjuvant to existing medication for at least 12 weeks. The primary effectiveness measure was the Clinical Global Impression Scale (CGI). Other scales included the Young's Mania Rating Scale (YMRS), and the Hamilton Depression scale (HAMD21). Measures prior to adding topiramate were compared to those repeated at 4, 8 and 12 weeks. Tolerance, and weight changes were monitored.. There was significant reduction in both depressive and manic symptoms with adjunctive treatment. The mean BMI at 12 weeks of topiramate treatment dropped by 2 points (p<0.0001).. Topiramate is an effective adjunctive treatment in bipolar refractory patients and the significant weight reduction effects may result in important medical risk reductions, and make topiramate attractive for some obese bipolar patients.

Topics: Adult; Anti-Obesity Agents; Bipolar Disorder; Drug Resistance; Female; Fructose; Humans; Male; Obesity; Psychiatric Status Rating Scales; Topiramate; Treatment Outcome; Weight Loss

Patients with bipolar disorder (BD) have an increased risk of obesity as well as psychotropic-associated weight gain. The objective of this study was to compare sibutramine and topiramate as adjunctive treatments for psychotropic-associated weight gain in overweight or obese outpatients with BD.. In this 24-week, open-label, flexible-dose, comparison trial, 46 outpatients with bipolar disorders who had a body mass index (BMI) > or =30 kg/m(2), or > or =27 kg/m(2) with obesity-related comorbidities, and psychotropic-associated weight gain were randomly assigned to receive sibutramine (n = 18; 5-15 mg/day) or topiramate (n = 28; 25-600 mg/day). The primary outcome measure was weight loss. Secondary measures included changes in BMI, percent body weight loss, and mood symptoms.. Patients randomized either to sibutramine or topiramate lost comparable amounts of weight (4.1 +/- 5.7 and 2.8 +/- 3.5 kg, respectively) and displayed similar rates of weight loss (0.85 and 0.82 kg/week, respectively). However, only four (22%) patients receiving sibutramine and six (21%) patients receiving topiramate completed the 24-week trial. In addition, the attrition patterns for the two drugs were different, with patients discontinuing topiramate doing so early in treatment and patients discontinuing sibutramine doing so throughout treatment. Also, higher ratings of manic and depressive symptoms significantly increased risk for early topiramate discontinuation compared to that for sibutramine.. Adjunctive sibutramine and topiramate may have comparable weight loss effects in overweight or obese bipolar patients with psychotropic-associated weight gain, but are each associated with similarly high discontinuation rates. In addition, they may have different attrition profiles. Compared to sibutramine, discontinuation of topiramate may be more likely to occur early in treatment and may be more dependent upon manic and depressive symptoms.

Topics: Adult; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Appetite Depressants; Bipolar Disorder; Body Mass Index; Cyclobutanes; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fructose; Humans; Lithium Compounds; Male; Middle Aged; Obesity; Psychiatric Status Rating Scales; Psychotic Disorders; Topiramate; Weight Gain

This pilot study evaluated the efficacy and safety of adjunctive topiramate compared with placebo in the treatment of patients with a diagnosis of schizoaffective disorder, bipolar type (SAD-BT).. A sample of 48 adult patients with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) diagnosis of SAD-BT (supported by the Structured Clinical Interview for DSM-IV Axis I Disorder, Patient Edition) were randomly assigned in a 2:1 ratio (favoring topiramate) to 8 weeks of double-blind treatment with topiramate (100-400 mg/day) or placebo. Patients who had achieved a > or =20% decrease from baseline in their Positive and Negative Syndrome Scale (PANSS) total scores were given the opportunity to continue for an additional 8 weeks of double-blind treatment. The dosage of the study medicine was continued unchanged from the earlier 8-week study period. At the end of the study period, the study medicine was tapered and discontinued over a 2-week period. Primary efficacy was assessed at 8 weeks using the mean change between treatment groups of the PANSS total scores in the intent-to-treat population of randomized patients. Several secondary measures were also assessed. Safety analyses included monitoring of adverse events, vital signs, electrocardiogram (ECG) and laboratory values.. Even though both treatments reduced scores on various psychopathology rating scales, adjunctive topiramate treatment (nearly 275 mg/day) did not show increased efficacy relative to placebo on the primary outcome measure (PANSS scale) or any of the secondary outcome measures. Topiramate-treated patients lost significantly more body weight than placebo-treated patients, which led to a significant reduction in body mass index (BMI). Relative to adjunctive placebo, topiramate-treated patients experienced higher rates of paresthesia, sedation, word-finding difficulty, sleepiness, and forgetfulness, but these differences were not statistically significant. There were no clinically significant abnormalities in either the ECG or laboratory results. There were no serious adverse events in the study. Further, there was no worsening of the PANSS total scores (to > or =10% from baseline), and no significant differences between the treatments on worsening of total Montgomery-Asberg Depression Rating Scale (MADRS) scores [1/13 (7.7%) for placebo; 1/25 (4.0%) for topiramate].. This pilot study did not support clinical efficacy for adjunctive topiramate treatment in patients with SAD-BT. There were no major safety or tolerability issues in this study. Confirming the results of other studies, topiramate-treated patients did experience greater body weight loss and reduction in BMI.

Topics: Adult; Bipolar Disorder; Body Mass Index; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Electrocardiography; Female; Fructose; Humans; Male; Pilot Projects; Psychiatric Status Rating Scales; Psychotic Disorders; Topiramate; Treatment Outcome

To investigate the efficacy and safety of topiramate versus placebo as adjunctive therapy for the outpatient management of bipolar I disorder.. In this 12-week, randomized, double-blind, placebo-controlled trial, adults with bipolar I disorder (DSM-IV criteria) experiencing a manic or mixed episode with a Young Mania Rating Scale (YMRS) score of >or= 18 while taking therapeutic levels of valproate or lithium received adjunctive topiramate or placebo. Topiramate was titrated from 25 to 400 mg/day over 8 weeks and was continued for 4 additional weeks. The study was conducted from October 2001 through October 2003. The primary outcome measure was the change in YMRS score from baseline to last study visit during the double-blind phase.. The mean +/- SD change in YMRS score from baseline was -10.1 +/- 8.7 (-40.1%) in the topiramate group (N = 143) and -9.6 +/- 8.2 (-40.2%) in the placebo group (N = 144, p = .797). Greater than 50% reduction in YMRS was achieved by 39% of the topiramate group and 38% of the placebo group (p = .914). No significant treatment differences were observed for secondary efficacy measures. Compared with adjunctive placebo, adjunctive topiramate did not worsen mania or induce depression. Paresthesia, diarrhea, and anorexia were more common in the topiramate group. The topiramate group achieved greater reductions than the placebo group in body weight (-2.5 vs. 0.2 kg, p < .001) and body mass index (-0.84 vs. 0.07 kg/m(2), p < .001).. In patients treated with lithium or valproate, there was no difference in the reduction of YMRS score in the topiramate and placebo groups. Both groups showed declines of 40%. Topiramate reduced body weight significantly relative to placebo without worsening depressive or manic symptoms.

Topics: Adult; Antimanic Agents; Bipolar Disorder; Chemotherapy, Adjuvant; Double-Blind Method; Drug Therapy, Combination; Female; Fructose; Humans; Lithium Compounds; Male; Neuroprotective Agents; Topiramate; Treatment Outcome; Valproic Acid

Mood stabilizers and atypical antipsychotics are commonly combined for the treatment of bipolar mania. The aim of this study was to compare the effectiveness and tolerability of topiramate and divalproex in combination with risperidone for treating acute mania patients in a naturalistic treatment setting. Seventy-four patients who met the DSM-IV criteria for bipolar mania were enrolled in this study. In order to assess the efficacy and the extrapyramidal symptoms (EPS), the Young Mania Rating Scale (YMRS), Clinical Global Impression (CGI) and Simpson-Angus Rating Scale (SARS) were measured at the baseline and at weeks 1, 3 and 6. From the baseline to the endpoint, the YMRS and CGI scores were reduced by 67.9% and 56.6% in the topiramate plus risperidone group (TPMG). The YMRS and CGI scores were also reduced by 63.7% and 58.2% in the divalproex plus risperidone group (DVPG). The weight and body mass index (BMI) increased significantly by 3.6% and 3.3% from the baseline to the endpoint in the DVPG, while they decreased by 0.5% and 0.4%, respectively, with no significant difference in the TPMG. There were no serious adverse events in either group. Despite the methodological limitations, topiramate was effective and tolerable for treating acute mania and may also be a promising alternative to a weight-gain liable mood stabilizer (MS) such as divalproex.

Topics: Acute Disease; Adolescent; Adult; Aged; Antimanic Agents; Antipsychotic Agents; Basal Ganglia Diseases; Bipolar Disorder; Body Mass Index; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Neuroprotective Agents; Psychiatric Status Rating Scales; Risperidone; Topiramate; Valproic Acid

The weight-gain caused by many psychotropic drugs is a major cause for poor compliance with such medications and could also increase cardio-vascular morbidity among psychiatric patients. Recent reports have shown that the anticonvulsant topiramate causes weight loss in various patient groups. The drug has also shown effectiveness in open trials as a mood stabilizer in patients with affective disorders, but not in controlled trials in the acute treatment of mania. We used topiramate to treat 12 patients with affective disorders who had a body-mass index > 30 kg/m2.. Topiramate was prescribed as part of our routine clinical practice, as an add-on medication, or as a replacement of a mood stabilizer. Patients' weight was recorded in 1 to 2 monthly intervals. Patients were followed up for between 6 and 12 months. The final dose of topiramate varied from 200 to 600 mg/day.. Topiramate was effective in reducing the weight in 10 out of the 12 patients. At six months the 12 patients had lost a mean of 7.75 kg (SD = 6.9 kg, p < 0.001) and at 12 months 9 patients had lost a mean of 9.61 kg (SD = 6.7 kg, p = 0.003). Three patients stopped the treatment: one due to side effects, one due to possible side effects, and one suffered a manic relapse and showed no sustained weight loss. There were no other clear changes in the course of illness of the patients.. The evidence of a strong weight-reducing potential of topiramate is indisputable and clinically significant. Topiramate could be considered in the treatment of bipolar patients who are overweight, or whose concerns about weight gain compromise their compliance with long-term prophylactic medication. So far there is no evidence that topiramate has anti-manic effect and it should not be used as monotherapy.

Topics: Adult; Aged; Anti-Obesity Agents; Anticonvulsants; Bipolar Disorder; Body Mass Index; Case-Control Studies; Comorbidity; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Mood Disorders; Obesity; Psychotropic Drugs; Topiramate; Weight Loss

To assess the efficacy of topiramate monotherapy for acute mania in children and adolescents with bipolar disorder type I.. This double-blind, placebo-controlled study was discontinued early when adult mania trials with topiramate failed to show efficacy. Efficacy end points included the Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale for Children, Children's Depression Rating Scale, Children's Global Assessment Scale, and Clinical Global Impressions-Improvement.. Fifty-six children and adolescents (6-17 years) with a diagnosis of bipolar disorder type I received topiramate (n=29, 52%) or placebo (n=27, 48%). The only statistically significant differences in efficacy measures between treatment groups were the difference between slopes of the linear mean profiles of the YMRS (p=.003) using a post hoc repeated measures regression and the change in Brief Psychiatric Rating Scale for Children at day 28 (-14.9 versus-5.9, p=.048) using observed data. Adverse events with topiramate included decreased appetite, nausea, diarrhea, and paresthesia.. Topiramate was well tolerated; however, the results are inconclusive because of premature termination resulting in a limited sample size. Adequately powered controlled trials are necessary to determine whether topiramate has efficacy in reducing symptoms of acute mania in children and adolescents.

Topics: Acute Disease; Adolescent; Antimanic Agents; Bipolar Disorder; Child; Double-Blind Method; Female; Fructose; Humans; Male; Pilot Projects; Prospective Studies; Topiramate; Treatment Outcome

To assess open-label adjunctive topiramate in the treatment of outpatients with unstable bipolar disorder (BD).. Outpatients with DSM-IV-defined BD (I or II) exhibiting mood instability were enrolled in this 16-week, open-label, multicentre study. Topiramate was added to existing mood stabilizers and other psychotropic treatments. The primary effectiveness measure was the Clinical Global Impression of Severity (CGI-S) scale; other scales included the Young Mania Rating Scale (YMRS) and the Montgomery-Asberg Depression Rating Scale (MADRS). Safety assessments included monitoring adverse events, measuring tremor, monitoring vital signs and weight, and laboratory indices. We also evaluated patient satisfaction with treatment.. A total of 109 patients were enrolled. Intent-to-treat analysis showed significant improvement from baseline in the CGI-S, YMRS, and MADRS, starting at Week 2 (P < 0.001), with further accrual of benefit between Week 2 and Week 16 (P < 0.001). The mean modal dosage of topiramate during the stable dosing period was 180 mg daily. There was a mean 1.8 kg decrease in patient weight from topiramate initiation to Week 16 (P < 0.001). Topiramate was well tolerated by most patients; 11% withdrew from the study owing to adverse events. We noted a significant reduction in the mean severity score for preexisting tremor by Week 8 of treatment (P < 0.005); no notable changes in vital signs were observed. At Week 16, 50% of the patients were "completely satisfied" with topiramate treatment.. Adjunctive topiramate treatment can reduce the severity of manic and depressive symptoms, as well as reducing tremor and weight in outpatients with BD I or II.

Topics: Adult; Aged; Anticonvulsants; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Female; Fructose; Humans; Male; Middle Aged; Topiramate

A considerable number of patients with bipolar disorder fail to respond completely to mood stabilizers. The anti-epileptic topiramate shares some pharmacological actions with carbamazepine and valproate. We therefore explored the efficacy and tolerability of topiramate in the prophylaxis of bipolar disorder.. Fifty-six patients receiving outpatient treatment for bipolar affective disorder who had been on mood stabilizers, and had relapsed at least once in the past 12 months, were treated with topiramate in an add-on design and were evaluated for 1 year. Patients were assessed biweekly for the first 3 months and every month thereafter.. Fifty out of 56 patients completed the 1-year study, which indicated that adjunctive topiramate was associated with a significant reduction of new manic and depressive episodes compared to the past 12 months. The most common adverse effects were reduced appetite, fatigue and somnolence.. This was an open-label, uncontrolled study involving retrospective evaluation of episodes prior to the initiation of treatment, and the use of more than one mood stabilizer in a few patients. However, these preliminary observations of adjunctive topiramate as a maintenance treatment encourage further investigations, especially with controlled trials, for its long-term effect.

Topics: Adult; Anticonvulsants; Bipolar Disorder; Female; Fructose; Greece; Humans; Male; Middle Aged; Retrospective Studies; Topiramate; Treatment Outcome

To evaluate the point prevalence of the metabolic syndrome in patients with schizoaffective disorder--bipolar type.. Consenting patients who were participants in an ongoing clinical trial of adjunctive topiramate treatment for schizoaffective disorder, bipolar type were evaluated at baseline for the point prevalence of the metabolic syndrome. The criteria for the metabolic syndrome included: (a) waist circumference > 102 cm (40 inches) in males, or > 88 cm (35 inches) in females; (b) fasting serum triglyceride levels > or = 150 mg/dL; (c) fasting high density lipoproteins (HDL) cholesterol <40 mg/dL in men or <50 mg/dL in women; (d) blood pressure > or = 130/85 mmHg; and (e) fasting glucose > or = 110 mg/dL. Subjects who had at least three of these five criteria were defined as meeting criteria for the metabolic syndrome.. Thirty-six subjects (males = 15, females = 21) were evaluated, and three were excluded for missing data. Among those 33 subjects with complete data, 14 subjects (42.4%, males = 7, females = 7, African Americans = 6, Caucasians = 8) met criteria for the metabolic syndrome. Not unexpectedly, those with the metabolic syndrome were significantly more likely to be obese, and have significantly higher mean systolic and diastolic blood pressure, mean fasting triglyceride levels and larger mean waist circumferences, and significantly lower HDL cholesterol levels; and a trend toward higher fasting blood glucose levels. Furthermore, the fasting mean total cholesterol in those with the metabolic syndrome was 217 mg/dL (+/-46).. This preliminary report suggests that the point prevalence of the metabolic syndrome in patients with schizoaffective disorder appears to be higher than that reported in the general population of the USA. Targeted weight reduction and life style change strategies (increased exercise, smoking cessation, stress reduction) may provide useful interventions to decrease the morbidity and mortality that accompanies the presence of the metabolic syndrome in patients with psychiatric illnesses.

Topics: Adult; Anti-Obesity Agents; Antipsychotic Agents; Bipolar Disorder; Body Mass Index; Cholesterol, HDL; Comorbidity; Demography; Double-Blind Method; Female; Fructose; Humans; Hypercholesterolemia; Male; Middle Aged; Prevalence; Psychotic Disorders; Time Factors; Topiramate; Triglycerides

The safety and efficacy of the combination of risperidone and topiramate in the long-term treatment of mania were assessed in a 12-month, multicenter open study.. Subjects (N = 58) who met DSM-IV criteria for bipolar disorder and for a manic episode received both risperidone and topiramate for the treatment of their manic symptoms. Patients with mixed episodes were excluded. Risperidone could be discontinued at any point, but patients had to be on topiramate therapy for at least 12 months to be considered completers. Efficacy was assessed with the Young Mania Rating Scale (YMRS) and a modified version of the Clinical Global Impressions for Bipolar Disorder (CGI-BP-M). Safety was assessed with systematic collection of side effect data, weight, and the Hamilton Rating Scale for Depression (HAM-D) scores, to address the risk of switch into depression.. 41 patients (70.7%) completed the study. There was a significant improvement on the YMRS (p <.001) and the CGI-BP-M subscales for manic symptoms (p <.005) and long-term outcome (p <.005) from week 2 onward. Relapse rates were significantly lower during the 12-month study period compared to the precedent year (p <.0001). There was no increase in depressive symptoms as measured by the HAM-D. 37 patients (63.8 %) experienced at least 1 adverse event, the most frequent of which was somnolence (N = 7, 12.1%). At endpoint, the patients' mean weight had decreased an average of 1.1 +/- 0.4 kg.. Despite the limitations inherent to the open design, this naturalistic study suggests that the combination of risperidone and topiramate may be a valuable option for the short- and long-term treatment of mania.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Pilot Projects; Risperidone; Surveys and Questionnaires; Topiramate; Treatment Outcome

We evaluated the efficacy and safety of adjunctive topiramate in bipolar II patients who were either treatment-resistant to or unable to tolerate lithium, carbamazepine or valproate. Nineteen DSM-IV bipolar II patients received increasing doses of open-label topiramate as adjunctive therapy for their hypomanic (n=15) or depressive (n=4) symptoms. Sixteen patients completed the 12-week follow-up. There were highly significant improvements in YMRS, HDRS and CGI-BP-M scores (p=0.0001). Of the fifteen hypomanic patients, eight (53%) were rated as responders to topiramate (50% reduction in YMRS scores), and five (33%) met criteria for remission (YMRS score pound 8). Two of the four patients with a depressive episode at study entry (50%) were rated as responders (50% reduction in HDRS score), and one (25%) achieved remission (HDRS score pound 6). Topiramate was generally well tolerated. One third of the patients experienced weight loss. These preliminary results suggest that adjunctive topiramate may be useful in treating bipolar II disorder.

Topics: Adult; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Carbamazepine; Drug Resistance; Drug Therapy, Combination; Female; Fructose; Humans; Lithium; Male; Middle Aged; Psychiatric Status Rating Scales; Topiramate; Treatment Outcome; Valproic Acid

Antiepileptic drugs (AEDs) are commonly employed in the treatment of bipolar disorder. The efficacy and tolerability of topiramate, a novel anticonvulsant, and bupropion SR when added to mood stabilizer therapy were compared under single-blind conditions (rater-blinded) in patients meeting DSM-IV criteria for bipolar I/II depression.. A total of 36 out-patients with Hamilton Depression Rating Scale (HDRS-17) scores > or = 16 were randomized to receive escalating doses of either topiramate (50-300 mg/day) or bupropion SR (100-400 mg/day) for 8 weeks. Data were analyzed on an intent-to-treat basis using the last observation carried forward method.. The percentage of patients meeting a priori response criteria (> or = 50% decrease from baseline in mean HDRS-17 total score) was significant for both topiramate (56%) and bupropion SR (59%) [t(17) = 2.542, p = 0.04 and t(17) = 2.661, p = 0.03, respectively]. Baseline demographic and clinical parameters were comparable between the two treatment groups. The mean doses of study medication were 176 mg/day (SD = 102 mg/day) for the topiramate-treated group and 250 mg/day (SD = 133 mg/day) for the bupropion SR-treated group. A significant and comparable reduction in depressive symptoms was observed from baseline to endpoint following topiramate and bupropion SR treatment, according to a > or = 50% reduction in the HDRS-17. Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups (p = 0.001), however, differences between the topiramate-treated group and the bupropion SR-treated group were not significant [t(36) = 1.754, p = 0.097]. Both topiramate and bupropion SR were generally well tolerated. Thirteen patients discontinued the study: 2 because of lack of efficacy, 1 due to withdrawal of consent and 10 following side-effects (six in the topiramate and four in the bupropion SR-treated group). There were no cases of affective switch in either arm. Weight loss was experienced by patients in both groups (mean weight loss at endpoint was 1.2 kg in bupropion SR and 5.8 kg in topiramate) [t(17) = 2.325, p = 0.061 and t(17) = 2.481, p = 0.043, respectively].. These preliminary data suggest that adjunctive topiramate may reduce depressive symptom severity in acute bipolar depression. The antidepressant efficacy of this compound requires confirmation via double-blind placebo controlled investigation.

Topics: Acute Disease; Adult; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Bupropion; Depressive Disorder; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Single-Blind Method; Topiramate; Treatment Outcome

The hypothesis that exposure to traumatic events may sensitize or kindle limbic nuclei has led to efforts to treat posttraumatic stress disorder (PTSD) with anticonvulsants. Based on the kindling hypothesis of PTSD, this open-label study assesses clinical response to topiramate as a potential treatment for DSM-IV PTSD.. A naturalistic data review was conducted of medical records of all adult outpatients (9 men. 26 women symptomatic for a mean +/- SD of 18 +/- 15 years with DSM-IV chronic civilian PTSD) treated with topiramate, 12.5 to 500 mg/day, as add-on (N = 28) or monotherapy (N = 7). The last 17 patients completed the PTSD Checklist-Civilian Version (PCL-C) before treatment and at week 4. Dosage titration started at 12.5 to 25 mg/day and increased in 25- to 50-mg increments every 3 to 4 days until a therapeutic response was achieved or the drug was no longer tolerated. The mean duration of treatment was 33 weeks (range, 1-119 weeks).. Topiramate decreased nightmares in 79% (19/24) and flashbacks in 86% (30/35) of patients, with full suppression of nightmares in 50% and of intrusions in 54% of patients with these symptoms. Nightmares or intrusions partially improved in a median of 4 days (mean = 11 +/- 13 days) and were fully absent in a median of 8 days (mean = 35 +/- 49 days). Response was seen in 95% of partial responders at a dosage of 75 mg/day or less, and in 91% of full responders at a dosage of 100 mg/day or less. Mean reductions in PCL-C score from baseline to week 4 were highly significant (baseline score = 60 vs. week 4 score = 39, p < .001), with similar reductions in reexperiencing, avoidance, and hyperarousal criteria symptoms. Thirteen patients discontinued for various reasons during the > 2-year study period. Except for a single instance of acute secondary narrow-angle glaucoma, there were no serious side effects.. Topiramate appeared effective as add-on or monotherapy for chronic PTSD. It demonstrated a rapid onset of action and minimally serious, dose-related side effects without the development of tolerance. Double-blind studies are indicated.

Topics: Adolescent; Adult; Age of Onset; Aged; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Chronic Disease; Comorbidity; Dose-Response Relationship, Drug; Dreams; Drug Administration Schedule; Drug Therapy, Combination; Female; Fructose; Hallucinations; Humans; Life Change Events; Male; Middle Aged; Personality Inventory; Stress Disorders, Post-Traumatic; Topiramate; Treatment Outcome

To review the literature on efficacy of third generation anticonvulsants for treatment of bipolar disorder and provide clinical recommendations.. 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.. 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.. 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.

Topics: Acetates; Amines; Anticonvulsants; Bipolar Disorder; Cyclohexanecarboxylic Acids; Double-Blind Method; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Nipecotic Acids; Placebos; Tiagabine; Topiramate; Treatment Outcome; Triazines; Zonisamide

A series of open studies suggests that topiramate has efficacy in bipolar disorder. To further investigate the potential value of topiramate as an antimanic agent, we conducted an open trial in 11 manic patients.. Eleven patients with bipolar I disorder with an acute manic episode (DSM-IV) were treated with a mood stabilizer and/or antipsychotics in sufficient and fixed doses. All had a Young Mania Rating Scale (YMRS) score of at least 24 (mean +/- SD = 33.5+/-8.1). Topiramate was added after stable plasma levels of concomitant mood stabilizers had been reached and was titrated within 1 week to a final dose in the range of 25 to 200 mg/day, depending on clinical efficacy and tolerability. Topiramate was discontinued after 10 days, while concomitant medication remained unchanged. After 5 days, topiramate was reintroduced at similar or increased dosages for another 7 days. Patients were assessed with the YMRS; the Clinical Global Impressions scale version for bipolar patients; and the 21-item Hamilton Rating Scale for Depression.. Seven of the 11 patients initially showed a good antimanic response with > 50% reduction in YMRS score. One patient showed psychotic features following rapid increase in topiramate dosage and dropped out on day 10. After discontinuation of topiramate, 7 of the remaining 10 patients worsened (increase of > or = 25% in YMRS score), 2 remained stable, and 1 discontinued follow-up after good recovery. After reintroducing topiramate, all patients improved again within a week, with 8 of 9 meeting the responder criterion of > or = 50% YMRS score reduction when comparing baseline values with those of day 22. With the exception of the patient who developed psychosis, topiramate was well tolerated. Concomitant medication did not interfere with plasma levels of drug, except for carbamazepine level in 1 patient.. The antimanic response among patients in this study appears reproducibly linked to the addition of topiramate.

Topics: Adult; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Drug Administration Schedule; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Research Design; Topiramate; Treatment Outcome

Topiramate, a structurally novel anticonvulsant, is being evaluated for other neurological conditions such as migraine, neuropathic pain, and essential tremor, and also for psychiatric conditions such as bipolar disorder, bulimia, post-traumatic stress disorder, and schizoaffective disorder, in addition to obesity. This article will focus on the use of topiramate for bipolar disorder.. The pharmacological profile of topiramate is compared to other established and putative mood stabilizers, and a rationale for its use in bipolar disorder is presented. Data from open clinical trials of topiramate for depression, mania, and rapid-cycling bipolar disorder are summarized. Preliminary data from one pilot dose-finding, double-blind, random-assignment, placebo-controlled, 3-week parallel group study of two doses of topiramate for acute bipolar I mania is reported. Safety data regarding topiramate was reviewed. Finally, the potential place of this agent in bipolar illness is considered.. The pharmacological advantages for topiramate are low protein binding, minimal hepatic metabolism and mainly unchanged renal excretion, a 24-h half-life, and minimal drug interactions. Open clinical studies suggest a 50-65% response for refractory bipolar mania, and a 40-56% response for refractory bipolar depression in mainly add-on treatment. Open clinical studies of topiramate for rapid-cycling subjects and those for comorbid bulimia, substance abuse, post-traumatic stress, migraine, and obesity report effectiveness. The primary efficacy endpoint data (change from baseline Y-MRS total scores) of the placebo-controlled, random assignment parallel group phase II dose-finding study were not statistically significant. However, once the antidepressant-associated manias (28 of the sample, of 97 subjects) were excluded from the controlled study, the post-hoc analyses indicated the higher dose (512 mg/day) topiramate treatment group showed a statistically significant reduction in endpoint Y-MRS change scores as compared to placebo (p < 0.03). Adverse effects of topiramate in bipolar subjects include attention, concentration and memory problems, fatigue, sedation, transient paraesthesias, nausea, and anorexia. Some subjects experience word-finding difficulty. Weight loss may be seen in several topiramate-treated subjects with bipolar disorder.. Topiramate appears to show promise as an addition to the agents available to treat bipolar disorder. More definitive controlled data on the efficacy of topiramate in the acute and continuation phases as well as for the prophylaxis either as monotherapy or as combination treatment of bipolar disorder are ongoing, and the results are awaited.

Topics: Acetates; Acute Disease; Amines; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Carbamazepine; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Lithium; Randomized Controlled Trials as Topic; Topiramate; Triazines; Valproic Acid

To preliminarily explore the spectrum of effectiveness and tolerability of the new antiepileptic drug topiramate in bipolar disorder, we evaluated the response of 56 bipolar outpatients in the Stanley Foundation Bipolar Outcome Network (SFBN) who had been treated with adjunctive topiramate in an open-label, naturalistic fashion.. In this case series, response to topiramate was assessed every 2 weeks for the first 3 months according to standard ratings in the SFBN, and monthly thereafter while patients remained on topiramate. Patients' weights, body mass indices (BMIs), and side effects were also assessed.. Of the 54 patients who completed at least 2 weeks of open-label, add-on topiramate treatment, 30 had manic, mixed, or cycling symptoms, 11 had depressed symptoms, and 13 were relatively euthymic at the time topiramate was begun. Patients who had been initially treated for manic symptoms displayed significant reductions in standard ratings scores after 4 weeks, after 10 weeks, and at the last evaluation. Those patients who were initially depressed or treated while euthymic showed no significant changes. Patients as a group displayed significant decreases in weight and BMI from topiramate initiation to week 4, to week 10, and to the last evaluation. The most common adverse side effects were neurologic and gastrointestinal.. These preliminary open observations of adjunctive topiramate treatment suggest that it may have antimanic or anticycling effects in some patients with bipolar disorder, and may be associated with appetite suppression and weight loss that is often viewed as beneficial by the patient and clinician. Controlled studies of topiramate's acute and long-term efficacy and side effects in bipolar disorder appear warranted.

Topics: Adult; Anticonvulsants; Bipolar Disorder; Body Mass Index; Female; Fructose; Humans; Male; Psychiatric Status Rating Scales; Time Factors; Topiramate

Anticonvulsant agents such as carbamazepine and valproate are alternatives to lithium in treating subjects with bipolar disorder. Topiramate (Topamax), a new antiepileptic agent, is a candidate drug for bipolar disorder. We evaluated topiramate as adjunctive treatment for bipolar patients.. Eighteen patients with DSM-IV bipolar I disorder [mania (n = 12), hypomania (n = 1), mixed episode (n = 5), and rapid cycling (n = 6)], and two subjects with schizoaffective disorder bipolar type, resistant to current mood-stabilizer treatment were initiated on topiramate, 25 mg/day, increasing by 25-50 mg every 3 7 days to a target dose between 100 and 300 mg/day, as other medications were held constant for 5 weeks. The Young Mania Rating Scale (Y-MRS), Hamilton Depression Rating Scale (Ham-D), and Clinical Global Impression-Bipolar Version Scale (CGI-BP) were used to rate subjects weekly.. By 5 weeks, 12 (60%) subjects were responders, i.e., 50% reduction in the Y-MRS scores and a CGI of 'much' or 'very much improved'. Three subjects were 'minimally improved', four showed no change, and one was 'minimally worse'. Six subjects had parasthesia, three experienced fatigue, and two had 'word-finding' difficulties; in all cases, side effects were transient. All patients lost weight with a mean of 9.4 lb in 5 weeks, and a significant reduction in body mass index (BMI) occurred too.. Topiramate appears to have efficacy for the manic and mixed phases of bipolar illness. Other preliminary data suggest antidepressant efficacy too. Among obese bipolar subjects, the weight loss potential of topiramate may be beneficial. If controlled trials confirm these initial results, topiramate may be a significant addition to the available treatments for bipolar disorder.

Topics: Acetates; Adult; Aged; Amines; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Body Mass Index; Carbamazepine; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Follow-Up Studies; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lithium; Male; Middle Aged; Topiramate; Treatment Outcome; Valproic Acid

Topics: Aggression; Antipsychotic Agents; Bipolar Disorder; Child; Humans; Metformin; Topiramate; Weight Gain

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Depression; Female; Humans; Intellectual Disability; Lithium; Olanzapine; Pica; Topiramate

Topiramate is a novel antiepileptic drug that is used as an adjunctive in the treatment of partial and secondary generalized seizures. In recent years, psychiatrists have paid more attention to topiramate as a mood stabilizer and as an agent for treating eating disorders, especially in binge eating disorder (BED) and bulimia nervosa.. Herein, we report a case of topiramate precipitating a manic episode in a bipolar patient comorbid with BED, who complained of emotional instability and binge-eating behaviors.. In this patient, acute manic episode was induced by topiramate treatment at a daily dose of 75 mg for three days.. The dose of topiramate was decreased to 25 mg per day promptly, and the patient gradually became calm but the BED symptoms recurred, then the dose of topiramate was increased to 50 mg per day again. Meanwhile, the dosage of quetiapine was escalated up to 500 mg per night to stabilize her mood.. With a combination of quetiapine 500 mg per night and topiramate 50 mg per day, the emotion and eating problems of this patient concurrently improved.. These findings indicated that patients with a history of bipolar disorder and comorbid BED have a tendency to develop manic episode when taking topiramate. Careful monitoring of mood alterations after topiramate supplement to mood stabilizers is necessary in this population.

Topics: Anticonvulsants; Binge-Eating Disorder; Bipolar Disorder; Disease Progression; Female; Humans; Topiramate; Young Adult

Additional medications are needed for inflammatory bowel disease (IBD) as existing therapies are incompletely effective and can be costly and toxic. Preclinical studies suggest that topiramate (an anticonvulsant) may have disease-modifying properties in IBD, but its efficacy in humans is unknown.. To evaluate whether topiramate use is associated with clinical benefit in IBD patients.. We conducted a retrospective cohort study using administrative claims data from the MarketScan databases. Persons with IBD were identified between 2000 and 2010. New users of topiramate were compared with users of other anticonvulsant and anti-migraine medications. The primary outcome was a new prescription for an oral steroid (≥14 days). Secondary outcomes included initiation of biologic agents, abdominal surgery, and hospitalization. Cox proportional hazard modeling was used to adjust for potential confounders.. We identified 773 new users of topiramate and 958 users of comparator drugs. After adjusting for potential confounders, topiramate use was not associated with the primary outcome of steroid prescriptions [hazard ratio (HR) 1.14, 95 % confidence interval (CI) 0.74, 1.73]. Results did not differ significantly by IBD subtype. There was no difference between topiramate users and users of comparator drugs with respect to post-exposure initiation of biologic agents (HR 0.93, 95 % CI 0.39, 2.19), abdominal surgery (HR 1.04, 95 % CI 0.17, 6.41), or hospitalization (HR 0.86, 95 % CI 0.62, 1.19).. In this large U.S. administrative claims study, topiramate use was not associated with markers of IBD flares. These results cast doubt on whether topiramate may be an effective adjunct to current IBD therapy.

Topics: Adult; Anticonvulsants; Bipolar Disorder; Child; Child, Preschool; Databases, Factual; Female; Follow-Up Studies; Fructose; Humans; Infant; Infant, Newborn; Inflammatory Bowel Diseases; Male; Middle Aged; Migraine Disorders; Peripheral Nervous System Diseases; Pharmacoepidemiology; Proportional Hazards Models; Retrospective Studies; Seizures; Topiramate; Treatment Outcome; Young Adult

Topics: Adult; Analgesics; Bipolar Disorder; Comorbidity; Female; Fructose; Humans; Migraine Disorders; Topiramate; Treatment Outcome

Topiramate is used to treat a variety of neurologic and psychiatric diseases due to its benign safety profile. Data regarding the toxicity and toxicokinetics of topiramate in acute overdose are limited. A case of massive, acute ingestion resulting in the highest reported topiramate level is presented, including toxicokinetic evaluation. A 37-year-old woman presented with coma unresponsive to naloxone following topiramate ingestion. She had normal vital signs without respiratory depression. She was intubated for airway protection, given 3.5 mg lorazepam IV for facial and neck muscle twitching, and transferred to our facility. No additional sedation was required for 18 h on the ventilator. Following mental status improvement, the patient was extubated. Confusion, dysarthria, and imbalance resolved over the next 2 days. Nonanion gap metabolic acidosis persisted for 3 days. Peak serum topiramate level was 356.6 microg/ml (reference range, 5-20 microg/ml). Massive topiramate ingestion led to prolonged coma with normal vital signs and nonanion gap metabolic acidosis. Coma of this severity has not been previously reported. Serum half-life, which has not been studied after overdose, was 16 h. Despite the large ingestion and significant presenting symptoms, the patient recovered fully with supportive intensive care alone. Massive acute topiramate ingestion may lead to nonanion gap metabolic acidosis and prolonged coma which resolves with intensive supportive care. Toxicokinetic data following large, suicidal ingestion of topiramate were similar to previously published pharmacokinetic information.

Topics: Acidosis; Adult; Anticonvulsants; Bipolar Disorder; Blood Gas Analysis; Coma; Critical Care; Drug Overdose; Female; Fructose; Gas Chromatography-Mass Spectrometry; Humans; Hypnotics and Sedatives; Lorazepam; Respiration, Artificial; Topiramate

Topiramate and phenytoin possess mood stabilizing properties. The mechanism of action of anticonvulsants used in the treatment of bipolar depression is complex and still not completely elucidated. Na(+) channels are present at distinct sites in neurons, where they sub serve different functions and play distinct roles. The fact that most of the anticonvulsants used in the treatment of bipolar disorders are blockers of voltage-gated Na channels has determined our interest in evaluating the role of ion channels in bipolar disorders.. The scope of this study was to determinate if sodium channels are important for topiramate and phenytoin to exert their antidepressant-like functioning.. The role of Na(+) channels in the mechanism of action of the anticonvulsants was investigated by using veratrine a selective activator of Na channels in a mice model of depression, the forced swimming test. Veratrine 0.125 mg/kg and topiramate or phenytoin (16 and 32 mg/kg) were given IP 45 and 30 min, respectively, before the test.. The administration of topiramate and phenytoin induce a decrease in the immobility time on the FST which can be considered as an antidepressant-like activity. The antidepressant-like effect of the anticonvulsants was completely reversed by veratrine suggesting that the antidepressant-like effect of topiramate and phenytoin on the FST might be due to their Na(+) channels blocking properties.

Topics: Animals; Antidepressive Agents; Bipolar Disorder; Depressive Disorder; Disease Models, Animal; Dose-Response Relationship, Drug; Fructose; Locomotion; Male; Membrane Transport Modulators; Mice; Neuropsychological Tests; Phenytoin; Random Allocation; Sodium Channel Agonists; Sodium Channels; Swimming; Time Factors; Topiramate; Veratrine

Adolescent mania is often misdiagnosed. This case study describes the clinical course and diagnostic reclassification from schizophrenia to bipolar disorder in a 15-year-old girl. This case study also describes the pedigree of the siblings, familial aggregation, and anticipation of mood disorders. In addition, we present the successful use of topiramate, a new antiepileptic drug, which is increasingly being used as a mood stabilizer in paediatric bipolar disorder. The efficacy of topiramate in this case supports its role as a promising agent in treatment-resistant adolescent mania associated with familial aggregation.

Topics: Adolescent; Age of Onset; Anticipation, Genetic; Anticonvulsants; Bipolar Disorder; Depressive Disorder, Major; Diagnosis, Differential; Drug Therapy, Combination; Family; Female; Fructose; Humans; Lithium Compounds; Pedigree; Schizophrenia; Topiramate; Treatment Outcome

Topics: Adolescent; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Fructose; Humans; Immunoassay; Marijuana Abuse; Patient Compliance; Quetiapine Fumarate; Topiramate

Topics: Adolescent; Bipolar Disorder; Female; Fructose; Humans; Neuroprotective Agents; Topiramate

Topics: Adolescent; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Fever; Fructose; Humans; Olanzapine; Rhabdomyolysis; Topiramate

Topics: Adolescent; Adult; Anticonvulsants; Bipolar Disorder; Dose-Response Relationship, Drug; Female; Fructose; Humans; Male; Randomized Controlled Trials as Topic; Retrospective Studies; Smoking; Topiramate; Treatment Outcome

The anticonvulsant topiramate (TPM) has been recently proposed as a novel adjuvant therapy for bipolar disorder and schizophrenia, yet its efficacy remains controversial. As both disorders are characterized by gating deficits, we tested the effects of TPM on the behavioral paradigm of prepulse inhibition (PPI) of the acoustic startle response, a validated animal model of sensorimotor gating. TPM (10, 18, 32, 58, 100 mg/kg, intraperitoneal, i.p.) enhanced PPI in rats in a dose-dependent fashion, prevented the PPI reduction mediated by the dopaminergic agonist apomorphine (0.25 mg/kg, subcutaneous, s.c.) and potentiated the effects of the antipsychotic drugs haloperidol (0.05, 0.1 mg/kg, i.p.) and clozapine (2.5, 5 mg/kg, i.p.). Conversely, TPM elicited no significant effect on the PPI disruption mediated by the NMDA receptor antagonist dizocilpine (0.05, 0.1 mg/kg, s.c.) and surprisingly antagonized the attenuation of dizocilpine-induced PPI disruption mediated by clozapine (5 mg/kg, i.p.). Our results suggest that TPM may exert diverse actions on the neural substrates of sensorimotor gating. While the pharmacological mechanisms of such effects are still elusive, our findings might contribute to shed light on some controversies on the therapeutic action of TPM, and point to this drug as a putative novel adjuvant therapy for some clusters of gating disturbances.

Topics: Animals; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Brain; Dopamine; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Synergism; Excitatory Amino Acid Antagonists; Fructose; Glutamic Acid; Male; Neural Inhibition; Rats; Rats, Sprague-Dawley; Reflex, Startle; Schizophrenia; Synaptic Transmission; Topiramate

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Controlled Clinical Trials as Topic; Depression; Fructose; Humans; Lamotrigine; Lithium Compounds; Neuroprotective Agents; Olanzapine; Topiramate; Triazines

Topics: Adolescent; Adult; Anticonvulsants; Attention Deficit and Disruptive Behavior Disorders; Bipolar Disorder; Child; Disruptive, Impulse Control, and Conduct Disorders; Fructose; Humans; Receptors, Glutamate; Research Design; Topiramate; Treatment Outcome

Topics: Adult; Aggression; Akathisia, Drug-Induced; Anticonvulsants; Bipolar Disorder; Brain; Dose-Response Relationship, Drug; Female; Flunarizine; Fructose; Humans; Migraine Disorders; Mood Disorders; Topiramate; Withholding Treatment

Topics: Anticonvulsants; Antimanic Agents; Bipolar Disorder; Comorbidity; Drug Therapy, Combination; Female; Fructose; Gambling; Humans; Lithium Compounds; Middle Aged; Topiramate

Continuation treatment for bipolar disorder often consists of a mood stabilizer and a second-generation antipsychotic. Quetiapine has been shown to be an effective treatment for acute mania and acute bipolar depression, but there are limited data for its use in continuation treatment. This study examined the effectiveness of open-label adjunctive quetiapine therapy for continuation treatment in patients with bipolar disorder. Prospectively collected life chart data from 63 outpatients with bipolar disorders, most recent episodes depressed, manic, or cycling, who received adjunctive quetiapine therapy as part of standard acute treatment were analyzed. Patients had 4 or more weeks of prequetiapine baseline data and at least 2 weeks of quetiapine treatment with no other medication changes. Patients were grouped by baseline symptoms; depression only, mania only, or both mania and depression (cycling group). Owing to small mania and well groups (n=4), differences between depression and cycling groups were examined and mania and well groups excluded. Fifty-five patients were included in the analyses. The primary outcome measure was change in mood severity from baseline to change in treatment regimen, as measured by the NIMH Life Charting Method. Patients received adjunctive quetiapine for a mean of 122 (SD=149) days. Both groups showed significant improvement in depression ratings and time spent depressed by week 10. Both groups showed significant improvement in overall mood. No between-group differences in improvement were found. Adjunctive quetiapine may be useful as continuation treatment in bipolar populations with both pure depressive and cycling symptoms. Further controlled studies are warranted.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Databases, Factual; Depression; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Lamotrigine; Lithium Compounds; Male; Middle Aged; Mood Disorders; Prospective Studies; Quetiapine Fumarate; Time Factors; Topiramate; Treatment Outcome; Triazines

A patient with a treatment-refractory bipolar disorder with ultradian cycling responded to adjunctive topiramate. Response was maintained during 3-year follow-up.

Topics: Activity Cycles; Adult; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benztropine; Bipolar Disorder; Drug Resistance; Drug Therapy, Combination; Follow-Up Studies; Fructose; Humans; Lithium Compounds; Loxapine; Parasympatholytics; Topiramate; Valproic Acid

To evaluate the efficacy and tolerability of topiramate monotherapy in adults with acute manic or mixed episodes of bipolar I disorder.. In four trials, adults hospitalized with acute mania, a diagnosis of bipolar I disorder, history of > or =1 previous manic or mixed episodes, and > or =20 Young Mania Rating Scale (YMRS) score were randomized to double-blind treatment with topiramate (target doses: 200, 400, or 600 mg/day) or placebo; two trials included an active comparator (lithium, 1500 mg/day). The core study duration in all trials was 3 weeks; three trials also had 9-week double-blind extensions. The primary efficacy variable was mean change from baseline in YMRS in the core 3-week study.. Changes in YMRS score during 3 weeks were not significantly different for topiramate versus placebo (mean YMRS reductions, -5.1 to -8.4). Mean YMRS reductions in lithium-treated groups were significantly greater (p < or = 0.001 versus placebo and topiramate). A similar pattern was observed after 12 weeks of double-blind treatment in studies with double-blind extensions. Paresthesia, appetite decrease, dry mouth, and weight loss were more frequently associated with topiramate than with placebo.. These studies do not support the efficacy of topiramate as monotherapy in acute mania or mixed episodes in adults with bipolar I disorder. Topiramate was not associated with mood destabilization measured as mania exacerbation or treatment-emergent depression. Lithium was confirmed as an effective therapy in this population.

Topics: Acute Disease; Adolescent; Adult; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Double-Blind Method; Female; Fructose; Humans; Lithium; Male; Middle Aged; Multicenter Studies as Topic; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome; Weight Loss

Topics: Adult; Anticonvulsants; Bipolar Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fructose; Humans; Lithium; Panic Disorder; Topiramate; Weight Gain

The authors describe four cases of catatonia in which topiramate treatment was used. Commonly effective therapies, including benzodiazepines and divalproex, were proven refractory. In all four cases, subjects experienced complete remission of catatonic symptoms and tolerated treatment well. In one case, all psychotropic medications were discontinued because the patient became delirious. The delirium resolved after discovery and treatment of a urinary tract infection. Catatonic agitation relapsed when topiramate was withdrawn but remitted again when topiramate and lorazepam therapy was restored. In two cases, continued topiramate therapy was accompanied by sustained remission. These case reports present a novel approach to the treatment of catatonia.

Topics: Adult; Aged; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Cataplexy; Catatonia; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Fructose; Humans; Lorazepam; Male; Middle Aged; Recurrence; Schizophrenia, Catatonic; Topiramate

Topics: Adult; Anti-Obesity Agents; Bipolar Disorder; Female; Fructose; Humans; Male; Middle Aged; Obesity; Topiramate; Weight Gain

Topics: Adolescent; Anticonvulsants; Attention Deficit and Disruptive Behavior Disorders; Bipolar Disorder; Comorbidity; Drug Administration Schedule; Female; Fructose; Humans; Psychiatric Status Rating Scales; Topiramate; Treatment Outcome

To evaluate the effectiveness of lithium augmentation of topiramate on mood symptoms, binge eating behavior, and body weight in obese bipolar patients with binge eating disorder (BED) seeking weight management.. We conducted a naturalistic study of 12 consecutive outpatients with bipolar disorders, BED, and obesity who received lithium augmentation for mood instability during the course of topiramate-based pharmacotherapy for obesity and BED. Lithium was added to topiramate (mean dose 514 mg i.d.) and titrated to a mean dose of 1009 mg i.d. (mean plasma concentration 0.7 mmol/L). Treatment response was assessed by comparing changes in clinical severity scales for mood and eating disorders, weekly binge eating frequency, and weight for the 2 months before and the first 2 months during lithium treatment.. A statistically significant improvement in global severity of mood symptoms was observed after as compared to before lithium augmentation. Statistically insignificant reductions in weight and in binge frequency and severity were also observed after lithium addition.. Optimal weight loss treatment in obese patients with comorbid bipolar and BEDs may require stabilization of mood. The combination of lithium and topiramate may have a role in the management of this difficult-to-treat population.

Topics: Adult; Anti-Obesity Agents; Antimanic Agents; Bipolar Disorder; Body Mass Index; Body Weight; Bulimia Nervosa; Comorbidity; Drug Interactions; Female; Follow-Up Studies; Fructose; Humans; Lithium Chloride; Male; Middle Aged; Obesity; Severity of Illness Index; Statistics, Nonparametric; Surveys and Questionnaires; Topiramate

Topiramate is an antiepileptic drug, recently also used in the treatment of psychiatric diseases. Inasmuch as topiramate and valproate, which are currently used for aggressive behavior, share several pharmacological mechanisms (positive modulatory effect on the GABA activity and negative modulatory effect on glutamatergic neurotransmission), the objective of the present study was to compare the pharmacological effects of topiramate with those of valproate and their combination in patients with psychiatric disorders showing marked aggression and agitation. A retrospective, case-controlled, mirror-image study was carried out in a sample of 45 inpatients affected by schizophrenia, schizoaffective and bipolar disorder, and hospitalized in a maximum-security Canadian psychiatry hospital. Overt Aggression Scale, Agitation-Calmness Evaluation Scale, number and intensity of psychotic episodes, number of episodes of withdrawal from group activities per week, and number of therapeutic isolation per week and of strict surveillance intervention per week were evaluated before and after the treatments. Results indicate that patients treated with topiramate show a decrease in the average score of the Overt Aggression Scale, a decrease of episodes of agitation and of strict surveillance interventions. This effect was similar to the group treated with valproate or with the combination of valproate-topiramate. However, valproate therapy, but not topiramate therapy, decreased the intensity of agitation episodes measured by the Agitation-Calmness Evaluation Scale; valproate and the combination topiramate-valproate decreased the number of psychotic disorganization episodes as well. These results suggest that topiramate could be a valid medicine in the control of aggression in psychosis. Double-blind, randomized, placebo-controlled studies need to further assess this pharmacological indication.

Topics: Adult; Aggression; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Case-Control Studies; Drug Therapy, Combination; Female; Fructose; Humans; Male; Patient Dropouts; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Topiramate; Treatment Outcome; Valproic Acid

Topics: Bipolar Disorder; Female; Fructose; Humans; Middle Aged; Topiramate

Topics: Adult; Antidepressive Agents; Bipolar Disorder; Female; Fructose; Humans; Lamotrigine; Neuroprotective Agents; Neutropenia; Topiramate; Triazines

Two cases of patients with a severe comorbidity of alcohol abuse treated with topiramate are reported. The first case is a 52-year-old patient who has been suffering from schizophrenia for many years. Topiramate prescription was associated with a discontinuation of his chronic, refractory alcohol consumption. The second case is a 41-year-old patient with bipolar disorder that mainly manifests itself through manic episodes. Topiramate treatment allowed him to decrease his alcohol intake to an acceptable level. Consequently, his bipolar symptoms also improved, without the appearance of any side effects. Thus, topiramate may improve alcohol intake among patients with schizophrenia or bipolar disorder. Certain studies have shown the efficacy of topiramate in alcoholic patients without such associated disorders, but further research is needed for this special population.

Topics: Adult; Alcohol Drinking; Alcoholism; Bipolar Disorder; Fructose; Humans; Male; Middle Aged; Schizophrenia; Topiramate

The aim of this study was to assess topiramate as adjunctive treatment in children and adolescents hospitalized with bipolar disorders.. Medical records of all children and adolescents with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV-TR) (APA, 2000) diagnosis of bipolar disorder, type I, hospitalized for an acute manic, mixed, or depressive episode, were reviewed. The primary outcome measure was the Clinical Global Impression-Severity (CGI-S) score.. Twenty-five (25) children and adolescents received topiramate, with a mean final dose of 126 mg/day (range, 25-350 mg). Overall CGI-S scores significantly improved from 5.3+/-1.0 to 3.5+/-0.7, and mania CGI-S scores decreased from 5.4+/-1.0 to 3.3+/-0.9. Sixteen (16) of 25 (64%) bipolar patients were classified as responders (defined by an endpoint overall CGI-I score of less than or equal to 2). No serious adverse events occurred during treatment. Of 25 patients evaluated, 1 (4%) experienced mild sedation while treated with topiramate.. Preliminary results of this retrospective chart review suggest that adjunctive topiramate may be associated with improvements in children and adolescents hospitalized for an acute manic, mixed, or depressive episode. Randomized and controlled trials with adjunctive topiramate in this population are needed to further explore this observation.

Topics: Adolescent; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Child; Drug Therapy, Combination; Female; Fructose; Hospitalization; Humans; Male; Retrospective Studies; Topiramate; Treatment Outcome

Topics: Adult; Anti-Obesity Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Interactions; Drug Therapy, Combination; Fructose; Humans; Leukopenia; Male; Topiramate; United Kingdom; Weight Gain

Topics: Adolescent; Anticonvulsants; Bipolar Disorder; Brain; Chronic Disease; Fructose; Humans; Male; Topiramate

Olanzapine is an effective drug for the long-term treatment of bipolar disorder but is associated with burdensome weight gain. Topiramate is a novel anticonvulsant that may induce weight loss in some patients. This is the first study to address the long-term efficacy and impact on weight of the combination of olanzapine and topiramate in bipolar patients. Twenty-six Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition bipolar spectrum patients received olanzapine plus topiramate cotherapy for treatment of their manic (n = 14), hypomanic (n = 6), depressive (n = 2), and mixed (n = 1) symptoms for 1 year. Three rapid cycling patients were also enrolled despite being euthymic. Efficacy was assessed with the Young Mania Rating Scale, the Hamilton Depression Rating Scale, and the Modified Clinical Global Impressions for Bipolar Disorder. Weight, body mass index, and side effects were collected at every visit. Thirteen (50%) patients completed the 1-year follow-up. By intent-to-treat, patients significantly improved from baseline in Young Mania Rating Scale scores (P < 0.0001), Hamilton Depression Rating Scale (P < 0.05), and Modified Clinical Global Impressions for Bipolar Disorder subscales (mania P < 0.0001, depression P < 0.05, overall P < 0.0001). Most patients gained weight during the first month of combined treatment (mean weight gain 0.7 +/- 0.6 kg), but at the 12-month endpoint, the mean weight change was -0.5 +/- 1.1 kg. The combination of olanzapine and topiramate was efficacious for the long-term treatment of bipolar patients and appeared to carry some benefits for controlling weight gain. Given the limitations of the open, uncontrolled design, further trials are warranted with this combination.

Topics: Adult; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Olanzapine; Statistics, Nonparametric; Topiramate; Treatment Outcome; Weight Gain

Topics: Adult; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Carbonic Anhydrase Inhibitors; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Female; Fructose; Half-Life; Humans; Lithium Carbonate; Metabolic Clearance Rate; Topiramate

To report observations on the efficacy and tolerability of topiramate in a sample of five patients with severe symptoms of bulimia nervosa and comorbid mood and/or anxiety disorders.. Topiramate was added to other psychotropic medication under open-label conditions up to the maximum tolerated dose or until remission of the eating disorder was achieved.. Topiramate almost completely eliminated binging and purging behavior in three of the five patients. Improvement was maintained throughout the period of follow-up for up to 18 months. One patient showed a partial, temporary response, and the fifth was intolerant of the drug and unable to complete an adequate trial.. These results suggest strongly that the efficacy of topiramate in patients with bulimia nervosa with and without comorbid mood and anxiety disorders should be investigated more fully.

Topics: Adult; Anxiety Disorders; Bipolar Disorder; Bulimia; Chronic Disease; Comorbidity; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Recurrence; Topiramate; Treatment Outcome

Topics: Alcoholism; Anticonvulsants; Behavior, Addictive; Bipolar Disorder; Comorbidity; Female; Fructose; Humans; Male; Middle Aged; Topiramate; Treatment Outcome

To investigate breakthrough mania secondary to a right temporal lobe neoplasm in a bipolar patient previously stabilized on sodium divalproex.. Right hemispheric brain tumors involving the orbitofrontal or basotemporal cortex are a rare cause of secondary mania. In such cases, early neurologic signs may be difficult to distinguish from bipolar symptoms. Breakthrough mania secondary to brain neoplasm in a bipolar patient stabilized on medication is an extremely rare phenomena which has not been previously reported.. The clinical course of a bipolar subject stabilized on valproate who developed mania secondary to a right temporal lobe astrocytoma is described. Serial brain magnetic resonance imaging (MRI), baseline electroencephalogram (EEG), and neuropsychiatric evaluations were used to examine the relationship between the patient's brain mass and behavioral disturbances.. Symptoms were those that accompanied prior episodes of mania. In addition, signs of temporal lobe dysfunction were evident including periods of detachment, déjà vu experiences, and olfactory hallucinations. In the context of mania, depersonalization was initially attributed to bipolar symptoms. Only several months later, when olfactory hallucinations and alterations in consciousness became evident, was a temporal lobe lesion suspected. Neuropsychiatric abnormalities responded to a combination of surgical intervention, radiation therapy, and topiramate, however the tumor was advanced and invasive at diagnosis resulting in a poor prognosis.. This case suggests that clinicians examining unexplained cases of breakthrough mania should be vigilant for early signs of temporal lobe dysfunction, which could aid in detecting treatable lesions.

Topics: Anticonvulsants; Antimanic Agents; Astrocytoma; Bipolar Disorder; Brain Neoplasms; Disease Progression; Electroencephalography; Female; Fructose; Hallucinations; Humans; Magnetic Resonance Imaging; Middle Aged; Temporal Lobe; Topiramate; Valproic Acid

Topics: Anticonvulsants; Bipolar Disorder; Epilepsy, Temporal Lobe; Female; Fructose; Humans; Middle Aged; Topiramate

To evaluate the effectiveness and safety of topiramate as add-on, long-term therapy for treatment-resistant bipolar-spectrum disorders, 34 DSM-IV bipolar-spectrum patients, including bipolar I (n = 28), bipolar II (n = 3), bipolar not otherwise specified (n = 2), and schizoaffective disorder bipolar type (n = 1), considered to be resistant to treatment with lithium, carbamazepine, and valproate, received increasing doses of topiramate as adjunctive therapy for their manic (n = 17), depressive (n = 11), hypomanic (n = 3), or mixed (n = 3) symptoms. Outcome measures included the Young Mania Rating Scale (YMRS), the Hamilton Rating Scale for Depression (HAM-D), and the Clinical Global Impression (CGI) for Severity. Patients were followed up for 6 months. Twenty-five patients (74%) completed the 6-month follow-up. Nine patients (26%) dropped out early due to lost of follow-up (n = 4), worsening of symptoms (n = 2), side effects (n = 1), hospitalization due to intercurrent illness (n = 1), and noncompliance (n = 1). By intent-to-treat analysis, there was a significant reduction in YMRS, HAM-D, and CGI scores (p < 0.0001 for all measures at the endpoint) after the introduction of topiramate. Most therapeutic effects appeared between weeks 2 and 6. Fifty-nine percent of manic patients and 55% of depressed patients were considered to be responders to the drug, which was well tolerated; only one patient discontinued due to side effects. The most common side effect was paraesthesia (n = 2). Ten patients experienced moderate weight loss during the follow-up period. The mean topiramate dose at endpoint was 202 +/- 65 mg/day. These preliminary results indicate that adjunctive topiramate may be useful in the long-term treatment of bipolar spectrum disorders, even in the most difficult-to-treat patients.

Topics: Adult; Anticonvulsants; Bipolar Disorder; Drug Resistance; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Statistics, Nonparametric; Topiramate

Topics: Bipolar Disorder; Child, Preschool; Drug Therapy, Combination; Female; Fructose; Humans; Risperidone; Topiramate; Weight Gain

Topiramate, a novel antiepileptic agent, has shown promise in the treatment of bipolar disorder. Patients attending a bipolar specialty clinic and treated with topiramate were identified by chart review, and data were harvested from systematic prospective assessments used routinely in the clinic. Fourteen patients who received topiramate for an average of 22.4 weeks were identified. All but one of these patients were considered to be highly refractory to standard treatment and 13 met the criteria for at least one comorbid psychiatric condition. Nine of these patients (64%) experienced an increased level of functioning and decrease in symptom severity during treatment with adjunctive topiramate. Eleven patients remained on treatment for longer than 2 weeks. Eight of these patients (73%) experienced a significant improvement in their comorbid conditions. Patients with a body mass index (BMI) of > or = 28 (n = 4) experienced a mean weight loss of 29.7 lb while on topiramate. Topiramate appears to be a promising agent for the treatment of bipolar disorder associated with comorbid psychiatric conditions and obesity.

Topics: Adolescent; Adult; Anti-Obesity Agents; Anticonvulsants; Bipolar Disorder; Body Mass Index; Drug Resistance; Female; Fructose; Humans; Male; Middle Aged; Obesity; Prospective Studies; Psychiatric Status Rating Scales; Topiramate

The purpose of this study was to evaluate the efficacy of topiramate in the treatment of acute manic symptoms. Fourteen patients, admitted with an acute manic episode, were treated with topiramate. All required supplementation therapy with benzodiazepines. Nine patients received topiramate as monotherapy; four of them required zuclopenthixol acutard 100 mg/48 h intramuscularly (im) for not more than 6 days. In three treatment-resistant patients, topiramate was added to the existing therapy. Finally, in two patients topiramate was coadministered with an antipsychotic from the beginning. Patients were assessed every week for 4 weeks with the Bech and Rafaelsen Mania Scale (BRMS). Mean BRMS scores declined from 26.2 to 11.6 in the fourth week (P<.001); a significant decline (P<.001) was observed after the first week. Response rate (> or = 50% reduction of BRMS) was 61.5% (8 out of 13 patients). All patients tolerated topiramate well. Reduced appetite and weight loss was observed in four patients; however, two patients presented weight gain. These preliminary findings provide support for a modest efficacy of topiramate, especially as monotherapy, in the treatment of acute mania.

Topics: Acute Disease; Adult; Aged; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Clopenthixol; Female; Fructose; Hospitalization; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Topiramate; Weight Loss

The objective of this study was to evaluate the effectiveness, safety, and tolerability of the anticonvulsant agent, topiramate, as adjunctive treatment for children and adolescents with bipolar disorders.. The outpatient medical charts of children and adolescents with a Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnosis of bipolar disorder, type I or II, and who were treated with topiramate were retrospectively reviewed by two child and adolescent psychiatrists using the Clinical Global Impression (CGI) scale and the Clinical Global Assessment Scale (CGAS). Separate CGI ratings were made for mania and overall bipolar illness.. Twenty-six patients (mean age 14 +/- 3.5 years) with bipolar disorder, type I (n = 23) or II (n = 3), who had been treated (mean duration 4.1 +/- 6.1 months) with topiramate (mean dose 104 +/- 77 mg/day) were identified. Response rate (defined by a CGI-Improvement score of < or = 2 at endpoint) was 73% for mania and 62% for overall illness. CGAS scores significantly improved from baseline to endpoint. No serious adverse events were reported.. Although controlled trials are necessary, this retrospective study suggests that topiramate is effective and well tolerated as an adjunctive treatment for children and adolescents with bipolar disorder.

Topics: Adolescent; Adult; Age Factors; Bipolar Disorder; Child; Child, Preschool; Drug Therapy, Combination; Female; Fructose; Humans; Male; Neuroprotective Agents; Psychiatric Status Rating Scales; Retrospective Studies; Topiramate; Treatment Outcome

Topiramate, a fairly new anticonvulsant, is increasingly being used as a mood stabilizer in bipolar and schizoaffective disorders. One common side effect is a reduced appetite that often results in weight loss. This finding raises the interesting question of whether both mood and body weight can be stabilized in patients who have gained weight while being treated with neuroleptics for one of the disorders mentioned above.. We studied the body weight, subjective sense of well-being, and psychopathology in two adolescent patients who were being treated with topiramate (alone or in combination with a neuroleptic drug). Both patients had reduced appetite, while body weight either remained stable or was reduced.. The patients reported both improved control of food intake and mood stabilization.. We conclude that adolescents with affective disturbance who have gained weight on neuroleptic drugs may benefit from topiramate in terms of mood stabilization and body weight control.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Combined Modality Therapy; Diet, Reducing; Dose-Response Relationship, Drug; Follow-Up Studies; Fructose; Humans; Male; Obesity; Psychotic Disorders; Topiramate

Psychopharmacology research aims to expand the therapeutic ratio between efficacy, on the one hand, and adverse events and safety, on the other. The novel antipsychotics are now the antipsychotics of choice in the treatment of bipolar disorders. They have the advantages of potential antidepressant properties and low risks of extrapyramidal side effects and, especially, of tardive dyskinesia. However, novel antipsychotics may also have varying propensities to cause side effects, such as somnolence, hyperprolactinemia, weight gain (sometimes significant), and possibly diabetes mellitus. The increasing use of these novel agents requires careful assessment and monitoring of emergent side effects and diligent consideration of associated medical complications. Two new anticonvulsants, lamotrigine and topiramate, have recently shown promise in the treatment of bipolar disorders. Most of their adverse effects can be avoided by slow titration toward the recommended doses. In contrast to carbamazepine and valproic acid, topiramate may be associated with weight loss.

Topics: Anticonvulsants; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Female; Fructose; Humans; Lamotrigine; Male; Obesity; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Risperidone; Thiazoles; Topiramate; Triazines

A potential model for bipolar disorder, quinpirole-induced biphasic locomotion, was used for a preliminary evaluation of behavioral effects of oral anticonvulsant treatment. Quinpirole, a D2/D3 agonist, induces a biphasic locomotor response starting with inhibition and followed by excitation, resembling the oscillating nature of bipolar disorder. The present study developed a paradigm for oral administration of anticonvulsants that resulted in therapeutic blood levels and tested the effects of treatment on the quinpirole-induced response. Eleven days treatment with valproate (12 g/liter water), phenytoin (6 g/kg food), and carbamazepine (8 g/kg food) resulted in therapeutic blood levels and in a borderline significant reduction in quinpirole-induced hyperactivity without effects on the hypoactive phase. Valproate effects became more significant at the height of the hyperactivity response. Eleven days treatment with topiramate (30 mg/kg) resulted in a significant attenuation of quinpirole-induced hyperactivity, qualitatively similar to the effects of the other anticonvulsants. The results suggest that mood-stabilizing anticonvulsant drugs including topiramate may attenuate quinpirole-induced hyperactivity.

Topics: Administration, Oral; Animals; Anticonvulsants; Bipolar Disorder; Brain; Carbamazepine; Disease Models, Animal; Dopamine Agonists; Drug Administration Schedule; Fructose; Hyperkinesis; Motor Activity; Neurons; Phenytoin; Quinpirole; Rats; Receptors, Dopamine; Topiramate; Valproic Acid

Topics: Adult; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Drug Interactions; Female; Fructose; Humans; Lithium Chloride; Topiramate

Topics: Adult; Anticonvulsants; Bipolar Disorder; Body Image; Bulimia; Cognition; Female; Fructose; Humans; Topiramate

Topics: Acetates; Amines; Anticonvulsants; Bipolar Disorder; Central Nervous System Diseases; Cyclohexanecarboxylic Acids; Drug Information Services; Fructose; Gabapentin; gamma-Aminobutyric Acid; Gastrointestinal Diseases; Humans; Incidence; Lamotrigine; Mental Disorders; Neurotoxicity Syndromes; Topiramate; Triazines; Valproic Acid

Topics: Anticonvulsants; Bipolar Disorder; Female; Fructose; Humans; Middle Aged; Psychiatric Status Rating Scales; Topiramate

Topics: Anticonvulsants; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Child; Child Behavior Disorders; Cognition Disorders; Fructose; Humans; Male; Topiramate

Topiramate is an antiepileptic agent, which is being investigated as a mood-stabilizer. Three obese individuals with DSM-IV bipolar I disorder and type II diabetes mellitus received topiramate treatment in combination with antipsychotics and valproate or carbamazepine. In addition to improved mood stability, these individuals lost between 16 to 20.5% of their pre-topiramate body weight and also achieved significant glycemic control.

Topics: Adult; Anticonvulsants; Bipolar Disorder; Body Mass Index; Diabetes Mellitus, Type 2; Female; Fructose; Humans; Hyperglycemia; Male; Middle Aged; Obesity; Time; Topiramate; Weight Loss

This small-scale pilot study was performed to grossly document safety and any evidence of efficacy of topiramate in bipolar disorder. Ten patients hospitalized for acute mania were given open-label topiramate monotherapy for up to 28 days. The mean Young Mania Rating Scale (YMRS) score decreased from 32 (range, 26-40) at baseline to 22 (range, 2-40) at the end of the study. Five patients exhibited evidence of moderate to marked improvement, three subjects had at least a 50% reduction in YMRS scores, and the other two patients experienced an improvement of 25% to 49% on the YMRS. The preliminary findings of this small series suggest that topiramate may be effective in acute mania. Double-blind controlled trials are now needed to further investigate the efficacy and safety of topiramate in bipolar disorder.

Topics: Adult; Anti-Anxiety Agents; Bipolar Disorder; Brief Psychiatric Rating Scale; Female; Fructose; Humans; Male; Middle Aged; Pilot Projects; Topiramate

We describe a case of bilateral angle-closure glaucoma associated with oral topiramate therapy.. Interventional case report. Case report with echographic illustration.. A 51-year-old man developed bilateral acute angle-closure glaucoma 2 weeks after beginning topiramate therapy for bipolar affective disorder. Laser peripheral iridotomy was performed in the right eye without resolution of the acute attack. Echography revealed lens thickening and ciliochoroidal detachments in both eyes. Visual acuity, intraocular pressure, and anterior and posterior segment anatomy normalized 2 weeks after cessation of topiramate therapy.. Topiramate, a new sulfa-derivative antiepileptic medication, may cause idiosyncratic ciliochoroidal detachments and ciliary body edema leading to anterior displacement of the lens-iris diaphragm, lens thickening, and acute angle-closure glaucoma.

Topics: Acute Disease; Administration, Oral; Anticonvulsants; Bipolar Disorder; Choroid Diseases; Fructose; Glaucoma, Angle-Closure; Humans; Intraocular Pressure; Male; Middle Aged; Topiramate; Ultrasonography; Visual Acuity

Topics: Adult; Bipolar Disorder; Borderline Personality Disorder; Comorbidity; Drug Overdose; Feeding and Eating Disorders; Female; Fructose; Humans; Substance-Related Disorders; Topiramate; Weight Gain

Topics: Adult; Anticonvulsants; Bipolar Disorder; Epilepsy, Temporal Lobe; Fructose; Humans; Male; Topiramate

Topiramate is a novel anticonvulsant agent with a broad spectrum mechanism of action, and recent clinical reports indicate that it may have mood stabilizing properties in bipolar disorder. Therefore, we treated a 41-year-old woman who had 12 previous hospitalizations for acute mania during a 10-year history of bipolar I disorder with this compound. Since 1991, the patient had been treated with carbamazepine, valproate and lamotrigine with limited success. At the beginning of a new manic episode, topiramate was started in the outpatient clinic. Eight weeks after initiation of treatment, the patient was hospitalized. This inpatient treatment lasted less than 3 weeks. Subsequently, the patient has not been hospitalized again. Topiramate was well tolerated. Even though, during subsequent topiramate treatment, a serious life event (suicide attempt of brother) induced re-occurence of the patient's psychopathology, which did not require hospitalization. Fortunately, inpatient treatment was not necessary due to an increase of topiramate dosage and addition of risperidone and clonazepam. The patient, now on 200 mg/day, is mostly asymptomatic and has functioned well for over 17 months, in contrast to 13 hospitalizations during the previous 10 years.

Topics: Acute Disease; Adaptation, Psychological; Adult; Antimanic Agents; Bipolar Disorder; Clonazepam; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fructose; Humans; Life Change Events; Patient Readmission; Recurrence; Risperidone; Topiramate

Topiramate, a newer antiepileptic agent, may benefit several neurological and psychiatric states, including bipolar disorder.. A physically healthy, stockily built, 47-year-old, hypomanic Asian male with a >20-year history of uneventful use of psychotropic agents received topiramate in a dose that was stepped up to 100 mg/day across 10 days. He developed dysphoria, confusion, word-finding difficulties, and difficulties in maintaining a train of thought; the symptoms vanished within a week of drug discontinuation, and reappeared 1-2 days after rechallenge at a dose of 25 mg/day.. It appears that, while confusion is usually a dose-dependent adverse effect of topiramate, certain patients may idiosyncratically develop this adverse effect at very low doses.

Topics: Anticonvulsants; Bipolar Disorder; Confusion; Dose-Response Relationship, Drug; Drug Administration Schedule; Fructose; Humans; Male; Middle Aged; Psychoses, Substance-Induced; Topiramate

Topics: Adult; Anticonvulsants; Bipolar Disorder; Depressive Disorder; Dose-Response Relationship, Drug; Female; Fructose; Humans; Topiramate

Topics: Acetates; Adult; Amines; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Cyclohexanecarboxylic Acids; Dibenzothiazepines; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lithium; Quetiapine Fumarate; Topiramate

The objective of this paper was to determine if topiramate is effective as treatment for bipolar spectrum disorders in a naturalistic setting. All charts of outpatients treated with topiramate (n = 76) were reviewed, and clinical response was assessed retrospectively using the Clinical Global Impressions Scale for Improvement. Mild improvement was seen in 47% (n = 36) and moderate-to-marked improvement in 13% (n = 10). Responders received a higher mean dose (180 mg/day) than did nonresponders (83.2 mg/day, p = 0.002). Topiramate dose was also higher in those who lost weight (138.3 mg/day) than in those who did not (70 mg/day, p = 0.007). Weight loss was experienced by 50% of the sample, with a mean loss of 14.2 lbs. Side effects were reported by 82% (n = 62) of the population, including cognitive effects, sedation, parasthesias, nausea, insomnia, headache, and dizziness. Adverse effects led 36% (n = 27) of the total sample to discontinue treatment with topiramate. Topiramate led to significant weight loss in about half of this bipolar population, while also improving mood symptoms at least mildly in most patients. Topiramate response and weight loss were both dose-related, with efficacy, in particular, associated with higher doses (mean = 180 mg/day) than frequently used in current clinical practice.

Topics: Adult; Aged; Anticonvulsants; Antidepressive Agents; Bipolar Disorder; Data Collection; Dose-Response Relationship, Drug; Female; Fructose; Humans; Male; Medical Records; Middle Aged; Psychiatric Status Rating Scales; Topiramate; Treatment Outcome; Weight Loss

Topiramate is a newly developed anticonvulsant agent with possible mood-stabilizing properties. Little is known about the short- and long-term effects of topiramate monotherapy in bipolar disorder. We here present the case of a 60-year-old female bipolar patient who received topiramate alone as maintenance treatment after recovering from euphoric mania. During 7 months, she was free from new manic symptomatology and she was able to reduce her overweight by 16.5 kg. The patient who is known to have a strongly hyperthymic temperament described symptoms of fatigue and sedation and eventually discontinued topiramate monotherapy. When she presented again in our bipolar clinic, severe euphoric mania had developed. After hospitalization, she slowly responded to oral sodium valproate loading plus zotepine. Her weight increased again and so did her triglyceride serum levels. Topiramate treatment and discontinuation did not seem to affect cholesterol serum levels.

Topics: Adult; Affect; Bipolar Disorder; Body Weight; Female; Fructose; Humans; Lipids; Neuroprotective Agents; Topiramate

Topics: Abnormalities, Drug-Induced; Acetates; Adult; Amines; Anti-Anxiety Agents; Anticonvulsants; Bipolar Disorder; Carbamazepine; Cognition Disorders; Cyclohexanecarboxylic Acids; Dizziness; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fructose; Gabapentin; gamma-Aminobutyric Acid; Heart Defects, Congenital; Humans; Lamotrigine; Nausea; Obesity; Stevens-Johnson Syndrome; Topiramate; Triazines; Valproic Acid

Topics: Adult; Anticonvulsants; Bipolar Disorder; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Female; Fructose; Humans; Liver Function Tests; Topiramate

Topics: Adult; Anticonvulsants; Bipolar Disorder; Comorbidity; Depressive Disorder; Female; Fructose; Humans; Obesity; Topiramate; Weight Gain

Topics: Adult; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Fructose; Haloperidol; Humans; Recurrence; Topiramate; Treatment Outcome