topiramate and Depressive-Disorder

Alcoholism remains a serious cause of morbidity and mortality despite progress through neurobiological research in identifying new pharmacological strategies for its treatment. Drugs that affect neural pathways that modulate the activity of the cortico-mesolimbic dopamine system have been shown to alter drinking behavior, presumably because this dopaminergic system is closely associated with rewarding behavior. Ondansetron, naltrexone, topiramate, and baclofen are examples. Subtyping alcoholism in adults into an early-onset type, with chronic symptoms and a strong biological predisposition to the disease, and a late-onset type, typically brought on by psychosocial triggers and associated with mood symptoms, may help in the selection of optimal therapy. Emerging adults with binge drinking patterns also might be aided by selective treatments. Although preliminary work on the pharmacogenetics of alcoholism and its treatment has been promising, the assignment to treatment still depends on clinical assessment. Brief behavioral interventions that encourage the patient to set goals for a reduction in heavy drinking or abstinence also are part of optimal therapy.

Topics: Adult; Aged; Alcohol Deterrents; Alcoholism; Baclofen; Chronic Disease; Depressive Disorder; Female; Fructose; Humans; Hypothalamo-Hypophyseal System; Limbic System; Male; Naltrexone; Ondansetron; Pituitary-Adrenal System; Prefrontal Cortex; Receptors, Dopamine D2; Receptors, GABA; Topiramate; Young Adult

This article deals with the effect of antiepileptic drugs on mood when applied in epileptic patients. The author points that depressive symptoms occur significantly more frequently in epilepsy and there are more common factor in the mechanism of action of the antiepileptic and antidepressive agents. The relevant literature is surprisingly poor. Primary and large analysis regarding affective disorders coexisting with epilepsy is still lacking. From this aspect some antiepileptic drugs have not been investigated at all. The consequences of the papers originates from indirect sources like adverse events profiles of the study drugs or from psychometric tests performed for avoiding exclusion criteria of psychological nature. On the other hand the paper deals also with the difficulties of such kind of investigations concerning the classification of depressive signs presenting with epilepsy, special considerations of inclusion of appropriate patients and particular limits of the measuring and follow-up of the observed effect. As the result of the detailed analysis of the literature the author recommends lamotrigine, carbamazepine and oxcarbazepine as first choice antiepileptic drug for epileptic patients suffering from depressive disorder, too. On the contrary, phenobarbital, topiramate and vigabatrin are able to worsen the affective symptoms. Aimed, randomized, controlled studies are necessary for recognizing the whole spectrum of psychotropic effects of antiepileptic drugs and for their successful and individually tailored application in patients in their comorbid states. Author calls the attention for the importance of the treatment of depressive states frequently occurring in epileptic patients. These symptoms modify patient compliance and are able to influence even the epileptic process itself.

Topics: Affect; Anticonvulsants; Antidepressive Agents; Carbamazepine; Depressive Disorder; Epilepsy; Fructose; Humans; Lamotrigine; Mood Disorders; Oxcarbazepine; Patient Compliance; Phenobarbital; Psychometrics; Topiramate; Triazines; Vigabatrin

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

Alcoholism and nicotine dependence share many neurobiological underpinnings; the presence of one drug can cause a person to crave the other. Depressive illness can complicate comorbid alcohol and nicotine dependence by exacerbating the negative affect encountered during attempts to abstain from one or both drugs. Given the morbidity and mortality associated with cigarette smoking, it is imperative to identify treatments to promote smoking cessation and address comorbid psychiatric conditions contemporaneously. Pharmacotherapeutic options demonstrating varying degrees of efficacy and promise in preclinical and clinical studies include nicotine replacement therapy (NRT), selective serotonin reuptake inhibitors (SSRIs), bupropion, varenicline, tricyclic antidepressants, and bupropion plus NRT. Topiramate has shown potential for promoting smoking cessation in alcoholics, although its safety in depressed patients has not been fully explored. The efficacy of medications for treating nicotine dependence is generally enhanced by the inclusion of behavioral interventions such as cognitive behavioral therapy. When group cohesion and social support are stressed, success rates increase among depressed smokers undergoing smoking cessation treatment. Additional treatment strategies targeting dually dependent individuals with comorbid psychiatric disorders, including special populations such as women and adolescents, await further investigation.

Topics: Alcoholism; Antidepressive Agents; Bupropion; Clinical Trials as Topic; Cognitive Behavioral Therapy; Combined Modality Therapy; Comorbidity; Depressive Disorder; Fructose; Humans; Nicotine; Psychotherapy, Group; Smoking Cessation; Topiramate

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

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

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

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

Dysregulation of the monoaminergic systems is likely a sufficient but not a necessary cause of depression. A wealth of data indicates that neuropeptides, e.g., NPY, CRH, somatostatin, tachykinins and CGRP play a role in affective disorders and alcohol use/abuse. This paper focuses on NPY in etiology and pathophysiology of depression. Decreased peptide and mRNA NPY were found in hippocampus of both the genetic, e.g., the FSL strain, and environmental rat models of depression, e.g., chronic mild stress and early life maternal separation paradigms. Rat models of alcoholism also show altered NPY. Furthermore, NPY is also reduced in CSF of depressed patients. Antidepressive treatments tested so far (lithium, topiramate, SSRIs, ECT and ECS, wheel running) increase NPY selectively in rat hippocampus and in human CSF. Moreover, NPY given icv to rat has antidepressive effects which are antagonized by NPY-Y1 blockers. The data support our hypothesis that the NPY system dysregulation constitutes one of the biological underpinnings of depression and that one common mechanism of action of antidepressive treatment modalities may be effects on NPY and its receptors. In a novel paradigm, early life maternal separation was superimposed on "depressed" FSL and control rats and behavioral and brain neurochemistry changes observed in adulthood. The consequences were more deleterious in genetically vulnerable FSL. Early antidepressive treatment modulated the adult sequelae. Consequently, if these data are confirmed, the ethical and medical question that will be asked is whether it is permissible and advisable to consider prophylactically treating persons at risk.

Topics: Animals; Antidepressive Agents; Depressive Disorder; Disease Models, Animal; Electroconvulsive Therapy; Fructose; Hippocampus; Humans; Lithium Compounds; Maternal Deprivation; Neuropeptide Y; Rats; Rats, Inbred Strains; RNA, Messenger; Selective Serotonin Reuptake Inhibitors; Social Environment; Topiramate

In this cross-sectional study, the neuropsychiatric profiles of 42 patients with juvenile myoclonic epilepsy (JME) who were treated with valproate (VPA) or topiramate (TPM) in monotherapy were compared with the aim of verifying the relationship between cognitive dysfunction, psychiatric disorders, and factors related to epilepsy. Patients with JME taking VPA 500-1750 mg/day or TPM 50-175 mg/day were selected. For all patients, psychiatric profiles were evaluated with the Scheduled Clinical Interview, axes I and II (SCID I and SCID II), or the Brazilian version of the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS-PL). Neuropsychological measures included intellectual functions, attention, memory, executive functions, and language. Patients taking TPM exhibited worse neuropsychological performance on attention, short-term memory, processing speed, and verbal fluency functions related to frontal lobes, which may be dysfunctional in JME. Anxiety disorders were associated with lack of seizure control and having had more than 20 lifetime generalized tonic-clonic seizures.

Topics: Adolescent; Anticonvulsants; Anxiety Disorders; Cross-Sectional Studies; Depressive Disorder; Female; Fructose; Humans; Male; Mental Disorders; Myoclonic Epilepsy, Juvenile; Neuropsychological Tests; Seizures; Topiramate; Valproic Acid

To clarify the role of hippocampal sclerosis (HS) in developing psychiatric and cognitive adverse events during therapy with topiramate (TPM) in patients with temporal lobe epilepsy (TLE).. We analyzed the data of 70 patients with TLE and HS and 128 patients with cryptogenic TLE matched for age, sex, starting dose, and titration schedule of TPM. They were selected from the first consecutive 431 patients started on TPM between 1995 and 1999.. Patients with HS were more likely to develop cognitive adverse events (CAEs; p = 0.002) and depression (p = 0.018) and to be receiving a polytherapy regimen (p = 0.007). However, regression analysis demonstrated that only HS was a predictive factor for the occurrence of CAEs (OR = 2.4; p < 0.001) and depression (OR = 2.3; p = 0.02).. Patients with TLE and HS were more prone to develop CAEs and depression than were patients with cryptogenic TLE, during TPM therapy, despite the same titration schedule. The presence of HS and not duration of epilepsy or polytherapy regimen represented the main risk factor.

Topics: Adult; Anticonvulsants; Cognition Disorders; Depressive Disorder; Drug Therapy, Combination; Epilepsy, Temporal Lobe; Female; Fructose; Hippocampus; Humans; Male; Middle Aged; Regression Analysis; Risk Factors; Sclerosis; Topiramate

Topics: Adult; Antidepressive Agents, Second-Generation; Appetite; Depressive Disorder; Drug Therapy, Combination; Female; Fluoxetine; Fructose; Humans; Neuroprotective Agents; Obesity; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; Topiramate; Weight Loss

Topics: Agoraphobia; Alcoholism; Cyclohexanols; Depressive Disorder; Female; Fructose; Hallucinations; Humans; Infarction, Posterior Cerebral Artery; Middle Aged; Neuroprotective Agents; Obesity; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Topiramate; Venlafaxine Hydrochloride

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

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