topiramate and Anxiety-Disorders

Alcohol use disorders (AUDs) represent a significant health burden worldwide. Currently, there are three medications approved by the U.S. Food and Drug Administration for the treatment of AUDs, and other drugs are being prescribed off-label for this purpose. However, response rates for pharmacologic treatment are low, and extant research suggests that treatment effects may partially depend on genetic factors. Personalized medicine, or using a patient's genetics and/or personal history to determine efficacy of treatment prior to prescription, is an emerging tool that will help clinicians treat their patients more effectively and safely. This review systematically discusses current findings from AUD pharmacotherapy trials examining disulfiram, acamprosate, naltrexone, the injectable naltrexone, and topiramate. Furthermore, it presents pharmacogenetics findings associated with these medications in an attempt to further the field of personalized medicine. Research from trials examining AUDs and comorbid major depressive disorder and anxiety disorders is also presented, and pharmacogenetic findings for these treatments are discussed. Lastly, the authors comment on the present and future states of the field of personalized medicine for AUD.

Topics: Acamprosate; Alcohol Deterrents; Alcohol-Related Disorders; Anxiety Disorders; Comorbidity; Depressive Disorder, Major; Disulfiram; Fructose; Humans; Naltrexone; Pharmacogenetics; Precision Medicine; Taurine; Topiramate; United States

The amygdala, a temporal lobe structure that is part of the limbic system, has long been recognized for its central role in emotions and emotional behavior. Pathophysiological alterations in neuronal excitability in the amygdala are characteristic features of certain psychiatric illnesses, such as anxiety disorders and depressive disorders. Furthermore, neuronal excitability in the amygdala, and, in particular, excitability of the basolateral nucleus of the amygdala (BLA) plays a pivotal role in the pathogenesis and symptomatology of temporal lobe epilepsy. Here, we describe two recently discovered mechanisms regulating neuronal excitability in the BLA, by modulating GABAergic inhibitory transmission. One of these mechanisms involves the regulation of GABA release via kainate receptors containing the GluR5 subunit (GluR5KRs). In the rat BLA, GluR5KRs are present on both somatodendritic regions and presynaptic terminals of GABAergic interneurons, and regulate GABA release in an agonist concentration-dependent, bidirectional manner. The relevance of the GluR5KR function to epilepsy is suggested by the findings that GluR5KR agonists can induce epileptic activity, whereas GluR5KR antagonists can prevent it. Further support for an important role of GluR5KRs in epilepsy comes from the findings that antagonism of GluR5KRs is a primary mechanism underlying the antiepileptic properties of the anticonvulsant topiramate. Another mechanism regulating neuronal excitability in the BLA by modulating GABAergic synaptic transmission is the facilitation of GABA release via presynaptic alpha1A adrenergic receptors. This mechanism may significantly underlie the antiepileptic properties of norepinephrine. Notably, the alpha1A adrenoceptor-mediated facilitation of GABA release is severely impaired by stress. This stress-induced impairment in the noradrenergic facilitation of GABA release in the BLA may underlie the hyperexcitability of the amygdala in certain stress-related affective disorders, and may explain the stress-induced exacerbation of seizure activity in epileptic patients.

Topics: Adrenergic alpha-Agonists; Amygdala; Animals; Anticonvulsants; Anxiety Disorders; Depression; Dose-Response Relationship, Drug; Epilepsy, Temporal Lobe; Fructose; GABA Agonists; gamma-Aminobutyric Acid; Humans; Neurons; Norepinephrine; Rats; Receptors, Adrenergic, alpha-1; Receptors, Kainic Acid; Synaptic Transmission; Topiramate

Topics: Adolescent; Adult; Aged; Anticonvulsants; Anxiety Disorders; Female; Fructose; Glaucoma, Angle-Closure; Humans; Male; Middle Aged; Migraine Disorders; Myopia; Pain; Personality Disorders; Topiramate; Weight Loss

Topics: Anti-Anxiety Agents; Anticonvulsants; Anxiety Disorders; Carbamazepine; Fructose; GABA Agonists; gamma-Aminobutyric Acid; Humans; Lamotrigine; Nipecotic Acids; Synapses; Tiagabine; Topiramate; Triazines; Valproic Acid

Limited population-based data are available on antiepileptic drug (AED) treatment patterns in women of childbearing age with epilepsy; the current population risk is not clear.. To examine the AED treatment patterns and identify differences in use of valproate sodium and topiramate by comorbidities among women of childbearing age with epilepsy.. A retrospective cohort study used a nationwide commercial database and supplemental Medicare as well as Medicaid insurance claims data to identify 46 767 women with epilepsy aged 15 to 44 years. The eligible study cohort was enrolled between January 1, 2009, and December 31, 2013. Data analysis was conducted from January 1, 2017, to February 22, 2018.. Cases required an International Classification of Diseases, Ninth Revision, Clinical Modification-coded epilepsy diagnosis with continuous medical and pharmacy enrollment. Incident cases required a baseline of 2 or more years without an epilepsy diagnosis or AED prescription before the index date. For both incident and prevalent cases, focal and generalized epilepsy cohorts were matched by age, payer type, and enrollment period and then compared.. Antiepileptic drug treatment pattern according to seizure type and comorbidities.. Of the 46 767 patients identified, there were 8003 incident cases (mean [SD] age, 27.3 [9.4] years) and 38 764 prevalent cases (mean [SD] age, 29.7 [9.0] years). Among 3219 women in the incident epilepsy group who received AEDs for 90 days or more, 3173 (98.6%) received monotherapy as first-line treatment; among 28 239 treated prevalent cases, 18 987 (67.2%) received monotherapy. In 3544 (44.3%) incident cases and 9480 (24.5%) prevalent cases, AED treatment was not documented during 180 days or more of follow-up after diagnosis. Valproate (incident: 35 [5.81%]; prevalent: 514 [13.1%]) and phenytoin (incident: 33 [5.48%]; prevalent: 178 [4.53%]) were more commonly used for generalized epilepsy and oxcarbazepine (incident: 53 [8.03%]; prevalent: 386 [9.89%]) was more often used for focal epilepsy. Levetiracetam (incident: focal, 267 [40.5%]; generalized, 271 [45.0%]; prevalent: focal, 794 [20.3%]; generalized, 871 [22.2%]), lamotrigine (incident: focal, 123 [18.6%]; generalized, 106 [17.6%]; prevalent: focal, 968 [24.8%]; generalized, 871 [22.2%]), and topiramate (incident: focal, 102 [15.5%]; generalized, 64 [10.6%]; prevalent: focal, 499 [12.8%]; generalized, 470 [12.0%]) were leading AEDs prescribed for both focal and generalized epilepsy. Valproate was more commonly prescribed for women with comorbid headache or migraine (incident: 53 of 1251 [4.2%]; prevalent: 839 of 8046 [10.4%]), mood disorder (incident: 63 of 860 [7.3%]; prevalent: 1110 of 6995 [15.9%]), and anxiety and dissociative disorders (incident: 57 of 881 [6.5%]; prevalent: 798 of 5912 [13.5%]). Topiramate was more likely prescribed for those with comorbid headache or migraine (incident: 335 of 1251 [26.8%]; prevalent: 2322 of 8046 [28.9%]).. Many women appear to be treated with valproate and topiramate despite known teratogenicity risks. Comorbidities may affect selecting certain AEDs despite their teratogenicity risks.

Topics: Adolescent; Adult; Anticonvulsants; Anxiety Disorders; Comorbidity; Dissociative Disorders; Epilepsies, Partial; Epilepsy, Generalized; Female; Headache Disorders; Humans; Lamotrigine; Levetiracetam; Mental Disorders; Migraine Disorders; Mood Disorders; Oxcarbazepine; Phenytoin; Retrospective Studies; Risk; Teratogens; Topiramate; Valproic Acid; Young Adult

Anxiety disorders are associated with increased impairments in psychosocial functioning, work productivity and health-related quality of life. In addition, anxiety is a common symptom of ethanol withdrawal and it strongly contributes to relapse. Benzodiazepines are frequently prescribed for relief of anxiety and ethanol withdrawal symptoms but considerable side effects, such sedation, tolerance and dependence, are observed during treatment. Therefore, better drugs are needed for the treatment of anxiety states. The purpose of this study was to investigate whether topiramate would reduce basal levels of anxiety and ethanol-withdrawn induced anxiety in male rats; the elevated plus maze (EPM) was used as an animal model of anxiety. In Experiment 1, topiramate (0, 10, and 40 mg/kg, i.g.) and diazepam (1 mg/kg, i.p.) was acutely and repeatedly administered to naive rats. In Experiments 2 and 3, topiramate (0 or 40 mg/kg, i.g.) was acutely and chronically administered in early (72 hr after ethanol removal) and protracted (21 days after ethanol removal) ethanol-withdrawn rats, respectively. Acute and repeated topiramate treatment induced anxiolytic-like effects in naive rats. Early ethanol withdrawal increased anxiety, and acute topiramate administration counteracted the anxiogenic-like effects of ethanol removal. Protracted withdrawal did not produce lasting changes in anxiety but topiramate was equally effective at reducing anxiety in ethanol-withdrawn and control animals. Importantly, no signs of tolerance to the anxiolytic effects of topiramate were observed. In conclusion, these data support a role for topiramate in the treatment of basal levels of anxiety and ethanol withdrawal-induced anxiety. (PsycINFO Database Record

Topics: Animals; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Behavior, Animal; Diazepam; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Fructose; Male; Rats; Rats, Wistar; Substance Withdrawal Syndrome; Topiramate

Topics: Adult; Anticonvulsants; Anxiety Disorders; Behavioral Symptoms; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Drug Substitution; Female; Fructose; Humans; Medication Adherence; Psychiatric Status Rating Scales; Psychotropic Drugs; Sexual Behavior; Sexual Dysfunctions, Psychological; Topiramate; Treatment Outcome

Serotonin reuptake inhibitors (SRIs) are considered first-line treatments for obsessive-compulsive disorder (OCD). Many patients achieve some response but remain symptomatic despite an adequate SRI trial. Recent neuroimaging data found abnormally high glutamatergic concentrations in children with OCD. Following selective serotonin reuptake inhibitor (SSRI) treatment, a decrease in OCD symptom severity was associated with a decrease in caudate glutamatergic concentrations. We initiated an investigation of adjunctive topiramate (an anticonvulsant agent with glutamatergic properties) in the treatment of patients with OCD who were partially or nonresponsive to SRI treatment. Sixteen consecutive outpatients with OCD (mean age = 41.1 years; range = 21-58 years), who were partial or nonresponders to SRI monotherapy or SRI combination therapy (antipsychotic, other antidepressant, or benzodiazepines), and had topiramate added over a minimum of 14 weeks, were reviewed. Baseline and endpoint Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I) were evaluated retrospectively. Eleven of 16 patients were responders (68.8%) with a CGI-I score of much improved or very much improved. The mean dose of topiramate was 253.1 +/- 93.9 mg/day. The mean time to response was 9.2 +/- 4.5 weeks. CGI-S scores decreased significantly from initiation of topiramate until 26 weeks, from 6.1 +/- 0.9 to 4.5 +/- 1.3 (P < .001). This case series suggests some preliminary evidence that the addition of topiramate may be useful in treatment-resistant OCD.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Anxiety Disorders; Caudate Nucleus; Drug Resistance; Drug Synergism; Female; Fructose; Glutamic Acid; Humans; Male; Mental Disorders; Middle Aged; Obsessive-Compulsive Disorder; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; 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

Alprazolam is successful in reducing anxiety but has a high addictive/misuse potential. Topiramate is a novel anticonvulsant which has been used as a mood stabilizer. Other anticonvulsants, such as carbamazepine and valproate, have been used in alcohol and benzodiazepine withdrawal. Topiramate has recently been used in alcohol, cocaine and opiates withdrawal. There has been also one report of topiramate use in midazolam withdrawal. In our case of a patient with recurrent major depressive disorder, subthreshold anxiety disorder and addiction to alprazolam, topiramate appears to be efficient and safe in alprazolam withdrawal.

Topics: Adult; Alprazolam; Anti-Anxiety Agents; Anticonvulsants; Antidepressive Agents, Second-Generation; Anxiety Disorders; Cyclohexanols; Depressive Disorder, Major; Female; Fructose; Humans; Substance Withdrawal Syndrome; Substance-Related Disorders; Topiramate; Treatment Outcome; Venlafaxine Hydrochloride

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

Antidepressants, including selective serotonin reuptake inhibitors (SSRIs), have been associated with significant weight gain, a problem that frequently leads to noncompliance and premature discontinuation of treatment. Topiramate is a novel anticonvulsant that has also been used as a mood stabilizer and augmentation agent in mood disorders. Topiramate has been observed to have an interesting side effect of weight loss in some individuals. In this study, topiramate was added to the treatment regimen of patients with a primary DSM-IV anxiety disorder who had experienced substantial SSRI-induced weight gain, in an attempt to induce weight loss.. Topiramate was added to SSRI treatment in 15 anxiety disorder patients, starting at a dose of 50 mg/day and titrating up to a target daily dose of 100 mg/day, with a maximum dose of 250 mg/day. Subjects' weight was measured at baseline and after 5 and 10 weeks of treatment.. Before topiramate treatment, SSRI-treated subjects in this sample had gained a mean of 13.0 +/- 8.4 kg (28.6 +/- 18.5 lb). After the addition of a mean dose of 135.0 +/- 44.1 mg/day of topiramate for approximately 10 weeks, subjects lost a mean of 4.2 +/- 6.0 kg (9.3 +/- 13.3 lb).. Topiramate may have a role in managing SSRI-induced weight gain in anxiety disorder patients.

Topics: Adult; Anxiety Disorders; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Topiramate; Treatment Outcome; Weight Gain