topiramate and Stress-Disorders--Post-Traumatic

Posttraumatic stress disorder (PTSD) is a chronic and debilitating condition for which clinicians sometimes turn to anticonvulsants as a treatment for symptoms. This study was a systematic review and meta-analysis of randomized controlled trials (RCT) that have assessed the efficacy of topiramate as monotherapy or adjunctive therapy, compared to placebo, for the treatment of PTSD in adults. Prescribers may be reluctant to turn to topiramate, given the commonly reported side effects of impaired cognition, sedation, fatigue, and headache. We searched PubMed, PsycInfo, and Cochrane Central databases for relevant trials. Five studies were identified as RCTs and thus met inclusion criteria; one additional nonpublished study was identified via phone contact with its authors. Of these six studies, one was excluded from the statistical meta-analysis due to its high dropout rate (16 of 40 participants). One of these studies was excluded from a stratified analysis of symptom types because this subscale data were unavailable.  For overall symptomatology, topiramate showed a medium, but not significant effect, standardized mean difference (SMD) = 0.55, p = .082. Topiramate showed a small and significant reduction of hyperarousal symptoms, SMD = 0.35, 95% CI [0.029, 0.689], p = .033. Topiramate did not significantly reduce reexperiencing symptoms, SMD = 0.29, 95% CI [-0.019, 0.597], p = .067, or avoidance symptoms, SMD = 0.20, 95% CI [-0.105, 0.509], p = .198. Results did not differ significantly between veteran and nonveteran subjects, or between topiramate as monotherapy and adjunctive therapy. Further studies on topiramate will clarify its role in PTSD treatment.

Topics: Anticonvulsants; Arousal; Avoidance Learning; Chemotherapy, Adjuvant; Drug Therapy, Combination; Humans; Randomized Controlled Trials as Topic; Stress Disorders, Post-Traumatic; Topiramate

We reviewed the existing literature on the efficacy of anticonvulsants in treating post-traumatic stress disorder.. We performed a literature search using PubMed, EMBASE and the Cochrane database on 30 September 2013. Randomized,controlled studies that investigated the efficacy of anticonvulsants for post-traumatic stress disorder were included in this review. Studies with retrospective designs, case reports and case series were excluded.. A total of seven studies met the inclusion criteria for this review. Three studies used topiramate with negative findings regarding its efficacy. Two studies used divalproex, both of which failed to show superiority over placebo. One study used lamotrigine, with favourable results, and one study used tiagabine, with negative results.. Future long-term studies with larger sample sizes are needed to investigate the clinical utility of anticonvulsants for posttraumatic stress disorder treatment.

Topics: Anti-Anxiety Agents; Anticonvulsants; Fructose; Humans; Lamotrigine; Nipecotic Acids; Stress Disorders, Post-Traumatic; Tiagabine; Topiramate; Triazines; Valproic Acid

Posttraumatic stress disorder (PTSD) is an important mental health issue in terms of the number of people affected and the morbidity and functional impairment associated with the disorder. The purpose of this study was to examine the efficacy of all treatments for PTSD.. PubMed, MEDLINE, PILOTS, and PsycINFO databases were searched for randomized controlled clinical trials of any treatment for PTSD in adults published between January 1, 1980, and April 1, 2012, and written in the English language. The following search terms were used: post-traumatic stress disorders, posttraumatic stress disorder, PTSD, combat disorders, and stress disorders, post-traumatic.. Articles selected were those in which all subjects were adults with a diagnosis of PTSD based on DSM criteria and a valid PTSD symptom measure was reported. Other study characteristics were systematically collected. The sample consisted of 137 treatment comparisons drawn from 112 studies.. Effective psychotherapies included cognitive therapy, exposure therapy, and eye movement desensitization and reprocessing (g = 1.63, 1.08, and 1.01, respectively). Effective pharmacotherapies included paroxetine, sertraline, fluoxetine, risperidone, topiramate, and venlafaxine (g = 0.74, 0.41, 0.43, 0.41, 1.20, and 0.48, respectively). For both psychotherapy and medication, studies with more women had larger effects and studies with more veterans had smaller effects. Psychotherapy studies with wait-list controls had larger effects than studies with active control comparisons.. Our findings suggest that patients and providers have a variety of options for choosing an effective treatment for PTSD. Substantial differences in study design and study participant characteristics make identification of a single best treatment difficult. Not all medications or psychotherapies are effective.

Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Female; Fructose; Humans; Male; Psychotherapy; Risperidone; Stress Disorders, Post-Traumatic; Topiramate; Treatment Outcome

To evaluate the use of topiramate for the treatment of posttraumatic stress disorder (PTSD).. Ovid MEDLINE (1950 to June week 4, 2010), International Pharmaceutical Abstracts (1970 to May 2010), ISI Web of Science (1945 to July 3, 2010), and Iowa Drug Information Service (searched July 6, 2010) were searched using the terms posttraumatic stress disorder and topiramate. Guidelines and other sources were identified from bibliography searches.. All English-language human studies and case reports that evaluated the use of topiramate for treatment of PTSD were evaluated.. One case report, 1 case series, 2 open-label trials, and 1 placebo-controlled trial that used topiramate (monotherapy or adjunct) to treat civilian PTSD were identified and evaluated. The case report and case series reported subjective reduction of symptoms, and the open-label trials reported a significant reduction in PTSD Checklist-Civilian score. The placebo-controlled trial found no significant difference in Clinician-Administered PTSD Scale (CAPS) score. One open-label trial and 2 placebo-controlled trials that used topiramate in combat-related PTSD were identified and evaluated. The open-label trial reported a significant reduction in CAPS score, and 1 placebo-controlled trial reported a statistically significant difference in CAPS score. However, the other placebo-controlled trial found no significant differences. In some of the trials evaluated, the clinical significance of outcomes reported is difficult to determine. Adverse effects were reported throughout the trials but generally were not considered serious.. Based on the limited evidence available, topiramate is a possible alternative or adjunct option for patients with PTSD that is refractory to standard treatments.

Topics: Anticonvulsants; Combat Disorders; Female; Fructose; Humans; Male; Stress Disorders, Post-Traumatic; Topiramate; Treatment Outcome; United States; Veterans

The course of posttraumatic stress disorder (PTSD) is frequently and severely complicated by co-occurring alcohol use disorder (AUD), yet there are few reports of pharmacologic treatments for these comorbid conditions. The objective of this pilot study was to obtain a preliminary assessment of the efficacy and safety of topiramate in reducing alcohol use and PTSD symptoms in veterans with both disorders.. This was a prospective 12-week, randomized, double-blind, placebo-controlled pilot trial of flexible-dose topiramate up to 300 mg/d in 30 veterans with PTSD and AUD. The primary outcome measure was frequency of drinking. Secondary outcomes consisted of other measures of alcohol use and PTSD symptom severity.. Within-group analyses showed that topiramate treatment was associated with significant reductions in frequency and amount of alcohol use and alcohol craving from baseline through week 12. Between-group analyses showed that topiramate reduced frequency of alcohol use and alcohol craving significantly more than placebo and tended to reduce drinking amount. Topiramate treatment was also associated with decreased PTSD symptom severity and tended to reduce hyperarousal symptoms compared with placebo. Topiramate transiently impaired learning and memory, with significant recovery by the end of treatment.. These preliminary results indicate that in veterans with co-occurring PTSD and AUD, topiramate may be effective in reducing alcohol consumption, alcohol craving, and PTSD symptom severity-particularly hyperarousal symptoms. Topiramate was associated with transient cognitive impairment but was otherwise well tolerated.

Topics: Adult; Alcohol Drinking; Alcohol-Related Disorders; Cognition Disorders; Craving; Diagnosis, Dual (Psychiatry); Double-Blind Method; Female; Fructose; Humans; Male; Medication Adherence; Middle Aged; Pilot Projects; Stress Disorders, Post-Traumatic; Topiramate; Treatment Outcome; Veterans

To evaluate the efficacy and tolerability of topiramate in patients with posttraumatic stress disorder (PTSD).. We conducted a 12-week double-blind, randomized, placebo-controlled study comparing topiramate to placebo. Men and women aged 18-62 years with diagnosis of PTSD according to DSM-IV were recruited from the outpatient clinic of the violence program of Federal University of São Paulo Hospital (Prove-UNIFESP), São Paulo City, between April 2006 and December 2009. Subjects were assessed for the Clinician-Administered Posttraumatic Stress Scale (CAPS), Clinical Global Impression, and Beck Depression Inventory (BDI). After 1-week period of washout, 35 patients were randomized to either group. The primary outcome measure was the CAPS total score changes from baseline to the endpoint.. 82.35% of patients in the topiramate group exhibited improvements in PTSD symptoms. The efficacy analysis demonstrated that patients in the topiramate group exhibited significant improvements in reexperiencing symptoms: flashbacks, intrusive memories, and nightmares of the trauma (CAPS-B; P= 0.04) and in avoidance/numbing symptoms associated with the trauma, social isolation, and emotional numbing (CAPS-C; P= 0.0001). Furthermore, the experimental group demonstrated a significant difference in decrease in CAPS total score (topiramate -57.78; placebo -32.41; P= 0.0076). Mean topiramate dose was 102.94 mg/d. Topiramate was generally well tolerated.. Topiramate was effective in improving reexperiencing and avoidance/numbing symptom clusters in patients with PTSD. This study supports the use of anticonvulsants for the improvement of symptoms of PTSD.

Topics: Adult; Ambulatory Care; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Neuroprotective Agents; Stress Disorders, Post-Traumatic; Topiramate; Treatment Outcome

Topiramate might be effective in the treatment of posttraumatic stress disorder (PTSD) because of its antikindling effect and its action in both inhibitory and excitatory neurotransmitters. Open-label studies and few controlled trials have suggested that this anticonvulsant may have therapeutic potential in PTSD. This 12-week randomized, double-blind, placebo-controlled clinical trial will compare the efficacy of topiramate with placebo and study the tolerability of topiramate in the treatment of PTSD.. Seventy-two adult outpatients with DSM-IV-diagnosed PTSD will be recruited from the violence program of Federal University of São Paulo Hospital (UNIFESP). After informed consent, screening, and a one week period of wash out, subjects will be randomized to either placebo or topiramate for 12 weeks. The primary efficacy endpoint will be the change in the Clinician-administered PTSD scale (CAPS) total score from baseline to the final visit at 12 weeks.. The development of treatments for PTSD is challenging due to the complexity of the symptoms and psychiatric comorbidities. The selective serotonin reuptake inhibitors (SSRIs) are the mainstream treatment for PTSD, but many patients do not have a satisfactory response to antidepressants. Although there are limited clinical studies available to assess the efficacy of topiramate for PTSD, the findings of prior trials suggest this anticonvulsant may be promising in the management of these patients.. NCT 00725920.

Topics: Adolescent; Adult; Anticonvulsants; Combat Disorders; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Personality Inventory; Placebos; Psychiatric Status Rating Scales; Stress Disorders, Post-Traumatic; Topiramate; Treatment Outcome; Warfare

This double-blind, placebo-controlled trial assessed efficacy and safety of topiramate monotherapy in civilian posttraumatic stress disorder (PTSD).. Outpatients (18-64 years) with DSM-IV non-combat-related PTSD and Clinician-Administered PTSD Scale (CAPS) scores >or= 50 were eligible. Topiramate was started at 25 mg/day and titrated by 25-50 mg/week to 400 mg/day or maximum tolerated dose. Data were collected between April 26, 2002, and February 4, 2004. Primary efficacy, change in total CAPS score, and secondary efficacy measures were assessed by analysis of covariance in the intent-to-treat (ITT) population with last observation carried forward.. The ITT population comprised 38 patients with mean +/- SD baseline total CAPS scores of 88.3 +/- 13.8 (topiramate, N = 19) and 91.1 +/- 13.7 (placebo, N = 19). Although a decrease in total CAPS score was noted (topiramate, -52.7; placebo, -42.0), this difference was not statistically significant (p = .232). Topiramate-treated patients exhibited significant reductions in reexperiencing symptoms (CAPS cluster B: topiramate, 74.9%; placebo, 50.2%; p = .038) and Treatment Outcome PTSD scale (topiramate, 68.0%; placebo, 41.6%; p = .025). Reductions approaching statistical significance, based on a nominal p value, were noted in mean total Clinical Global Impressions-Improvement Scale scores (topiramate, 1.9 +/- 1.2; placebo, 2.6 +/- 1.1; p = .055).. These preliminary results suggest that further, adequately powered studies of topiramate for the treatment of civilian PTSD are warranted.

Topics: Adolescent; Adult; Anticonvulsants; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Severity of Illness Index; Stress Disorders, Post-Traumatic; Topiramate; Treatment Outcome

Topiramate, a novel anticonvulsant, has been reported to rapidly reduce symptoms of posttraumatic stress disorder (PTSD) in an open-label trial. The present study was designed as a test of topiramate's efficacy as adjunctive therapy in a 7-week, randomized, double-blind, placebo-controlled trial.. Forty male veterans with PTSD in a residential treatment program were randomized to flexible-dose topiramate or placebo augmentation. The primary outcome measures were PTSD symptom severity and global symptom improvement.. Baseline Clinician-Administered PTSD Scale scores were 62.1 +/- 13.9 for placebo and 61.0 +/- 22.2 for topiramate. There was a high dropout rate from the study (55% topiramate; 25% placebo), with 40% of topiramate and 10% of placebo dropping because of adverse events (AEs). No significant treatment effects of topiramate versus placebo were observed for the primary treatment outcomes. Subjects reporting central nervous system-related AEs and with higher baseline severity of depression were more likely to discontinue because of AEs.. Primary outcome measures failed to demonstrate a significant effect for topiramate over placebo; however, high dropout rate in the treatment group prohibits definitive conclusions about the efficacy of topiramate in this population.

Topics: Age Factors; Anticonvulsants; Chronic Disease; Combat Disorders; Double-Blind Method; Drug Administration Schedule; Exanthema; Fructose; Humans; Male; Middle Aged; Patient Dropouts; Psychiatric Status Rating Scales; Severity of Illness Index; Stress Disorders, Post-Traumatic; Time Factors; Topiramate; Treatment Outcome; Urinary Tract Infections; Veterans

In order to confirm therapeutic effects of topiramate on posttraumatic stress disorder (PTSD) observed in a prior study, a new prospective, open-label study was conducted to examine acute responses in chronic, nonhallucinatory PTSD.. Thirty-three consecutive newly recruited civilian adult outpatients (mean age 46 years, 85% female) with DSM-IV-diagnosed chronic PTSD, excluding those with concurrent auditory or visual hallucinations, received topiramate either as monotherapy (n = 5) or augmentation (n = 28). The primary measure was a change in the PTSD Checklist-Civilian Version (PCL-C) score from baseline to 4 weeks, with response defined as a >/= 30% reduction of PTSD symptoms.. For those taking the PCL-C at both baseline and week 4 (n = 30), total symptoms declined by 49% at week 4 (paired t-test, P < 0.001) with similar subscale reductions for reexperiencing, avoidance/numbing, and hyperarousal symptoms. The response rate at week 4 was 77%. Age, sex, bipolar comorbidity, age at onset of PTSD, duration of symptoms, severity of baseline PCL-C score, and monotherapy versus add-on medication administration did not predict reduction in PTSD symptoms. Median time to full response was 9 days and median dosage was 50 mg/day.. Promising open-label findings in a new sample converge with findings of a previous study. The use of topiramate for treatment of chronic PTSD, at least in civilians, warrants controlled clinical trials.

Topics: Adult; Anticonvulsants; Chronic Disease; Drug Administration Schedule; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Patient Dropouts; Personality Inventory; Prospective Studies; Psychotropic Drugs; Stress Disorders, Post-Traumatic; 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

Fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine have previously shown efficacy for posttraumatic stress disorder (PTSD). One prior study using US Department of Veterans Affairs (VA) medical records data to compare these agents found no differences in symptom reduction in clinical practice. The current study addresses several weaknesses in that study, including limited standardization of treatment duration, inability to account for prior treatment receipt, use of an outdated symptomatic assessment for PTSD, and lack of functional outcome.. A total of 834 VA outpatients were identified with DSM-5 clinical diagnoses of PTSD between October 2016 and March 2018 who initiated one of the medications and met prespecified criteria for treatment duration and dose, combined with baseline and endpoint DSM-5 PTSD Checklist (PCL-5) measurements. Twelve-week acute-phase changes in PCL-5 score and remission of PTSD symptoms were compared among patients receiving the different medications, as was use of acute psychiatric services in the subsequent 6-month continuation phase.. In the acute phase, patients improved by a mean of 6.8-10.1 points on the PCL-5 and 0.0%-10.9% achieved remission of PTSD symptoms. Those taking venlafaxine were significantly more likely to achieve remission (P = .008 vs fluoxetine and P < .0001 vs paroxetine, sertraline, and topiramate). In the continuation phase, there were no differences in acute psychiatric care use between medications. Those who continued their medication were less likely to use acute psychiatric services (HR = 0.55; P = .03).. There may be an advantage to venlafaxine over other agents in achieving acute-phase remission for DSM-5 PTSD in routine clinical practice, but this finding requires further study. Regardless of the agent chosen, medication cessation during the continuation phase is associated with a higher risk of acute psychiatric care use.

Topics: Acute Disease; Adult; Carbonic Anhydrase Inhibitors; Female; Fluoxetine; Humans; Male; Medication Adherence; Outcome Assessment, Health Care; Paroxetine; Remission Induction; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Sertraline; Stress Disorders, Post-Traumatic; Topiramate; United States; United States Department of Veterans Affairs; Venlafaxine Hydrochloride

Fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine have consistently shown efficacy for posttraumatic stress disorder (PTSD) in meta-analyses of randomized controlled trials. However, no study has compared the effectiveness of these agents in routine clinical practice. We conducted a retrospective comparative effectiveness study of these 5 medications using electronic medical record data.. We identified 2,931 Department of Veterans Affairs outpatients initiating treatment for PTSD between fiscal years 2004 and 2013 who received 1 of the 5 medications at an adequate dose and duration, combined with baseline and endpoint PTSD Checklist (PCL) measurements. Patients were identified based on clinical diagnoses of PTSD (DSM-IV criteria). We weighted participants in order to balance pretreatment characteristics. We compared continuous changes on total PCL score, symptom cluster scores, and sleep items, as well as categorical changes including reliable improvement and loss of PTSD diagnosis, using weighted regression analyses. We conducted exploratory analysis to determine whether any patient characteristics or service use variables predicted loss of PTSD diagnosis.. Patients improved by a mean of 5-6 points on the PCL over approximately 6 months of treatment. While half of patients had a reliable improvement of 5 points or more on the PCL, less than a fifth achieved loss of PTSD diagnosis. There were no differences between medications. The only significant (P < .001) predictor of loss of PTSD diagnosis was concurrent treatment with evidence-based psychotherapy.. Available evidence-based medications for PTSD are equally effective in clinical practice. Although effective, our data suggest that patients choosing medication treatment for PTSD should consider concurrent treatment with evidence-based psychotherapy in order to maximize their chances of meaningful improvement.

Topics: Adult; Anticonvulsants; Female; Fluoxetine; Humans; Male; Medical Records; Middle Aged; Outpatients; Paroxetine; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Sertraline; Stress Disorders, Post-Traumatic; Topiramate; Treatment Outcome; United States; United States Department of Veterans Affairs; Venlafaxine Hydrochloride

Topics: Adult; Anticonvulsants; Depressive Disorder, Major; Dextromethorphan; Excitatory Amino Acid Antagonists; Fructose; Humans; Male; Opioid-Related Disorders; Stress Disorders, Post-Traumatic; Topiramate

Topics: Alcohol Drinking; Alcohol-Related Disorders; Female; Fructose; Humans; Male; Stress Disorders, Post-Traumatic; Topiramate; Veterans

Nowhere is it more important to maintain peek mental functioning than in a combat zone. Conditions ranging from pain to head injury to post-traumatic stress disorder can cause impairments in neuropsychological function and place service members at risk. Medications can sometimes help alleviate these problems, but also have the risk of further slowing cognitive function or impairing reaction time. Standard methods of neuropsychological testing are often not available in a combat environment. New technologies are being advanced that can allow portable, computerized neuropsychological testing to be performed at almost any location. We present a case that demonstrates how the use of such handheld technology can assist a military physician in assessing the influence of medication on reaction time and in determining if and when a service member is ready to return to combat.

Topics: Brain Injuries; Cognition; Fructose; Headache; Humans; Iraq War, 2003-2011; Male; Mental Competency; Military Medicine; Military Personnel; Neuropsychological Tests; Physical Fitness; Stress Disorders, Post-Traumatic; Topiramate; Young Adult

Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder that is common among combat veterans and may lead to very poor sleep and disturbing nightmares.. To examine the safety and effectiveness of topiramate as add-on therapy for the management of combat-related PTSD and to examine the effects of topiramate on sleep and alcohol consumption.. We conducted an 8-week open-label pilot study of topiramate for male combat veterans (N = 43) with PTSD, with analysis of veterans who completed the protocol. Psychometric, sleep, and alcohol consumption assessments were conducted at baseline and at week 8.. Twenty-nine subjects completed the 8-week study. Significant reductions in Clinician Administered PTSD Scale scores were observed at the 8-week endpoint (from 86.3 +/- 21.1 to 67.1 +/- 25.1; p < 0.01). Decreases were seen in both Stanford Sleepiness Scale scores (from 10.5 +/- 0.72 to 9.0 +/- 0.58; p = 0.08) and Mississippi PTSD scores (from 120.4 +/- 6.5 to 111.5 +/- 20.9; p = 0.08), but the extent of the changes did not attain statistical significance for either scale. There was a significant reduction in the proportion of patients with nightmares (from 100% to 62%; p < 0.001) and patients who experienced anxiety that interfered with falling asleep (from 90% to 62%; p < 0.05). The proportion of patients with high-risk drinking patterns also decreased (from 31% to 14%). Two serious adverse events were reported during the study: an increase in low back pain and an episode of acute confusion.. When used in addition to other empiric therapy, topiramate may be effective at reducing general symptoms of combat-related PTSD and reducing high-risk alcohol intake and nightmares. Further randomized controlled trials of topiramate for the treatment of combat-related PTSD are warranted.

Topics: Adult; Aged; Aged, 80 and over; Alcoholism; Combat Disorders; Fructose; Humans; Male; Middle Aged; Pilot Projects; Stress Disorders, Post-Traumatic; Surveys and Questionnaires; Topiramate; Veterans

Two patients with posttraumatic stress disorder (PTSD) were treated successfully with the anti-epileptic drug topiramate. Nightmares and the re-experiencing of traumatic events were particularly responsive to the treatment. Topiramate acted rapidly at a relatively low dosage and seems to be an important addition to the limited range of drugs availablefor treating severe symptoms of PTSD.

Topics: Adult; Anticonvulsants; Dose-Response Relationship, Drug; Female; Fructose; Humans; Male; Stress Disorders, Post-Traumatic; Topiramate; Treatment Outcome

Exaggerated acoustic startle is a prominent symptom of post-traumatic stress disorder (PTSD); however, its physiological basis is not well understood, and there are few available treatments. Neurobiological research has suggested that anti-kindling agents and/or glutamate antagonists can attenuate the acoustic startle response (ASR) in animal models. The anticonvulsant topiramate is an AMPA antagonist that also demonstrates potent anti-kindling effects and may, therefore, have promise in treating trauma-enhanced ASR.. To evaluate the ability of topiramate to attenuate stress-induced increases in ASR in a previously validated animal model of PTSD.. Male Sprague-Dawley rats ( n=36) served as controls or received single prolonged stress (SPS). SPS consisted of 2 h restraint, forced swim and ether anesthesia, then a 7-day "undisturbed" period. Animals then received vehicle, 10 mg/kg or 30 mg/kg of topiramate orally, twice daily for 7 days. ASR was assessed for all animals before and after the study, in light and dark environments.. SPS produced a sustained increase in the ASR in both environments, an effect that was significantly reduced by topiramate. Meanwhile the ASR of control animals remained unaffected by topiramate.. The current results provide one of the few demonstrations of a single stress episode producing sustained enhancement of ASR. In addition, topiramate demonstrates promise in treating exaggerated acoustic startle symptoms in PTSD or other stress-related disorders.

Topics: Acoustic Stimulation; Animals; Disease Models, Animal; Fructose; Male; Rats; Rats, Sprague-Dawley; Reflex, Startle; Stress Disorders, Post-Traumatic; Topiramate

This study examined the effects of topiramate (TPM) on glucocorticoid receptors (GRs) in mononuclear leukocytes of nine men and four women with chronic and recurring post-traumatic stress disorder (PTSD) and a group of comparison subjects (nine men, four women). A measure of 60 ml of blood was withdrawn by venipuncture at 0800 and mononuclear leukocytes were isolated. The cells were incubated with a series of concentrations of dexamethasone (DEX) without or with 50 micromol/l of TPM to evaluate the effects of DEX to inhibit lysozyme activity and the effect of TPM on it. ANCOVA compared the IC(50) for lysozyme inhibition under conditions of DEX only and TPM+DEX. TPM affected lysozyme IC(50) in the direction of increasing the sensitivity of the receptor in the sample as a whole. This effect was more pronounced in the mononuclear leukocytes from participants in the PTSD group, particularly in cells from subjects whose pretreatment lysozyme IC(50) was relatively higher (eg, reflecting decreased glucococorticoid receptor responsiveness), compared to the rest of the sample. In conclusion, further investigation of the actions of TPM on GR and other neuroendocrine systems may prove useful in understanding some of the other established clinical effects of this agent.

Topics: Adult; Aged; Anticonvulsants; Binding Sites; Case-Control Studies; Demography; Dexamethasone; Drug Interactions; Female; Fructose; Glucocorticoids; Humans; Inhibitory Concentration 50; Leukocytes, Mononuclear; Male; Middle Aged; Muramidase; Receptors, Glucocorticoid; Stress Disorders, Post-Traumatic; Surveys and Questionnaires; Topiramate

Topics: Anticonvulsants; Fructose; Humans; Kindling, Neurologic; Memory; Receptors, AMPA; Stress Disorders, Post-Traumatic; Topiramate; Treatment Outcome

Topics: Acetates; Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Stress Disorders, Post-Traumatic; Topiramate

Posttraumatic stress disorder (PTSD) is a serious and debilitating mental condition that affects a significant proportion of the general population at some time in their lives. To date, however, the U.S. Food and Drug Administration has approved only 1 pharmacologic treatment for this indication. Additional effective therapies are urgently required to control the destructive symptoms experienced by individuals with PTSD. This article reviews the effects of the novel antiepileptic drug topiramate on 3 patients meeting DSM-IV criteria for chronic PTSD. In these previously treatment-refractory patients, topiramate had a marked effect: reducing and even eliminating trauma-related intrusive memories and nightmares and normalizing depressed mood. Adverse events were effectively controlled with careful drug titration and discontinuation of concomitant therapies. These findings, together with observations in more than 30 additional patients (reported elsewhere), suggest that further study of topiramate as a treatment for PTSD is warranted.

Topics: Adult; Anticonvulsants; Chronic Disease; Dreams; Female; Fructose; Humans; Male; Memory; Middle Aged; Stress Disorders, Post-Traumatic; Topiramate; Treatment Outcome