J Clin Psychopharmacol. 2005 Jun;25(3):211-217.
Influence of Topiramate on Olanzapine-Related Adiposity in Women:
A Random, Double-Blind, Placebo-Controlled Study.
Nickel MK, Nickel C, Muehlbacher M, Leiberich PK, Kaplan P,
Lahmann C, Tritt K, Krawczyk J, Kettler C, Egger C, Rother WK, Loew TH.
*Clinic for Psychosomatic Medicine, Inntalklinik, Simbach/Inn, Germany;
daggerUniversity Clinic for Psychiatry 1, CDK, Salzburg, Austria and double
daggerDepartment of Psychosomatic Medicine, University Clinic, Regensburg,
Germany.
ABSTRACT:: The aim of this study was to compare the efficacy of topiramate
versus a placebo in the treatment of adiposity in women undergoing olanzapine
therapy. We also assessed changes health-related quality of life, the
patient's actual state of health, and psychologic impairments. The 10-week,
random, double-blind, placebo-controlled study included 43 women who had
been treated with olanzapine (mean dose 7.8 +/- 3.6 in the topiramate
group and 7.2 +/- 3.1 in the placebo group) and had gained weight as a
side effect. The subjects were randomly assigned to topiramate (n = 25)
or a placebo (n = 18). Primary outcome measures were weight checks and
self-reported changes on the scales of the SF-36 Health Survey, Bf-S Scale
of Well-Being, and the Adjective Checklist EWL-60-S. Weight loss was observed
and was significantly more pronounced in the topiramate-treated group
(difference in weight loss between the 2 groups: 5.6 kg, 95% CI = -8.5,
-3.0, P < 0.001). In comparison with the placebo group, significant
changes on 7 (7/8) scales of SF-36 Health Survey (all P < 0.001), on
all 6 scales of the EWL-60-S, and on the Bf-S were observed in the topiramate-treated
subjects after 10 weeks. All patients tolerated topiramate well. Topiramate
appears to be a safe and effective agent in the treatment of weight gain
that occurred during olanzapine treatment. Significantly positive changes
in health-related quality of life, the patient's actual state of health,
and psychologic impairments were observed.
Epilepsy Behav. 2005 May 3;
Effect of topiramate on cognitive function and activity level
following neonatal seizures.
Zhao Q, Hu Y, Holmes GL.
Section of Neurology, Neuroscience Center at Dartmouth, Dartmouth
Medical School, Hanover, NH, USA.
Topiramate, an antiepileptic drug with a number of mechanisms of action
including blockade of AMPA/KA receptor subtypes, was assessed as a neuroprotective
agent following seizures. We administered topiramate or saline chronically
during and following a series of 25 neonatal seizures. After completion
of the topiramate treatment, animals were tested in the water maze for
spatial learning and the open field for activity level. Brains were then
examined for cell loss and sprouting of mossy fibers. Rats treated with
topiramate performed significantly better in the water maze than rats
treated with saline. Topiramate treatment also reduced the amount of seizure-induced
sprouting in the supragranular region. There were no differences between
topiramate- and saline-treated rats in activity level in the open field,
swimming speed, or weight gain. These findings show that long-term treatment
with topiramate after neonatal seizures changes the long-term consequences
of seizures and improves cognitive function.
Brain Dev. 2005 Apr;27(3):228-32.
Clinical experience with Topiramate to counteract neuroleptic
induced weight gain in 10 individuals with autistic spectrum disorders.
Canitano R.
Division of Child Neuropsychiatry, General University Hospital of Siena,
Viale Bracci 1, 53100 Siena, Italy.
Children and adolescents with autistic spectrum disorders are treated with neuroleptics to limit behavioral disturbances such as aggression, hyperactivity and self-injury. They may experience substantial weight gain when undergoing treatment with atypical antipsychotics actually employed. Topiramate (TPM) is an antiepileptic medication that is being progressively demonstrating a wider spectrum of action, mainly as an agent for weight control and as a mood stabilizer. It was administered to a group of children and adolescents with autistic spectrum disorders with the aim of reversing weight gain. This is an open study over an observation period of 18 months of 10 children and adolescents, eight males and two females, mean age 13 years, SD +/-3.6, range 8-19 years with a diagnosis of autistic disorder or pervasive developmental disorder not otherwise specified according to DSM-IV. Starting dosage of TPM was 0.5mg/kg followed by titration of 0.5mg/kg on a weekly basis, up to 1-3mg/kg/day as the maintenance dosage. Eight subjects were undergoing long-term treatment with risperidone, one with pimozide and one was temporarily not on antipsychotics. Six patients took TPM on a regular basis and four dropped out. Variable degrees of weight reduction were observed in four patients, two subjects showed weight increase. Behavioral adverse effects were observed in three patients causing rapid withdrawal of the medication. TPM should be used with caution in autistic spectrum disorders because this population has a high risk of behavioral disruption.
J Pharm Biomed Anal. 2005 Mar 9;37(3):529-34. Epub 2004 Dec 19.
Determination of topiramate and its degradation product in liquid
oral solutions by high performance liquid chromatography with a chemiluminescent
nitrogen detector.
Styslo-Zalasik M, Li W.
Global Analytical Development, Johnson & Johnson Pharmaceutical Research
& Development, LLC, 1000 Route 202, Raritan, NJ 08869, USA.
Topiramate is a sulfamate-substituted monosaccharide that is prescribed
for the treatment of epilepsy. It has been a challenge to develop analytical
methods for topiramate formulations because the compounds of interest
do not have chromophores that are active above 190nm and because of interference
from excipients. This paper describes a simple, specific, precise, accurate,
and sensitive method using a chemiluminescent nitrogen detector. The method
has a validated linearity range of 32-4800ng of topiramate and excellent
precision (system repeatability). The limit of quantitation was determined
to be 0.1% for the degradation product w/w versus topiramate. The method
has been successfully used for probe stability studies in support of early
phase formulation development.
CNS Spectr. 2005 Mar;10(3 Suppl 3):1-13.
Treatment-refractory epilepsy: an evidence-based approach to
antiepileptic monotherapy.
Harden CL, Kanner AM, Bautista JF, Brown TR.
Comprehensive Epilepsy Center, Weill College of Cornell University, New
York, NY, USA.
Treatment options for epilepsy have increased in the last decade with
the introduction of several new antiepileptic drugs (AEDs). As drug selection
becomes more challenging, the use of evidence-based guidelines to aid
in treatment decisions has become increasingly valued. The American Academy
of Neurology's (AAN) guidelines for the use of new AEDs in refractory
epilepsy offers many benefits, including expert panel recommendations
based on clinically relevant questions with evidence-based responses.
However, lack of evidence from randomized-controlled trials, particularly
as they relate to monotherapy, limits the recommendations and their use
in practice. The studies of new AEDs as monotherapy in treatment-refractory
epilepsy are difficult to incorporate into clinical use because they are
driven by Food and Drug Administration requirements to show superiority
over placebo or pseudoplacebo (ie, low dose of active drug) rather than
by clinical questions. However, based on Class I evidence, the AAN guidelines
have granted Level A recommendations (established effectiveness) for oxcarbazepine
and topiramate monotherapy, and a Level B recommendation (probable effectiveness)
for lamotrigine monotherapy in the use of refractory partial epilepsy.
There is insufficient evidence to recommend gabapentin, levetiracetam,
tiagabine, or zonisamide monotherapy. No monotherapy AED trials have been
conducted in refractory generalized epilepsy. Because no differences in
efficacy have been reported for AEDs as initial therapy of partial seizures,
differences in adverse events, such as weight gain, tremor, and hair loss,
are key in drug selection. More comparative studies between the AEDs are
necessary for both monotherapy and add-on therapy for treatment-refactory
epilepsy.
Neurology. 2005 Mar 8;64(5):792-8.
Effects of topiramate and gabapentin on cognitive abilities in
healthy volunteers.
Salinsky MC, Storzbach D, Spencer DC, Oken BS, Landry T, Dodrill
CB.
Oregon Health and Science University, Portland, OR, USA. Salinsky@OHSU.edu
OBJECTIVE: To evaluate the cognitive effects of topiramate (TPM) and
gabapentin (GBP). METHODS: Forty healthy volunteers were randomized to
a 12-week course of TPM, GBP, or placebo. Doses were gradually escalated
over 10 weeks to a maximum of 400 mg/day of TPM or 3,600 mg/day of GBP
or to the highest tolerated dose. Subjects were interviewed and examined
biweekly. Cognitive testing was performed prior to initiating the drug
and again 12 weeks later, at least 2 weeks after achieving plateau dosing.
For each subject and cognitive measure, test-retest Z scores were calculated
based on regression equations derived from 73 healthy volunteers. Group
comparisons utilized the Wilcoxon test. RESULTS: There were significant
TPM vs GBP and TPM vs placebo differences in test-retest Z scores for
four of six target cognitive measures (Digit Symbol, Story Recall, Selective
Reminding, Controlled Oral Word Association), always indicating worse
retest performance for subjects receiving TPM. Overall, 12 of 24 cognitive
measures were similarly affected. TPM effects were large, and several
target measures averaged >2 SD of negative change. One measure was
significantly affected by GBP. CONCLUSIONS: Topiramate (TPM) impaired
cognitive test performance, whereas gabapentin had minimal effects. The
effects of TPM were of sufficient magnitude potentially to affect daily
and occupational function.
