Topiramate anticonvulsant

Changes in body weight associated with anticonvulsants have been reviewed (116), including the effects of the antiepileptic drugs that have been most commonly associated with this adverse effect (valproic acid, carbamazepine, vigabatrin, and gabapentin) (117). Unlike most anticonvulsants, topiramate, felbamate, and zonisamide can cause weight loss. 

Thermospray ionization has also been used with quadrupole mass spectrometry to investigate the novel anticonvulsant topiramate in rat brain [16]. Topi-ramate crosses the blood—brain barrier and the concentration of the drug remains in the micromolar range for more than 6 hr. Samples were collected every 15 min over this time period, and the authors planned to analyze the dialysate without further sample cleanup. Distilled water was used as the perfusion medium to minimize the effect of dialysis salts on the mass spectrometer. I lowcver, it is important to note that microdialysis is best performed with matching ionic... 

The anticonvulsant topiramate has also been reported to be effective in reducing binge and purge frequencies in comparison with placebo. However, bothersome side-effects such as paresthesias, impaired cognition, and renal calculi may lessen its usefulness. Naltrexone is a possible adjunct in patients who are refractory to SSRIs, especially those with comorbid alcoholism and/or self-injurious behavior. ... 

Anticonvulsants Carbamazepine, valproic acid, gabapentin, topiramate... 

Other anticonvulsants, such as gabapentin and topiramate, are also being used by some clinicians, but controlled trials are lacking. 

Anticonvulsants, especially topiramate, and serotonergic drugs, especially ondansetron, show promise in initial, but well-designed, randomized controlled trials.43 Further studies are needed. Buspirone is well studied, but results are inconsistent. 

Anticonvulsants (barbiturates, including phenobar-bital and primidone carbamazepine felbamate phenytoin topiramate vigabatrin)... 

Anticonvulsants. Several antiseizure medicines have been studied in the treatment of PTSD, and some results have been encouraging. Open label studies, first with carbamazepine (800-1200 mg/day) and later with valproate (500-2000 mg/ day), demonstrated overall improvement in PTSD patients, though not for intrusive recollections per se. Recent open label studies of gabapentin, lamotrigine, tiagabine, and topiramate have suggested these anticonvulsants might also be helpful for some PTSD symptoms. 

Topiramate, derived from D-fruc-tose, has complex, long-lasting anticonvulsant actions that cooperate to limit the spread of seizure activity it is effective in partial seizures and as an add-on in Lennox-Gastaut syndrome. 

Topiramate, a sulfamate-substituted derivative of the monosaccharide cf-fructose, is an anticonvulsant agent (AHFS, 2000). The spectrum of topiramate s anticonvulsant activity resembles that of CBZ and phenytoin (Shank et ah, 2000). Topiramate has shown preliminary antimanic (McElroy et al., 2000) and possibly antidepressant efficacy in treatment-refractory, manic patients with BD type I (Calabrese et ah, 1998). 

The pharmacokinetics of topiramate are linear with peak plasma concentrations (occurring in about 2 hours) of 25 pM after 400 mg daily (Shank et al., 2000). Topiramate is poorly bound to plasma proteins (15%) and it binds to erythrocytes. In rats the maximal concentration in the brain when administered at 10 mg/kg was 10 pM (Shank et ah, 2000). It is not extensively metabolized in humans and is eliminated (70%) unchanged in urine. Six minor metabolites have been identified, none with anticonvulsant activity. The average elimination half-life is 21 hours (Shank et ah, 2000). 

Controlled trials of combinations of mood stabilizers with single mood stabilizer, or of the newer anticonvulsants (e.g., lamotrigine and topiramate) are in process. Open trials have included add-on medications and heterogeneous samples. 

These data suggest that there is more available information for use of lithium than for other mood stabilizers, and that adolescents hospitalized with adolescent-onset, acute mania have rates of response between 50% and 80%. Supplementation with sedating medication appears to be common but not systematically evaluated. Children hospitalized with mania also respond to lithium, but their comorbid disorders often need separate attention. Open trials with DVP in hospitalized adolescents are also supported. There is much less information on CBZ and there are no data on newer anticonvulsants such as lamotrigine, topiramate, or gabapentin. These data are largely consistent with data from studies of hospitalized adults with classic mania. 

Virtually all anticonvulsants are or have been of interest for the treatment of bipolar disorder. However, the importance of controlled data cannot be understated. For example, gabapentin, an anticonvulsant that initially received much attention as a potential mood stabilizer, was compared with placebo and did not appear to stabilize mood (Frye et al. 2000 Pande et al. 2000). Similar negative results were seen with topiramate in placebo-controlled trials for the treatment of mania. Although these medications might be useful adjuncts in some patients, given the currently expanded pharmacopoeia of medications with positive controlled trial data in bipolar disorder, we do not recommend the primary use of agents that have only case reports as an evidence base or controlled studies with predominantly negative results. 

Various anticonvulsants lamotrigine magnesium sulfate paraldehyde topiramate... 

Other agents with anticonvulsant properties that may be of use m the treatment of bipolar disorder include topiramate, gabapentin, tiagabine and carbamazepine (Janicak et al., 2001). 

Propranolol, amitriptyline, and some calcium channel blockers have been found to be effective for the prophylaxis of migraine in some patients. They are of no value in the treatment of acute migraine. The anticonvulsants valproic acid and topiramate (see Chapter 24) have... 

Another group of mood-stabilizing drugs that are also anticonvulsant agents have become more widely used than lithium. These include carbamazepine and valproic acid for the treatment of acute mania and for prevention of its recurrence. Lamotrigine is approved for prevention of recurrence. Gabapentin, oxcarbazepine, and topiramate are sometimes used to treat bipolar disorder but are not approved by FDA for this indication. Aripiprazole, chlorpromazine, olanzapine, quetiapine, risperidone, and ziprasidone are approved by FDA for the treatment of manic phase of bipolar disorder. Olanzapine plus fluoxetine in combination and quetiapine are approved for the treatment of bipolar depression. 

Topiramate. Topiramate is another compound approved as an anticonvulsant and in clinical testing as a mood stabilizer. Its mechanism of action appears to be to enhance... 

FIGURE 7-27. Shown here is an icon of topiramate s pharmacologic actions. By interfering with calcium channels and sodium channels, topiramate is thought both to enhance the inhibitory actions of gamma aminobutyric acid (GABA) and to reduce the excitatory actions of glutamate. Topiramate is also a carbonic anhydrase inhibitor (CAI) and as such has independent anticonvulsant actions. 

---