Anticonvulsant agents topiramate

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). 

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. 

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. 

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). 

Topiramate is itself a second-line augmenting agent for numerous other anticonvulsants, lithium, and antipsychotics in treating bipolar disorder... 

Certain anticonvulsants developed initially for the treatment of epilepsy, such as topiramate and zonisamide, have been found to have a beneficial effect in mood disorders, particularly bipolar disorder. In addition, patients treated with these compounds lose weight. They were therefore seen as potential therapeutic agents for use in obese patients with BED. 

A review of the second-generation anticonvulsants reveals that screening or serendipity led to the development of felbamate (10), 1am-otrigine (11), zonisamide (13), topiramate (15), and levetiracetam (16) on the other hand, clobazam (4d) and oxcarbazepine (12) were developed by structural variation of known agents (78). Only three, vigabatrin (8), gabapentin (9), and tiagabine (14), were developed by mechanism-based rational development (78). 

The place in therapy of the newer anticonvulsants, such as gabapentin, levetiracetam, tiagabine, topiramate, and zon-isamide, is controversial. Many clinicians consider these agents to be less effective than established mood stabilizers based on initial studies and avoid them for monotherapy in bipolar disorder. 

Other anticonvulsants frequently prescribed to autistic patients include topira-mate, gabapentin, and carbamazepine (Oswald and Sonenklar, 2007). Evidence from controlled studies for the use of these agents for treatment of autistic symptoms other than seizures is not available, although results from open studies with topiramate (Canitano, 2005 Hardan et al., 2004) suggest that this drug is worthy of further investigation. A placebo-controlled trial of oxcarbazepine in childhood autism is underway (clinicaltrials.gov). 

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