Anticonvulsant agents gabapentin

Bertrand S et al. The anticonvulsant, antihyperalgesic agent gabapentin is an agonist at brain gamma-aminobutyric acid type B receptors negatively coupled to voltage-dependent calcium channels. J Pharmacol Exper Therap 2001 298 15-24. 

Gabapentin is used in combination with other anticonvulsant agents in the management of partial seizures (Bruni, 1998) with or without secondary generalization (Morris, 1999). A few (McElroy et al., 1997 Knoll et ah, 1998), but not all (Dimond et al., 1996), preliminary reports suggested that gabapentin may have an-timanic efficacy in adults with BD. 

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. 

For patients who are unable to tolerate a tricyclic antidepressant, the choice of agent should consider the patients underlying mental state. If the patient has concomitant depression, another antidepressant such as ven-lafaxine, nefazodone, or mirtazapine may be the appropriate choice. If the patient does not have concomitant depression, an anticonvulsant agent such as gabapentin may be an acceptable alternative. 

Compare the actions of gabapentin with those of other anticonvulsant agents. 

Since gabapentin does not act by conventional mechanisms and has little or no cross-reactivity with neurotransmitter receptors, concurrent use with other agents produces a synergistic effect. This allows less of the anticonvulsant agent to be used, minimizing side effects,- and increasing patient compliance. 

Agents Acetaminophen or NSAID combinations with opioids Adjuncts Tricyclic antidepressants Anticonvulsants Radiopharmaceuticals (Bone pain) Acetamnophen (See above) Opioids Titrate Amitriptyline 10-50 mg Imipramine 10-50 mg NSAIDs (See above) Gabapentin (Neurontin) 3.6 g... 

Pharmacology Gabapentin is an oral antiepileptic agent. The mechanism by which it exerts its anticonvulsant and analgesic actions is unknown. 

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). 

Gabapentin is itself an augmenting agent to numerous other anticonvulsants in treating epilepsy and to lithium, atypical antipsychotics and other anticonvulsants in the treatment of bipolar disorder... 

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). 

Peripheral neuropathy is also common with advanced CKD and is typically indistinguishable from other types of neuropathy (e.g., diabetic neuropathy). Symptoms are often uncomfortable for the patient and prompt many clinicians to initiate pharmacologic therapy in an attempt to reduce these symptoms. Tricyclic antidepressants (e.g., amitriptyline) and anticonvulsants (e.g., phenytoin and gabapentin) may have some benefit in alleviating symptoms of neuropathy however, risks and benefits must be considered for agents... 

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. 

Pharmacologic treatment of RLS includes dopaminergic agents, benzodiazepines, opioids, or anticonvulsants. In mild cases of RLS, benzodiazepines may be first-line agents. Clonazepam, lorazepam, triazolam, and temazepam have been effective. Clonazepam 0.5 to 2 mg is most frequently studied. Opiates such as methadone 5 to 20 mg, codeine 30 to 120 mg, and oxycodone 2.5 mg are very effective, but the development of tolerance is a concern. Abuse potential with opiates is also a concern due to the chronic nature of the condition. Other agents that have been used include apomorphine, amantadine, tramadol, magnesium, oxycodone, propoxyphene, gabapentin, bromocriptine, clonidine, and carbamazepine. Tolerance may de-... 

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). 

---