NEUROMODULATORS

Medication Names:

Gabapentin (Neurontin®), Tiagabine (Gabitril®), Topiramate (Topamax®), Carbamazepine (Tegretol®), Lamotrigine (Lamictyl®)), Phenytoin (Dilantin®), Valproate (Depakote®), Clonazepam (Klonopin®)

On Label Use:

Seizures of varioius types due to this class of medication's ability to stabilize plasma membranes in nerve transmission

Pain Use:

Membrane stabilization cuts down transmission of ectopic nerve impulses and independent nerve firing caused by damaged nerves, recruitment of touch fibers, sympathetic feedback loops and microneruomas at damaged nerve sites. Actions of these medications include sodium channel blocking, GABA reuptake inhibition, Non-NMDA glutamate receptor blocking, GABA synthesis, and GABA sub-receptor stimulation. Tiagabine gives a particularly unique profile due to its specific action as a Selective GABA reuptake inhibitor.

Therapeutic Benefit:

Phenytoin and Carbamezepine have more limited applicability because it appears that their specific type of sodium channel blocking is effective in more paraoxysmal and lancinating pain. They are most effective with Trigeminal Neuralgia. Tiagabine, Gabapentin, Lamotrigine, Topiramate and Valproate are more effective with a broader range of neuropathic pain disorders. They also tend to have a lower side effect profile. In particular, Tiagabine, Gabapentin and Topiramate appear to be quite safe with generally better tolerated side effects. This class of drugs can reduce or eleminate burning, dyesthetic, lancinating, and electrical types of pain. Tiagabine stimulates GABAergic restraint of excessive Glutamatergic tone and serves to inhibit the excessive action of Glutamate in pain states. Theoretically this should decrease wind-up pain, the basic contributor to the disease of chronic pain.

Dose Range:

This varies by medication and is limited by side effects, that can range from relatively benign to severe.

Tiagabine 2 mg to 56 mg starting at night to 8 mg then divided doses bid to tid
Gabapentin 1200 to 4800 mg daily in three divded doses
Topiramate 100 to 400 mg daily in bid divided doses
Phenytoin 300 to 400 mg daily with blood levels
Carbamazepine 200 mg to 1200 mg with blood levels, LFTs, CBC
Valproate 250 mg to 1500 mg with blodd levels, LFTs
Clonazepam 0.5 to 20 mg daily

Titration:

These medications are best titrated up slowly in order to avoid side effects common to anticonvulsants of drowsiness, ataxia, confusion, and short term memory loss. When discontinuing these medications, it is best to taper them down, to avoid precipitating seizures in patients with overt or occult seizure disorders.

Side Effects:

Lightheadedness, drowsiness, memory loss, confusion, ataxia, abdominal cramps, peripheral edema, depression.

Lamotrigine may cause a severe occasionally fatal rash, including Stevens-Johnson Syndrome. There may also be benign rashes and if any rash occurs the medication should be stopped.

Rare cases of fatal liver Toxicity have occurred with Valproate. LFT's and frequent Valproate levels should be drawn

Carbamazepine may cause agranulocytosis that can be irreversible in nature. It can also cause severe liver damage. CBCs and LFTs should be drawn every 3 to 6 months on this medication. Carbamazepine induces liver enzymes that autometabolize Carbamazepine and may require adjustments upward to maintain blood levels after a few months. Toxicity can lead to stupor and coma, with respiratory depression and death.

Phenytoin can cause gingival hypertrophy and induction of liver enzymes that may affect the metabolism of other medications

Topirimate can cause narrow angle glaucoma and should be stopped if it does so. Topirimate may cause weight loss.

Gabapentin may cause weight gain and reversible short term memory loss

Drug Interactions:

Chloramphenicol, dicumarol, disulfram, isoniazid, cimetadine, valproate, phenylbutazoneand sulfonamides may increase the plasma concentration of phenytoin. Carbamazepine may reduce plama levels of phenytoin. Phenobarbitol and phenytoin may mutually raise and lower blood levels of either drug. Ethanol may raise phenytoin levels. Phenytoin may lower concentrations of bcps and corticosterioids.

Phenobarbitol, Phenytoin, Valproate may all decrease Carbamezepine levels. Carbamezepine lowers Haloperidol and Valproate. Propoxyphene and Erythromycin may lower carbamazepine levels.

Valproate increases phenobarbitol levels. The combination of valproate and clonazepam may very rarely cause absence seizures.

Dependency or Abstinence Syndrome:

If patients have an underlying seizure disorder or subclinical lowered seizure thresholds, sudden cessation of these types of medications can precipitate seizures.

Clonazepam will cause a benzodiazepine dependency and abstinence syndrome, usually above a 2 mg daily dose. Abrupt cessation can cause agitation, status epilepticus grand mal seizures, delerium tremens and death.

 



 

 

 

Bay Area Pain Medical Associates provides the information as a guideline for physicians interested in up to date knowledge about the treatment of pain in their patients. We provide this as a public service without endorsing any specific treatment. Much of the medication used in managing pain is for "off label" use. Physicians using these medication are responsible for researching their efficacy, side effects, therapeutic benefits, interactions, titration and cessation, before deciding whether to use them in their practice. While we have provided information on these subjects, we do not feel this should serve as a substitute for looking up medications in standard texts and resources. When medications are left out of dosing, titration, drug interaction and side effect categories, it is because we do not think they should be used by anyone except for pain specialists.