Section 3.4.4

Other Anticonvulsants (used as mood stabilizers)

General Description

Gabapentin (Neurontin), lamotrogine (Lamictal), topiramate (Topramax), tiagabine (Gabitril), and ethosuximide (Zarontin), are anticonvulsants that have been developed recently.

Gabapentin is structurally related to gamma-aminobutyricacid (GABA), and increases GABA levels. Lamotrogine blocks Na+ channels and inhibits release of glutamate. Topiramate also blocks Na+ channels and blocks glutamate.

Gabapentin has no hepatic metabolism and is entirely eliminated via the kidneys. Lamotrogine is primarily metabolized by the hepatic glucuronyl transferase enzyme system. Topiramate is primarily eliminated by the kidneys, but is also metabolized by the hepatic cytochrome system. Tiagabine and ethosuximide are both primarily metabolized by the cytochrome enzyme system.

Indications for Medication

These anticonvulsants should usually be reserved for the treatment of bipolar patients who either do not respond to or cannot tolerate lithium, or valproate. While their use in psychiatry as mood stabilizers is considered "off label," there is a body of currently accepted clinical literature supporting the use of these anticonvulsants in cases where the other approved mood stabilizers have not been effective or were not tolerated.

There are clinical studies showing that gabapentin may have use with rapid cycling, anxiety, and pain management. Similarly, there are studies of lamotrigine showing efficacy with bipolar depression as well as mania prophylaxis.

Clinical Guidelines

Gabapentin is used in doses of up to 2700 mg /day, and is started at 100mg tid, with increases up to 200-300mg tid. Lamotrigine is used in doses of up to 500 mg /day, and is started at 25 mg bid, with increases by 50 mg per week. Topiramate is used in doses of up to 200 mg /day, and is started at 25 mg bid, with increases by 50 mg per week. Tiagibine is used in doses of 12 to 40 mg /day, while ethosuximide is used in doses of 1000 to 1500 mg /day.

Because of the binding properties, the usual serum level monitoring of anticonvulsants is not done with these medications. Screening and annual monitoring of hepatic and renal function should be done.

Adverse Effects

The most common adverse effects for these medications are somnolence, ataxia and dizziness, which occur 20 to 30 % of the time. Tolerance may develop if the dose is increased slowly and by taking the drug with meals.

There is a rare but serious side effect risk of a life-threatening rash (Stevens-Johnson syndrome) with lamotrigine, and this medication should be discontinued at the first sign of rash.

Drug-Drug Interactions

There are no drug-drug interactions known with gabapentin. Lamotrigine and topiramate both have a potential drug interaction when used with carbamazepine or valproate. Topiramate may lead to decreased effectiveness of some oral contraceptives.

The consent form for these medications is "Mood Stabilizing Medication (Anti-convulsant)".

The following table is derived from CalOPTIMA's prescribing information
 

GENERIC NAME/ TRADE NAME

 

FORMULARY STATUS

 

STARTING DOSE

 

Tablet size

 

MAXIMUM DAILY DOSE

COST/MONTH ?

Carbamazepine / Tegretol

CalOptima /HCA

200mg BID

100, 200mg

1200mg

$100

Carbamazepine SR Tegretol-XR or Carbatrol

CalOptima /HCA

200mg BID

100, 200, 400mg

1200mg

$75

Divalproex / Depakote

CalOptima /HCA

250mg BID

125, 250, 500mg

4500mg

$380

Valproic Acid / Depakene

CalOptima /HCA

250mg BID

250mg

4500mg

$45

Gabapentin / Neurontin

CalOptima

300mg TID

100, 200, 300

3600mg

$350

Lamotrigine / Lamictal

y CalOptima

50mg BID

25, 100, 150, 200mg

500mg

$235**

Tiagabine / Gabitril

y CalOptima

16mg BID

4, 12, 16, 20mg

64mg

$230

Topiramate / Topamax

y CalOptima

200mg BID

25, 100, 200mg

400mg

$190

Ethosuximide / Zarontin

CalOptima

500mg QD

250mg

1500mg

$150

y = restricted to psychiatrists.

?= Cost based on AWP for brand as of October 1998, MAIC for generic; rounded up to nearest $5 increment

** A Lower cost is achieved by cutting 100mg tablets in half for the 50mg dose.