CHAPTER 30 LAMOTRI

GINE

Introduction
Peak 2-4hrs, half life 25hrs
It does not:
Has not been shown to inhibit the reuptake of NE, dopamine or ser
otonin.
It has effect on 5HT3r, but too weak to contribute to any profile
Does not exhibit high binding affinity to adrenergic, dopamine, GAB
A, Histamine, opioid, muscarinic acetylcholine receptors.
It does:
Inhibition of sodium channels
Antagonistic action on N-type calcium channels
Antiglutamatergic action

Indications and Efficacy

Maintenance Therapy in Bipolar I Disorder
Lamotrigine was superior at prolonging time to depressive episode
Lithium was superior at prolonging time to a manic, hypomanic or
mixed episode
Acute Monotherapy and Adjunctive Therapy in Bipolar De

pression
Lamotrigine (200mg/day) has significant antidepressant efficacy on

MADRS, Ham-D Item 1, CGI-S, CGI-I, but not overall Ham-D score
CANMAT: recommend Lamotrigine as 1st line agent
Good utility as an add-on to Lithium

Additional Efficacy Considerations

To date, only OFC and quetiapine approved for treatment

of acute bipolar depression

OFC vs Lamotrigine (Brown 2006)
Response and remission rates were comparable
Suicidal /self-injuries more in lamotrigine group
Favorable Hba1c, prolactin, total cholesterol, HDL, LDL, TG, BW in

lamotrigine group

Add-On trial (van der Loos 2009)

Have Lithium for 8 wks first (keep at 0.6 2.5mmol/L)
Lamotrigine group: Better MADRS and response rate
Lamotigine does not possess antimanic activity

Dosing and Drug-Drug Interactions

25mg 2 wks 50mg 2wks 100mg 1 wk 200

mg
Lamotrigine + valproate
25mg QOD 2 wks 25mg QD 2 wks 50mg 2 wks 1

00mg

Lamotrigine + enzyme-inducing AED

Decreases lamotrigine by 40% - 50%
50mg 2 wks 100mg 2 wks 400mg
Lamotrigine + estrogen
Decreases lamotrigine by 64%

Side Effects and Toxicity

Headache, changes in sleep, nausea, dizziness
Rash
Exanthematic maculopapular eruption
If occur, hold next dose and seek consultation
Greatest risk in first 8 wks of Tx
Rash in 5 days usually nondrug cause
Retitrate if stop for > 1 wk
Aseptic meningitis
Meningismus, photophobia, headache, vomiting, fever
Complete recovery upon discontinuation

Use During Pregnancy

Extensive placental transfer (23% - 50%)
When treating with valproate/carbamazapine, neural tube

defects occur in 1% - 5%
First trimester lamotrigine monotherapy associated with cl
eft lip/ cleft palate.
International Lamotrigine Pregnancy Registry
14/414(2.9%) congenital malformations, similar to background risk

of 2% - 3%

Limiting dosage during first trimester should be considere

d.
Pregnancy Category C