Conversion to lamotrigine monotherapy from valproate monotherapy in older adolescent patients with epilepsy.
BACKGROUND
Pharmacokinetic interactions can make necessary anti-epileptic medication (AED) changes hazardous for children with epilepsy. We report the utility of a dosing algorithm designed to maintain stable trough lamotrigine (LTG) concentrations during conversion from valproate (VPA) to LTG monotherapy in adolescents aged 16-20 years.


METHODS
Patients were enrolled into the study if they required a change in their AED regimen due to lack of efficacy or intolerable side effects. Conversion to LTG monotherapy took place in a four part treatment algorithm. Lamotrigine was escalated according to a target dose of 200 mg/day over 8-weeks. Valproate was withdrawn over a period of 2-6 weeks, depending on the initial dose. Lamotrigine dose was further escalated to 500 mg/day and continued for four weeks as mono therapy. Trough serum concentrations of LTG were measured during each phase of the trial.


RESULTS
Twelve of 16 patients completed the study. After the LTG escalation to 200 mg/day, mean trough serum concentrations of 8.0 microg/mL did not differ significantly from the 9.5 microg/mL after VPA withdrawal or the 9.2 microg/mL after 4 weeks of monotherapy at 500 mg/day. Adverse events led to premature discontinuation for one subject. Two subjects withdrew due to worsening seizures during LTG monotherapy possibly due to non-compliance. Limitations of the trial include the open label design and small sample size of the sub-analysis.


CONCLUSIONS
In adolescent patients, this algorithm produces stable LTG serum concentrations with favorable tolerability during a transition from VPA to LTG mono therapy.
Baumann
Robert J
RJ
University of Kentucky, Lexington KY, USA.
Fakhoury
Toufic A
TA
Kustra
Robert P
RP
Vuong
Alain
A
Hammer
Anne E
AE
Messenheimer
John A
JA
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D014227:Triazines / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D014635:Valproic Acid / Q000627:therapeutic use*
D000927:Anticonvulsants; D014227:Triazines; D014635:Valproic Acid; D000077213:Lamotrigine