The role of titration schedule of topiramate for the development of depression in patients with epilepsy.
OBJECTIVE
To determine whether a fast titration schedule of topiramate (TPM) has different effects on the occurrence of depression, in relation to other risk factors for TPM-induced depression, including history of depression (HxDEP), febrile seizures (FS), and hippocampal sclerosis (HS).


METHODS
Using data from a large case registry of patients prescribed TPM, two models were constructed: Model 1 examined the independent effect of rapid TPM titration after separate adjustment for FS, HxDEP, and HS. Model 2 examined effect of the cooccurrence of rapid titration on the development of depression with each of these risk factors.


RESULTS
A total of 423 patients were included (51.8% females), mean age (SD) 35.5 (11.8) years, mean duration of epilepsy of 22.2 (11.5) years. Forty-four patients (10.4%) developed depression during TPM therapy. A rapid TPM titration was associated with 5-fold increased risk of depression that increased to 12.7-fold in the presence of both FS and rapid TPM titration, 23.3-fold in the presence of both HxDEP and rapid TPM titration, and 7.6-fold in the presence of both HS and rapid TPM titration schedule.


CONCLUSIONS
Our study suggests that a rapid titration schedule is associated with an increased risk of developing depression during TPM therapy. HxDEP and FS are major contraindications to the use of a rapid titration, with a 23.3-fold and 12.7 fold increased risk, respectively.
Mula
Marco
M
Section of Neurology, Department of Clinical & Experimental Medicine, Amedeo Avogadro University, Novara, Italy. marcomula@yahoo.it
Hesdorffer
Dale C
DC
Trimble
Michael
M
Sander
Josemir W
JW
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use*; D003863:Depression / Q000139:chemically induced*; D004334:Drug Administration Schedule; D004827:Epilepsy / Q000188:drug therapy*; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D015233:Models, Statistical; D017186:Titrimetry / Q000379:methods*; D000077236:Topiramate
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose