Effects of gabapentin on the motor response to levodopa: a double-blind, placebo-controlled, crossover study in patients with complicated Parkinson disease.
BACKGROUND
Motor fluctuations and dyskinesias affect many parkinsonian patients chronically treated with levodopa. Imbalance between gabaergic direct and indirect striatopallidal pathways may originate them. Manipulating GABA neurotransmission may be effective in the treatment of these patients. Gabapentin is an antiepileptic drug that increases the synthesis and release of GABA. Previous studies suggest that gabapentin may be useful in Parkinson disease (PD).


OBJECTIVE
To know the effects of gabapentin on the motor response to levodopa in PD patients with motor complications.


METHODS
A randomized double-blind, placebo-controlled, cross-over trial with four weeks of treatment.


METHODS
A tertiary referral center.


METHODS
Twenty subjects with PD and motor fluctuations and dyskinesias on stable antiparkinsonian treatment, took gabapentin up to a maximum dose of 2.400 mg/d in three doses and placebo.


METHODS
Three levodopa challenges were performed: at the beginning of the study and at the end of each period of treatment (4 weeks). Basal (off) and best (on) motor status were assessed by the UPDRS III. Latency to peak effect, magnitude of motor response (difference between "on" and "off" scores in the UPDRS III), duration of motor response and severity and duration of dyskinesias after each levodopa challenge were assessed. Patients' diaries were administered.


RESULTS
: Fifteen patients completed the study. A significant improvement in the basal UPDRS III resulting in a significant reduction in the magnitude of the motor response after gabapentin was obtained (P < 0.001). No other changes were observed, either on pharmacological parameters or in levodopa-induced dyskinesias. Number of daily hours spent in "on," "on with dyskinesias" and "off" also remained unchanged. Tolerance was good, dizziness being the most common side effect.


CONCLUSIONS
Gabapentin improved parkinsonian symptoms (basal UPDRS III and magnitude of the motor response) following levodopa. This improvement was not reflected in the daily motor situation of patients. Dyskinesias remained unchanged. Gabapentin was well tolerated. Further studies are needed to know the impact of these results in the long-term.
Van Blercom
N
N
Centro de Neurología y Neurocirugía funcional, Clínica Quirón, San Sebastián, Spain.
Lasa
A
A
Verger
K
K
Masramón
X
X
Sastre
V M
VM
Linazasoro
G
G
D000085:Acetates / Q000627:therapeutic use*; D000368:Aged; D000588:Amines; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003509:Cyclohexanecarboxylic Acids; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy; D000077206:Gabapentin; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects*; D009460:Neurologic Examination; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000978:Antiparkinson Agents; D003509:Cyclohexanecarboxylic Acids; D007980:Levodopa; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin