The natural history and the effects of gabapentin in amyotrophic lateral sclerosis

Glutamate excitotoxicity seems to play an important role in the aetiopathog enesis and progression of Amyotrophic Lateral Sclerosis (ALS). Gabapentin i s a modulator of the glutamatergic system and has been shown to prolong sur vival in the transgenic model of familial ALS. It has also been demonstrate d to slow the decline of arm strength in human sporadic cases. The aim of o ur study was to assess the effects of different dosages and duration of tre atment of gabapentin on the natural history and survival of ALS patients. A total of 110 patients affected by definite ALS entered the study. After a 6-12 month period of observation, patients were randomly assigned to receiv e oral gabapentin 500 mg/day (Group A) or 1000 mg/day (Group B) for 6 month s. In addition a group of patients received gabapentin 500 mg/day for 6 mon ths and 1000 mg/day for a further 6 months (Group C). A group of 121 patien ts referred to our Institute, who received only symptomatic treatment, was considered as the control group (Group D). Each patient was seen at entry a nd every 3 months. All average slopes were negative but the comparison of a ll slopes showed a trend toward a slower rate of decline of muscle strength loss in all treated groups of patients compared with the control group. Th e differences were statistically significant. Analysis between the pretreat ment and treatment period showed a statistically significant decrease of th e decline of muscle strength and Norris score during the treatment period. Survival analysis showed a significantly longer survival in treated patient s of Groups B and C. Our study suggests that gabapentin may be an effective drug for ALS; hence a controlled trial involving a sufficient large number of patients is warranted. (C) 1998 Elsevier Science B.V. All rights reserv ed.