MS_GBP

MS and Gabapentin

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Gabapentin [GBP] is a well-tolerated antiepileptic drug found to be effective for a variety of symptoms in multiple sclerosis (MS). A literature study in August 2005 with Entrez PubMed revealed 30 quotations of which 14 were reviews and 16 could be characterized as case-reports (5), open clinical studies (8) or randomized controlled trials of brief duration with cross-over (2). One study [16] were reporting adverse effects in 16 of 94 patients receiving GBP. The abstract does not reveal any details and this study was restricted to the internet findings. These are summarized below: <>

Ref..	Study Design	Duration	Dosage G	n	Indication	Reported effect
1	RCT, c-o	2 days	1200	15	spasticity and painful muscle spasms	Pos. G
2	Case-Rep.				refractory dysesthetic limb pain
3	Open			25	intractable pain of reflex sympathetic dystrophy	Pos. G
4	Open		600-1200	21	varous paroxysmal symptoms	Pos. 18/18
5	Open			7	therapy refractory trigeminal neuralgia	7/7 pos. G
6	Case-Rep.	3 month	400	2	spasticity	2/2 pos. G
7	RCT, c-o	6 days	2700		spasticity	Pos. G
8	Open	8 weeks	max 600	24	nocturnal painful spasms	20/22 pos. G
9	Open		av.810	11	trigeminal neuralgia	10/11 pos. G
10	Open c-o		1200	8	acquired nystagmus	4/5
11	Case-Rep.	5 weeks	900-1500	3	acquired nystagmus	3/3
12	Case-Rep.		3000	1	acquired nystagmus	1/1
13	Case-Rep.			1	acquired nystagmus	1/1
14	Open	12 month		10	Tremor	Pos. G
15	Open				varous paroxysmal symptoms
16	Report			94	(adverse effects)

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GBP was used on the following indications: painful tonic spasms [1,6-8,15], dysaesthetic or paraesthetic symptoms [2,4,15], acquired nystagmus [4, 10-13] tremor [14] and therapy refractory trigeminal neuralgia [4,5,9], for the latter indication generally in combination with low-dose carbamazepin. The studies were generally short (2 days – 12 weeks reported in 5 of the 15 studies, not reported in 9 studies) and doses of 600-1200 mg GBP daily prevailed. All studies reported a positive effect (exception: 2 letters without abstract) in the vast majority of cases.

<> The studies report a symptomatic effect, generally valued as inferior to the causal effect aimed for other long-lasting therapy studies. Based on the recognition, that a causal effect can only be claimed in a minority of these patients, but also on the absense of reports from the use of GBP on the course of disease in a longitudinal study, there are still many open questions to the value of GBP in relation to other drugs used in MS. It is an interesting, comparatively inexpensive substance (explaining the absense of long-term studies for its effect upon the course of disease), and the adverse effects are generally mild, only rarely causing a disruption of therapy. However, an evaluation of its effects, beyond that upon disturbing symptoms of MS, will be difficult in the absense of interest from the university hospitals.

Literature:

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1: Mueller ME, Gruenthal M, Olson WL, Olson WH. Gabapentin for relief of upper motor neuron symptoms in multiple sclerosis. Arch Phys Med Rehabil. 1997 May;78(5):521-4.
2: Samkoff LM, Daras M, Tuchman AJ, Koppel BS. Amelioration of refractory dysesthetic limb pain in multiple sclerosis by Gabapentin. Neurology 1997;49:304-5.
3: Houtchens MK, Richert JR, Sami A, Rose JW. Open label Gabapentin treatment for pain in multiple sclerosis. Mult Scler 1997;3:250-3.
4: Solaro C, Lunardi GL, Capello E, Inglese M, Messmer Uccelli M, Uccelli A, Mancardi GL. An open-label trial of Gabapentin treatment of paroxysmal symptoms in multiple sclerosis patients. Neurology 1998 51:609-11.
5: Khan OA. Gabapentin relieves trigeminal neuralgia in multiple sclerosis patients. Neurology 1998;51:611-4.
6: Dunevsky A, Perel AB. Gabapentin for relief of spasticity associated with multiple sclerosis. Am J Phys Med Rehabil 1998;77:451-4.
7: Cutter NC, Scott DD, Johnson JC, Whiteneck G. Gabapentin effect on spasticity in multiple sclerosis: a placebo-controlled, randomized trial. Arch Phys Med Rehabil 2000;81:164-9.
8: Solaro C, Uccelli MM, Guglieri P, Uccelli A, Mancardi GL. Gabapentin is effective in treating nocturnal painful spasms in multiple sclerosis. Mult Scler 2000;6:192-3.
9: Solaro C, Messmer Uccelli M, Uccelli A, Leandri M, Mancardi GL. Low-dose Gabapentin combined with either lamotrigine or carbamazepine can be useful therapies for trigeminal neuralgia in multiple sclerosis. Eur Neurol 2000;44:45-8.
10: Bandini F, Castello E, Mazzella L, Mancardi GL, Solaro C. Gabapentin but not vigabatrin is effective in the treatment of acquired nystagmus in multiple sclerosis: How valid is the GABAergic hypothesis? J Neurol Neurosurg Psychiatry 2001;71:107-10.
11: Stahl JS, Rottach KG, Averbuch-Heller L, von Maydell RD, Collins SD, Leigh RJ. A pilot study of Gabapentin as treatment for acquired nystagmus. Neuroophthalmology 1996;16:107-13.
12: Jain S, Proudlock F, Constantinescu CS, Gottlob I. Combined pharmacologic and surgical approach to acquired nystagmus due to multiple sclerosis. Am J Ophthalmol 2002;134:780-2.
13: Fabre K, Smet-Dieleman H, Zeyen T. Improvement of acquired pendular nystagmus by Gabapentin: Bull Soc Belge Ophtalmol 2001;282:43-6.
14: Lopez del Val LJ, Santos S. [Gabapentin in the treatment of tremor; article in Spanish]. Rev Neurol 2003;36:322-6.
15: Yetimalar Y, Gurgor N, Basoglu M. Clinical efficacy of Gabapentin for paroxysmal symptoms in multiple sclerosis. Acta Neurol Scand 2004;109:430-1.
16: Solaro C, Brichetto G, Battaglia MA, Messmer Uccelli M, Mancardi GL. Antiepileptic medications in multiple sclerosis: adverse effects in a three-year follow-up study. Neurol Sci 2005;25:307-10.

Inserted Aug. 19, 2005

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