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. 2002 Sep;73(3):246–249. doi: 10.1136/jnnp.73.3.246

A randomised placebo controlled exploratory study of vitamin B-12, lofepramine, and L-phenylalanine (the "Cari Loder regime") in the treatment of multiple sclerosis

D Wade 1, C Young 1, K Chaudhuri 1, D Davidson 1
PMCID: PMC1738034  PMID: 12185153

Abstract

Objective: To determine whether combination therapy with lofepramine, L-phenylalanine, and intramuscular vitamin B-12 (the "Cari Loder regime") reduces disability in patients with multiple sclerosis.

Methods: A placebo controlled, double blind, randomised study carried out in five United Kingdom centres on outpatients with clinically definite multiple sclerosis, measurable disability on Guy's neurological disability scale (GNDS), no relapse in the preceding six months, and not on antidepressant drugs. Over 24 weeks all patients received vitamin B-12, 1 mg intramuscularly weekly, and either lofepramine 70 mg and L-phenylalanine 500 mg twice daily, or matching placebo tablets. Outcome was assessed using the GNDS, the Kurtzke expanded disability status scale; the Beck depression inventory, the Chalder fatigue scale, and the Gulick MS specific symptom scale.

Results: 138 patients were entered, and two were lost from each group. There was no statistically significant difference between the groups at entry or at follow up. Analysis of covariance suggested that treated patients had better outcomes on four of the five scales used. Both groups showed a reduction of 2 GNDS points within the first two weeks, and when data from all time points were considered, the treated group had a significant improvement of 0.6 GNDS points from two weeks onwards.

Conclusions: Patients with multiple sclerosis improved by 2 GNDS points after starting vitamin B-12 injections. The addition of lofepramine and L-phenylalanine added a further 0.6 points benefit. More research is needed to confirm and explore the significance of this clinically small difference.

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Selected References

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  1. Berne-Fromell K., Fromell H., Lundkvist S., Lundkvist P. Is multiple sclerosis the equivalent of Parkinson's disease for noradrenaline? Med Hypotheses. 1987 Aug;23(4):409–415. doi: 10.1016/0306-9877(87)90062-4. [DOI] [PubMed] [Google Scholar]
  2. Brañas P., Jordan R., Fry-Smith A., Burls A., Hyde C. Treatments for fatigue in multiple sclerosis: a rapid and systematic review. Health Technol Assess. 2000;4(27):1–61. [PubMed] [Google Scholar]
  3. Chalder T., Berelowitz G., Pawlikowska T., Watts L., Wessely S., Wright D., Wallace E. P. Development of a fatigue scale. J Psychosom Res. 1993;37(2):147–153. doi: 10.1016/0022-3999(93)90081-p. [DOI] [PubMed] [Google Scholar]
  4. Di Fabio R. P., Soderberg J., Choi T., Hansen C. R., Schapiro R. T. Extended outpatient rehabilitation: its influence on symptom frequency, fatigue, and functional status for persons with progressive multiple sclerosis. Arch Phys Med Rehabil. 1998 Feb;79(2):141–146. doi: 10.1016/s0003-9993(98)90290-8. [DOI] [PubMed] [Google Scholar]
  5. Freeman J. A., Langdon D. W., Hobart J. C., Thompson A. J. The impact of inpatient rehabilitation on progressive multiple sclerosis. Ann Neurol. 1997 Aug;42(2):236–244. doi: 10.1002/ana.410420216. [DOI] [PubMed] [Google Scholar]
  6. Gulick E. E. Model confirmation of the MS-Related Symptom Checklist. Nurs Res. 1989 May-Jun;38(3):147–153. [PubMed] [Google Scholar]
  7. Kurtzke J. F. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444–1452. doi: 10.1212/wnl.33.11.1444. [DOI] [PubMed] [Google Scholar]
  8. Poser C. M., Paty D. W., Scheinberg L., McDonald W. I., Davis F. A., Ebers G. C., Johnson K. P., Sibley W. A., Silberberg D. H., Tourtellotte W. W. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983 Mar;13(3):227–231. doi: 10.1002/ana.410130302. [DOI] [PubMed] [Google Scholar]
  9. Rossier Philippe, Wade Derick T. The Guy's Neurological Disability Scale in patients with multiple sclerosis: a clinical evaluation of its reliability and validity. Clin Rehabil. 2002 Feb;16(1):75–95. doi: 10.1191/0269215502cr447oa. [DOI] [PubMed] [Google Scholar]
  10. Sharrack B., Hughes R. A. Clinical scales for multiple sclerosis. J Neurol Sci. 1996 Jan;135(1):1–9. doi: 10.1016/0022-510x(95)00261-y. [DOI] [PubMed] [Google Scholar]
  11. Sharrack B., Hughes R. A. The Guy's Neurological Disability Scale (GNDS): a new disability measure for multiple sclerosis. Mult Scler. 1999 Aug;5(4):223–233. doi: 10.1177/135245859900500406. [DOI] [PubMed] [Google Scholar]
  12. Tubridy N., Behan P. O., Capildeo R., Chaudhuri A., Forbes R., Hawkins C. P., Hughes R. A., Palace J., Sharrack B., Swingler R. The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group. Neurology. 1999 Aug 11;53(3):466–472. doi: 10.1212/wnl.53.3.466. [DOI] [PubMed] [Google Scholar]

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