Survival in patients with amyotrophic lateral sclerosis, treated with an array of antioxidants.
Between 1983 and 1988 we treated 36 patients with sporadic amyotrophic lateral sclerosis (ALS) by an array of antioxidants and added other drugs to the regimen whenever a patient reported deterioration. Our customary prescription sequence was N-acetylcysteine (NAC); vitamins C and E; N-acetylmethionine (NAM); and dithiothreitol (DTT) or its isomer dithioerythritol (DTE). Patients with a history of heavy exposure to metal were also given meso 2,3-dimercaptosuccinic acid (DMSA). NAC, NAM, DTT, and DTE were administered by subcutaneous injection or by mouth or by both routes, the other vitamins and DMSA by mouth alone. The hospital pharmacy supplied NAC and NAM injections fluid as 100 ml bottles of 5.0 and 5.85% solutions, respectively. DTT was delivered in special double-walled capsules of 200 mg. DTT/DTE injection fluid was added to the NAC and NAM bottles, the final DTT/DTE concentrations never exceeding 0.5%. DMSA was provided in 250 mg capsules. All of the 36 patients used NAC and DTT/DTE; 29 also used vitamins C and E; 21 also used NAM; and 7 also used DMSA, DMSA, NAM, vitamins C and E were tolerated well. In many patients, DTT, DTE, NAC and NAM induced pain, redness and swelling at the injection sites in that order of decreasing frequency. DTT and DTE did often and NAC did sometimes cause gastric pain, nausea and other abdominal discomfort. Comparison of survival in the treated group and in a cohort of untreated historical controls, disclosed a median survival of 3.4 years (95% confidence interval: 3.0-4.2) in the treated and of 2.8 (95% confidence interval 2.2-3.1) years in the control patients. This difference may be explained by self-selection of our highly motivated treated group and by its initial survival of diagnosis for an average of 8.5 months before onset of treatment. We conclude that antioxidants neither seem to harm ALS patients, nor do they seem to prolong survival.
Department of Pharmacy E-0, University of Amsterdam, UK.
A
A
Vyth
J G
JG
Timmer
P M
PM
Bossuyt
E S
ES
Louwerse
J M
JM
de Jong
D000111:Acetylcysteine / Q000008:administration & dosage; D000284:Administration, Oral; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000401:mortality*; D000975:Antioxidants / Q000008:administration & dosage*; D002214:Capsules; D002614:Chelating Agents / Q000008:administration & dosage; D004226:Dithioerythritol / Q000008:administration & dosage; D004229:Dithiothreitol / Q000008:administration & dosage; D016166:Free Radical Scavengers / Q000008:administration & dosage; D005750:Gastric Juice / Q000737:chemistry; D006801:Humans; D007279:Injections, Subcutaneous; D008715:Methionine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004113:Succimer / Q000008:administration & dosage; D013439:Sulfhydryl Reagents / Q000008:administration & dosage; D016019:Survival Analysis
D000975:Antioxidants; D002214:Capsules; D002614:Chelating Agents; D016166:Free Radical Scavengers; D013439:Sulfhydryl Reagents; D004226:Dithioerythritol; C006379:N-acetylmethionine; D008715:Methionine; D004113:Succimer; D004229:Dithiothreitol; D000111:Acetylcysteine