J Clin Psychiatry 57 (4): 167-173 (Apr 1996)
A double-blind placebo-controlled study of vitamin E treatment of tardive
dyskinesia.
Lohr JB, Caligiuri MP
San Diego VA Medical Center, CA 92161, USA.
BACKGROUND: This study was designed to determine if vitamin E is effective
in reducing the severity of abnormal movements in patients with tardive
dyskinesia (TD). METHOD: Thirty-five patients completed a double-blind
placebo-controlled parallel-group study of vitamin E. Seventeen of the
patients were randomly assigned to receive 800 IU b.i.d. of vitamin E and
18 were assigned to placebo for 2 months. Twenty-nine patients had a
diagnosis of schizophrenia and 6 of mood disorder. Patients were assessed
using modified versions of the Abnormal Involuntary Movement Scale
(mAIMS), Simpson-Angus Scale for extrapyramidal side effects, and Brief
Psychiatric Rating Scale. Additionally, a subgroup of 23 patients were
assessed using instrumental measurements of dyskinesia. RESULTS: There
was a significant reduction of dyskinesia in the vitamin E group, but not
the placebo group, on both the mAIMS and the instrumental assessments.
The overall reduction in mAIMS in the active group was 24%, with 5 (29%)
of 17 patients demonstrating greater than 33% reduction in score. There
was a greater reduction in mean mAIMS score (35%) with vitamin E in the
subgroup of patients with TD for 5 years or less compared with the
reduction (11%) in patients with TD for greater than 5 years. No change
was observed in parkinsonism. In the patients with schizophrenia, there
was a reduction in positive symptoms after vitamin E. CONCLUSION: Vitamin
E appears to be effective in reducing the severity of TD, especially in
patients who have had TD for 5 years or less.
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Br J Psychiatry 167 (5): 610-617 (Nov 1995)
The Nithsdale Schizophrenia Surveys. XIV: Plasma lipid peroxide and serum
vitamin E levels in patients with and without tardive dyskinesia, and in
normal subjects.
McCreadie RG, MacDonald E, Wiles D, Campbell G, Paterson JR
Crichton Royal Hospital, Dumfries.
BACKGROUND. Tardive dyskinesia (TD) may be mediated through free radical
damage to neurons. Plasma lipid peroxide levels are a measure of radical
damage to fats. Vitamin E is a free radical scavenger. METHOD. One hundred
and twenty-eight schizophrenic patients were examined for TD using the
Abnormal Involuntary Movements Scale. Blood samples were taken to measure
plasma lipid peroxide, serum vitamin E and cholesterol, and vitamin
E:cholesterol ratios. Twenty-four patients were also examined in October
1993, January 1994, and April 1994. Biochemical results were compared in
81 patients and 79 normal subjects. RESULTS. Patients with and without TD
did not differ in median plasma lipid peroxide and serum vitamin E
levels, or vitamin E:cholesterol ratios. Correlations between seasonal
change scores in TD and biochemical measurements were low. Lipid peroxide
levels were higher and vitamin E:cholesterol ratios lower in patients
than in normal subjects. Vitamin E levels were lowest in in-patients and
in those living in supported accommodation. CONCLUSIONS. The results do
not support the hypothesis that TD is mediated through free radical
damage to neurons, but suggest increased free radical activity in
schizophrenia.
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Am J Psychiatry 151 (6): 925-926 (Jun 1994)
Effectiveness of vitamin E for treatment of long-term tardive dyskinesia.
Dabiri LM, Pasta D, Darby JK, Mosbacher D
Department of Psychiatry, San Mateo County Mental Health Services, Calif.
Eleven patients with tardive dyskinesia were treated in a double-blind
study of vitamin E or placebo for 12 weeks. Abnormal Involuntary Movement
Scale (AIMS) ratings were performed before and after treatment. Patients
receiving vitamin E showed a significant reduction in their AIMS scale
score, but patients receiving placebo showed no significant change.
Vitamin E had a helpful effect even for patients whose tardive dyskinesia
was mild and long-term.
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Am J Psychiatry 150 (9): 1405-1407 (Sep 1993)
Vitamin E treatment of tardive dyskinesia.
Adler LA, Peselow E, Rotrosen J, Duncan E, Lee M, Rosenthal M, Angrist B
Psychiatry Service, New York Department of Veterans Affairs Medical Center,
NY 10010.
OBJECTIVE: The authors studied the effects of vitamin E treatment of tardive
dyskinesia; earlier studies have produced contradictory results. METHOD:
Twenty-eight patients with tardive dyskinesia were treated in a
double-blind, parallel-group comparison study of 8-12 weeks of treatment
with vitamin E (1600 IU/day) or matching placebo capsules. RESULTS: The
Abnormal Involuntary Movement Scale scores of the patients treated with
vitamin E improved significantly compared to the scores of the patients
given placebo. CONCLUSIONS: These results support earlier findings of the
efficacy of vitamin E in treating tardive dyskinesia.
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Pharm World Sci 15 (4): 146-150 (Aug 20 1993)
Vitamin E in extrapyramidal disorders.
Bischot L, Van den Brink G, Porsius AJ
Department of Pharmacotherapy, Faculty of Pharmacy, Utrecht University, The
Netherlands.
In this article the effect of vitamin E on two extrapyramidal disorders,
tardive dyskinesia and Parkinson's disease, is reviewed. After a brief
description of the symptoms, the current hypotheses for the pathogenesis
of these diseases are described. A summary of the clinical research that
has been done to establish the effectiveness of vitamin E is given. In
tardive dyskinesia four clinical trials (double-blind,
placebo-controlled) showed improvement in the symptoms with vitamin E in
doses of up to 1,600 IU/day. Preliminary studies concerning Parkinson's
disease suggested that vitamin E (2,000 IU/day) probably cannot prevent
the development of the disease. It was suggested that vitamin E is able
to slow the progression of the illness. The results from a large
double-blind, placebo-controlled clinical trial, however, did not show
any beneficial effect of vitamin E in Parkinson's disease.
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J Postgrad Med 39 (3): 124-126 (Jul 1993)
Vitamin E in the treatment of tardive dyskinesia.
Akhtar S, Jajor TR, Kumar S
Central Institute of Psychiatry, Ranchi, Bihar.
In a double-blind placebo controlled trial, the efficacy of Vitamin E in
the treatment of tardive dyskinesia (TD) was studied in 32 patients. After
a two week wash-out phase a baseline (0 week) TD rating was assessed on the
tardive dyskinesia rating scale (TDRS). Subsequently, the patients
entered a four week treatment phase during which 17 patients received
capsules of vitamin E (600 mg) and 15 patients received identical placebo
capsules. In the first week the patients received 1 capsule daily which
was then increased to two capsules per day from the second to the fourth
week. All patients were rated on the TDRS at the end of each week. The
baseline TDRS score in the vitamin E group was significantly higher than
the placebo group. This was hence adjusted and the results were then
subjected to analysis of co- variance. The TDRS score after four weeks
treatment was significantly lower in the vitamin E group as compared to
the placebo group (p = 0.03).
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J Neural Transm Gen Sect 92 (2-3): 197-201 (1993)
Vitamin E attenuates the development of haloperidol-induced dopaminergic
hypersensitivity in rats: possible implications for tardive dyskinesia.
Gattaz WF, Emrich A, Behrens S
Unit Neurobiology of Functional Psychoses, Central Institute of Mental
Health, Mannheim, Federal Republic of Germany.
Chronic haloperidol treatment in rats results in behavioural supersensi-
tivity to dopamine agonists. This mechanism has been suggested as a possible
animal model for tardive dyskinesia. In the present study the
simultaneous administration of vitamin E to chronic haloperidol treatment
in rats prevented the development of behavioural supersensitivity to
apomorphine. This finding suggest that the concomitant administration of
vitamin E to neuroleptics might prevent the development of tardive
dyskinesia in humans.
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Int Clin Psychopharmacol 8 (3): 151-153 (1993)
Tardive dyskinesia, lipid peroxidation, and sustained amelioration with
vitamin E treatment.
Peet M, Laugharne J, Rangarajan N, Reynolds GP
Academic Department of Psychiatry, Northern General Hospital, Sheffield, UK.
Plasma levels of thiobarbituric acid reactive substances (TBARS) were
measured as an indicator of lipid peroxidation, in 14 patients suffering
from tardive dyskinesia (TD). There was a highly significant positive
correlation between plasma TBARS (both basal and iron stimulated) and
severity of TD. Patients were then treated for 1 month with the free
radical scavenger vitamin E (1200 i.u. daily). Following vitamin E
treatment, there was a clinically and statistically significant
amelioration of TD, and this improvement was maintained at follow-up 7-13
months later. There was no consistent or significant change in plasma
TBARS levels related to treatment with vitamin E.
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Psychopharmacol Bull 29 (3): 371-374 (1993)
Vitamin E in tardive dyskinesia: time course of effect after placebo
substitution.
Adler LA, Peselow E, Duncan E, Rosenthal M, Angrist B
Psychiatry Service, New York Department of Veterans Affairs Medical Center
(DVAMC), NY 10010.
Alpha-tocopherol (vitamin E) has been found to be effective in the treatment
of tardive dyskinesia (TD). Studies to date have been short in duration and
have not found long-term carryover effects of vitamin E. The present
study examined the persistence of the effects of vitamin E after longer
term (36-week) treatment was discontinued. Vitamin E significantly
improved TD over this period. However, the effects of vitamin E persisted
so that TD scores approached baseline only after 12 weeks of placebo
substitution.
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Hosp Community Psychiatry 44 (1): 25-34 (Jan 1993)
Progress in the treatment of tardive dyskinesia: theory and practice
Feltner DE, Hertzman M
National Institute of Mental Health, St. Elizabeths Hospital, Washington,
D.C. 20032.
OBJECTIVE: About 20 percent of patients receiving long-term treatment with
neuroleptic medications develop tardive dyskinesia. A 1988 review of
treatment studies for the disorder found that 40 percent of patients
showed at least 50 percent improvement in symptoms. This paper reviews
studies published since 1984, including those not reviewed in 1988, to
learn whether new or improved treatments for the disorder have been
developed. METHODS: Twenty-five open, blind, or double-blind studies
(with a minimum of five patients) published between 1984 and May 1992
were examined. The studies involved neuroleptics, including clozapine,
dopaminergic and dopamine-depleting agents, GABAergic drugs, vitamin E,
calcium channel blockers, and adrenergic drugs. RESULTS AND CONCLUSIONS:
Overall, only 26 percent of patients who participated in the studies
reviewed had a 50 percent or greater reduction in symptoms. The authors
conclude that treatment of tardive dyskinesia remains a highly individual
process and recommend that future studies be more carefully designed.
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Am J Psychiatry 149 (6): 773-777 (June 1992)
Treatment of tardive dyskinesia with vitamin E
Egan MF, Hyde TM, Albers GW, Elkashef A, Alexander RC, Reeve A, Blum A,
Saenz RE, Wyatt RJ
Neuropsychiatry Branch, NIMH, Washington, D.C. 20032.
OBJECTIVE: Vitamin E (alpha-tocopherol), a free-radical scavenger, has been
reported to improve symptoms of tardive dyskinesia. The authors attempted
to replicate this finding under more controlled conditions in a larger
study group. METHOD: Fifteen inpatients and six outpatients with tardive
dyskinesia received up to 1600 IU/day of vitamin E for 6 weeks in a
double-blind, placebo-controlled crossover study. Abnormal Involuntary
Movement Scale (AIMS) examinations of these patients were videotaped and
rated independently by two trained raters. Levels of neuroleptic
medication and vitamin E were measured during both treatment periods.
Eighteen patients who demonstrated high blood levels of vitamin E were
included in the data analysis. RESULTS: Vitamin E levels were
significantly higher while the patients were receiving vitamin E than
while they were receiving placebo. For all 18 patients, there were no
significant differences between AIMS scores after receiving vitamin E and
AIMS scores after receiving placebo. In agreement with previous studies,
however, the nine patients who had had tardive dyskinesia for 5 years or
less had significantly lower AIMS scores after receiving vitamin E than
after receiving placebo. There were no changes in neuroleptic levels
during vitamin E treatment. CONCLUSIONS: Vitamin E had a minor beneficial
effect on tardive dyskinesia ratings in a selected group of patients who
had had tardive dyskinesia for 5 years or less. This effect was not due
to an increase in blood levels of neuroleptic medications.
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Am J Psychiatry 149 (3): 391-393 (Mar 1992)
Vitamin E in the treatment of tardive dyskinesia: a double-blind
placebo-controlled study.
Shriqui CL, Bradwejn J, Annable L, Jones BD
Centre de recherche Universite Laval Robert-Giffard, Department of
Psychiatry, Laval University, Beauport, Quebec, Canada.
The authors compared vitamin E with placebo in a double-blind randomized
crossover study of 27 patients with tardive dyskinesia. Each treatment
period lasted for 6 weeks. Vitamin E showed no differences from placebo
in the treatment of tardive dyskinesia.
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Brain Res Bull 26 (2): 251-258 (Feb 1991)
Partial attenuation of chronic fluphenazine-induced changes in regional
monoamine metabolism by D-alpha-tocopherol in rat brain.
Jackson-Lewis V, Przedborski S, Kostic V, Suber F, Fahn S, Cadet JL
Department of Neurology, Columbia-Presbyterian Medical Center, New York, NY
10032.
Recent evidence has suggested a role for free radicals in tardive dys-
kinesia. We, therefore, investigated the effects of chronic administration
of fluphenazine decanoate (FLU) and/or vitamin E (VIT E) on regional
monoamine metabolism in rat brain. Chronic FLU caused significant
increases in dopamine (DA) in nucleus accumbens and brainstem,
significant decreases in dihydroxyphenylacetic acid (DOPAC) in frontal
cortex, nucleus accumbens and hippocampus and significant decreases in
homovanillic acid (HVA) in nucleus accumbens, caudate-putamen and
brainstem. Coadministration of FLU and VIT E normalized HVA in
caudate-putamen, nucleus accumbens and brainstem as well as DOPAC in
nucleus accumbens and hippocampus. Chronic FLU caused significant
increases in norepinephrine (NE) levels in all regions studied. VIT E
attenuated FLU-induced increases in NE levels in nucleus accumbens and
hippocampus. Significant increases in serotonin (5-HT) levels occurred in
nucleus accumbens and hippocampus whereas significant decreases in
5-hydroxyindole-acetic acid (5-HIAA) occurred in all brain regions after
chronic FLU. Coadministration of VIT E attenuated the changes observed in
hippocampal 5-HIAA but potentiated the FLU-induced increases in 5-HT in
this region. Our data suggest that VIT E can attenuate some of the
FLU-induced changes in monoamine metabolism. Results are discussed in
relation to possible involvement of free radicals in monoamine metabolism
during chronic neuroleptic use.
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Am J Psychiatry 147 (4): 505-506 (Apr 1990)
Vitamin E in the treatment of tardive dyskinesia
Elkashef AM, Ruskin PE, Bacher N, Barrett D
Department of Psychiatry, Baltimore VA Medical Center, MD.
Eight subjects with persistent tardive dyskinesia were treated with vitamin
E and placebo in a randomized, double-blind crossover study. Their mean
score on the Abnormal Involuntary Movement Scale (AIMS) was significantly
lower after treatment with vitamin E than after placebo administration.
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Int J Vitam Nutr Res Suppl 30: 56-68 (1989)
Use and safety of elevated dosages of vitamin E in adults.
Machlin LJ
Subjects with a variety of enteropathies, hemolytic anemias, acute
respiratory distress syndrome, hepatitis, Gaucher's disease as well as
those on TPN and hemodialysis, often have low ("deficient") blood levels of
vitamin E. A deficiency of vitamin E can be manifested by accelerated red
blood cell destruction and neuromuscular deficit. Supplementation of these
patients may be advisable. Neurological dysfunction has been observed in
adults. with prolonged vitamin E deficiency resulting from lipid malabsorp-
tion. Long-term treatment with high doses of vitamin E results in
improvement. Administration of 800 IU/day of vitamin E to subjects with
G6PD deficiency, sickle-cell anemia and beta-thalassemia has resulted in
improvement of hematological parameters. Supplementation with 300 IU/day
for 3-6 months has resulted in improved walking distances and improved
blood flow in patients with intermittent claudication. In a limited
number of controlled studies, 300-600 IU/day resulted in improvement in
premenstrual syndrome, tardive dyskinesia and also arthritis.
Epidemiological studies suggest that high levels of serum vitamin E are
associated with lower risk of certain cancers, cardiovascular disease and
infections. In some cases the high levels are difficult to obtain by diet
alone. High levels of vitamin E are contraindicated in subjects who are
receiving vitamin K antagonists as anticoagulant therapy. Except for this
interaction with vitamin K, there are no specific side effects associated
with high doses of vitamin E. Thus, there are various reasons for
supplementations with vitamin E and, with the exception noted, the risk
of such supplementation is very low.
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Schizophr Bull 14 (2): 291-296 (1988)
Vitamin E in the treatment of tardive dyskinesia: the possible involvement
of free radical mechanisms.
Lohr JB, Cadet JL, Lohr MA, Larson L, Wasli E, Wade L, Hylton R, Vidoni C,
Jeste DV, Wyatt RJ
Department of Psychiatry, San Diego Veterans Administration Medical Center,
La Jolla, CA 92161.
One of the major problems associated with long-term neuroleptic treatment
is persistent tardive dyskinesia (TD), for which there is no satisfactory
treatment. We have recently proposed that some cases of TD are associated
with neuronal dysfunction resulting from excess free radical production
occurring during catecholamine metabolism. We therefore decided to assess
the efficacy of a powerful free radical scavenging agent,
alpha-tocopherol (vitamin E), on the clinical signs of TD. We treated 15
patients with persistent TD with alpha-tocopherol and matched placebo in
a randomized crossover design. Patients demonstrated a significant
overall reduction in scores on the Abnormal Involuntary Movements Scale
(AIMS) after treatment with alpha-tocopherol, but not after placebo. The
mean reduction in the AIMS score with alpha-tocopherol was 43 percent,
with seven patients showing a greater than 50 percent reduction in their
dyskinesia. There was also a trend for a decrease in scores on the Brief
Psychiatric Rating Scale, but no change was observed in scores on the
Simpson-Angus Scale for Extrapyramidal Side Effects. Our findings are
consistent with the possibility that alpha-tocopherol is beneficial in
the treatment of some patients with TD, but further research is necessary
to establish the efficacy of this agent.
