Vitamin E in the treatment of tardive dyskinesia.
S Akhtar, TR Jajor, S Kumar
Central Institute of Psychiatry, Ranchi, Bihar.
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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Akhtar S, Jajor T R, Kumar S. Vitamin E in the treatment of tardive dyskinesia. J Postgrad Med 1993;39:124-6
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Akhtar S, Jajor T R, Kumar S. Vitamin E in the treatment of tardive dyskinesia. J Postgrad Med [serial online] 1993 [cited 2020 Aug 4 ];39:124-6
Available from: http://www.jpgmonline.com/text.asp?1993/39/3/124/621
Tardive dyskinesia (TD) is a late appearing neurological syndrome associated with prolonged use of antipsychotic drugs. It is characterised by variable mixture of orofacial dyskinesia, chorea, athetosis, dystonia, tics, and facial grimacing. The reported prevalence of TD in chronic institutionalised patients and outpatients has varied between 0.5% to 65%, a mean value of about 20% can be estimated from different surveys. A number of hypotheses have been put forth to explain this syndrome. A recent hypothesis proposes that TD may be due to excessive production of free radicals in the basal ganglia, which in turn may damage the neuronal membrane through lipid peroxidation. Increased metabolism of dopamine is thought to be responsible for the increased production of free radicals. Vitamin E (alpha tocopherol) acts as free radical scavanger protecting against lipid peroxidation. Hence, vitamin E has been tried in the treatment of TD,. The present study was conducted to confirm the result of efficacy of vitamin E in TD.
The study was conducted at a referral centre of the eastern part of the country, which provides inpatient and outpatient psychiatric services. Inpatients suffering from TD while receiving the antipsychotic drugs were included in the study. The psychiatric diagnosis was based on research diagnosis criteria of Spitzer et al and diagnosis of TD was made by research diagnosis criteria of Schooler et al. Patients with any significant medical illness or any neurological illness were excluded from the study. Pregnant patients and those with a history of allergic reaction to vitamin E were also excluded.
All patients first entered a washout phase of two weeks. During this phase the patients were kept only on their respective antipsychotic and antiparkinsonian medication. All other medications including those aimed at treating TD were stopped. The medications were kept constant during the entire study period. A baseline (0 week) assessment was carried out. The patients were assessed on 'Brief psychiatric rating scale' (BPRS) and 'Tardive dyskinesia rating scale' (TDRS).
The patients were then randomly assigned in a double blind manner to receive either one capsule of 600mg vitamin E or an identical placebo. After the first week the dose was increased to two capsules per day. The dosage of vitamin E was based on earlier studies,. The total duration of treatment was four weeks. During this treatment phase the patients were rated weekly on TDRS by two trained psychiatric residents, (interrater reliability r=0.74), who rated the same patients on all occasions.
The results were analysed using 't' test and analysis of co- variance for basal difference between the two groups. Both, the investigators and raters were blind to the nature of therapy - active drug or placebotill the completion of analysis.
Thirty-two patients were enrolled in the study, of which 17 received vitamin E and 15 received placebo. As can be seen from [Table:1], there was no significant difference in the demographic profile of the two groups. [Table:2] shows the TDRS score of 2 groups at baseline and over the four weeks of treatment. The baseline (0 week) TDRS score was significantly higher in the vitamin E group as compared to placebo (p <0.05). Analysis of covariance was carried out. For this purpose the difference was adjusted as an integral part of the methodology of analysis. There was a gradual reduction in the TDRS score in both the groups. However, the adjusted TDRS score at the end of treatment (4 weeks) was significantly lower in the vitamin E group as compared to the placebo group (p = 0.03). There were no side- effects and dropouts in either group.
The results of the present study confirm the findings of earlier studies that administration of vitamin E in patients with TD causes a reduction in the TD ratings,. These two studies had smaller sample sizes, 15 and 10 patients respectively. We studied a comparatively larger sample of 32 patients. Moreover, the earlier studies had used 'Abnormal involuntary movement scale' (AIMS) to assess the progress of TD. Recently, Schooler made a comparison between AIMS and TDRS in assessing patients with TD. The author concluded that AIMS was suitable for screening purposes or routine clinical monitoring. However, where detailed assessment was required, TDRS was the instrument of choice. In our study, the patients were assessed on TDRS which is much more comprehensive and sensitive than AIMS. Vitamin E caused significantly greater reduction in the TD ratings after 4 weeks of treatment as compared to placebo.
Vitamin E is an anti-oxidant, which can remove free radicals. The beneficial effect of Vitamin E on TD may be due to its action on free radicals so that the toxic effect of free radicals on neurons is minimised. At present, the exact etiology of TD is not known and therefore, one can only postulate the mode of action of vitamin E.
The present study can be considered to be pilot study and the effect of vitamin E on TD should be confirmed in larger studies involving cross-over design and longer duration of treatment. Only thereafter one can recommend routine administration of Vitamin E alongwith antipsychotic drugs for minimising the problem of TD.
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