Tardive dyskinesia (TD) is a potentially permanent side effect of drugs used to control
and other psychoses. This late-developing (tardy, or tardive) complication consists of annoying, mostly uncontrollable movements (dyskinesias). Typical symptoms include repetitive sucking or blinking, slow twisting of the hands, or other movements of the face and limbs. TD can cause tremendous social embarrassment to particularly vulnerable individuals.
Several different theories have been proposed for the development of TD.1
According to one, long-term treatment with antipsychotic drugs causes the brain to become overly sensitive to the neurotransmitter dopamine, resulting in abnormal movements. According to another, imbalances among different neurotransmitters can cause or aggravate symptoms. In a third theory, TD may arise in part from damage to the brain caused by free radicals generated by schizophrenia treatments. All of these theories may contain some truth.
Unfortunately, discontinuing medication that caused TD usually doesn’t help, and may even worsen the dyskinesia as well as the underlying schizophrenia.2
Drugs such as L-dopa and oxypertine may improve TD but present their own significant risk of side effects. Fortunately, newer medications for schizophrenia that are less likely to cause TD have been developed in recent years.
antioxidant, a substance that works to neutralize free radicals in the body. As noted above, it has been suggested that free-radicals may play a role in TD. If this is true, it makes sense that vitamin E might help prevent or treat the condition.
Between 1987 and 1998, at least five
double-blind studies were published which indicated that vitamin E was beneficial in treating TD.3,4 Although most of these studies were small and lasted only 4 to 12 weeks, one 36-week study enrolled 40 people.5 Three small double-blind studies reported that vitamin E was not helpful.6,7 Nonetheless, a statistical analysis of the double-blind studies done before 1999 found good evidence that vitamin E was more effective than placebo.8 Most studies found that vitamin E worked best for TD of more recent onset.9
However, in 1999, the picture on vitamin E changed with the publication of one more study—the largest and longest to date.10
This double-blind study included 107 participants from nine different research sites who took 1,600 IU of vitamin E or placebo daily for at least 1 year. In contrast to most of the previous studies, this trial failed to find vitamin E effective for decreasing TD symptoms.
Why the discrepancy between this study and the earlier ones? The researchers, some of whom had worked on the earlier, positive studies of vitamin E, were at pains to develop an answer.11,12
They proposed a number of possible explanations. One was that the earlier studies were too small or too short to be accurate, and that vitamin E really didn’t help at all. Another was the most complicated: that vitamin E might help only a subgroup of people who had TD—those with milder TD symptoms of more recent onset—and that fewer of these people had participated in the latest study. They also pointed to changes in schizophrenia treatment since the last study was done, including the growing use of antipsychotic medications that do not cause TD.
The bottom line:
The effectiveness of vitamin E for a given person is simply not known. Given the lack of other good treatments for TD, and the general safety of the vitamin, it may be worth discussing with your physician.
For more information, including dosage and safety issues, see the full
According to one theory, TD symptoms may be caused or aggravated by an imbalance between two neurotransmitters, dopamine and acetylcholine. The nutrient
and several related substances—
lecithin, CDP-choline, and
—have been suggested as possible treatments, with the goal of increasing the amount of acetylcholine the body produces. Lecithin and CDP-choline are broken down by the body to produce choline, and choline provides one of the building blocks for acetylcholine. DMAE (2-dimethylaminoethanol, sometimes called deanol) may also increase production of acetylcholine, although this has been questioned.
Although a variety of small studies have been conducted on these substances, evidence for their effectiveness is mixed at best. Three small double-blind studies of lecithin had conflicting results: one found lecithin more helpful than placebo,20 one found it to be barely superior,21 and one found it no better than placebo.22 In two small double-blind trials of choline itself, some people experienced decreased TD symptoms on choline compared to placebo but other people did not, and several people grew worse.23,24
CDP-choline, a natural substance closely related to choline, has also been the subject of a couple of small studies with mixed results. An
open study of 10 people found it helpful for TD,25 but a tiny double-blind study did not find any evidence of benefit.26
The substance DMAE is better studied than these other cholinergic treatments for TD—but the preponderance of evidence suggests it is not effective. Of 12 double-blind studies reviewed, only one found DMAE to be significantly effective when compared with placebo.29 A meta-analysis of proposed treatments for TD found DMAE to be no more effective than placebo.30
A 6-week double-blind, placebo-controlled study of 22 individuals with schizophrenia and TD found that
melatonin at a dose of 10mg/day significantly improved TD symptoms.44
One small pilot study suggests that
may be helpful for the treatment of TD. In this 4-week, double-blind crossover trial of 15 people, treatment with vitamin B
6 significantly improved TD symptoms as compared to placebo.31
Benefits were seen beginning at 1 week of treatment.
A follow-up study tested the benefits of vitamin B
6 used over a period of 26 weeks in 50 people with tardive dyskinesia, and, once again, the supplement proved more effective than placebo.45
Preliminary evidence suggests that
BCAAs (branched-chain amino acids) might decrease TD symptoms.32
Other proposed treatments include
but so far evidence for their effectiveness is weak at best. Two double-blind trials of evening primrose oil, which contains large amounts of the essential fatty acid
GLA (gamma-linolenic acid), found that it was not significantly more effective than placebo at reducing TD.37
ginkgo biloba has also been investigated as a treatment for tardive dyskinesia. One randomized study involving 157 subjects found that ginkgo (240 mg/day for 12 weeks) was more helpful than placebo in reducing tardive dyskinesia symptoms in people with schizophrenia.46
An informal 20-year study of more than 60,000 people treated with antipsychotic drugs plus high doses of vitamins found that only 34 of them (0.5%) developed TD.38 This is far fewer than might be expected: the estimated rate of TD among people treated with traditional antipsychotic medications is 20 to 25%.39
These results were based on reports from 80 psychiatrists who routinely used high-dose vitamins along with drugs to treat people with schizophrenia. Vitamins typically included
vitamin B6, and
in varying dosages. However, because the study design was very informal, it is not possible to draw firm conclusions from its results.
There is some concern that the amino acid
phenylalanine, present in many protein-rich foods, may worsen TD.40,41,42 In a double-blind study of 18 people with schizophrenia, those who took phenylalanine supplements had more TD symptoms than those who took placebo.43
Other herbs and supplements may interact adversely with drugs used to treat
schizophrenia. For more information, see the individual drug article in the Drug Interactions
section of this database.
Rotrosen, J, Adler L, Lohr J, et al. Antioxidant treatment of tardive dyskinesia.
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Alphs L, Davis JM. Noncatecholaminergic treatments of tardive dyskinesia.
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Elkashef AM, Wyatt RJ. Tardive dyskinesia: possible involvement of free radicals and treatment with vitamin E.
Adler LA, Edson R, Lavori P, et al. Long-term treatment effects of vitamin E for tardive dyskinesia.
Shriqui CL, Bradwejn J, Annable L, et al. Vitamin E in the treatment of tardive dyskinesia: a double-blind, placebo-controlled study.
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Soares, KV, BcGrath JJ. The treatment of tardive dyskinesia—a systematic review and meta-analysis.
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Adler LA, Rotrosen J, Edson R, et al. Vitamin E treatment for tardive dyskinesia.
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Joe SH, et al. Effect of lecithin on tardive dyskinesia.
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Gelenberg AJ, Dorer DJ, Wojcik JD, et al. A crossover study of lecithin treatment of tardive dyskinesia
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Domino EF, May WW, Demetriou S, et al. Lack of clinically significant improvement of patients with tardive dyskinesia following phosphatidylcholine therapy.
Growdon JH, Hirsch MJ, Wurtman RJ, et al. Oral choline administration to patients with tardive dyskinesia
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Nasrallah HA, Dunner FJ, Smith RE, et al. Variable clinical response to choline in tardive dyskinesia.
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Arranz J, Ganoza C. Treatment of chronic dyskinesia with CDP-choline.
Gelenberg AJ, Wojcik J, Falk WE, et al. CDP-choline for the treatment of tardive dyskinesia: a small negative series.
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Casey DE, Denney D. Letter: Dimethylaminoethanol in tardive dyskinesia.
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Lerner V, Miodownik C, Kaptsan A, et al. Vitamin B
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Richardson MA, Berans ML, Weber JB, et al. Branched chain amino acids decrease tardive dyskinesia symptoms.
Kunin RA. Manganese and niacin in the treatment of drug-induced tardive dyskinesias.
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Gardos G, Cole JO, Matthews JD, et al. The acute effects of a loading dose of phenylalanine in unipolar depressed patients with and without tardive dyskinesia.
Mosnik DM, Spring B, Rogers K, et al. Tardive dyskinesia exacerbated after ingestion of phenylalanine by schizophrenic patients.
Shamir E, Barak Y, Shalman I, et al. Melatonin treatment for tardive dyskinesia: a double-blind, placebo-controlled, crossover study.
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Lerner V, Miodownik C, Kaptsan A, et al. Vitamin B
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2010 Sep 21. [Epub ahead of print]
Last reviewed September 2014 by EBSCO CAM Review Board
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