Tardive dyskinesia (TD) is a potentially permanent side effect of drugs used
to control schizophrenia 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.
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. 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.
Treatment
Principal Proposed Treatments for Tardive Dyskinesia:
Vitamin E
Vitamin E, an antioxidant, works to neutralize free radicals in the body. If the
free-radical theory of TD is accurate, it makes sense that vitamin E might help
prevent or treat the condition. In the early 1990s, scientific evidence began to
gather suggesting that vitamin E might, indeed, be a safe and effective TD
treatment. Studies were persuasive enough that many conventional physicians
began prescribing vitamin E for TD. However, the latest, largest, and
longest-term study of vitamin E casts doubt on the effectiveness of this remedy.
What Is the Scientific Evidence for Vitamin E?
Between 1987 and 1998, at least five double-blind studies were published which
indicated that vitamin E was beneficial in treating TD. Although most of these
studies were small and lasted only 4 to 12 weeks, one 36-week study enrolled 40
individuals. Three small double-blind studies reported that vitamin E was not
helpful. Nonetheless, a statistical analysis of the double-blind studies done
before 1999 found good evidence that vitamin E was more effective than placebo.
Most studies found that vitamin E worked best for TD of more recent onset.
However, in 1999, the picture on vitamin E changed with the publication of one
more study—the largest and longest to date. 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. 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 individual 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 vitamin E
article.
Other Proposed Treatments for Tardive Dyskinesia:
Choline and Related Substances
According to one theory, TD symptoms may be caused or aggravated by an imbalance
between two neurotransmitters, dopamine and acetylcholine. The nutrient choline
and several related substances—lecithin, CDP-choline, and DMAE—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, one found it to be barely superior, and one found it no better
than placebo. 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.
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, but a tiny double-blind study did not find any
evidence of benefit.
Of the various so-called cholinergic treatments for TD, the best studied is DMAE—but
the preponderance of evidence suggests it is not effective. Although some case
reports and open studies seemed to suggest that DMAE might decrease TD symptoms,
properly designed studies using double-blind methods and placebo-control groups
have not borne this out. Of 12 double-blind studies reviewed, only one found
DMAE to be significantly effective when compared with placebo. A meta-analysis
of proposed treatments for TD found DMAE to be no more effective than placebo.
It seems likely, though not entirely certain, that the benefits seen in open
studies and individual cases resulted from the placebo effect. However, it is
also possible that particular individuals respond well to DMAE—or to other
cholinergic treatments—even if most dont.
Other Natural Treatments
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.
A recent pilot study suggests that vitamin B6 may be helpful for the treatment
of TD. In this 4-week double-blind crossover trial of 15 individuals, treatment
with vitamin B6 significantly improved TD symptoms as compared to placebo.
Benefits were seen after 1 week of treatment. For more information, including
dosage and safety issues, see the full vitamin B6 article.
Preliminary evidence suggests that BCAAs (branched-chain amino acids) might
decrease TD symptoms. Other proposed treatments include niacin,manganese, and
essential fatty acids, but so far evidence for their effectiveness is
contradictory or weak. 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.
Prevention: High-Dose Vitamins?
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. This is far fewer than might be expected: the estimated rate of TD among
people treated with traditional antipsychotic medications is 20 to 25%. 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 C, niacin, B6, and E in varying dosages. However, because the
study design was very informal, it is not possible to draw firm conclusions from
its results.
Phenylalanine: A Supplement to Avoid
There is some concern that the amino acid phenylalanine, present in many
protein-rich foods, may worsen TD. In a double-blind study of 18 people with
schizophrenia, those who took phenylalanine supplements had more TD symptoms
than those who took placebo.