Natural treatments for tardive dyskinesia

DEFINITION: Treatment of the mostly uncontrollable bodily movements caused by side effects of first-generation antipsychotic drugs.

• PRINCIPAL PROPOSED NATURAL TREATMENT: Vitamin E
• OTHER PROPOSED NATURAL TREATMENTS: Branched-chain amino acids, choline, 2-dimethylaminoethanol, gamma-linolenic acid, lecithin, manganese, melatonin, niacin, vitamin B₆, vitamin C
• HERBS AND SUPPLEMENTS TO USE ONLY WITH CAUTION: Phenylalanine

Introduction

Tardive dyskinesia (TD) is a potentially permanent side effect of drugs used to control schizophrenia and other psychoses. The primary drugs associated with TD include Thorazone (chlorpromazine), Prolixin (fluphenazine), Haldol (haloperidol), Trilafon (perphenazine), and Compazine (prochlorperazine). 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 persons.

Several theories have been proposed for the development of TD. According to one theory, long-term treatment with antipsychotic drugs causes the brain to become overly sensitive to the neurotransmitter dopamine, resulting in abnormal movements. According to another theory, neurotransmitter imbalances 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 these theories may contain some truth. Discontinuing medication that caused TD usually does not help, and it may even worsen the dyskinesia and the underlying schizophrenia. Drugs such as L-dopa (Levodopa) and oxypertine (Equipertine) may improve TD but present their own significant risk of side effects. Second-generation antipsychotics, sometimes called atypical antipsychotics, are used more commonly in the twenty-first century and are less likely to cause TD. However, regardless of the generation of antipsychotics, some research indicates that between 20 and 50 percent of individuals taking these medications develop TD.

In 2017, the US Food and Drug Administration approved the first medications developed to treat TD—Ingrezza (valbenazine) and Austedo (deutetrabenazine). Preliminary research indicates vitamin E supplements are safe to use with these medications to improve outcomes, but longitudinal research is needed to determine the safety and efficacy of this combination.

Principal Proposed Natural Treatments

Vitamin E. Vitamin E is an antioxidant, a substance that works to neutralize free radicals in the body. As noted, 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, a minimum of five double-blind studies were published that indicated that vitamin E was beneficial in treating TD. Although most of these studies were small and lasted only four to twelve weeks, one thirty-six-week study enrolled forty people. 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 with a more recent onset.

However, in 1999, opinions 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 international units of vitamin E or placebo daily for a minimum of one year. In contrast to most of the previous studies, this trial failed to find vitamin E effective for decreasing TD symptoms.

Why is there a discrepancy between this study and the earlier ones? The researchers, some of whom had worked on the earlier, positive studies of vitamin E, worked 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 did not help. 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 effectiveness of vitamin E for a given person is simply not known. Research indicates that it is more effective in preventing TD and keeping symptoms from worsening than reversing the condition. Given the general safety of the vitamin, it may be worth discussing with one’s physician. A physician should approve the chosen dose of vitamin E, as research varies concerning the safe limits of these supplements.

Other Proposed Natural Treatments

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 that 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 the 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 with 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 small studies with mixed results. An open study of ten people found it helpful for TD, but a small double-blind study did not find any evidence of benefit.

The substance DMAE is better studied than these other cholinergic treatments for TD, but the preponderance of evidence suggests it is not effective. Of twelve 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.

Other natural treatments. A six-week, double-blind, placebo-controlled study of twenty-two people with schizophrenia and TD found that melatonin at a dose of ten mg per day significantly improved TD symptoms. One small pilot study suggested that vitamin B₆ may be helpful for the treatment of TD. In this four-week, double-blind, crossover trial of fifteen people, treatment with vitamin B₆ significantly improved TD symptoms compared with placebo. Benefits were seen beginning at one week of treatment. A follow-up study tested the benefits of vitamin B₆ used for twenty-six weeks in fifty people with tardive dyskinesia, and, once again, the supplement proved more effective than placebo.

Preliminary evidence suggested that BCAAs (branched-chain amino acids) might decrease TD symptoms. Other proposed treatments include niacin, manganese, clonazepam, and Ginkgo biloba, but 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 gamma-linolenic acid, found that it was not significantly more effective than placebo at reducing TD.

Prevention: High-dose vitamins? An informal twenty-year study of more than sixty thousand people treated with antipsychotic drugs plus high doses of vitamins found that only thirty-four of them (0.5 percent) 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 percent. These results were based on reports from eighty psychiatrists who routinely used high-dose vitamins along with drugs to treat people with schizophrenia. Vitamins typically included C, niacin, B₆, and E in varying dosages. However, because the study design was informal, it is impossible to draw firm conclusions from its results.

Some research indicates that exercise and stress relief activities, including yoga, qigong, tai chi, meditation, mindfulness training, and anaerobic exercises such as swimming, may improve symptoms of TD. Incorporating these activities offers a low-risk treatment option that may improve TD or improve overall health and well-being.

Herbs and Supplements to Use Only with Caution

There is some concern that the amino acid phenylalanine, present in many protein-rich foods, may worsen TD. In a double-blind study of eighteen people with schizophrenia, those who took phenylalanine supplements had more TD symptoms than those who took a placebo. Other herbs and supplements may interact adversely with drugs used to treat schizophrenia.

Bibliography

Bergland, Christopher. "Is Tardive Dyskinesia Reversible?" VerywellHealth, 20 Sept. 2024, www.verywellhealth.com/is-tardive-dyskinesia-reversible-5217232. Accessed 27 Sept. 2024.

Bhidayasiri, Roongroj, et al. “Updating the Recommendations for Treatment of Tardive Syndromes: A Systematic Review of New Evidence and Practical Treatment Algorithm.” Journal of the Neurological Sciences, vol. 389, 2018, pp. 67-75. doi:10.1016/j.jns.2018.02.010. Accessed 27 Sept. 2024.

Lerner, V., et al. “Vitamin B₆ Treatment for Tardive Dyskinesia.” Journal of Clinical Psychiatry, vol. 68, 2007, pp. 1648-54.

"Tardive Dyskinesia." Cleveland Clinic, 10 July 2024, my.clevelandclinic.org/health/articles/6125-tardive-dyskinesia. Accessed 27 Sept. 2024.

Watson, Stephanie. "9 Ways to Feel More in Control of Your Movements with Tardive Dyskinesia." Healthline, 18 Jan. 2024, www.healthline.com/health/tardive-dyskinesia-feel-more-control. Accessed 27 Sept. 2024.