Tardive dyskinesia (TD) is an involuntary neurological movement disorder caused by the use of dopamine receptor blocking drugs that are prescribed to treat certain psychiatric or gastrointestinal conditions such as;
As well as;
SSRIs: fluoxetine, sertraline
TCAs: amitriptyline, amitriptyline-perphenazine, amoxapine, doxepin, imipramine
Stimulants, have been associated with TD. Stimulants include caffeine, nicotine, guarana, ginseng, legal amphetamines, ephedrine, and illicit amphetamine and methamphetamine.
More likely to get it if you;
Are a woman who has gone through menopause
Are over age 55
Abuse alcohol or drugs
Are African-American or Asian-American
There are two FDA-approved medicines to treat tardive dyskinesia:
⦁ Valbenazine (Ingrezza)
⦁ Deutetrabenazine (Austedo)
Both of these medicines work in similar ways to regulate the amount of dopamine flow in brain areas that control certain kinds of movements. Both of these medicines can sometimes cause drowsiness.
Vitamin B6 (Note - Vitamin B5 has a half life of 25 days and is easy to develop Vitamin B6 toxicity with supplements)
Studies are ongoing to determine possible new drug therapies for the treatment of tardive dyskinesia. Choline, lithium, bromocriptine, baclofen, methyldopa, valproate, clonidine, propranolol, amantadine, clonazepam, and nifedipine have occasionally been helpful but in most cases do not improve dyskinesia. Tetrabenazine is often useful for symptomatic treatment of tardive dyskinesia and is currently available for use in the US. However, it carries the risk of causing or aggravating depression. Other experimental drugs are being tested to reduce or eliminate the symptoms of tardive dyskinesia.
Other therapeutic agents for which there is some anecdotal support include, levodopa (see carbidopa/levodopa), benzodiazepines, botulinum toxin, reserpine, tetrabenazine, and dopamine-depleting agents. Ondansetron, a selective 5-hydroxytryptamine-3 antagonist, has helped some individuals with TD. Discontinuance of anticholinergic therapy may relieve TD. A controversial strategy for treating TD is to continue or increase the dose of the dopamine antagonist.
Medication-Induced Tardive Dyskinesia: A Review and Update (2017) (excellent document to read)
Medications and Supplements Used to Treat Tardive Dyskinesia
A number of medications and supplements have been identified that ameliorate TD symptoms.
Cholinergic agents are used as muscle stimulants to diagnose myasthenia gravis and to treat glaucoma. These agents can also improve the Parkinsonian features of TD. Donepezil, a reversible acetylcholinesterase inhibitor, is currently the only cholinergic medication that has shown benefit against TD.109 Overall, however, cholinergic agents are not a widely accepted treatment for TD as sufficient evidence is lacking to suggest they are more helpful than other treatments.
Clozapine, Quetiapine, Olanzapine, and Apomorphine.
Clozapine, a serotonin and dopamine receptor antagonist, is an atypical APD used to treat schizophrenia. Clozapine is the best current medication recommended for patients who require antipsychotics and simultaneously have TD,111 as clozapine has been reported to reverse TD symptoms.112,113 Clozapine has been linked to TD; however, the incidence is much lower compared to other atypical APDs.114 Drugs with similar mechanisms of action such as quetiapine, a weak striatal dopamine antagonist, and olanzapine, a dopamine and serotonin receptor antagonist, have also been shown to be effective in ameliorating TD symptoms.115 Apomorphine, a dopamine receptor antagonist, can be given in conjunction with L-DOPA to decrease dyskinesias.
Tetrabenazine, a vesicular monoamine transporter inhibitor, decreases the severity of TD symptoms.14 However, tetrabenazine is rapidly metabolized and therefore needs to be administered frequently.117 Analogs of tetrabenazine such as valbenazine, a (+)-α-isomer of tetrabenazine, have been approved for clinical trials for the treatment of TD. In a phase IIb randomized, parallel, double-blind, placebo-controlled clinical trial of patients with moderate to severe TD, 67% of patients treated with valbenazine reported a “much improved” or “very much improved” Abnormal Involuntary Movement Scale score compared with 16% of patients taking placebo.
While certain benzodiazepines can cause TD, evidence suggests that some may be beneficial in treating TD.118 Sharma's proposed guidelines for treating TD include clonazepam and were successful in a patient who presented with TD symptoms after long-term treatment with trifluoperazine (a typical APD), citalopram, trihexyphenidyl, and propranolol.119 A case report published in 2001 related that 2 mg/day of clonazepam for 1 year successfully alleviated the TD symptoms of a 66-year-old female, and she did not develop tolerance during the 1-year period.
Propranolol is a beta-adrenergic receptor antagonist used to treat high blood pressure, cardiac arrhythmias, and migraines. A retrospective study of 47 patients with TD that persisted for 17 months after discontinuation of APDs reported that low-dose propranolol appeared to be well tolerated in this patient population, and 64% of the patients saw an improvement in their TD symptoms.
Amantadine is a noncompetitive glutamate receptor antagonist. It is postulated to work by increasing presynaptic release of dopamine and blocking presynaptic dopamine reuptake. Amantadine has been shown to be effective in treating L-DOPA–induced TD in patients with Parkinson disease.
Branched-Chain Amino Acids.
Some evidence suggests that an inability to clear ingested forms of the amino acid phenylalanine is associated with TD. Branched-chain amino acids (BCAAs) are reported to decrease TD symptoms123 because they decrease plasma phenylalanine by stimulating protein synthesis and insulin release.124 BCAAs also decrease the accumulation of tyrosine, another amino acid and an important precursor to dopamine, that reduces overall dopamine synthesis in the nervous system.124 Most important, BCAAs also seem to be effective at decreasing TD symptoms while an APD medication is still on board or the patient has a history of APD exposure.123 BCAAs are available over the counter in a flavored powder preparation to mix with water, so they may be a promising, practical, and inexpensive treatment for TD.
The American Academy of Neurology recommends clonazepam and ginkgo biloba, an extract of the ginkgo biloba tree leaf that is used as a dietary supplement, to enhance cognitive function to treat TD.
Antioxidant Medications and Supplements.
Because evidence suggests that oxidative stress may contribute to TD, several antioxidant medications and supplements are increasingly being used to treat TD: zonisamide, yi gan san (a Chinese herb), levetiracetam, melatonin, omega-3 fatty acids, piracetam, resveratrol, vitamin B6, and vitamin E. A comprehensive update on these medications is available in a 2015 review by Lerner et al.118
Specific Medical research on alternate treatments
A randomized, double blind, placebo controlled design was used to determine the effectiveness of MEL (20 mg/day) during 12 weeks in 7 patients with TD. Six patients with TD were treated with placebo. In two patients treated with MEL a significant improvement (more than 60%) of the values of AIMS was detected. In the remainder five, as well as in the patients treated with placebo, no difference was observed during the 12 weeks.
Nineteen patients chronic DSM-IV schizophrenia of 31.3+/-7.0 years' duration, were randomly assigned in a double-blind, placebo-controlled, crossover trial to receive slow-release melatonin, 2 mg/day (low dosage), or placebo for 4 weeks. Supraphysiologic doses of melatonin do not positively affect tardive dyskinesia.
Using a double-blind, placebo-controlled, crossover study, we evaluated the efficacy of 10 mg/d of melatonin for 6 weeks in 22 patients with schizophrenia and TD. The decrease in AIMS score was 2.45 for the melatonin and 0.77 for the placebo treatment groups. This is the first clinical evidence for efficacy of melatonin in the treatment of TD.
Forty-seven patients were analyzed, mean age 63 years. Neuroleptics were discontinued in all patients and duration of TD at the time propranolol was initiated 17 months. Propranolol resulted in improvement in 64% and 77% of those had a moderate to complete or near-complete response. Mean daily dose was 69 mg and duration of therapy 14 months. Three patients stopped the propranolol due to adverse effects: hypotension (2), nightmares (1). Severity of TD and duration of propranolol therapy were associated with response.
A double-blind, intensive case design was used to study the effect of propranolol on tardive dyskinesia. No short-term improvement was observed, but two of the four subjects responded to long-term propranolol use.
In October 1979 I thought itnmmight be worth trying propranolol to modify the annoying mouth movements. Initially, I prescribed 10 mg to be taken four times a day; I soon increased the dose to 40 mg to be taken twice a day. Over approximately 6 weeks the mouth movements decreased; propranolol was continued at 80 mg/d. I last saw the patient 1 week before the time of writing, when she stated that she had run out of the propranolol and had not bothered to renew the prescription. She found that the mouth movements returned quite rapidly; therefore, she immediately began taking propranolol again, 40 mg twice a day.
Branched-Chain Amino Acids
Definition - A branched-chain amino acid (BCAA) is an amino acid having aliphatic side-chains with a branch (a central carbon atom bound to three or more carbon atoms). Among the proteinogenic amino acids, there are three BCAAs: leucine, isoleucine and valine. Non-proteinogenic BCAAs include 2-aminoisobutyric acid.
Long-standing tardive dyskinesia were randomly assigned to receive branched-chain amino acids or placebo. Treatment frequency was three times a day, 7 days a week for 3 weeks. A robust and highly significant difference was observed between patients who received high-dose branched-chain amino acids (222 mg/kg of body weight t.i.d.) (N=18) and those who received placebo (N=18) in the percent change in tardive dyskinesia symptoms from baseline to the end of the 3-week trial. Significant and marked differences were seen between the two groups at the >/=30% and >/=60% levels of decrease in tardive dyskinesia symptoms.
A 2-week trial of a BCAA medical food administered three times a day was conducted in nine men with long neuroleptic treatment histories. Frequency counts of TD movements were collected by videotape throughout the trial and these tapes were analyzed in blind random sequence for both patient and time for TD symptom level changes subsequent to completion of the trial. A statistically significant decrease in the level of TD symptoms was observed for the sample. The symptom changes were also clinically significant in that six of the nine subjects had symptom decreases of at least 58%, with all subjects having a decrease of at least 38%.
TD evaluation at baseline and after 1 and 2 weeks of BCAA treatment given in the form of a drink administered 3 times daily. TD symptom decreases were substantial in 5 of the 6 participants, ranging from 40% to 65%. Two of the subjects received an additional course of treatment, and further reductions in TD symptoms over those seen in the 2-week trial were observed.
Omega-3 Fatty Acids
I found two research articles that both said there was no improvement in TD with the use of Omega 3 fatty acids.
Serum calcium levels were measured in 25 chronically ill psychotic inpatients with involuntary movements, in comparison with 25 otherwise indistinguishable patients without such a syndrome. Those with involuntary movements were significantly more likely to have a serum calcium level below the normal range.
Laboratory studies include....
B. Serum electrolytes- to omit abnormalities of sodium and calcium metabolism that may cause movement disorders.
The blood test showed a light hypermagnesaemia (2.5 mg/dL) not related to a large ingestion of magnesium nor with any symptom of renal failure and levels of calcium of 9.70 mg/dL, which are in the upper levels of normal concentration (normal values: 8.89 - 10.0).
The only treatment was removal of haloperidol treatment.
Forty-eight hours after hospital admission, the patient was discharged. At that time the levels of magnesium in blood were slightly reduced. The blood test was showing an haloperidol concentration of 0.4 μg/L, a maintained leucocytosis and anaemia. Calcium level was of 9 mg/dL, and blood magnesium levels were of 2.1 mg/dL, being both
value considered normal.
Our suggestion is to control the calcium and magnesium levels in
patients receiving a chronic haloperidol treatment to prevent these
There is involvement of calcium in triggering the oxidative damage and excitotoxicity, both of which play central role in haloperidol-induced orofacial dyskinesia and associated alterations.
Results of the present study indicate that haloperidol-induced calcium ion influx is involved in the pathogenesis of tardive dyskinesia
The co-administration of haloperidol and Mg supplementation prevented RS generation in cortex, striatum and SN, and PC levels in the SN.These outcomes indicate that Mg supplementation may be a useful alternative to prevent movement disturbances resulting of classic antipsychotic pharmacotherapy as haloperidol.
Also see above.