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Tardive Dyskinesia Fast Facts

Tardive dyskinesia (TD) is a movement disorder that causes involuntary muscle movements, usually in the face, jaw, lips, and tongue. The arms and legs can also be affected.

TD is a side effect of certain medications used to treat some psychiatric and gastrointestinal disorders.  

As many as a quarter of people who take these drugs over a long period of time eventually develop TD.

TD symptoms usually resolve when a doctor adjusts the person’s medication.

United Brain Association

TD symptoms usually resolve when a doctor adjusts the person’s medication.

What is Tardive Dyskinesia?

Tardive dyskinesia (TD) is a movement disorder that causes involuntary movements of the face, jaw, lips, and/or tongue. In some cases, involuntary movement of the arms and legs is also present.

The disorder is a side effect of certain medications commonly used to treat various psychiatric and gastrointestinal disorders. TD usually only affects people who take the medicines regularly over a period of years, but among those people, as many as 1 in 4 will develop TD.

Symptoms of Tardive Dyskinesia

Common symptoms of TD include:

  • Lip-smacking
  • Chewing movements
  • Thrusting of the tongue
  • Blinking
  • Grimacing
  • Difficulty swallowing
  • Twisting movement of the neck
  • Quick, jerking movement of the arms or legs (chorea)
  • Slow, writhing movement of the arms or legs (athetosis)

What Causes Tardive Dyskinesia?

TD is a reaction to the prolonged use of certain medications. The most common of these medications is a class of drug called a neuroleptic, which is used to treat a variety of psychiatric and neurological conditions, including:

Medications used to treat some gastrointestinal disorders may also cause TD. These disorders include:

  • Gastroesophageal reflux disease (GERD)
  • Gastroparesis

Although we still don’t know precisely what causes TD, some factors increase an individual’s risk of developing the condition. Risk factors include:

  • Age, sex, and race. Older people are at increased risk of TD, as are Black people and women.
  • Family history of TD
  • Diabetes
  • Human immunodeficiency virus (HIV) infection
  • Traumatic brain injury (TBI)
  • Smoking
  • Substance abuse

Is Tardive Dyskinesia Hereditary?

Scientists don’t know why some people develop TD, while others who take similar triggering medications never experience symptoms. However, having a family history of TD increases a person’s risk of developing the condition, suggesting genetics might play a role. Researchers have not identified any specific gene or genes associated with TD, and the condition is likely caused by a combination of genetic and environmental factors.

How Is Tardive Dyskinesia Detected?

Identifying TD symptoms early and treating them promptly may help lessen their severity. Because of this, it is recommended that people who are taking medications that may cause TD undergo regular screenings for the emergence of symptoms.

How Is Tardive Dyskinesia Diagnosed?

People taking medications associated with TD and experiencing movement-related symptoms may be screened for the condition by their doctor. If your doctor suspects TD, they will likely order a combination of tests, exams, and treatments to rule out other sources of your symptoms.

Diagnostic steps may include:

  • Medical history interviews to look for a pattern of symptoms or risk factors
  • Physical and neurological exams to identify specific symptoms
  • Blood, urine, or laboratory tests to rule out other possible causes of symptoms
  • Imaging exams (MRI, CT, or PET scans) to rule out other disorders
  • Electroencephalogram (EEG) to measure the brain’s electrical activity
  • Electromyography (EMG) to measure electrical interaction between muscles and nerves

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Tardive Dyskinesia Treated?

The first step in the treatment of TD is usually evaluating the patient’s current medication plan. Doctors may change the dosage of the drug that is causing the symptoms, or they may prescribe a different medicine to treat the underlying disorder. It is essential never to stop taking any medication or attempt to adjust the dosage on your own without consulting a doctor.

In many cases, TD symptoms resolve when the dosage of the triggering medication is addressed. However, if symptoms continue, your doctor may pursue different treatment options.

Medications

Some medications have proven effective at treating TD symptoms. Drugs commonly used include:

  • Valbenazine
  • Deutetrabenazine
  • Clonazepam

Deep Brain Stimulation

Deep brain stimulation (DBS) is a surgical procedure in which electrodes are implanted in the brain. These electrodes deliver electrical pulses controlled by a pacemaker-likely device implanted under the skin of the chest to the parts of the brain affected by TD. The electrical pulses block the abnormal nerve signals that cause TD symptoms.

How Does Tardive Dyskinesia Progress?

In most cases, TD symptoms improve when the underlying trigger is addressed. In cases where the symptoms persist, or the condition goes untreated, TD can have harmful long-term effects, including: 

  • Depression
  • Anxiety
  • Social isolation
  • Relationship problems
  • Problems at work

In rare cases, physical complications can be permanent and severe. Possible complications include:

  • Breathing difficulties
  • Swallowing difficulties
  • Speech difficulties
  • Drooping eyelids
  • Drooping mouth

How Is Tardive Dyskinesia Prevented?

There is no reliable way to prevent TD. However, if you are taking any medications that can cause the condition, you should be watchful for symptoms. You should also consult with your doctor about regular screenings, especially if you have any risk factors that increase your likelihood of developing TD.

Tardive Dyskinesia Caregiver Tips

Aside from its physical symptoms, TD can cause serious mental health-related issues. People with the disorder are likely to be self-conscious and vulnerable to social isolation. The support of loved ones and caregivers is essential to limiting TD’s secondary effects.

Tips to help your loved one and yourself:

  • Educate yourself about the disease, its effects, and the side effects of medications used to treat it.
  • Encourage a healthy lifestyle. You may also explore alternative therapies and activities such as meditation, yoga, tai chi, or massage.
  • Join a support group for caregivers. Caregivers are at risk of developing physical and mental health issues, too. So take time for yourself, and get the help you need when you feel overwhelmed.

By definition, people with Tardive dyskinesia almost always also suffer from other brain-related issues, a condition called co-morbidity. In addition to the mental health-related issues being treated by the medications that cause TD, research has suggested that people with some disorders are at increased risk of developing TD. These disorders include:

Tardive Dyskinesia Brain Science

Scientists aren’t sure of the precise biochemical mechanism that causes TD, but they know it is related to a brain chemical called dopamine. Dopamine is a neurotransmitter, a brain chemical that helps brain cells communicate with one another. It is crucial for transmitting movement signals from the brain to the body’s muscles.

The drugs that cause TD are dopamine antagonists, which means they block the action of dopamine in the central nervous system. Problems with dopamine are part of many different disorders, including psychiatric disorders and some gastrointestinal problems. Because of this, blocking dopamine helps to relieve the symptoms of these disorders.

TD seems to arise when, after a long period of exposure to these drugs, the brain’s chemistry changes and nerve cells become hypersensitive to dopamine, causing them to send abnormal movement signals to the muscles. Researchers have not yet discovered why some people are susceptible to this effect and others are not.

Tardive Dyskinesia Research

Title: Randomized Controlled Trial of Pyridoxine for Tardive Dyskinesia

Stage: Recruiting

Principal investigator: Gregory Pontone, MD, MHS

Johns Hopkins University School of Medicine

Baltimore, MD

Purpose: Tardive dyskinesia (TD) is an involuntary movement disorder that can occur following long-term treatment with antipsychotic medications and for which few treatment options exist. This study will test the efficacy of pyridoxine (also known as vitamin B6) for TD. This will be an eight-week double-blind, placebo-controlled, randomized trial measuring the effect of pyridoxine 400 mg/day on the severity of involuntary muscle movements in people who meet Schooler-Kane criteria for TD.

Participants: Approximately 50 subjects will be recruited from the UNC Schizophrenia Treatment and Evaluation Program (STEP) and other local psychiatric clinics.

 

Procedures (methods): Symptoms of TD will be assessed using the Abnormal Involuntary Movement Scale (AIMS). Pharmacological Intervention: All participants who meet entry criteria will be randomized to one of two treatment groups: pyridoxine or placebo.

Overview of Procedures: All procedures will be conducted at either the University of North Carolina Hospitals in Chapel Hill or the North Carolina Psychiatric Research Center (NCPRC), a specialized program of the University of North Carolina Center for Excellence in Community Mental Health, in Raleigh.

Screening: During the initial clinic visit and after providing written informed consent, prospective subjects’ psychiatric and medical histories will be reviewed, physical exams conducted, demographics and vital signs obtained, and blood and urine collected. The Structured Clinical Interview for DSM-V, the Columbia Suicide Severity Rating Scale (C-SSRS), and the Clinical Global Impressions-Severity (CGI-S) will be used to evaluate psychopathology. Involuntary muscle movements will be assessed using the Abnormal Involuntary Movement Scale (AIMS). The AIMS exam will be video recorded. Other neurological side effects of antipsychotic medications will be assessed using the Barnes Akathisia Scale (BARS) and Simpson-Angus Scale (SAS).

The baseline visit will be scheduled within 28 days of the screening visit. Vital signs and weight will be measured. A blood test to measure baseline pyridoxine level will be collected. A battery of assessments will be administered, including the Clinical Global Impressions-Severity (CGI-S), the Alcohol Use Scale, Substance Use Scale, Brief Psychiatric Rating Scale (BPRS), Columbia Suicide Severity Rating Scale (C-SSRS), AIMS (video recorded), BARS, and SAS.

At the completion of the baseline visit, subjects who continue to meet study inclusion criteria will be randomized to one of two treatment groups (pyridoxine or placebo). Subjects assigned to the pyridoxine group will receive 200 mg per day for one week and then 400 mg per day, as tolerated, for the remainder of the study. Subjects assigned to the placebo group will receive matching placebo capsules.

After study enrollment, subjects will be scheduled for Week 1 and Week 2 study visits. These visits will assess medication management (i.e., adverse events/side effects, adherence), collect vital signs, assess current psychiatric status, and assess neurological symptoms using the AIMS (video recorded), BARS, and SAS. The CGI-S will be performed at both Week 1 and Week 2. However, the C-SSRS will be completed at Week 2 only.

Study visit at Week 4 and end-of-study visit at Week 8 will be similar to Week 2, with the addition of the BPRS, Substance Use Scale, and Alcohol Use Questionnaire. A blood test to measure pyridoxine levels will also be collected during these visits. The study drug is discontinued at the Week 8 visit.

A follow-up visit at Week 10, two weeks after stopping the treatment, will consist of assessing for adverse events/side effects, collecting vital signs, administrating the CGI-S and C-SSRS, and performing the AIMS (video recorded), BARS, and SAS. The follow-up visit will help determine whether the potential benefits of pyridoxine for TD may continue after treatment is discontinued.

Vital signs, adverse events, and side effects will be obtained at all in-person study visits. Blood collection and laboratory testing will be done at Screening, Baseline, Week 4, and Week 8.

 

Title: Treatment of Tardive Dyskinesia With Galantamine

Stage: Completed

Principal investigator: Sarkis K. Mazmanian, PhD

California Institute of Technology (Caltech)

Pasadena, CA

Tardive dyskinesia (TD), a form of movement disorder, remains a problem for some patients who receive antipsychotic medications. Increasing evidence suggests that TD may result from antipsychotic-induced dysfunction in striatal cholinergic neurons. To test whether cholinesterase inhibitors compensate for diminished cholinergic activity underlying TD, researchers conducted a 30-week randomized, double-blind, placebo-controlled crossover study of galantamine in 36 patients with TD.

BACKGROUND: Tardive dyskinesia (TD) is an infrequent but important complication of treatment with antipsychotic medications. Although newer antipsychotics may be less likely to cause TD, it still occurs among some mentally ill patients previously treated with typical antipsychotics. Although usually mild, TD may be more troublesome in some patients. Unfortunately, there is no proven curative or suppressive treatment effective in all patients. Suppressive treatment with cholinergic agents derives from a hypothesized balance between dopaminergic and cholinergic neurotransmission in the extrapyramidal system. Although previous trials of cholinergic precursors have been unsuccessful in treating TD, their effect on central cholinergic neurotransmission remains uncertain, given the evidence of damage to striatal cholinergic neurons in patients with TD. In contrast, the recent development of cholinesterase inhibitors that effectively modify the central cholinergic deficit in Alzheimer’s disease prompted us to investigate the therapeutic effect of galantamine in patients with TD.

RESEARCH OBJECTIVES: We propose to complete a randomized, double-blind, placebo-controlled crossover trial in 36 patients to test; (1) whether galantamine is pharmacologically active in suppressing TD; (2) whether doses of 8-24 mg/day are sufficient for improvement; (3) whether there are any significant side effects in these patients.

METHODS: Thirty-six patients with abnormal involuntary movements meeting research criteria for TD, who are on stable doses of psychotropic medications, will be randomized to receive galantamine alternating with placebo in addition to their standard medications. After two baseline measurements, each patient will undergo 12-week treatment periods of galantamine and placebo with a 4-week washout period between treatments. Patients will be evaluated every two weeks throughout the study, using standardized rating scales for TD (AIMS) and other extrapyramidal side effects (SIMPSON, BARNES. During the active treatment period, patients will receive galantamine 4 mg BID for four weeks, followed by 8 mg BID for four weeks, and 12 mg BID for an additional four weeks. Placebo-galantamine differences will be examined by repeated-measures analysis of covariance for a two-period crossover design.

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