para>Occurs in all ages; however, advanced age is a major risk factor for TD. ‚
GENERAL PREVENTION
- Choosing an atypical neuroleptic as first-line therapy might reduce the risk of developing TD (2).
- If traditional neuroleptics must be used, limit long-term use and use the lowest effective doses.
- Continuous use of metoclopramide should be limited to <12 weeks.
- It is important that, prior to use, the risk and benefits be discussed with the patients. Informed consent should be obtained. Once started, monitor symptoms periodically.
COMMONLY ASSOCIATED CONDITIONS
- Presence of movement disorder
- Psychiatric disorders commonly treated with neuroleptics
DIAGNOSIS
HISTORY
- The diagnosis of TD is clinical, upon exclusion of other etiologies. According to the DSM-5, TD consists of involuntary athetoid or choreiform movements generally of the tongue, lower face/jaw, and extremities, of >8 weeks duration, developing in association with neuroleptic use.
- TD must be distinguished from other movement disorders. Documentation of the presence of movement disorders before initiation of antipsychotic medications is helpful in diagnosis (1).
- Abnormal movements must not be due to a neurologic condition or other general medical conditions (e.g., Huntington disease, Sydenham chorea, spontaneous dyskinesia, hyperthyroidism, heavy-metal poisoning, Wilson disease), ill-fitting dentures, or exposure to other medications that can cause acute reversible dyskinesia (e.g., L-dopa, bromocriptine, amantadine, Sinemet, Adderall, Ritalin, and Compazine).
- Other neuroleptic-induced movement disorders must be ruled out (e.g., tardive tourettism, blepharospasm, tardive akathisia, tardive myoclonus, tardive tremor, and tardive dystonia), as well as spontaneous dyskinesias and mental disorders.
- Question patient about a history of neurologic disorders that may involve the basal ganglia (e.g., cerebrovascular accident, encephalitis, head trauma, neoplasms).
- Attempt to elicit a family history for hereditary dyskinesias (e.g., Huntington disease).
- Ask about medication usage, particularly aforementioned medications. Note: Neuroleptics can mask TD, thus explaining onset after discontinuation of medication.
PHYSICAL EXAM
- Abnormal, involuntary movements of the tongue, lips, and extremities; facial grimacing; and swaying movements of the trunk or hips
- In one major report
- 75% of individuals with TD had orofacial dyskinesia.
- 50% had limb dyskinesia.
- 25% had axial dyskinesia.
- 10% had total-body involvement.
- Orofacial dyskinesia is common in the ≥60 years of age population.
- Limb + axial dyskinesia is more common in the younger population.
- Signs and symptoms must occur while taking neuroleptics or within 4 to 8 weeks of withdrawal from an oral or depot neuroleptic medication, respectively.
- Symptoms are usually more pronounced when the patient is awake and tend to resolve during sleep or voluntary movement (3).
- The signs typically are minimal to mild in nature and progress in severity with prolonged use.
DIFFERENTIAL DIAGNOSIS
- Huntington disease
- Sydenham chorea
- Spontaneous dyskinesia
- Wilson disease
- Thyrotoxicosis
- Blepharospasm
- Tardive akathisia
- Tardive dystonia
- Tourette syndrome
- Meige syndrome (3)
- Physical signs may point the way to another diagnosis.
- Tachycardia, sweating, and a goiter suggest thyrotoxicosis.
- Jaundice, hepatomegaly, or Kayser " “Fleischer rings suggest a workup for Wilson disease.
- Dementia in addition to the movement disorder (chorea) and postural instability require a workup for Huntington disease.
DIAGNOSTIC TESTS & INTERPRETATION
Only used to rule out other causes ‚
Initial Tests (lab, imaging)
- Rule out Wilson disease: low serum ceruloplasmin due to an abnormal copper transporter gene and elevated 24-hour urine copper collection; in addition, liver function tests and liver transaminases may be abnormal, along with elevated hepatic copper levels. Also, check the copper transporter gene in patients in whom Wilson disease is suspected.
- Thyroid-stimulating hormone, calcium, syphilis serology
- Connective tissue disease screening tests (CBC, ESR, urinalysis, chemistry panel, rheumatoid factor, antinuclear antibodies) are useful to exclude systemic lupus erythematosus and other vasculitides.
- Obtain RBC counts to exclude polycythemia rubra vera.
Diagnostic Procedures/Other
Screen for dyskinetic movements before initiating antipsychotics and at regular-scheduled intervals (e.g., every 6 months). Several questionnaires elicit this information and rate TD on a severity scale; the most commonly used is the Abnormal Involuntary Movement Scale (AIMS). ‚
TREATMENT
MEDICATION
First Line
Cessation of neuroleptic or metoclopramide use (via taper) should be the initial option. Therapies have produced no more than a modest improvement in TD symptoms, so prevention and early detection are the best treatment options. See "General Prevention. " ¯ ‚
Second Line
No definitive treatment algorithm for TD ‚
- Amantadine 100 to 300 mg/day (4)[B]. One randomized controlled trial (RCT) reported a 15% reduction in dyskinesia in patients who had amantadine 300 mg added onto their neuroleptic.
- Tetrabenazine 12.5 to 200 mg/day (4)[C]. Tetrabenazine and reserpine are drugs that act on the presynaptic vesicles by depleting their dopamine stores. Limited data from nonrandomized trials suggest that tetrabenazine may be effective in treating TD.
- Benzodiazepines provide GABA agonistic effects. They can benefit patients with TD in reducing dyskinesia and possible anxiety associated with the symptoms. Only recommended for short-term use. One class I, double-blind, RCT showed reduction in dyskinesia and dystonic symptoms with clonazepam (4)[B].
- As a last resort, the clinician may resume the antipsychotic agent in an attempt to suppress TD; only for patients with life-threatening psychiatric disease or permanent TD that is treatment resistant.
ADDITIONAL THERAPIES
Some case reports show that electroconvulsive therapy might improve TD in patients with underlying psychiatric disease. ‚
COMPLEMENTARY & ALTERNATIVE MEDICINE
- Vitamin E, a free-radical scavenger, has been found in a number of studies to reduce the severity of TD, although more recent studies suggest it is indicated primarily for newly diagnosed TD.
- Ginkgo biloba extract (4)[B]: One class I RCT found that patients AIMS scores significantly decreased after taking Ginkgo biloba compared to placebo.
- Botulinum toxin has been recommended for localized forms of TD such as cervical dystonia, blepharospasm, or retrocollis. It should be avoided in patients with neuromuscular conditions. Efficacy data has come from open-label, retrospective studies (4)[C].
- Branched chain amino acids may be effective in the treatment of TD.
- Vitamin B6 demonstrated good safety and efficacy as a treatment for TD in two double-blinded, randomized, crossover, placebo-controlled studies.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Instruct patients and family members to be vigilant of early signs of any movement disorder.
- Warn that TD may be exacerbated by stimulant use (Ritalin, Adderall), neuroleptic withdrawal, and anticholinergics. Symptoms are affected by emotional states and stress.
- Patient should attend regular clinic visits for physician monitoring.
PROGNOSIS
TD can range from be mild to moderate, with resolution of symptoms, to severe and irreversible. ‚
REFERENCES
11 Aquino ‚ CC, Lang ‚ AE. Tardive dyskinesia syndromes: current concepts. Parkinsonism Relat Disord. 2014;20(Suppl 1): s113 " “s117.22 Jankelowitz ‚ SK. Treatment of neurolept-induced tardive dyskinesia. Neuropsychiatr Dis Treat. 2013;9:1371 " “1380.33 Meyer ‚ TA, Belson ‚ TE, McAllister ‚ R. Tardive dyskinesia: a distressing drug-induced movement disorder. US Pharm. 2014;39(1):HS13 " “HS16.44 Bhidayasiri ‚ R, Fahn ‚ S, Weiner ‚ WJ, et al. Evidence-based guideline: treatment of tardive syndromes: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013;81(5):463 " “469.
ADDITIONAL READING
- Correll ‚ CU, Schenk ‚ EM. Tardive dyskinesia and new antipsychotics. Curr Opin Psychiatry. 2008;21(2):151 " “156.
- de Leon ‚ J, Susce ‚ MT, Pan ‚ RM, et al. Polymorphic variations in GSTM1, GSTT1, PgP, CYP2D6, CYP3A5, and dopamine D2 and D3 receptors and their association with tardive dyskinesia in severe mental illness. J Clin Psychopharmacol. 2005;25(5):448 " “456.
- Lerner ‚ PP, Miodownik ‚ C, Lerner ‚ V. Tardive dyskinesia (syndrome): current concepts and modern approaches to its management. Psychiatry Clin Neurosci. 2015;69(6):321 " “334.
- Ormerod ‚ S, McDowell ‚ SE, Coleman ‚ JJ, et al. Ethnic differences in the risks of adverse reactions to drugs used in the treatment of psychoses and depression: a systematic review and meta-analysis. Drug Saf. 2008;31(7):597 " “607.
- Peng ‚ LY, Lee ‚ Y, Lin ‚ PY. Electroconvulsive therapy for a patient with persistent tardive dyskinesia: a case report and literature review. J ECT. 2013;29(3):e52 " “e54.
CODES
ICD10
G24.01 Drug induced subacute dyskinesia ‚
ICD9
333.85 Subacute dyskinesia due to drugs ‚
SNOMED
- Tardive dyskinesia (disorder)
- Neuroleptic-induced tardive dyskinesia
CLINICAL PEARLS
- 2nd-generation antipsychotics still have a risk for TD.
- The older the patient and/or the longer the duration of antipsychotic use, the higher the risk of TD.
- Use the minimum effective dosage and duration of antipsychotic medications that are effective.
- TD can begin after the discontinuation of antipsychotics (up to 4 weeks).
- Ensure that oral dyskinesias are not triggered by other medical/neurologic conditions or ill-fitting dentures.