History and exam

Key diagnostic factors

common

exposure to dopamine receptor-blocking agents

TD is a clinical diagnosis based on a history of exposure to dopamine receptor-blocking agents.

Consider TD in a patient presenting with stereotypic oro-bucco-lingual movements that occur over a period of at least 4 weeks following use of a dopamine receptor-blocking agent for at least 3 months (or at least 1 month in people ages >60 years).[2] Signs and symptoms may develop during exposure to or following withdrawal of a causative drug (within 4 weeks of withdrawal from an oral drug, or within 8 weeks from a long-acting injectable drug).[2]

Antipsychotics (particularly typical antipsychotics) are the usual causative agents. Several other drugs may also result in TD, for example:

  • Chronic use of prokinetic agents (e.g., metoclopramide)

  • Selective serotonin-reuptake inhibitors (e.g., citalopram)

  • Serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine)

  • Tricyclic antidepressants (e.g., amitriptyline)

  • Lithium

  • Cinnarizine (an antihistamine/calcium antagonist).

Consult your local drug formulary for a full list of drugs that may cause TD.

stereotypic involuntary movements of the mouth and tongue

TD is characterized by stereotypical involuntary movements involving the mouth and tongue (commonly referred to as oro-buccal-lingual dyskinesia). These may include:

  • A continuous chewing motion

  • Lip smacking

  • Lip puckering

  • Tongue writhing

  • Facial grimacing.

Some patients may have transiently sustained jaw opening, deviation, or closure with jaw clenching and teeth grinding (bruxism) as part of cranial tardive dystonia.[3][5]

Other diagnostic factors

uncommon

blepharospasm

Involuntary blinking or other eyelid movements may be seen in some patients with TD as part of cranial tardive dystonia.[3][5]

dystonia of the trunk and limbs

Patients may also develop tardive dystonia of the arms, legs, and trunk, the latter typically manifested by trunk arching (opisthotonus). Rarely, patients may develop choreic and athetoid movements of trunk and limbs.[3][5]

tardive myoclonus

A less typical type of involuntary movement that may be part of TD phenomenology.

tardive tics (tourettism)

A less typical type of involuntary movement that may be part of TD phenomenology.

tardive chorea

A less typical type of involuntary movement that may be part of TD phenomenology.

tardive akathisia

A less typical type of involuntary movement that may be part of TD phenomenology.

tardive tremor

A less typical type of involuntary movement that may be part of TD phenomenology.

tardive parkinsonism

A less typical type of involuntary movement that may be part of TD phenomenology.

tardive oral and/or genital pain

Some patients with TD develop chronic painful oral and genital sensations, which are termed tardive pain.[4]

Risk factors

strong

use of dopamine receptor-blocking agents

There is an increased risk of TD with cumulative exposure to dopamine receptor-blocking agents (e.g., antipsychotics, metoclopramide). That the features of TD occur in the context of long-term use (at least 3 months, or at least 1 month in people ages >60 years) of dopamine receptor-blocking agents is a criterion for diagnosis.[2] A meta-analysis of 41 studies found the prevalence of TD to be 30% in patients receiving typical (first-generation) antipsychotics and 21% in patients receiving atypical (second-generation) antipsychotics.[8] Consult your local drug formulary for a full list of drugs that may cause TD.

age >50 years

Older age is a commonly reported risk factor for the development of TD.[4][11][12]

weak

history of acute dystonic reaction, akathisia, or drug-induced parkinsonism with previous medication use

Some studies have reported that patients who developed acute or subacute adverse effects of dopamine receptor-blocking agents after taking them in the past are more likely to develop TD in the future.[12][18][19]

alcohol and substance misuse

Several epidemiologic studies have found an association between long-term use of alcohol and recreational drugs with the emergence of TD in patients on dopamine receptor-blocking agents.[20][21] While the exact mechanism remains unclear, N-methyl-D-aspartate (NMDA)-mediated excitotoxicity is presumed to have a role.[21]

postmenopause

Postmenopausal women have a higher risk of TD.[2] It is presumed that estrogen has a protective effect against TD (probably through dopamine-mediated behaviors and antioxidant effects).[22]

smoking

The exact mechanism is unknown. It is presumed that nicotine-induced dopaminergic modulation along with neurotoxicity resulting from the free radicals in cigarette smoke may predispose people who smoke to a higher risk of TD.[23]

African-American ethnicity

A reported risk factor for developing TD in association with dopamine receptor-blocking agent use.[11]

The exact cause is unknown, but several studies have reported a significant association between African-American ethnicity and TD, even when the dose of antipsychotics and duration of exposure are taken as covariates.[24]

diabetes mellitus

Studies have reported conflicting results regarding the association of diabetes mellitus with TD. The mechanism is unclear.[25][26]

brain injury

There are a few reports of an association of acquired brain injury with TD.[11][27][28]

dementia

Older studies report an association of cognitive dysfunction with TD; however, the literature on this association is sparse.[29][30]

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