History and exam

Key diagnostic factors

common

exposure to dopamine receptor-blocking drugs

Tardive dyskinesia (TD) is a clinical diagnosis based on a history of exposure to dopamine receptor-blocking drugs.

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 drug for at least 3 months (or at least 1 month in people aged >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, including: chronic use of prokinetic drugs (e.g., metoclopramide); selective serotonin-reuptake inhibitors (SSRIs; e.g., citalopram); serotonin-noradrenaline reuptake inhibitors (SNRIs; e.g., duloxetine); tricyclic antidepressants (e.g., amitriptyline); lithium; and cinnarizine (an antihistamine/calcium antagonist).[4][5][13]​ Consult your local drug information source for a full list of drugs that may cause TD.

stereotypic involuntary movements of the mouth and tongue

Tardive dyskinesia is characterised 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; and facial grimacing.[3][5]

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 tardive dyskinesia 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 tardive dyskinesia phenomenology.

tardive tics (tourettism)

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

tardive chorea

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

tardive akathisia

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

tardive tremor

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

tardive parkinsonism

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

tardive oral and/or genital pain

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

Risk factors

strong

use of dopamine receptor-blocking drug

There is an increased risk of tardive dyskinesia (TD) with cumulative exposure to dopamine receptor-blocking drugs (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 aged >60 years) of dopamine receptor-blocking drugs 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 information source 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 tardive dyskinesia.[4][11][12]

weak

history of acute dystonic reaction, akathisia, or drug-induced parkinsonism with previous use of dopamine-receptor blocking drug

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

alcohol and substance misuse

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

post-menopause

Post-menopausal women have a higher risk of tardive dyskinesia (TD).[2] It is presumed that oestrogen has a protective effect against TD (probably through dopamine-mediated behaviours 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 tardive dyskinesia.[23]

African-American ethnicity

A reported risk factor for developing tardive dyskinesia (TD) in association with dopamine receptor-blocking drug 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 tardive dyskinesia. The mechanism is unclear.[25][26]

brain injury

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

dementia

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

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