Tardive dystonia often has an insidious and progressive presentation. Although associated with a latent and thus “tardive” onset, the presentation may occur anywhere from days to years following initial exposure to dopamine receptor antagonism. Patients have reported that unusual sensory symptoms, along with strange somatic sensations, have preceded the onset of tardive dystonia. For example, neck pain has been found to precede the onset of cervical dystonia. Furthermore, research has determined that the development of tardive manifestations presents as focal dystonia, most notably torticollis or blepharospasm, followed by pharyngeal dystonia, oromandibular dystonia, and dystonia of the lips and tongue.

Dystonias of the arms, legs, and trunk are less frequent. On examination, pharyngeal dystonia will present as dysphagia, whereas oromandibular dystonia may present as a severe speech disturbance.[4] Tardive dystonia will less often occur focally and instead tends to distribute more diffusely.

Prompt recognition and subsequent intervention are paramount in the setting of tardive dystonia. Proper evaluation begins with reviewing the primary diagnosis, describing the precipitating motor abnormalities, assessing symptom severity, and finally, by developing a treatment plan based upon the specific phenomenology. It is important that the clinician review the full medical profile, as alternative dopaminergic antagonizing medications have been known to induce tardive syndromes. Such inciting agents include dopamine receptor blocking anti-emetics, including prochlorperazine, metoclopramide, and promethazine.[9]

Upon the proper identification of tardive dystonia, the offending agent(s) should be modified and if possible, discontinued. Clinical judgment will indicate whether abrupt cessation or a gradual taper is most appropriate. Some experts suggest simply cross-tapering to an alternative antipsychotic with a lower EPS profile, such as clozapine.

Drug-induced EPS are believed to precipitate following the blockade of nigrostriatal dopamine tracts, ultimately resulting in an increased ratio of cholinergic to dopaminergic activity. Therefore, drugs that antagonize cholinergic activity and increase striatal dopaminergic function will theoretically normalize the biochemical imbalance.[10]

One study reviewed the therapeutic efficacy of specific pharmacologic interventions and revealed “at least some benefit” in 53% of patients following the administration of tetrabenazine, 44% with anticholinergic agents, 56% with benzodiazepines, and 56% with baclofen.[4] The most robust therapeutic effects were experienced following botulin toxin administration, where 83% of patients endorsed “considerable relief.”[4] Other therapeutic agents to consider include L-dopa, dopamine agonists, amantadine, beta-blockers, anticonvulsants, choline, and vitamin E.

The list of differential diagnoses for tardive dystonia is extensive and includes primary and secondary etiologies of dystonias. Secondary forms of dystonia include metabolic abnormalities, toxic states, neurodegenerative disorders, and structural abnormalities of the brain.[11]

Drug-induced dystonic syndromes can be distinguished by acknowledging a history of neuroleptic treatment, negative family history of primary dystonia, and the absence of associated neurological signs. It is not uncommon for patients on chronic neuroleptics to present with tardive syndromes. Furthermore, patients can experience more than one of these tardive syndromes simultaneously, further complicating matters. These latent motor abnormalities can be further subdivided into three major subtypes, including tardive dyskinesia, tardive dystonia, and tardive akathisia.

Tardive dyskinesia is characterized by truncal, appendicular, or orobuccolingual choreiform movements; whereas tardive dystonia manifests as stereotyped twisting and turning muscle spasms. Tardive dyskinesia also tends to have a later age of onset than tardive dystonia.[4] One study found the mean age of onset of tardive dyskinesia in a research group to be 57 years old and that of tardive dystonia to be 37 years old.[9] Tardive akathisia shares less in common with its two sister tardive syndromes and is defined as an unpleasant inner sense of restlessness or unease, ultimately indistinguishable from acute akathisia.

Once established, the progression of the dystonia tends to evolve in a stepwise fashion over months to years, with subsequent involvement of additional body parts. Studies reveal that progression to maximum intensity and distribution occurs within 2 years from onset. More rapid progression has been noted in the population with a younger age at onset.[4] Tardive syndromes can be a source of intense distress and potential disability. Unfortunately, these syndromes can be permanent, even after the discontinuation of the offending agent.[9] 

One study attempted to demarcate outcome groups based upon symptom resolution following treatment. In this study of 107 patients being treated for tardive dystonia, 14% were in remission, 39% were improved, and 50% noted either no improvement or exacerbating symptomatology.[4] Within this cohort, those who discontinued their neuroleptic were more likely to have experienced symptom remission. More specifically, those who discontinued antipsychotics more rapidly benefitted from a higher likelihood of remission.[4] Remission was reached within a mean of 2.4 years from the discontinuation of all neuroleptic agents.[4] Furthermore, dystonia appears irreversible in those exposed to neuroleptics for greater than 10 years.

The severity of tardive dystonia ranges on a spectrum from imperceptible to frank disability. Subtle impairments include muscle tightness and cramps, leading to mastication and speech discomfort. More intense complications include oculogyric crisis, dysphagia, dysarthria, as well as lethal respiratory stridor. In severe instances, dystonic reactions can induce apnea, leading to fatality. Less common complications include dystonic involvement of axial, limb, and truncal muscle groups leading to Pisa syndrome, camptocormia, and opisthotonus.[3]

Prognosis improves when EPS symptoms are detected promptly.[9] Moreover, lower doses of neuroleptics have been associated with a decreased incidence of dystonia, as well as antipsychotics with minimal dopamine antagonism.[12] This association has been the foundational impetus for the development of novel agents with less dopamine antagonism. Because of their reduced activity at the dopamine receptor, atypical antipsychotics tend to be preferred over high potency first-generation antipsychotics.[13] One study found that haloperidol had a four-fold greater risk of inducing dystonic manifestations than atypical antipsychotics.[14][15][16] Some clinicians prefer to administer prophylactic anticholinergic agents when prescribing neuroleptics to obviate potential EPS.[17]

Tardive dystonia can be debilitating and possibly even life-threatening. It is critical that the interprofessional team be knowledgeable and up to date regarding the possible precipitation of tardive dystonia. All members of the team must remain vigilant in the event the patient begins to experience prodromal symptomatology, as research suggests more rapid intervention results in better patient outcomes.[9] In the inpatient setting, nurses and staff members will most likely have the most contact with patients, and therefore if they observe concerning manifestations, they should promptly notify the clinician. Teamwork and proactive management will result in the best possible patient care.