Is there a rational management strategy for tardive dyskinesia?

Introduced into clinical practice more than a half century ago, antipsychotics are still the mainstay of schizophrenia treatment. However, from the earliest reports, antipsychotic efficacy was seemingly inseparable from extrapyramidal side effects (EPS) that manifested as acute and chronic involuntary movement disorders. Although acute extrapyramidal side effects could be prevented and treated, the late-arising symptoms of tardive dyskinesia (TD) seemed irreversible in most cases.

Concerns over TD stimulated extensive research and fueled efforts to develop new antipsychotics that spared the extrapyramidal motor system. Numerous industry-sponsored trials found a reduced risk of EPS—including TD—with newer, second-generation antipsychotics (SGAs), although this advantage diminished when modest doses of low- or mid-potency first-generation antipsychotics (FGAs) were used as the comparator.^1-3 Nevertheless, in addition to the continued potential risk of introducing new cases of TD—even with SGAs—several other factors underscore the need to develop a rational strategy for clinical management of TD, including:

• thousands of patients are left with TD as a legacy of past treatment
• the neurophysiologic mechanisms underlying TD are not well understood
• there is no uniformly effective treatment to reverse TD
• TD may be irreversible in most cases.

Prevention

Because there is no “gold standard” treatment for TD, it is important to minimize the risk of TD by taking preventive measures and detecting incipient signs of the disorder. Preventive principles include:

• confirming and documenting the indication for antipsychotics
• using conservative maintenance doses and opting for lower potency or newer agents
• informing patients and caregivers of risk
• assessing for incipient signs of TD using the Abnormal Involuntary Movement Scale (AIMS),⁴ which should be administered at least every 3 to 6 months.

Confirming the diagnosis

TD presents as a polymorphous involuntary movement disorder,^5-8 most often with nonrhythmic, repetitive, purposeless hyperkinetic symptoms. It usually affects orofacial and lingual musculature (“buccolinguomasticatory syndrome”) with chewing; bruxism; protrusion, curling, or twisting of the tongue; lip smacking, puckering, sucking, and pursing; retraction, grimacing or bridling of the mouth; bulging of the cheeks; or eye blinking and blepharospasm. Choreoathetoid movements of the fingers, hands, or upper or lower extremities also are common. Patients may experience axial symptoms affecting the neck, shoulders, spine, or pelvis. When severe, dyskinesias can affect breathing, swallowing, or speech, and interfere with walking and activities of daily living.

TD may present with nonchoreoathetoid symptoms that can be difficult to distinguish from acute EPS. These may co-exist with classic TD symptoms, but may represent separate subtypes with increased risk of progression, persistence, and severe disability. For example, tardive dystonia, which is estimated to occur in 1% to 4% of patients treated with antipsychotics,⁹ may be more generalized and disabling than TD, and may respond to anticholinergic agents. Akathisia and other movement disorders also occur as tardive variants.¹⁰

Multiple diagnostic schemes for TD have been proposed; criteria proposed by Schooler and Kane have been widely accepted (Table 1).¹¹ TD onset occurs insidiously over ≥3 months of antipsychotic treatment and may begin with tic-like movements or increased eye blinking. TD often is suppressed or masked by ongoing antipsychotic treatment and becomes apparent only when the drug is reduced, switched, or discontinued. Dyskinesias increase with emotional arousal, activation, or distraction, and diminish with relaxation, sleep, or volitional effort. As a result, TD symptoms fluctuate over time; therefore, repeated measurements are necessary for reliable assessment of severity and persistence.

The differential diagnosis of TD necessitates conducting a careful medical and neurologic evaluation of all patients with new-onset movement disorders. Clues to neurologic causes include a family history of movement disorders, sudden onset or progressive course, associated medical or neurologic abnormalities, and asymmetry of symptoms. Some of the medical, neurologic, and psychiatric conditions to consider are listed in Table 2.¹²

Table 1

Schooler-Kane diagnostic criteria for TD

Table 2

Differential diagnosis of tardive dyskinesia