Treatment decisions
If a patient develops TD, clinicians need to make several decisions (Algorithm). First, consider tapering any anticholinergic drugs unless acute EPS are prominent or tardive dystonia is present. Anticholinergic agents can worsen TD but not tardive dystonia; 60% of TD cases improve after discontinuing anticholinergics.13 Second, decide whether antipsychotics could be safely tapered or discontinued. If antipsychotics cannot be safely tapered, decide whether to maintain the patient’s present antipsychotic or switch to a more or less potent agent. Finally, decide whether a trial of an adjunctive antidyskinetic drug is warranted. All of these decisions require thorough discussion with patients and their families, accompanied by careful documentation.
Discontinuing, continuing, or switching antipsychotics. Discontinuing antipsychotics once TD becomes apparent is an option. However, the natural course of TD after drug withdrawal is unclear. Although drug withdrawal had been recommended to increase the odds of TD resolution, early studies showed withdrawing antipsychotics may lead to an initial worsening of TD in 33% to 53% of patients (unmasking or withdrawal dyskinesia).14 With long-term follow-up, 36% to 55% of patients eventually improved, which supports recommendations for drug reduction or withdrawal.14 However, complete and permanent reversibility beyond the withdrawal period is rare; Glazer et al found only 2% of patients showed complete reversal of TD after drug discontinuation.15,16 In a meta-analysis, Soares and McGrath17 reported 37% of patients assigned to placebo across studies showed at least some improvement in TD, but concluded insufficient evidence existed to support drug cessation or reduction as effective treatments for TD, especially when contrasted with robust evidence for the risk of psychotic relapse after drug withdrawal in patients with schizophrenia (53% within 9 months).18
A second option for a stable patient with good control of psychotic symptoms but established or long-term TD is to continue the antipsychotic, try to gradually reduce the dose, inform patients and caregivers of risks, document the decision, and monitor carefully. In most cases, TD may not progress even with continued antipsychotic treatment, although symptoms may worsen in some cases. However, in a patient with new-onset or early signs of TD, the clinician may be obligated to switch to a lower-potency antipsychotic or newer SGA to improve the chance of resolution; switching is discussed below.
Data on the change in prevalence of TD within a population during continued antipsychotic treatment have been inconsistent. Some studies show an increase, while others show a decrease or no change at all.19 However, prevalence rates obscure the dynamics of TD in individual patients. Roughly 50% of patients with TD have persistent symptoms, 10% to 30% have reduced symptoms, and 10% to 30% experience increased symptoms during treatment.13 Long-term studies estimated that up to 23% of patients may show loss of observable TD symptoms during treatment with FGAs in 1 year.19,20 Similarly, studies of SGAs have shown reduction of TD ratings; some found greater reductions, some found less reductions, and some no difference compared with FGAs.19,20 In some studies, improved TD outcomes were correlated with younger age, lower antipsychotic doses, reduced duration of drug treatment and dyskinesia, and increased length of follow-up.
In the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, there was a significant decline in TD severity ratings among 200 patients with TD at baseline who were randomized to receive 1 of 4 SGAs, but there were no significant differences among these SGAs in decline in AIMS scores (Figure).19 Fifty-five percent of these patients met criteria for TD at 2 consecutive post-baseline visits, 76% met criteria at some or all post-baseline visits, and 24% did not meet criteria at any subsequent visit. In addition, 32% showed ≥50% decrease and 7% showed ≥50% increase in AIMS score. Thus, similar to past evidence on the course of TD during treatment with FGAs or SGAs, most patients in this trial showed either persistence or fluctuation in observable TD symptoms.
Another alternative is to switch antipsychotics, keeping in mind the risk of destabilizing a patient and precipitating psychotic relapse. More potent antipsychotics—such as haloperidol—suppress TD in approximately 67% of patients and may be necessary to consider in patients with severe, disabling symptoms, although the safety of these drugs in relation to their impact on long-term TD outcome is unclear.13,21,22 On the other hand, lower-potency drugs and SGAs also have been associated with reduced TD symptoms23,24; this was confirmed by results of the CATIE trial cited above in which SGAs were associated with a significant reduction in TD severity ratings.19 Clozapine in particular has been recommended for suppressing TD, especially in cases of tardive dystonia.20 Surprisingly, data are limited and inconsistent in addressing whether high-potency FGAs suppress TD symptoms more than low-potency drugs or SGAs, and whether SGAs may suppress TD by mechanisms other than dopamine receptor blockade, which would enhance symptom remission.19,25,26