P T. 2008 January; 33(1): 32–34.
PMCID: PMC2730062
Aripiprazole (Abilify) and Tardive Dyskinesia
Thomas Schwartz, MD and Shafi Raza, MD
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Abstract

Second-generation (atypical) antipsychotic agents are being used within their indications as well as widely off-label because of their lower risk of causing extrapyramidal symptoms and tardive dyskinesia (TD). The risk of metabolic disorders has taken over much of clinical practice and the current literature on adverse effects. In this brief article, we discuss a case of TD that developed after a patient used aripiprazole as off-label augmentation for treatment-resistant depression. We emphasize the fact that TD is an adverse effect that must still be monitored.
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INTRODUCTION

Tardive dyskinesia (TD) is usually a late-developing, well-known neuromuscular adverse effect associated with the long-term use of first-generation (typical or conventional) anti-psychotic agents, such as chlorpromazine (Thorazine, Glaxo-SmithKline), haloperidol (Haldol, Ortho-McNeil), and fluphenazine (Prolixin, Apothecon). After months to years of therapy with dopamine-2 (D2) receptor–blockers, patients often experience involuntary choreiform, athetotic, or ballismic dyskinetic movements. These movements most commonly involve the mouth, tongue, facial muscles, and upper extremities. Axial dyskinesias may also occur.1

With the advent of the second-generation (atypical) anti-psychotic agents (SGAs), all of which utilize a serotonin-2 receptor (5-HT2) blockade, the risk of TD has apparently decreased, thereby allowing clinicians to treat schizophrenia with less possibility of a side-effect burden. Given this fact and the potential of these agents to treat several targeted symptoms (i.e., cognition, dysphoria, mania, and agitation), pharmaceutical companies have proceeded with studies and have gained approvals from the Food and Drug Administration (FDA) for most SGAs in areas other than schizophrenia, such as bipolar mania and depression and, in the case of risperidone (Risperdal, Janssen), autism.2,3 The off-label use of SGAs also continues to increase in the form of augmented therapies for resistant depression and anxiety.4,5 In fact, the FDA recently approved aripiprazole as the first augmentation (add-on) strategy for the treatment of unipolar major depression.

This article presents the case of a patient with treatment-resistant depression who experienced TD during augmentation therapy with aripiprazole (Abilify, Bristol-Myers Squibb/ Otsuka). Aripiprazole may be considered an “atypical atypical” agent; it is a partial dopamine agonist, not a full antagonist. Its unique profile allows for subtle increases in tonic dopamine neuron firing rates in brain areas that are hypofunctioning and for dampening of dopaminergic activity in areas that are hyperfunctioning. This blockade of hyperdominergic regions in the brain is thought to alleviate psychosis.
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RISK FACTORS FOR TARDIVE DYSKINESIA

Typical risk factors associated with the development of TD include older age, pre-existing movement or neurodegenerative disorders, female sex, the presence of affective illness, and neuroleptic exposure of more than six months.6 The use of higher-potency, first-generation agents is also more likely to increase the risk of TD and extrapyramidal symptoms (EPS). There is little doubt that conventional antipsychotic agents, compared with SGAs, are more likely to cause TD. However, among the SGAs currently available, those with more transient D2 receptor blockade and lower D2 affinity, such as quetiapine (Seroquel, AstraZeneca), are associated with the smallest risk, at least for EPS and probably TD.

At a therapeutic dose, it is noteworthy that aripiprazole has one of the highest D2 receptor affinities; however, because of its partial agonist properties, it has a lower risk of causing acute EPS and, probably, TD.7–10 A timely study of exposure to antipsychotic drugs in nongeriatric adults suggests that the incidence of TD with SGAs is 0.8%, compared with 5.4% with haloperidol, a high-potency, first-generation antipsychotic agent.11