Pharmacy and Therapeutics - January 2008 - (Page 32) CASE REPORT Aripiprazole (Abilify) and Tardive Dyskinesia Thomas Schwartz, MD, and Shafi Raza, MD 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. 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. 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 Case Study Ms. A., a 46-year-old woman, initially reported a long history of mood lability; possible premenstrual dysphoric disorder; and recurrent–moderate major depressive disorder (MDD). At the time of presentation to our clinic, she reported an increased quantity of sleep, sad and irritable mood, poor concentration, low levels of interests and enjoyment, visual illusions, increased feelings of guilt, and passive suicidal ideation that had been present consistently for two years. The patient had undergone an initial trial of fluoxetine (Prozac, Lilly) by another provider but otherwise had no previous psychiatric history. She was experiencing urinary incontinence, trigeminal neuralgia, and lumbar back pain. She used hydrocodone (Vicodin, Abbott) rarely, as needed, for trigeminal pain, and she was routinely using tolterodine (Detrol, Pfizer) for her bladder. Her family history was consistent with alcohol dependence and an anxiety disorder. We initially prescribed and escalated the dose of duloxetine (Cymbalta, Lilly), up to 120 mg/day, an antidepressant that she had been taking for approximately two years.Although she was not experiencing any adverse effects, she had only a partial response to this medication. Given the perceived clinical effectiveness and availability of some peer-reviewed literature, we discussed augmentation with a SGA. Disclosure: Dr. Schwartz has received financial support for research from Bristol-Myers Squibb during the past three years. INTRODUCTION Tardive dyskinesia (TD) is usually a late-developing, wellknown neuromuscular adverse effect associated with the longterm use of first-generation (typical or conventional) antipsychotic agents, such as chlorpromazine (Thorazine, GlaxoSmithKline), 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) antipsychotic 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 Dr. Schwartz is Associate Professor in the Department of Psychiatry at the State University of New York (SUNY), Upstate Medical University, in Syracuse, New York. Dr. Raza is completing an externship in psychiatry at the same institution. Accepted for publication November 6, 2007. 32 P&T® • January 2008 • Vol. 33 No. 1
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