Pharmacy and Therapeutics - January 2008 - (Page 33) Case Report: Aripiprazole and Tardive Dyskinesia All of the SGAs possess serotonin-2 receptor antagonism, an effective antidepressant mechanism in the FDA-approved antidepressant nefazodone (Serzone, Bristol-Myers Squibb).With this rationale in mind, we attempted low-dose augmentation with ziprasidone (Geodon, Pfizer), 40 mg/day for two weeks, but akathisia and activation of adverse effects prompted the patient to discontinue taking this drug. Aripiprazole was substituted, initially with a dose of 5 mg/day, which was gradually increased to 15 mg/day.The patient reported consistent and gradual improvement of her depressive symptoms throughout the next few visits, and she attained remission from depression several weeks later.There was no evidence of visual illusions or hallucinations. The patient did note a mild amount of weight gain of about 4 kg (about 9 pounds) as a primary side effect, but she clearly felt that the benefits of the medication in alleviating depression outweighed the side effects. An evaluation for metabolic syndrome was negative; fasting blood glucose and lipid levels were determined, and blood pressure was normal. After 15 months of compliant and consistent treatment with duloxetine and aripiprazole, the patient continued to report remission from depression. However, she then began to have involuntary lateral jaw movements, primarily on her left side, at a rate of two to three movements every few minutes. She reported no dentition problems or pre-existing nervous or motor tics. The patient underwent a series of voluntary movements so that we could test for the induction of or the natural occurrence of TD. The patient’s score of 9 (range, 0–42), as observed in the Abnormal Involuntary Movement Scale (AIMS), confirmed newonset TD. The aripiprazole dose was tapered and discontinued. Eight weeks later, the patient’s lateral movements completely resolved. Follow-up is ongoing. affective disorder. Both patients received 20 mg/day. After 10 days of discontinuing aripiprazole, one patient’s abnormal tongue movements ceased. In other case reports, aripiprazole was used to treat and alleviate TD induced by other neuroleptic agents in patients with bipolar and schizo affective illnesses. It is difficult to determine whether aripiprazole acted as a treatment or whether stopping the previous higher-potency neuroleptic agent allowed the remission of TD.18–21 Our own patient had an excellent response in terms of remission of depressive symptoms; she experienced a minimal amount of weight gain but ultimately developed lateral jaw movements, now considered to be TD. There was no evidence of dystonia, motor tics, nervous tics, or poor dentition to explain the involuntary movements. She was taking no other medication known for inducing dystonias or dyskinesias. AIMS testing revealed that the lateral jaw movements could be exacerbated during manipulation; her total score was 9, again suggestive of TD. In this case, our patient had probable risk factors for the development of TD, including affective disorder, female sex, and exposure to antipsychotic agents for more than six months. Her dose was a moderate 15 mg/day, but duloxetine probably influenced a mild inhibition of liver enzyme cytochrome P450 (CYP 2D6), allowing elevated aripiprazole blood levels. (Aripiprazole is a substrate for this liver enzyme metabolic system.) There have also been isolated reports of serotonergic antidepressants causing movement disorders such as parkinsonism, which might be a complicating factor in the development of this patient’s TD. In theory, SGAs are safer than conventional agents in terms of causing TD and EPS. Statistically, SGAs are also safer, but our case report underlies the continued need for appropriate informed consent, patient monitoring, and patient care because of the ability of these agents to produce potentially permanent neuromuscular adverse effects. We suggest that agents be used according to their FDA-approved indications when possible.22 If off-label use is prescribed, clinicians should be aware of the evidence base for each SGA in terms of the psychiatric illness being treated. In of f-label diagnostic prescribing, we propose that lowerpotency SGAs (i.e., quetiapine, aripiprazole, or ziprasidone) be used, even though our case example showed that a lower-potency SGA caused TD. We also encourage dosing for shorter periods of time, when feasible, and delineating the lowest effective dose on a caseby-case basis. DISCUSSION Our case represents new-onset oromandibular TD arising during the use of the atypical neuroleptic agent aripiprazole when used at the time in an off-label manner to manage treatment-resistant depression. The Naranjo Scale is a series of questions that attempt to link the probability of an adverse effect being directly related to a specific drug exposure. Our patient’s score was 5 (range, 0–12) on this scale.12 We then conducted a literature review of aripiprazole-induced TD. Maytal et al. had reported a similar case in which aripiprazole was used for depression and TD ensued. TD remitted several weeks after drug cessation.13 Zacher and Hatchett (2006) used aripiprazole 20 mg to treat bipolar illness. Pseudoparkinsonism occurred, and rabbit syndrome (characterized by rhythmic movements of the mouth) was considered to be a dystonic event but not necessarily TD.14 Another patient who was developmentally disabled with obsessive-compulsive disorder was treated with aripiprazole 10 mg. This patient experienced an acute dystonic face, tongue, and arm movements as well as upper limb athetosis. These acute dystonic events were alleviated with diphenhydramine (Benadryl, Pfizer).15 Sajbel and Evcimen and their colleagues16,17 reported two cases of aripiprazole-induced TD in two patients with schizo- CONCLUSION With their ability to reduce the risk of EPS, the atypical antipsychotic agents are the current drugs of choice for schizophrenia and bipolar illness as well as for many off-label applications. Almost all available SGAs have been linked to cases of TD, and a larger naturalistic evidence base is developing as patient exposures increase over time. Therefore, we need to continuously monitor individuals treated with antipsychotic medications regardless of their dose, diagnosis, or choice of SGAs over the conventional antipsychotic drugs. Vol. 33 No. 1 • January 2008 • P&T® 33
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