Extrapyramidal Side Effects Associated with Aripiprazole Administration in a Schizophrenic Patient

Sir: Aripiprazole, a novel antipsychotic acting as a “dopamine system stabilizer,” is known for its low propensity to cause extrapyramidal side effects (EPS) and appears to be effective and well tolerated in most schizophrenic patients [3]. We report a case in which aripiprazole exerted significant parkinsonism and akathisia.

Mr. A, a 29-year-old man with a four-month history of reference ideations, experienced auditory hallucinations and persecutory delusions one month prior to the time of this report. He claimed that he was “hearing voices keeping up a running commentary on my behavior” and that “classmates were substituted by imposters, who were meant to harm me.” After admission, Mr. A was started on treatment with aripiprazole 10 mg daily. Five days later, auditory hallucinations were eliminated; however, persecutory delusions persisted. Meanwhile, Mr. A presented with mild akathisia, a mask-like face, and bradykinesia. Because there was only partial remission of psychotic symptoms and side effects were tolerable, aripiprazole was increased to 15 mg daily for further symptom control, and biperiden (6 mg daily) as well as propranolol (20 mg daily) were co-administered.

One week later, we did not observe marked reduction in delusional intensity. However, significant EPS developed, and he presented with mask-like face, rigidity, marked bradykinesia, and shuffling gait. Because these side effects were extremely disturbing, aripiprazole was ultimately discontinued and substituted with risperidone 2 mg daily. Persecutory delusions attenuated significantly within five days, and parkinsonism gradually resolved after discontinuing aripiprazole.

Aripiprazole acts as a partial agonist at the D₂ and 5-HT_1A receptors and is also an antagonist at the 5-HT_2A receptor. The pharmacodynamics of aripiprazole is thought to be effective and well tolerated for schizophrenic patients [4]. However, several cases of aripiprazole-associated EPS have been reported [2] [5]. For example, Cohen et al. [1] reported on two cases of depressive patients presenting with marked EPS, associated with concomitant use of aripiprazole and antidepressants (sertraline and venlafaxine). It was postulated that serotonergic agents with modest dopaminergic activity (e.g., sertraline) or noradrenergic activity (e.g., venlafaxine) might have modified aripiprazole’s neurochemical effects.

In the case of Mr. A-a new-onset, drug-naïve schizophrenic patient-aripiprazole was the only agent prescribed. This medication, although partially effective, exerted intolerable EPS. Although it was possible that our patient’s EPS were related to his genetic propensity for parkinsonism, our report suggests that a systemic investigation into aripiprazole’s pharmacodynamic and side-effect profile would be welcome. We also recommend slow titration to target doses among some high-risk patients (e.g., young males) to decrease the risk of EPS and akathisia with aripiprazole in clinical settings.

References

• 1 Cohen S, Rulf D, Pies R. Extrapyramidal side effects associated with aripiprazole coprescription in two patients.  J Clin Psychiatry. 2005;  66 135-136
• 2 Desarkar P, Thakur A, Sinha VK. Aripiprazole-induced acute dystonia.  Am J Psychiatry. 2006;  163 1112-1113
• 3 Grunder G, Kungel M, Ebrecht M. et al . Aripiprazole: pharmacodynamics of a dopamine partial agonist for the treatment of schizophrenia.  Pharmacopsychiatry. 2006;  39 ((1, Suppl)) S21-S25
• 4 Mobascher A, Mobascher J, Schlemper V, Winterer G, Malevani J. Aripiprazole pharmacotherapy of borderline personality disorder.  Pharmacopsychiatry. 2006;  39 111-112
• 5 Sharma A, Sorrell JH. Aripiprazole-induced parkinsonism.  Int Clin Psychopharmacol. 2006;  21 127-129

Correspondence