Influence of aripiprazole once monthly on clinical symptoms and cognitive function in two schizophrenia patients: Preliminary results.

Abstract

We report on two schizophrenia patients who participated in an open-label pharmacokinetic study that required repeated-dose administration of aripiprazole once monthly (AOM). We examined the effects of AOM on cognitive function from baseline to 20 weeks after the start of AOM treatment. Cognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia, Japanese language version. The two patients were required to be symptomatically stable with no acute exacerbations for at least 1 month prior to switching, as judged by the treating psychiatrist. Publication has been authorized by a signed release from the patients or legal guardians. The first outpatient was a 29-year-old man with paranoid schizophrenia (duration of illness, 8 years). The patient had previously received a regimen of aripiprazole (9 mg/day), and we administered AOM (300 mg). The following characteristics were improved: verbal memory (z-score: −2.0 to −0.5), working memory (z-score: −1.5 to −0.9), verbal fluency (z-score: −2.8 to −2.1), attention and processing speed (z-score: −2.2 to −1.2), composite score (z-score: −1.8 to −0.2), Positive and Negative Syndrome Scale (PANSS) total score (80 to 74), positive score (15 to 13), negative score (23 to 21) and general score (42 to 40), Drug-induced Extrapyramidal Symptoms Scale (DIEPSS) (8 to 3), Barnes Akathisia Scale (3 to 2), and Abnormal Involuntary Movement Scale (AIMS) (5 to 0). The maximum and minimum steady-state serum concentrations of aripiprazole were 122 ng/mL and 105 ng/mL, respectively. The second inpatient was a 56-year-old man with disorganized schizophrenia (duration of illness, 37 years). The patient had previously received a regimen of aripiprazole (24 mg), and we administered AOM (400 mg). The following characteristics were improved: verbal memory (z-score: −3.0 to −0.4), verbal fluency (z-score: −1.5 to −1.2), attention and processing speed (z-score: −2.5 to −1.9), composite score (z-score: −1.5 to −1.4), PANSS total score (78 to 77), and general score (34 to 33), DIEPSS (7 to 2), and AIMS (2 to 0). The maximum and minimum steady-state serum concentrations of aripiprazole were 157 ng/mL and 130 ng/mL, respectively. Anticholinergics, benzodiazepines, and antipsychotics that negatively affected cognitive functioning were not administered to either patient. This is the report of two patients who received aripiprazole in long-acting injectable formulations. Consistent with this report, previous studies have reported improvement of cognition when switching from oral atypical antipsychotics to long-acting injectable risperidone.1 The two patients showed the highest improvement of verbal memory among cognitive dimension. Previous studies have reported improvement of verbal memory and fluency by administration of oral aripiprazole, and similar effects were observed in the present patients as well.2 During the maintenance phase, decrease in the negative symptoms and inhibition of extrapyramidal symptoms (EPS) are critical for the maintenance and improvement of cognitive function. In the present patients, AOM did not exacerbate the negative symptoms, and but improved EPS, which may have helped improve cognitive function. Furthermore, the steady-state plasma concentration ranges in the present patients were consistent with those observed in international repeated-dose studies.3 Therefore, the optimal doses of AOM (300 mg and 400 mg) can be used as treatment options that have high efficacy and tolerability for maintenance therapy of schizophrenia. Dr Suzuki has received honoraria from Janssen, Otsuka, Dainippon Sumitomo, Shionogi, and Yoshitomiyakuhin for lectures. Dr Sekiguchi has received honoraria from Janssen and Otsuka for lectures.