Comparison between olanzapine and aripiprazole treatment for 104 weeks after hospital discharge in schizophrenia spectrum disorders: a multicenter retrospective cohort study in a real-world setting.

RATIONALE: The long-term effectiveness of olanzapine and aripiprazole in real clinical conditions at flexible doses in patients after hospital discharge has not been evaluated yet. OBJECTIVES: This study was a multicenter retrospective cohort study. Patients with schizophrenia (n = 398) were prescribed olanzapine (n = 303) or aripiprazole (n = 95) at hospital discharge. The continuation of olanzapine or aripiprazole at 26, 52, or 104 weeks after the hospital discharge were compared using a Cox proportional hazards model and adjusted for possible confounders. RESULTS: The Kaplan-Meier survival curves revealed that the continuation of olanzapine at 26 (P = 0.001) and 52 weeks (P = 0.018) was significantly higher than that of aripiprazole but not at 104 weeks. Olanzapine was better than aripiprazole in efficacy at 26 (hazard ratio: 0.321, 95% confidence interval: 0.159-0.645, P = 0.001), 52 (hazard ratio: 0.405, 95% confidence interval: 0.209-0.786, P = 0.008), and 104 weeks (hazard ratio: 0.438, 95% confidence interval: 0.246-0.780, P = 0.005). Aripiprazole was better than olanzapine in tolerability at 104 weeks (hazard ratio: 4.574, 95% confidence interval: 1.415-14.787, P = 0.011). Rates after two years continuation of olanzapine and aripiprazole were not significantly different in patients with less than five years' duration of illness, but olanzapine was more commonly maintained for more than two years in those patients who had been ill for over five years' due to its greater efficacy. CONCLUSION: Olanzapine treatment showed better continuation rates at 26 and 52 after hospital discharge than aripiprazole, whereas maintenance with the two antipsychotics did not differ significantly at 104 weeks, due reduced tolerability of long-term olanzapine treatment.

Two-year effectiveness of risperidone and aripiprazole in the maintenance treatment of patients with recent-onset or chronic schizophrenia and related psychotic disorders: a retrospective multicenter study.

This study aimed to assess the comparative effectiveness of risperidone (RIS) versus aripiprazole (ARP) in patients with recent-onset or chronic schizophrenia during maintenance treatment and to examine the interaction between illness duration and the effectiveness of the treatment. All adult patients with schizophrenia and related disorders discharged from four psychiatric hospitals between 2006 and 2012 were screened and the 2-year continuation rates of monotherapy using RIS or ARP after discharge were examined retrospectively. The treatment continuation of the two drugs in patients with recent-onset (illness duration <5 years) or chronic schizophrenia (illness duration ≥5 years) and the moderator effect of illness duration on the effectiveness of the treatment were analyzed. Of 328 patients, 233 received RIS and 95 received ARP. No significant difference was found between the two drugs in the treatment continuation for the entire sample. However, there was a significant difference favoring ARP in the recent-onset subgroup mainly because of differences in tolerability, whereas RIS tended to present better outcomes in patients with chronic illness. Furthermore, there was a significant variation in the effectiveness of the treatment between recent-onset and chronic schizophrenia. Our results suggest that illness duration is an important moderator in terms of the long-term effectiveness of the two drugs.

Optimal Dosing of Risperidone and Olanzapine in the Maintenance Treatment for Patients With Schizophrenia and Related Psychotic Disorders: A Retrospective Multicenter Study.

OBJECTIVES: This study aims to determine the optimal tolerability dose ranges of risperidone (RIS) and olanzapine (OLZ) administered during schizophrenia maintenance phase. METHODS: Two-year continuation rates of prescription at discharge were examined using a retrospective cohort study method. Adult patients with schizophrenia and related psychotic disorders, receiving antipsychotic monotherapy with RIS or OLZ at discharge, were included. The primary outcome measures were the time to treatment discontinuation and 2-year continuation rates at 4 modal dose ranges of each drug. We estimated the optimal tolerability dose ranges by comparing the continuation rates at various modal doses. RESULTS: Of 648 patients, 344 received RIS and 304 received OLZ. The RIS 2-year continuation rates at 4 daily modal dose ranges were significantly different (0.5-2.5 mg: 46.0%, 3.0-5.0 mg: 40.0%, 5.5-7.5 mg: 30.0%, and 8.0-10.0 mg: 28.0%), with the difference favoring RIS at lower doses (0.5-5.0 mg) more than higher doses (5.5-10.0 mg). In contrast, there were no significant differences among OLZ 4 modal dose ranges (2.5-7.5 mg: 49.1%, 10.0-15.0 mg: 42.6%, 17.5-22.5 mg: 40.9%, and 25.0-30.0 mg: 39.0%). The time to treatment discontinuation significantly favored OLZ over RIS. However, it did not significantly differ between RIS and OLZ at lower doses. CONCLUSIONS: It is suggested that the optimal tolerability dose range during maintenance treatment is 0.5 to 5.0 mg/d for RIS and 2.5 to 30 mg/d for OLZ, and that RIS at lower doses is comparable with OLZ at lower doses.

Localized cortical dipole imaging using a small number of electrodes based on independent component analysis.

The spatial resolution of scalp potential mapping is limited because of low conductivity of a skull. Cortical dipole layer imaging has been proposed as a method to visualize brain electrical activity with high spatial resolution. According to this method, about 100 electrodes were required to measure whole brain electrical activity. In the present study, we investigated simplified cortical dipole imaging with a small number of electrodes. The density of electrodes and the spatial resolution are in a trade-off relation. Thus, the number of electrodes was reduced by limiting the visualization region of interest, without lowering the density of electrodes. Moreover, independent component analysis was applied to the multiple signal sources to extract an attention signal from the other signals and noise. In simulation, even if the number of electrodes was reduced to 25, the obtained results were almost equivalent to the case with whole brain electrodes. The proposed method was applied to human experimental data of movement-related potential. We confirmed that the proposed method provided high resolution cortical dipole imaging with localized distribution.

Unique pharmacological profile of aripiprazole as the phasic component buster.

RATIONALE: Aripiprazole is a recently introduced antipsychotic with a unique pharmacological profile, a dopamine partial agonist. Dopaminergic neural transmission has two different components, tonic and phasic, which have different physiological functions, but the effects of aripiprazole on tonic and phasic components are not reported. OBJECTIVE: Studies on antipsychotics including aripiprazole and tonic/phasic dopamine transmission are summarized. RESULTS: Antipsychotics exert efficacy without extrapyramidal side effects (EPS's) when their occupation of dopamine D2 receptors reaches 65-80%. When a "tightly binding" antipsychotic binds 70% of D2 receptors, the remaining 30% are available for endogenous dopamine to bind. These tight antipsychotics suppress dopamine transmission in both tonic/phasic components equally so that similar proportions are kept. Aripiprazole is effective when >90% of D2 receptors are occupied. In this condition, less than 10% of D2 receptors are available for endogenous dopamine to bind; however, EPS's do not occur because aripiprazole exerts partial dopaminergic agonistic activity. Because the concentration of aripiprazole in the brain is relatively constant and it binds to D2 receptors tightly, the added dopaminergic agonism may show a tonic nature. Thus, aripiprazole suppresses the phasic component relatively more than the tonic component. In contrast, under treatment with "loosely binding" antipsychotics, phasic dopaminergic transmission is relatively preserved. CONCLUSIONS: Tight antipsychotics suppress both tonic and phasic components equally. Aripiprazole suppresses the phasic component relatively more than the tonic; that is, aripiprazole is a phasic [corrected] component buster. By contrast, suppression of the phasic component by loosely binding antipsychotics may be relatively weak.