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.

Association between previous high-dose antipsychotic therapy and brexpiprazole discontinuation after the initiation of brexpiprazole in patients with schizophrenia or schizoaffective disorder.

The objective of this study was to identify the factors associated with brexpiprazole discontinuation after initiating brexpiprazole in patients with schizophrenia or schizoaffective disorder. All patients with schizophrenia or schizoaffective disorder who were started on brexpiprazole in our institution between May 2018 and April 2019 were retrospectively screened. The continuation rate of brexpiprazole during a follow-up period of 16 weeks was examined. Multivariate Cox regression analysis was conducted to identify predictors of brexpiprazole discontinuation. During the follow-up period, 52 out of 120 patients (43.4%) discontinued brexpiprazole. Thirty-three subjects discontinued due to a lack of efficacy, eight more due to intolerability and a further 11 for other reasons. The continuation rate of brexpiprazole among patients who were previously on high-dose antipsychotics (chlorpromazine-equivalent doses > 800 mg) was significantly lower than that in those who were previously on low-dose antipsychotics (chlorpromazine-equivalent doses ≤ 800 mg). The Cox regression analysis showed that only having been subject to a high dose of their previous antipsychotics was independently associated with an increased risk of brexpiprazole discontinuation (P < 0.001). Patients who were previously on high-dose antipsychotics discontinued brexpiprazole mainly due to inefficacy. Previous high-dose antipsychotic therapy is an independent risk factor for brexpiprazole discontinuation in patients with schizophrenia or schizoaffective disorder.

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.

Efficacy of second-generation antipsychotics in patients at ultra-high risk and those with first-episode or multi-episode schizophrenia.

AIM: The aim of this study was to examine the speed of response, doses, and safety of treatment with second-generation antipsychotics (SGAs) in patients at ultra-high risk (UHR) compared to those with schizophrenia. METHODS: A 12-week open-label, prospective study of SGAs was performed in UHR patients and those with first-episode schizophrenia (FES) and multi-episode schizophrenia (MES). The subjects were 14-30 years old and were recruited at Zikei Hospital, Okayama, Japan from December 1, 2006 to December 1, 2011. Treatment was carried out in a natural setting in an open-label format, but clinical evaluation was performed blind. The clinical rating scales include the Global Assessment of Functioning (GAF), the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression-Severity scale (CGI-S). RESULTS: UHR (n = 17), FES (n = 23), and MES (n = 21) patients all showed significant improvements on the GAF, PANSS, and CGI-S. However, the UHR patients showed significantly greater improvement on the GAF at weeks 4, 8, and 12 compared to the other groups, and a significantly lower modal dose of SGAs (chlorpromazine equivalent: 183 [201.1] mg/day, mean [SD]) was needed for improvement in the UHR group. Each group was also prescribed anticholinergic agents during the study period and the UHR group had significantly fewer extrapyramidal symptoms (only 6%) compared with the FES group. CONCLUSION: Our findings suggest that UHR patients have a better response to SGAs compared to patients with schizophrenia, and that these drugs can be given safely by minimizing the dosage of SGAs and using anticholinergic agents.

Influences of casein hydrolysate ingestion on cerebral activity, autonomic nerve activity, and anxiety.

This study examined the influences of the oral ingestion of casein hydrolysate from bovine milk at rest physiologically and psychologically. Eleven male university students were given a casein hydrolysate drink (H) or a maltitol drink as a control (C) in a crossover study. Just before and one hour after ingestion of each drink, the total-hemoglobin (tHb) concentrations at ten points of the prefrontal cortex to evaluate cerebral activity, and heart rate variability (HRV) to evaluate autonomic nerve activity through spectral analysis were measured as physiological indicators. The Japanese version of the State--Trait Anxiety Inventory--state anxiety (STAI-s) score was also used, as a psychological indicator. In comparison between H and C ingestion, a significant difference is observed only in tHb concentrations at one of ten points. At this point, the change in tHb concentration was lower after H ingestion compared to C ingestion. And in comparison between before and after ingestion of each drink, a significant increase in tHb concentration at two points after C ingestion, a significant increase in parasympathetic activity and decrease in sympathetic activity after H ingestion, and a significant decrease in STAI-s score in H ingestion were observed. These results suggest that ingestion of the casein hydrolysate may keep prefrontal cortex activity stable while maltitol ingestion partially increases the activity. Moreover, there is a possibility that casein hydrolysate might decrease sympathetic activity, increase parasympathetic activity, and lower anxiety. We conclude that the bovine milk casein hydrolysate may have more relaxing effects than maltitol.