Non response at week 4 as clinically useful indicator for antidepressant combination in major depressive disorder. A sequential RCT

We aimed to compare the efficacy and tolerability of mirtazapine versus SSRIs and to assess whether \ue2\u80\u9cnon-response at week 4\ue2\u80\u9d may be a clinical indicator for combining mirtazapine and SSRIs for subsequent treatment. One-hundred fifty-four outpatients with MDD were randomized to receive mirtazapine or SSRIs in step I (4 weeks). Non-responders in step I were randomly assigned to either mirtazapine or SSRIs monotherapy or their combination in step IIa while responders in step I continued the same monotherapy in step IIb for 4 weeks. In step I, mirtazapine showed significantly faster improvement as shown by higher remission rate at week 2 with NNT = 8 compared to SSRIs. Somnolence rate was higher in mirtazapine and nausea rate was higher in SSRIs. In step IIa, combination therapy showed a more favorable time course than SSRIs monotherapy. For subjects taking SSRIs in step I, combination therapy showed significant better improvement in the Hamilton Depression Rating (HAM-D) score both at week 6 (p = 0.006) and 8 (p = 0.013) than SSRIs monotherapy. About 80% of responders at week 4 could reach remission at week 8 and 64% of non-responders could not reach remission at week 8 for patients who continued monotherapy. When mirtazapine was added on for SSRIs non-responders at week 4, the remission rate increased by 5% and HAM-D score improved by 4 points. While for mirtazapine non-responders, SSRIs add-on was not equally effective. Mirtazapine may provide a faster improvement and \ue2\u80\u9cnon-response at week 4\ue2\u80\u9d may be indicator to mirtazapine add-on for patients receiving SSRIs

Remifentanil in electroconvulsive therapy: a systematic review and meta-analysis of randomized controlled trials

In electroconvulsive therapy (ECT), remifentanil is often used concurrently with anesthetics. The objective of this study was to provide an up-to-date and comprehensive review on how the addition of remifentanil to anesthetics affects seizure duration and circulatory dynamics in mECT. We performed a meta-analysis of RCTs that investigated seizure duration and circulatory dynamics in patients treated with ECT using anesthetics alone (non-remifentanil group) and with anesthetics plus remifentanil (remifentanil group). A total of 13 RCTs (380 patients and 1024 ECT sessions) were included. The remifentanil group showed a significantly prolonged seizure duration during ECT compared to the non-remifentanil group [motor: 9 studies, SMD\ua0=\ua01.25, 95\ua0% CI (0.21, 2.29), p\ua0=\ua00.02; electroencephalogram: 8 studies, SMD\ua0=\ua00.98, 95\ua0% CI (0.14, 1.82), p\ua0=\ua00.02]. The maximum systolic blood pressure (SBP) was significantly reduced in the remifentanil group compared to the non-remifentanil group [7 studies, SMD\ua0=\ua0 120.36, 95\ua0% CI ( 120.65, 0.07), p\ua0=\ua00.02]. Substantial heterogeneity was observed for meta-analyses for seizure durations, but a pre-planned subgroup analysis revealed that seizure duration was prolonged only when the use of the anesthetic dose was reduced in the remifentanil group. The results of our study suggest that addition of remifentanil to anesthesia in ECT may lead to prolonged seizure duration when it allows the use of reduced anesthetic doses. Further, the addition of remifentanil was associated with reduced maximum SBP

Serotonin 7 Receptor Variants Are Not Associated with Response to Second-Generation Antipsychotics in Japanese Schizophrenia Patients

Background: Individual differences in serotonin 7 receptor (5-HT7R) may result in variable response to antipsychotics with 5-HT7R antagonism. This study investigated the relationship between single nucleotide polymorphisms (SNPs) in the 5-HT7R gene (HTR7) and the efficacy of second-generation antipsychotic drugs with a high affinity for this receptor in Japanese schizophrenia. Methods: Perospirone or aripiprazole was administered to 100 patients with schizophrenia in a randomized controlled study. All patients were genotyped for three candidate SNPs (rs12412496, rs7916403, and rs1935349). Patient improvement on the Positive and Negative Syndrome Scale (PANSS) total score at 12 weeks was assessed as the primary outcome. PANSS 5-factor scores were investigated as the secondary outcome. Results: Improvement on the PANSS total score and genetic polymorphisms showed no correlation. The rs12412496-rs7916403-rs1935349 A-T-A haplotype was correlated with worse improvement in the cognition score (haplotype frequency: 0.285, p = 0.046, permuted p = 0.043). Conclusion: Our results show that HTR7 variants are not related to the overall improvement in schizophrenia symptoms

HTR1A gene polymorphisms and 5-HT1A receptor partial agonist antipsychotics efficacy in Schizophrenia

Individual differences in serotonin 1A (5-HT1A) receptor may result in variable response to antipsychotics with 5-HT1A receptor partial agonism. We investigated the relationship between 5-HT1A receptor gene (HTR1A) single nucleotide polymorphisms (SNPs) and efficacy of antipsychotics with 5-HT1A receptor partial agonism in Japanese patients with schizophrenia. Perospirone or aripiprazole was administered to 100 patients with schizophrenia in a randomized controlled study. Candidate SNPs were rs6295 (which affects HTR1A expression and function), rs1364043, rs878567, and rs10042486. Efficacy atweek 12 of treatment was evaluated using the Positive and Negative Syndrome Scale (PANSS) 5-factor subscales (excitement/hostility, depression/anxiety, cognition, positive, and negative). Rs1364043 T allele was correlated with the percent change in the PANSS 5-factor negative score (P < 0.01). Haplotype analysis showed that the rs10042486-rs6295-rs1364043 T-C-G haplotype was correlated with worse negative score improvement (haplotype frequency, 0.675; P = 0.014), and the relatively rare T-G-T haplotype correlated with better efficacy (haplotype frequency, 0.05; P = 0.031). This is the first study to show that rs10042486-rs6295-rs1364043 HTR1A variants may be correlated with the improvement of the PANSS 5-factor negative score during treatment with 5-HT1A partial agonist antipsychotics. Studies with larger sample sizes and in different ethnic groups are warranted

Antagonist and partial agonist at the dopamine D2 receptors in drug-na&#239;ve and non-drug-na&#239;ve schizophrenia: a randomized, controlled trial

Few data are available on the efficacy and safety of antipsychotics with different dopamine D2 receptor (D2-R)-binding properties in drug-na\uefve and non-drug-na\uefve schizophrenia. Thus, we aimed to assess whether antipsychotic medication history influences efficacy and tolerability in schizophrenia, based on a randomized controlled study of antipsychotics with mechanisms involving either full antagonism or partial agonism of D2-R. Patients with schizophrenia were recruited and given perospirone or aripiprazole in a 12-week, flexible-dose, open-label, randomized controlled study. Data were analyzed after dividing the patients into antipsychotic-na\uefve and antipsychotic-treated group according to antipsychotic medication histories. Efficacy and safety were evaluated using the Positive and Negative Syndrome Scale (PANSS), the Drug-Induced Extrapyramidal Symptoms Scale, and the Barnes Akathisia Rating Scale. In patients receiving perospirone, the antipsychotic-na\uefve group (n\ua0=\ua022) showed greater symptom improvement than that shown by the antipsychotic-treated group (n\ua0=\ua029), as assessed by efficacy evaluation scales such as the PANSS total, positive, and excited component score (p\ua0=\ua0.006, p\ua0<\ua0.001, p\ua0=\ua0.003, respectively). In patients receiving aripiprazole, however, there was no significant difference in efficacy between the antipsychotic-na\uefve (n\ua0=\ua018) and antipsychotic-treated (n\ua0=\ua031) groups. No significant intra-group or inter-group difference was noted with respect to any of the tolerability-related parameters assessed. The present study data support the hypothesis that antipsychotic medication history may influence efficacy in patients who receive a D2-R full antagonist but not a D2-R partial agonist

Cognitive function and risperidone long-acting injection vs. paliperidone palmitate in schizophrenia: A 6-month, open-label, randomized, pilot trial

Background: Recently, long-acting injection (LAI) of second-generation antipsychotics has become a valuable strategy for the treatment of schizophrenia. However, few studies have compared the effects of different LAI antipsychotics on cognitive functions so far. The present study aimed to compare the influence of risperidone LAIs (RLAI) and paliperidone palmitate LAIs (PP) on cognitive function in outpatients with schizophrenia. Methods: In this 6-month, open-label, randomized, and controlled study, 30 patients with schizophrenia who were treated with RLAIs were randomly allocated to the RLAI-continued group or the PP group. At baseline and 6 months, the patients were evaluated using the Brief Assessment of Cognition in Schizophrenia (BACS) that was the primary outcome of the study. The Subjective Well-being under Neuroleptic drug treatment-Short form (SWNS), the Positive and Negative Syndrome Scale (PANSS), and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) scores were secondary outcome variables and they were tested at the same time points. Results: The two groups did not differ in terms of PANSS, DIEPSS, or SWNS total score changes. However, the BACS score for the attention and processing speed item showed higher improvement in the PP group than the RLAI group (p = 0.039). Conclusions: The results of this preliminary study suggest that PPs may improve attention and processing speed more than RLAIs. Anyway, a replication in a larger and double-blind study is needed. Trial registration:UMIN000014470. Registered 10 July 201

The comparative effects of risperidone long-acting injection and paliperidone palmitate on social functioning in schizophrenia: A 6-month, open-label, randomized controlled pilot trial

Purpose: The aim of this study was to compare the effects of risperidone long-acting injection (RLAI) and paliperidone palmitate (PP) on non-acute-phase social functioning in patients with schizophrenia. Patients and Methods: In this 6-month pilot, open-label, randomized controlled study, 30 patients with schizophrenia who had been treated with RLAI were randomly allocated to the RLAI continuation group or switched to the PP group. Patients were evaluated at baseline and 6 months with the Social Functioning Scale (SFS) as the primary outcome variable and University of California San Diego Performance-Based Skills Assessment Brief (UPSA-B), Social Emotional Cognition Task (SECT), Positive and Negative Syndrome Scale (PANSS), and Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) scores as secondary outcomes. Results: At baseline, the two groups did not significantly differ in demographic or clinical features. The two groups did not differ in total score changes for the UPSA-B, the SECT, the PANSS, and the DIEPSS. However, the total scores and the two subscales of the SFS, i.e. independence-competence and independence-performance, were more improved in the PP group compared to the RLAI group (total scores, p = 0.038; competence, p = 0.001, and performance, p = 0.007, respectively). Conclusion: These results suggest that PP may improve the total social functioning, independent life competence, and performance as compared to the RLAI group. However, these results are preliminary and need independent replication in larger samples before any definitive statement can be made