Efficacy and safety of aripiprazole once-monthly versus oral aripiprazole in Chinese patients with acute schizophrenia: a multicenter, randomized, double-blind, non-inferiority study.

OBJECTIVE: The present study aimed to evaluate the efficacy and safety of aripiprazole once-monthly (AOM) compared to oral aripiprazole in treating acute schizophrenia. METHODS: This randomized, double-blind, non-inferiority study recruited patients from 15 trial sites across China from May 2017 to April 2019. Patients with an acute psychotic episode received AOM at 400 mg or oral aripiprazole at 10-20 mg for 12 weeks. The primary and secondary efficacy endpoints were the difference in scores from baseline to week 10, as assessed on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions-Severity (CGI-S) scores, respectively. RESULTS: A total of 436 patients were randomized. Among them, 159/218 (72.9%) and 165/218 (75.7%) in the AOM and oral aripiprazole groups completed 10 weeks of treatment, respectively. The least-squares (LS) mean changes from baseline to endpoint (week 10) in PANSS were - 33.6 for the AOM group and - 34.8 in the oral aripiprazole group, respectively, with a difference of - 1.2 (95% CI: - 4.1, 1.7). The non-inferiority margin of AOM to oral aripiprazole was - 4.1, which was above the lower limit of the pre-defined margin. The altered CGI-S score was - 2.2 and - 2.3 in the AOM and oral aripiprazole groups, respectively. The incidence of treatment-emergent adverse events (TEAEs) was similar in both groups. The rate of discontinuation due to TEAEs was 2.3% and 3.2% in the AOM and oral aripiprazole groups, respectively. CONCLUSIONS: This study confirmed the efficacy and safety of AOM for the treatment of Chinese patients with acute schizophrenia. The non-inferiority of AOM to oral aripiprazole was established, with comparable efficacy and tolerability. These findings suggested that AOM could be used as a treatment option for patients experiencing an acute episode of schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03172871.

Randomized controlled trial comparing changes in serum prolactin and weight among female patients with first-episode schizophrenia over 12 months of treatment with risperidone or quetiapine.

BACKGROUND: Increased serum prolactin and weight gain are common side effects of atypical antipsychotics but few studies have assessed the long-term pattern of these adverse effects. AIM: Compare the effects of risperidone and quetiapine on serum prolactin and weight over 12 months of treatment among female patients with first-episode schizophrenia. METHODS: Eighty female inpatients with first-episode schizophrenia were randomly assigned to receive risperidone (n=40) or quetiapine (n=40) for 12 months. Prolactin concentration, weight and height were measured one day before starting treatment and 1, 3, 6, 9 and 12 months after initiating treatment. Severity of symptoms was assessed at the same time periods using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Thirty-one patients in the risperidone group and 33 patients in the quetiapine group completed the 12 months of treatment. PANSS scores decreased at each follow-up assessment for both groups; the improvement was significantly greater in the risperidone group after 3 months and 6 months of treatment but by the 9th month of treatment the level of improvement in the two groups was similar. In the quetiapine group serum prolactin remained stable throughout the 12 months but in the risperidone group the serum prolactin level increased 3.5- to 5.2-fold over the one-year follow-up. Weight gain was seen in both groups, particularly during the first 3 months of treatment: 62% of the increase in BMI in both groups had occurred by the end of the 3rd month of treatment. No between-group differences in weight changes were observed. The correlation between changes in weight and changes in prolactin levels were weakly positive: rs=0.17(p=0.104) in the risperidone group and r=0.07 (p=0.862) in the quetiapine group. CONCLUSIONS: Risperidone and quetiapine had similar efficacy in the first year of treatment of first-episode schizophrenia though risperidone was more rapidly effective. Use of risperidone was associated with chronic hyperprolactinemia but this did not occur with quetiapine. Long-term use of both drugs was associated with sustained weight gain; the timing and magnitude of the weight gain is similar for the two drugs. Weight gain was not strongly related to changes in prolactin levels.

Association analysis of COMT/MTHFR polymorphisms and major depressive disorder in Chinese Han population.

BACKGROUND: In several previous biochemical and genetic studies, the Val158Met polymorphism of the gene encoding catechol-O-methyltransferase (COMT) and the C677T polymorphism of Methylenetetrahydrofolate reductase (MTHFR) have been suggested to be involved in the pathogenesis as well as the treatment response of major depressive disorder (MDD), but the results have been inconsistent. In this study, we investigate the association of COMT/MTHFR and their interactions with MDD and antidepressant response in Chinese Han population. METHODS: Three hundred and sixty eight depressed patients who met DSM-IV criteria for MDD were recruited for the study. Two hundred and nineteen normal controls were recruited from the local community. Patients and normal controls were genotyped for the functional COMT val158met and MTHFR C677T polymorphisms. Patients were characterized for clinical response to antidepressant treatment as measured by intra-individual changes of Hamilton Depression (HAMD-17) scores over 6 weeks. RESULTS: The T allele (OR=1.81; CI95%=1.40-2.34, P<0.001) and C/T genotype (OR=3.66; CI95% =2.53-5.28, P<0.001) of MTHFR C677T were significantly different between case and control groups. The COMT Met/Val genotype was more common among depressed individuals than among controls (OR=1.52, CI95%=1.04-2.21, P=0.02). LIMITATION: There is disequilibrium in age and sex between case and control groups. Though we control the two variables in the statistic analysis, to be more accurate, we need to increase sample size in further study. CONCLUSION: Individuals with the genotype COMT Met/Val and MTHFR C/T have more probability of suffering from MDD. However, there is no association between gene polymorphism and treatment response.

[Research on association of BDNF gene Val66Met polymorphism with efficacy of antidepressants and plasma BDNF level].

OBJECTIVE: To assess the association of BDNF gene Val66Met polymorphism with efficacy of antidepressant treatment and plasma BDNF level. METHODS: Two hundred and forty-nine ethnic Han Chinese patients with depression(study group), who have met the diagnostic criteria of DSM-IV, were prescribed with venlafaxine or paroxetine. Two hundred and two healthy individuals were recruited as the control group. General demographic information such as gender, age, educational status, occupation, and marriage status were collected. HAMD-17 was adopted as the primary rating tool to evaluate the severity of depression on the baseline and at the end of 1st, 2nd, 4th, 6th week of treatment. PCR-restriction fragment length polymorphism was applied to determine the Val66Met polymorphism of the BDNF gene in the two groups. Plasma BDNF concentration was measured with ELISA before and after 6 weeks of treatment. RESULTS: No significant differences have been found in HAMD scores and reduction of HAMD scores on the baseline and at the end of 1 st, 2nd, 4th, 6th weeks of treatment for each genotype. Nor were significant differences found in the Val66Met genotypes and allelic frequency between patients who achieved remission or not after 6 weeks' treatment as well as the healthy volunteers. The plasma BDNF level in depression patients was lower than that in healthy controls. The BDNF level has increased significantly after 6 weeks' treatment with both venlafaxine and paroxetine, but was still lower than the healthy controls. The BDNF level in the patients achieved remission who were treated with venlafaxine was similar to the normal controls, while those treated with paroxetine was still lower than normal controls. The BDNF level in patients who have not achieved remission was lower than normal controls. The BDNF level was not associated with the Val66Met polymorphism on the baseline and the end of 6th week. CONCLUSION: No association has been found between the efficacy of venlafaxine or paroxetine and the BDNF Val66Met polymorphism. The BDNF level of patients with depression is significantly lower than healthy controls on the baseline, and can be enhanced with the treatment. Particularly, the BDNF level in patients who achieved remission after the treatment of venlafaxine can rise to normal. The level of BDNF has certain value in the forecasting of efficacy in the anti-depression therapy. BDNF level is not associated with the Val66Met polymorphism of the BDNF gene.

[Effects of apolipoprotein E genetic polymorphism on susceptibility of depression and efficacy of antidepressants].

OBJECTIVE: To assess the effects of apolipoprotein E (APOE) polymorphism on the susceptibility of depression and the efficacy of antidepressants. METHODS: A total of 275 patients with depression, who met the diagnostic criteria of both CCMD-3 and DSM-4, were randomly assigned into venlafaxine group (n=136)and paroxetine group(n=139). Another 202 healthy subjects were enrolled as the control group. Hamilton Rating Scale for Depression (HAMD)-17 was adopted as the primary rating instrument to evaluate the severity of depression on the baseline and the end of the 1st, 2nd, 4th, 6th week after treatment, respectively. HAMD scores ≤7 was defined as remission, and the reduction of HAMD scores ≥50% was defined as response while <50% was defined as invalid. PCR-restriction fragment length polymorphisms (PCR-RFLP) was applied to detect the genetic polymorphism of the APOE in the case groups and control group. RESULTS: In the venlafaxine group, the remission rate was 52.9%(n=72), the response rate was 26.5%(n=36), and the invalid rate was 20.6%(n=28), whereas the corresponding data in the paroxetine group wee 42.4%(n=59), 31.7%(n=44), and 25.9% (n=36), respectively. There were no significant differences in the efficacy between the two groups(p>0.05). In the venlafaxine group, there were no significant differences in the genotypes and the allele distribution frequency of APOEΕ2/Ε3/Ε4 between the remitters, nonremitters, and healthy controls at the end of the 6th week(p>0.05), but there was significant differences in the allele distribution frequency between the nonremitters and healthy controls(p=0.02). In paroxetine group, there were no significant differences in the genotypes and the allele distribution frequency of APOEΕ2/Ε3/Ε4 among the remitters, nonremitters and healthy controls at the end of the 6th week(p>0.05), but there were significant differences in the allele distribution frequency between the nonremitters and healthy controls (p=0.04); in addition, there were also significant differences in Ε2/Ε3 and Ε4 allele between the two groups (p=0.014). CONCLUSIONS: The APOE gene may not play a major role in the pathogenesis of major depression. The efficacy of venlafaxine is same as paroxetine after treatment for six weeks. The APOE (Ε2+Ε3) allele may be an indicator of the bad efficacy of paroxetine treatment.

Tryptophan hydroxylase 2 gene is associated with major depressive disorder in a female Chinese population.

BACKGROUND: Previous candidate gene studies of major depressive disorder (MDD) have provided inconclusive evidence of association for genes with strong biological rationale for MDD. In this study, we aimed to investigate the association of tryptophan hydroxylase 2 gene with MDD and its treatment response in the Chinese Han population. METHODS: Three hundred and sixty eight depressed patients who met DSM-IV criteria for major depressive disorder were recruited for the study. 371 normal controls were recruited from local community. Patients and normal controls were genotyped for TPH2 (rs4290270 and rs7305115) variants by polymerase chain reaction. Male and female subjects were analyzed separately. RESULTS: No differences were found in the frequencies of the single alleles and genotypes of the tested polymorphisms between MDD patients and normal group. The frequency of the A-A haplotype was significantly higher in female MDD compared to healthy female controls (P<0.05). No significant association with treatment response was discovered in haplotype and single-marker analysis. LIMITATIONS: This study lacks a placebo control and we cannot definitively exclude the possibility that some patients in the responder group responded to the placebo effect alone. CONCLUSION: The result suggests that TPH2 gene may have a gender dependent effect on susceptibility to MDD but not with its treatment response in Chinese Han population. Further studies are needed to replicate the association that we observed.