Association Between Polymorphisms in Dopamine-Related Genes and Orthopedic Pain Expression in a Chinese Elderly Population.

OBJECTIVES: The dopaminergic pathway plays a vital role in pain expression. Here, our aim was to investigate the effects of polymorphisms in genes encoding the dopamine active transporter (SLC6A3) and dopamine receptor D2 (DRD2) on preoperative pain expression among patients preparing for orthopedic surgery. METHODS: Chinese elderly patients scheduled for orthopedic surgery were enrolled. The VAS was used to evaluate pain intensity (score range 0 to 10; 0 = no pain; 10 = worst pain possible). Depressive symptoms were evaluated via the 15-item Geriatric Depression Scale. DNA was isolated from venous blood samples, and single-nucleotide polymorphisms of SLC6A3 and DRD2 were genotyped. Multiple linear regressions analyses were carried out to adjust the results for confounders. RESULTS: A total of 294 patients with a mean age of 73.82 ± 8.03 years were enrolled in this study. After adjustment for confounders, rs393795 in SLC6A3 showed a significant association with preoperative VAS scores. Patients with the A/A genotype reported lower mean pain scores than did those with the A/C genotype (P = 0.026). Subsequent depression-stratified analysis of rs6276 in DRD2 revealed that patients with the A/A genotype had higher pain scores than did those with the G/G genotype (P = 0.043). No associations were found for DRD2 rs6277 in the whole study population or depression-stratified groups. CONCLUSION: Genetic variations in SLC6A3 and DRD2 may play an important role in pain expression among the elderly prior to orthopedic surgery.

The efficacy and tolerability of paliperidone in mania of bipolar disorder: A preliminary meta-analysis.

Paliperidone may be effective for the treatment of bipolar disorder (BD); however, the evidence has been mixed. This is the first meta-analysis to evaluate the efficacy, safety, and tolerability of paliperidone for the treatment of BD. We performed a systematic search of the literature using major electronic databases from inception to January 27, 2017. Randomized control trials (RCTs) investigating paliperidone treatment among patients with BD versus a placebo or other second-generation antipsychotics were included. We then performed exploratory random-effects meta-analysis. The 3 included RCTs compared paliperidone with placebo (667 patients received paliperidone and 369 received a placebo). The dose of paliperidone in the included studies ranged from 3 to 12 mg/day. Paliperidone did not significantly improve manic symptoms (Hedges' g = -0.221, p = .067, k = 5) compared with a placebo; however, it was superior to a placebo in improving psychosocial function (Hedges' g = -0.156, p = .042, k = 3) and general severity (Hedges' g = -0.205, p = .001, k = 5). Paliperidone was associated with a greater use of anticholinergic medications (p = .002), increased body weight (p < .001), and higher serum prolactin level (p < .001) compared with a placebo. Our preliminary results suggest that paliperidone does not offer significant benefits for the treatment of mania symptoms in BD compared with a placebo. In addition, treatment with paliperidone was associated with a higher incidence of adverse effects. Because of the limited number of studies, further well-designed RCTs are warranted. (PsycINFO Database Record

Efficacy, safety and tolerability of aripiprazole in bipolar disorder: An updated systematic review and meta-analysis of randomized controlled trials.

Numerous studies have investigated aripiprazole as a treatment for bipolar disorder (BD). therefore we conducted this comprehensive meta-analysis to investigate the efficacy and safety profile of aripiprazole in treating BD. Two authors conducted systematic searches of PubMed and ScienceDirect from inception until May 14th, 2017. Randomized controlled trials (RCTs) of people with BD who received aripiprazole were included. A total of 20 RCTs met the eligibility criteria, including two which investigated the efficacy of aripiprazole versus haloperidol (aripiprazole=340; haloperidol=337), three which compared aripiprazole versus lithium (aripiprazole=208; lithium=212), and 15 with multiple comparisons of aripiprazole versus a placebo (aripiprazole=1923; placebo=1499). Compared to a placebo, aripiprazole improved acute mania (Hedges' g: -0.299, p=0.001) and psychosis (Hedges' g: -0.296, p<0.001) in the acute mania state, but did not improve depressive symptoms (Hedges' g: -0.127, p=0.054) in the acute depressive state. Aripiprazole was associated with lower relapse rates in bipolar mania when used in combination versus a placebo in maintenance therapy (odds ratio: 0.522, p<0.029). Aripiprazole was also associated with higher levels of high density lipoprotein, lower dropout rates, but no difference in extrapyramidal symptoms in the maintenance phase versus a placebo or in comparison with other medications (haloperidol or lithium). Our results suggest that aripiprazole is effective and safe in treating bipolar mania. Further trials are necessary to evaluate the efficacy and tolerability versus other medications.

The DAOA gene is associated with schizophrenia in the Taiwanese population.

The gene D-amino acid oxidase activator (DAOA), which has a former name of G72, and the D-amino acid oxidase (DAO) gene have been suggested as candidate genes of schizophrenia. However, association studies have so far yielded equivocal results. We analyzed one single nucleotide polymorphism (SNP) for DAO (rs3741775) and seven SNPs for G72 (rs3916956, rs2391191, rs9558562, rs947267, rs778292, rs3918342, and rs1421292) in this study enrolling 248 schizophrenia cases and 267 controls in the Taiwanese samples. In SNP-based single locus association analyses, the rs778292 in the DAOA gene showed significant association with schizophrenia. The rs3741775 in the DAO gene could not withstand statistically significant after multiple corrections. Additionally, a three-SNP haplotype (rs778292-rs3918342-rs1421292) in the DAOA gene were observed to be significantly associated with schizophrenia. Among them, the TCT haplotype presented higher prevalence in controls than in cases whereas the TTT and CTT haplotype were significantly more frequent in cases than in controls. The study also provides significant evidence for epistatic interactions among DAOA and DAO gene in the development of schizophrenia. These results provide additional evidence and indicate that the DAOA gene and DAOA-DAO gene-gene interactions might play a role for schizophrenia in a Taiwanese sample.

Significant treatment effect of add-on ketamine anesthesia in electroconvulsive therapy in depressive patients: A meta-analysis.

Add-on ketamine anesthesia in electroconvulsive therapy (ECT) has been studied in depressive patients in several clinical trials with inconclusive findings. Two most recent meta-analyses reported insignificant findings with regards to the treatment effect of add-on ketamine anesthesia in ECT in depressive patients. The aim of this study is to update the current evidence and investigate the role of add-on ketamine anesthesia in ECT in depressive patients via a systematic review and meta-analysis. We performed a thorough literature search of the PubMed and ScienceDirect databases, and extracted all relevant clinical variables to compare the antidepressive outcomes between add-on ketamine anesthesia and other anesthetics in ECT. Total 16 articles with 346 patients receiving add-on ketamine anesthesia in ECT and 329 controls were recruited. We found that the antidepressive treatment effect of add-on ketamine anesthesia in ECT in depressive patients was significantly higher than that of other anesthetics (p<0.001). This significance persisted in both short-term (1-2 weeks) and moderate-term (3-4 weeks) treatment courses (all p<0.05). However, the side effect profiles and recovery time profiles were significantly worse in add-on ketamine anesthesia group than in control group. Our meta-analysis highlights the significantly higher antidepressive treatment effect of add-on ketamine in depressive patients receiving ECT compared to other anesthetics. However, clinicians need to take undesirable side effects into consideration when using add-on ketamine anesthesia in ECT in depressive patients.