Pharmacopsychiatry最新文献

Introduction: The importance of identifying relevant indicators of antidepressant efficacy is highlighted by the low response rates to antidepressant treatment for depression. The ABC gene family, encoding ATP-dependent transport proteins facilitating the transport of psychotropic drugs, has drawn attention. This study delved into the relationship between antidepressant efficacy and seven single nucleotide polymorphisms of ABCB1 and ABCB6 genes.

Methods: A total of 549 depressed patients participated in the study, and all completed a 6-week course of antidepressant treatment. Cognitive function was assessed at baseline and post-treatment. Patients were categorized based on post-treatment HAMD-17 scores (with HAMD≤7 indicating remission), and comparisons were made between different groups in terms of allelic gene frequencies and genotypes. Logistic regression was used to explore the interaction between cognitive function and genotype on efficacy. Dual-luciferase reporter assays were performed to compare the regulatory effects of rs1109866 allele variants on the ABCB6 promoter.

Results: There were no notable differences in allelic gene frequencies and genotypes between the remission and non-remission groups. Nonetheless, a significant interaction was identified between the rs1109866 genotype and language fluency-related indicators concerning efficacy (p=0.029) before correction. The dual-luciferase reporter assays demonstrated markedly higher fluorescence intensity of rs1109866-C compared to that of rs1109866-T (p<0.001).

Discussion: Relying solely on genetic polymorphisms of ABC family genes as predictors of antidepressant treatment response may not be sufficient. However, the interaction between the rs1109866 and cognition plays a pivotal role. The potentially enhanced transcriptional activity of rs1109866-C might offer insight into its impact on antidepressant efficacy.

Introduction: This study evaluates the impact of Parkinson disease (PD) medication in advanced PD on neuropsychological performance, psychiatric symptoms, impulsivity and the quality of life. In the 4-year period 27 patients with advanced PD, scheduled for deep brain stimulation (DBS) surgery (N=27, mean age: 58.9±7.1, disease duration: 10.0 years±4.2) were examined preoperatively. We hypothesized that a high dosage of PD medication or current use of dopamine agonists affect cognitive functioning and psychiatric wellbeing.

Methods: We performed two subgroup analyses with low versus high levodopa-equivalent Dosage (LED) medication and without versus with dopaminagonistic medication.

Results: The neuropsychological testing revealed significant differences in the verbal learn- and memory-test (VLMT) during the learning passage (U=36.500, Z=- 2.475, p=0.012) and in the subtest of the semantic fluency of Regensburg verbal fluency test (RWT) (t(25)=- 2.066, p=0.049) with better results for patients without dopaminagonistic medication. Pearson correlation analyses of LED in correlation with the clinical and cognitive dependent variables showed a significant higher PANSS total score in patients with higher LED medication (r=0.491, p=0.009). In addition, lower LED treatment was associated with significant higher scores in the impulsivity perseverance subtest (r=- 0.509, p=0.008).

Discussion: In conclusion, we found lower LEDs to be correlated with a better perseverance in the impulsivity test and additional treatment with a dopamine agonist influenced some verbal learning tasks and the PANSS total score in patients with advanced PD. This should be considered prior to DBS surgery.

Objectives: The determination of anesthetic depth has been used to assess the optimal moment for applying electrical stimuli in electroconvulsive therapy (ECT), as some of the anesthetics used can reduce its effectiveness. In this study, seizure quality was assessed using anesthetic depth measurement with the patient state index (PSI).

Methods: A prospective experimental study was conducted with a control group, including a sample of 346 stimulations (PSI=134; Control=212) in 51 patients admitted and diagnosed with major depressive disorders. Seizure adequacy variables (seizure time in electroencephalogram [EEG] and motor activity, visual evaluation of the EEG, ECT-EEG parameter rating scale [EEPRS], seizure concordance, central inhibition, automated parameters, and autonomic activation) were assessed using linear mixed-effects models for continuous variables and generalized linear mixed-effects models for dichotomous variables.

Results: The PSI group required lower stimulation energy. The use of the PSI was associated with longer seizure time, both motor and electroencephalographic, higher quality of the EEG recording, better seizure concordance, and higher values for the automated parameters of maximum sustained coherence and time to peak coherence.

Conclusions: The use of the PSI to measure anesthetic depth may reduce the electrical stimulus charge required and improve seizure quality in ECT modified with propofol.

The future of depression pharmacotherapy lies in a precision medicine approach that recognizes that depression is a disease where different causalities drive symptoms. That approach calls for a departure from current diagnostic categories, which are broad enough to allow adherence to the "one-size-fits-all" paradigm, which is complementary to the routine use of "broad-spectrum" mono-amine antidepressants. Similar to oncology, narrowing the overinclusive diagnostic window by implementing laboratory tests, which guide specifically targeted treatments, will be a major step forward in overcoming the present drug discovery crisis.A substantial subgroup of patients presents with signs and symptoms of hypothalamic-pituitary-adrenocortical (HPA) overactivity. Therefore, this stress hormone system was considered to offer worthwhile targets. Some promising results emerged, but in sum, the results achieved by targeting corticosteroid receptors were mixed.More specific are non-peptidergic drugs that block stress-responsive neuropeptides, corticotropin-releasing hormone (CRH), and arginine vasopressin (AVP) in the brain by antagonizing their cognate CRHR1-and V1b-receptors. If a patient's depressive symptomatology is driven by overactive V1b-signaling then a V1b-receptor antagonist should be first-line treatment. To identify the patient having this V1b-receptor overactivity, a neuroendocrine test, the so-called dex/CRH-test, was developed, which indicates central AVP release but is too complicated to be routinely used. Therefore, this test was transformed into a gene-based "near-patient" test that allows immediate identification if a depressed patient's symptomatology is driven by overactive V1b-receptor signaling. We believe that this precision medicine approach will be the next major innovation in the pharmacotherapy of depression.

Background: Currently, guidance on the most effective treatment for patients with clozapine-resistant schizophrenia-spectrum disorders (SSD) is lacking. While augmentation strategies to clozapine with aripiprazole and electroconvulsive therapy (ECT) have been demonstrated to be effective in patients with clozapine-resistant schizophrenia spectrum disorders (CRS), head-to-head comparisons between these addition strategies are unavailable. We therefore aim to examine the feasibility of a larger randomized, single-blind trial comparing the effectiveness, cost-effectiveness, and safety of aripiprazole addition vs. ECT addition in CRS.

Methods: In this multi-center, randomized, single-blind feasibility study, the feasibility of recruiting 20 participants with CRS who will be randomized to either aripiprazole or bilateral ECT addition will be assessed. The main endpoint is the number of patients willing to be randomized. The number of screened individuals and reasons to decline participation will be recorded. Effects will be estimated for the benefit of the foreseen larger trial. To that end, differences between both arms in symptom severity will be assessed using blinded video assessments. In addition, tolerability (e. g., cognitive functioning), safety, quality of life, recovery, and all-cause discontinuation will be compared. The follow-up period is 16 weeks, after which non-responders will be given the option to switch to the other treatment.

Discussion: Strengths of this feasibility trial include maintaining blinding with video assessment, a possibility to switch groups in case of non-response, and a broad set of outcome measures. Identification of factors contributing to non-participation and drop-out will generate valuable information on trial feasibility and may enhance recruitment strategies in a follow-up RCT.

Trial registration: The study has been approved by the Medical Research Ethics Committee of the Amsterdam University Medical Center, location AMC, and was registered on 1 May 2022 in the EU Clinical Trials Register (EudraCT) under the trial name 'EMECLO' (2021-006333-19).

Objective: To determine if the cardiac function and "endocrinium" of Chinese patients are associated with dopamine D₂ (DRD2) (rs6276) and DRD3 (rs6280, rs963468) genetic polymorphisms when treated with amisulpride.

Methods: This study enrolled 148 patients with schizophrenia who took amisulpride orally for 8 weeks. DRD2 (rs6276) and DRD3 (rs6280, rs963468) genetic polymorphisms were detected with TaqMan-MGB allelic discrimination.

Results: Analysis by multivariate covariance analysis (MANCOVA) showed that after adjusting for age, gender, and the baseline level, the increase in the level of aspartate aminotransferase (AST) and creatine kinase (CK) in the rs6276 AG group was higher than that in the AA and GG groups. Similarly, the changed estradiol (E₂) level in rs6276 GG and rs963468 GG groups was higher than that in the other two groups. Adjusting for covariates, the increased triglyceride (TG) level in rs6276 GG and rs963468 GG groups was the highest among their different genotype groups. The increase in the level of "AST" in the rs6280 TT group was higher than that in the CC and CT groups upon adjusting for covariates. Similarly, MANCOVA showed that the increase in the level of "CK" in the rs6280 CT group was higher than that in the CC and CT groups. Besides, the increased level of "PRL" in the rs6280 CC group and rs963468 GG group was higher than that in their other two genotypes groups.

Conclusion: DRD2 (rs6276) and DRD3 (rs6280, rs963468) polymorphisms can affect amisulpride tolerability since they are associated with the observed adverse reactions, including cardiac dysfunction and endocrine disorders in Chinese patients with schizophrenia.