Pharmacopsychiatry最新文献

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.

Introduction: While antipsychotics are often prescribed for behavioral and psychological symptoms of dementia (BPSD), typically on an off-label basis, these medications have serious adverse effects. This study investigated the long-term use of antipsychotics among inpatients with dementia displaying severe BPSD, focusing on how prescriptions change over time.

Methods: Medical charts at Kusakabe Memorial Hospital were retrospectively reviewed from October 2012 to September 2021. The study included patients diagnosed with dementia, admitted for BPSD, and were continuing antipsychotics at 3 months of their admission. Antipsychotic dosages were categorized as high (≥300 mg/d), medium (100-300 mg/d), and low (<100 mg/d) based on chlorpromazine equivalents and tracked until 15 months during hospitalization. Binary logistic regression was used to identify factors associated with dosage reductions between months 3 and 6.

Results: This study involved 188 patients, with an average age of 81.2 years, 67% of whom were diagnosed with Alzheimer's dementia. At 3 months, 15.4% were taking high, 44.1% on medium, and 40.4% on low dosages of antipsychotics. The highest average dosage was observed at 3 months, with a subsequent decrease over time. By the 12th month, 20-30% of patients in all dosage categories had stopped their antipsychotic medication. Significant factors for dosage reduction included higher initial doses (OR 1.003, 95%Cl: 1.001-1.006, P=0.01) and male gender (OR 2.481, 95%Cl: 1.251-4.918, P=0.009).

Discussion: A trajectory of antipsychotic dosage in inpatients with severe BPSD has rarely been reported. This research emphasizes the need for personalized strategies in managing long-term pharmacotherapy for this vulnerable group of patients.

Introduction: Pharmacoepidemiological data suggest that lithium prescriptions for bipolar disorder are gradually decreasing, with less attention having been paid to other indications.

Methods: We examined lithium prescriptions between 1994 and 2017 in data provided by the Drug Safety in Psychiatry Program AMSP, including psychiatric hospitals in Germany, Austria and Switzerland. We compared lithium use for different diagnoses before and after 2001 and in three periods (T1: 1994-2001, T2: 2002-2009, and T3: 2010-2017).

Results: In a total of 158,384 adult inpatients (54% female, mean age 47.4±17.0 years), we observed a statistically significant decrease in lithium prescriptions between 1994-2000 and 2001-2017 in patients with schizophrenia spectrum disorder from 7.7% to 5.1% and in patients with affective disorders from 16.8% to 9.6%. Decreases in use were also observed for diagnostic subgroups: schizoaffective disorder (ICD-10 F25: 27.8% to 17.4%), bipolar disorder (F31: 41.3% to 31%), depressive episode (F32: 8.1% to 3.4%), recurrent depression (F33: 17.9% to 7.5%, all: p<0.001) and emotionally unstable (borderline) personality disorder (6.3% to 3.9%, p=0.01). The results in T1 vs. T2 vs. T3 were for F25: 26.7% vs. 18.2% vs. 16.2%, F32: 7.7% vs. 4.2% vs. 2.7%, F33: 17.2% vs. 8.6% vs. 6.6% and for F31: 40.8% vs. 31.7% vs 30.0%, i. e. there was no further decrease for lithium use in bipolar disorder after 2002. Lithium's main psychotropic co-medications were quetiapine (21.1%), lorazepam (20.6%), and olanzapine (15.2%).

Discussion: In inpatients, the use of lithium has decreased in patients with bipolar disorder and also with various other psychiatric diagnoses.

Introduction: There have been substantial increases in the use of Schedule II stimulants in the United States. Schedule II stimulants are the gold standard treatment for attention-deficit hyperactivity disorder (ADHD), but also carry the risk of addiction. Since the neurocognitive deficits seen in ADHD resemble those of chronic cannabis use, and the rise in stimulant use is incompletely understood, this study sought to determine if recreational cannabis (RC) legalization increased distribution rates of Schedule II stimulants.

Methods: The distribution of amphetamine, lisdexamfetamine, and methylphenidate were extracted from the ARCOS database of the Drug Enforcement Administration. The three-year population-corrected slopes of distribution before and after RC sales were evaluated.

Results: Total stimulant distribution rates were significantly higher in states with RC sales after (p=0.049), but not before (p=0.221), program implementation compared to states without RC. Significant effects of time (p<0.001) and RC sales status (p=0.045) were observed, while time x RC sales status interaction effects were not significant (p=0.406).

Discussion: RC legalization did not contribute to a more pronounced rise in Schedule II stimulant distribution in states. Future studies could explore the impact of illicit cannabis use on stimulant rates and the impact of cannabis sales on distribution rates of non-stimulant ADHD pharmacotherapies and ADHD diagnoses.