Pharmacopsychiatry最新文献

Ketamine and esketamine (ESK) offer new treatment options for resistant depression. Unlike traditional antidepressants, they can be used in combination with non-selective monoamine oxidase inhibitors (NS-MAOI) without the risk of serotonergic syndrome. However, potential sympathomimetic synergy may lead to elevated blood pressure (BP). This series investigates whether cardiovascular parameters (heart rate, systolic [SP], and diastolic [DP] pressures) increase during ESK sessions and whether the ESK+NS-MAOI combination is associated with BP elevations.We collected cardiovascular parameters for ESK sessions conducted between 2018 and 2022. These parameters were measured at baseline and every 30 min for 2 h. Patients were categorized into two non-equivalent groups: those receiving ESK alone and those receiving ESK+NS-MAOI. A Bayesian random model was used to estimate the evolution of these parameters, while a Bayesian hierarchical model assessed factors contributing to BP elevation.ESK sessions (n=193), of which 116 involved NS-MAOI, were performed in 13 patients. SP, DP, and heart rate showed peak increases during sessions, but these changes were not clinically significant (SP+8.68 mmHg, DP+6.57 mmHg, and heart rate+3.5 bpm). No significant differences were found between the ESK-alone and ESK+NS-MAOI groups. The combination was not identified as a factor linked to BP elevations.These findings align with previous research on ketamine derivatives and suggest minimal peripheric sympathomimetic synergy with NS-MAOI. Bayesian models were used to account for biases intrinsically related to these ecological data and provide a foundation for future open adversarial collaborations. Registration NCT05530668.

Second-generation antipsychotic drugs, such as olanzapine, have been associated with metabolic side effects including significant weight gain. Recent evidence suggests that this adverse effect may be attenuated by metformin.Male Wistar rats were chronically treated with olanzapine, together with or without metformin, for 7 and 14 weeks. Feeding behavior, food intake, and weight gain were recorded, as well as plasma leptin and triglyceride levels were measured. The expression of hypothalamic candidate genes, Pomc and Npy, involved in appetite and energy balance expressions' was assessed by quantitative real-time polymerase chain reaction.Olanzapine alone caused significant body weight gain, and the co-administration of metformin for 14 weeks lowered body weight and food intake compared with both the 7-week and control groups. Plasma triglyceride levels did not differ among groups. Leptin levels were significantly higher in the olanzapine-only group and were lower in both metformin-olanzapine groups, more promising in the early co-treatment with metformin. Compared to the control group, the hypothalamus of the olanzapine treatment group exhibited downregulated Pomc expression and upregulated Npy expression.Early co-treatment with metformin significantly mitigated olanzapine-induced weight gain and food intake, demonstrating its potential in preventing metabolic side effects when initiated at the beginning of antipsychotic therapy.

Alcohol use disorder (AUD) is a prevalent neuropsychiatric disorder with serious health and social consequences. However, few licensed and successful pharmacotherapies exist for heterogeneous and complex disorders such as AUD, and these are poorly utilized. Preclinical and clinical findings suggest that the glucagon-like peptide-1 (GLP-1) system, a gut-brain peptide, is involved in the neurobiology of addictive behaviors. Additionally, the GLP-1 receptor (GLP-1R) has become a promising target for the treatment of AUD. Semaglutide, a novel GLP-1R agonist, has received clinical approval to treat type 2 diabetes in both subcutaneous and oral dosage forms. Studies have shown that it significantly reduces alcohol consumption and relapse of alcohol addiction in rats, suggesting its potential effectiveness for treating alcohol abuse in humans, particularly in overweight patients with AUDs. However, the use of semaglutide is associated with potential risks, such as gallbladder disease and clinical complications associated with delayed gastric emptying. This review evaluates the safety of semaglutide to inform its wider clinical application. Further extensive and in-depth studies on semaglutide are needed to reveal additional valuable clinical benefits.

The United States Food and Drug Administration approved the xanomeline-trospium combination in September 2024 for treating schizophrenia, based in part on three double-blind, randomized placebo-controlled trials in adults with schizophrenia experiencing acute psychosis. This random-effects model pairwise meta-analysis of those three trials found that xanomeline-trospium was comparable to placebo in terms of all-cause discontinuation, discontinuation rate due to adverse events, Simpson-Angus Scale score change, Barnes Akathisia Rating Scale score change, body weight change, body mass index change, blood pressure change, serum total cholesterol change, blood glucose change, QTc interval changes, and the incidence of headache, somnolence, insomnia, dizziness, akathisia, agitation, tachycardia, gastroesophageal reflux disease, diarrhea, increased weight, and decreased appetite. However, xanomeline-trospium was associated with a higher incidence of at least one adverse event, dry mouth, hypertension, nausea, vomiting, dyspepsia, and constipation, and increased serum triglyceride compared with placebo. Notably, xanomeline-trospium demonstrated superior efficacy than placebo in improving the Positive and Negative Syndrome Scale (PANSS) total score, PANSS positive subscale score, and PANSS negative subscale score.

Clozapine is a recommended treatment for psychotic symptoms in patients with Parkinson's disease (PD) and/or dementia. However, the therapeutic reference range for clozapine in these patients has not been established hitherto.The study was performed in three university hospitals in Germany and Switzerland, including clozapine-treated patients with PD and/or dementia. The primary outcome was tolerability based on reports of adverse drug reactions and/or changes in laboratory tests or electrocardiogram and/or clozapine discontinuation. We meta-analyzed demographic and pharmacokinetic parameters in patients tolerating clozapine well versus not. A meta-analytic summary receiver operating characteristic (SROC) to establish the clozapine upper level associated with poor tolerability was estimated.We analyzed a total of 99 patients suffering from PD (56.6%) and/or dementia (49.5%) with a mean age of 70.3±9.5 years and 41.4% females; poor tolerability was reported in 26 of 99 patients (26.3%). When comparing patients with and without poor tolerability, there were no differences in age, body mass index, sex, smoking, or clozapine dose, nor did we find statistically significant differences in clozapine levels (standardized mean difference 0.46, 95% confidence interval - 0.04 to 0.96, p=0.07), and heterogeneity was low (I²=0.0%). Clozapine blood levels above 193 ng/mL were associated with poor tolerability (SROC area-under-curve 0.6, sensitivity 39.7%, specificity 79.9%).One of four patients with PD and/or dementia treated with clozapine did not tolerate clozapine well, which was associated with a trend toward elevated clozapine concentrations. Monitoring drug levels may help to improve tolerability in these patients.

Depression affects a significant proportion of adults in the United States. Studies exploring the association between depression and bone mineral density (BMD) have shown mixed results. Moreover, the relationship between BMD and physical activity (PA) in individuals with depressive symptoms is unknown. In this paper, we evaluated the association of depressive symptoms and PA with BMD, as well as difference in BMD among females with depressive symptoms before and after menopause.Data from the 2011-2018 National Health and Nutrition Examination Survey were used. Multivariable linear regression was used to explore the relationship between BMD and exposure variables.The study included 9,238 participants, of whom 766 had depressive symptoms. The presence and severity of depressive symptoms were significantly associated with lower BMD (aCoef.=-0.0200 for depressive symptoms, -0.0017 for depressive symptom severity; p<0.001). Vigorous PA intensity was positively correlated with BMD, with and without controlling for depressive symptoms (aCoef.=0.0006; CI=[0.0003, 0.0008]; p<0.001). Additionally, high levels of vigorous PA showed a significant positive relationship with BMD (aCoef.=0.0141; CI=[0.0078, 0.0205]; p<0.001). Postmenopausal status was significantly associated with lower BMD. No significant interaction effects were observed between depressive symptoms and PA or menopausal status on BMD.Our study demonstrated the an association between depressive symptoms and low BMD, as well as a positive association between high-intensity vigorous PA and BMD. Future studies should aim to replicate our findings and evaluate the underlying mechanisms.

Low-grade inflammation (LGI) contributes to resistance against traditional antidepressants. However, whether the antidepressant and antisuicidal effects of ketamine on patients with treatment-resistant depression (TRD) differ between those with LGI and those without LGI remains unknown.This study included 167 patients with TRD, among whom 46 had LGI and 121 did not have LGI. The patients received a single infusion of either low-dose ketamine or a placebo. A C-reactive protein level of≥3 mg/L indicated LGI. Depressive symptoms were measured from baseline to day 3 by using the 17-item Hamilton Depression Rating Scale (HDRS) and the Montgomery-Asberg Depression Rating Scale (MADRS).Generalized estimating equation models revealed antidepressant effect of ketamine in patients with no LGI (HDRS scores: p<0.001; MADRS scores: p<0.001) but not in patients with LGI (all p>0.05). The antisuicidal effect of ketamine (indicated by the score on item 10 of the MADRS) was observed in both groups of patients with (p=0.046) and without LGI (p<0.001). However, ketamine was effective for TRD regardless of whether inflammation levels were high or low, while the placebo response was notably greater only in patients with LGI.This study suggests that among patients with TRD, only those without LGI respond to low-dose ketamine infusion. Whether the negative findings of the antidepressant effect of ketamine among patients with LGI may be because of the effect of the placebo infusion needs further investigation. Further randomized, placebo-controlled studies are needed to validate these findings.

Traditionally, the aetiology of schizophrenia has been attributed to dopaminergic neurotransmission, but more recent information points to the role of glutamate pathways. Glutamatergic involvement in schizophrenia might be extensible to drug response. The aim of the study was to explore whether the variation in glutamate receptors, transporters and metabolism can influence the outcome of drug treatments.A total of 45 polymorphisms in the genes GRIN1, GRIN2A, GRIN2B, GRIN3A, GRIA1, GRIK2, GRM2, GRM3, GRM5, GRM8, SLC1A1, SLC1A3 and GAD1 were genotyped in 258 patients with schizophrenia. Efficacy and side effects were evaluated with the Positive and Negative Symptoms Scale and the UKU scale, respectively, at baseline and after 12 weeks.The analysis revealed associations between outcomes, including response and adverse effects and genetic variants in several genes (GAD1, GRIA1, GRIN2A, GRIN3A, GRIK2, GRM2, GRM5, GRM8 and SLC1A3). An association of rs1864205 in GRIA1 with autonomic side effects bordered statistical significance after correction for multiple comparisons.Our results suggest that genetic variation in glutamatergic pathways can influence the efficacy and safety of antipsychotic drugs.

Background: This study aimed to assess the association between the risk of colorectal cancer (CRC) and exposure to mood stabilizers, antidepressants, and antipsychotics in patients with affective disorders.

Methods: This nested case-control study used data from the National Health Insurance Database of Taiwan collected between 2001 and 2011. All participants in this study had affective disorders. Then, 1209 patients with CRC and 1:10 matched controls were identified based on their demographic and clinical characteristics. A logistic regression model adjusted for demographic and clinical characteristics was used to determine the risk of developing CRC after exposure to psychotropic drugs.

Results: Among patients with affective disorders, exposure to mood stabilizers (reported as odds ratio; 95% confidence interval; 0.75; 0.57-0.98), antidepressants (0.83; 0.70-0.97), second-generation antipsychotics (0.67; 0.52-0.86), and first-generation antipsychotics (0.65; 0.52-0.81) were associated with a reduced risk of CRC compared to patients who were not exposed. When considering specific drugs, carbamazepine (0.34; 0.12-0.95), valproic acid (0.66; 0.46-0.95), gabapentin (0.44; 0.20-0.99), fluoxetine (0.82; 0.68-0.99), paroxetine (0.63; 0.45-0.87), and venlafaxine (0.72; 0.55-0.95) were associated with a lower risk of CRC.

Conclusion: Exposure to psychotropic drugs in patients with affective disorders is associated with a lower risk of CRC compared to those who were not exposed. Although the causal relationship between psychotropic drug exposure and reduced risk of CRC could not be inferred directly, these findings may help clinicians and patients in clinical decision-making.