Psychopharmacology bulletin最新文献

Early-onset schizophrenia is notorious for poor prognostication and treatment-refractoriness. Clozapine remains a viable option, albeit off-label, but is clearly underutilized in this population. Use is typically fraught with panoply of drastic side effects. Here, authors report on an adolescent case with schizophrenia that responded ultimately to clozapine. Add-on viloxazine was advantageous spanning different symptom domains, mitigating metabolic parameters and addressing clozapine-sialorrhea. This might open new venues for such complicated, yet commonplace, clinical scenarios.

Introduction: Major depressive disorder (MDD) is a primary cause of disability in adults, affecting daily functioning and decreasing quality of life. The focus on the role of nutraceuticals as adjunctive treatments to improve antidepressant response is paying growing interest. The study aims to compare the antidepressants response in the utilization of selective serotonin reuptake inhibitors (SSRIs) versus a combination of SSRIs and nutraceutical supplements based on S-Adenosyl methionine (SAMe), N-acetylcysteine (NAC) and folate in terms of efficacy and tolerability.

Methods: A case-control study was carried out between March 2018 and September 2019. Cases and controls were evaluated through the following scales: Hospital Anxiety Depression Scale (HADS); Clinical Global Impression (CGI); Patient Global Impression of Improvement (PGI-I); Antidepressant Adverse Events checklist (AES).

Results: A significant difference between the two groups of patients emerged at T₁ in the HADS-A (p = 0.004) score and in the CGI score (p = 0.01), due to a major improvement in patients with a nutraceutical co-prescription. At T₃ a significant statistical difference emerged, showing a greater improvement at HADS-D in the case group (p = 0.006), confirmed by a higher remission rate in patients taking a nutraceutical co-prescription. No differences in terms of adverse events emerged.

Conclusion: This study shows promising data about the role of nutraceuticals as adjunctive treatment in major depressive disorder to improve SSRIs efficacy, with good tolerability. More data are needed to confirm these results, particularly about the role of nutraceuticals to decrease the latency of SSRIs response.

Introduction: Phenazepam is commonly administered to patients diagnosed with major depressive disorder. Some proportion of such patients do not show adequate response to treatment regimen containing phenazepam, whereas many of them experience type A adverse drug reactions. Previous studies showed that CYP2D6 IS involved in the biotransformation of phenazepam, the activity of which is highly dependent on the polymorphism of the gene encoding it. Objective. The objective of the study was to evaluate the impact of 1846G>A polymorphism of the CYP2D6 gene on the concentration/dose indicator of phenazepam, using findings on enzymatic activity of CYP2D6 (as evaluated by the 6M-THBC/pinoline ratio measurement) and on CYP2D6 expression level obtained by measuring the hsa-miR-370-3p plasma concentration levels in patients suffering from major depressive disorder.

Material and methods: The study enrolled 191 patients with recurrent depressive disorder (age -40.0 ± 16.3 years). Treatment regimen included phenazepam in an average daily dose of 6.0 ± 2.3 mg per day. Treatment efficacy was assessed using the validated psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels we performed the real-time polymerase chain reaction (PCR Real-time). The activity of CYP2D6 was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of given isoenzyme and its metabolite in urine (6M-THBC/pinoline). Therapeutic drug monitoring has been performed using HPLC-MS/MS.

Results: Our findings didn't reveal the statistically significant results in terms of the treatment efficacy evaluation (HAMA scores at the end of the treatment course): (GG) 6.0 [4.0; 8.0] and (GA) 6.0 [5.0; 7.8], p > 0.999; the statistical significance in the safety profile was not obtained (the UKU scores): (GG) 3.0 [2.0; 4.0] and (GA) 3.0 [3.0; 3.0], p > 0.999. We didn't reveal a statistical significance for concentration/dose indicator of phenazepam in patients with different genotypes: (GG) 0.812 [0.558; 1.348] and (GA) 0.931 [0.630; 1.271], p = 0.645). Analysis of the results of the pharmacotranscriptomic part of the study didn't show the statistically significant difference in the hsa-miR-370-3p plasma levels in patients with different genotypes: (GG) 22.5 [16.9; 29.8], (GA) 22.7 [15.7; 31.5], p = 0.695. At the same time, correlation analysis didn't reveal a statistically significant relationship between the phenazepam efficacy profile evaluated by changes in HAMA scale scores and the hsa-miR-370-3p plasma concentration: rs = -0.01, p = 0.866. Also, we didn't reveal the correlation between the miRNA concentration and safety profile: rs = 0.07, p = 0.348. Also we did not reveal the relationship between the CYP2D6 enzymatic activity (as evaluated by 6M-THBC/pinoline ratio measurement) and the hsa-miR-370-3p plasma conc

Antiepileptic drugs (AEDs) are used in various pathologies such as including epilepsy, migraine, neuropathic pain, etc. They can improve symptoms but cause adverse events (ADRs). Case reports have reported that one rare but serious AED-induced adverse reaction that has appeared in case reports is myotoxicity from rhabdomyolysis. Rhabdomyolysis can be induced by a therapeutically dosed occur with therapeutic doses of antiepileptic drugs and is in most cases reversible, although rarely it can cause serious complications. Clinical manifestations of rhabdomyolysis range from a single isolated asymptomatic rise in serum CK levels to severe electrolyte imbalances, cardiac arrhythmia, acute and disseminated renal failure, intravascular coagulation, and other symptoms. Many clinical cases reported that both conventional older and newer AEDs, as well as propofol, can cause rhabdomyolysis, even if there are no conclusive data. It has recently been shown that genetic factors certainly contribute to adverse reactions of antiepileptic drugs. A study of genetic polymorphism in patients with AED-induced rhabdomyolysis may be useful to explain the rarity of this adverse event and to improve the treatment of these AED patients, in terms of AED type and dose adjustment.

Objectives: Clozapine is considered as effective medication for treatment resistant schizophrenia. Due to its potential severe adverse effects' clozapine is underused in the clinical settings. Information's on clinical use and monitoring of clozapine is lacking in middle east. This research analysis clozapine prescription and monitoring patterns a in a university teaching hospital in Saudi Arabia.

Experimental design: A retrospective observational study was conducted in the psychiatric department of a university hospital in Saudi Arabia. Patients on treatment with clozapine for minimum one year were reviewed and assessed for clozapine mandatory and non-mandatory requirements and its correlated factors.

Observation: Majority of patients were male [(n = 36) 63%] and the average age of was 36.8 ± 12.3. TRS schizophrenia[(n = 49),85%] was the common indications. Prior to initiation of clozapine all recommended guidelines was followed for all patients (100%). In addition to the blood monitoring and vitals LFT (80.75%) and weight (87.77%) were frequently measured. Hematological work up performed routinely throughout initial 18 weeks (71.9 %) and every month (59.6%). Weight gain (29.8%) was the most documented adverse effects.

Conclusion: The current study explored experiences with clozapine prescribing practices in a university hospital KSA and suggest that clozapine prescription is completely adhered with already existing guidelines in terms of dosing and monitoring. There exist a careful balance of benefit and risk in term of adverse reaction of clozapine in the local population.

Dopamine receptor blocking agents (DRBAs, also known as antipsychotics) are frequently used in hospitalized patients. These medications carry a significant side effect burden and should be used judiciously. This purpose of this study is to examine patient, disease, and medication characteristics associated with the use of DRBAs in the inpatient setting to better understand current prescribing patterns and opportunities for optimization. A retrospective analysis was performed of 17,224 patients with at least one inpatient DRBA order placed between 1/1/2018-12/31/2019. The study population at this community hospital network in the United States contained those with (71.0%) and without (29.0%) psychiatric diagnoses, and the mean number of DRBA medications for each patient was 2.4 +/- 1.1. The characteristics of single, male, government-sponsored health insurance, movement disorder, DRBA adverse effects, and medication non-adherence were associated with significantly greater mean total DRBA medications prescribed. Medication non-adherence and prescription of a long-acting injectable (LAI) DRBA were greater in single and male patients, while suicidality was more likely in those with a movement disorder or DRBA adverse effect. Specific agents were also significantly associated with cardiovascular disease and metabolic disorder diagnoses. Based on the findings of this study, several patient, disease, and medication factors are related to the use of DRBAs in the hospital setting. It is important to further explore these associations in order to determine the appropriateness of DRBA prescribing and identify areas for improvement.

Clozapine is a second generation antipsychotic agent which is drug of choice for treatment resistant schizophrenia. Tachycardia and postural hypotension are most frequently observed cardiovascular adverse effects, but reports on new-onset persistently elevated blood pressure are sparse. Mechanisms underlying clozapine induced hypertension also remain unclear. We report the case of a 32 year old normotensive male with persistently elevated systolic and diastolic blood pressure after clozapine initiation. Hypertension persisted throughout the phase of dose optimization and dose stabilization at 300 mg/day, requiring an addition of a beta blocker (atenolol) after a month of observation. The 24 hour urinary catecholamines were within normal limits. Autonomic function tests revealed severe loss of parasympathetic activity and cardiac autonomic tone. The case adds to limited information on autonomic dysfunction as a potential factor in clozapine induced hypertension.

Weight gain is a common side-effect of medications used to treat major depressive disorder (MDD). We sought to estimate the frequency of weight gain for obesogenic medications prescribed for MDD and to evaluate if bupropion mitigated risk for weight gain. We analyzed a prospective cohort of patients with weight available at baseline and 12 weeks (n = 1,032) or 24 weeks (n = 871) in a post hoc analysis of the Genomics Used to Improve DEpression Decisions (GUIDED) study of patients with MDD who failed at least one medication trial. We compared weight gain between those on versus not on medications with high risk for weight gain, including a subgroup receiving combination treatment with bupropion. A second analysis evaluated weight gain across traditional medication classes, adjusting for potential confounding variables. Those on medications identified as high risk for weight gain were significantly more likely to experience clinically significant weight gain (≥3%) at 12 weeks (29.3% vs. 16.3%, p < .001) and 24 weeks (33.5% vs. 23.5%, p = .015). No protection from clinically significant weight gain was observed among patients treated with a high-risk medication concomitantly with bupropion (N = 31, 35% and 52% with clinically significant weight gain at 12 and 24 weeks). Antipsychotic medications and tricyclic antidepressants were most often associated with clinically significant weight gain. This study helps quantify the real-world risk of weight gain for patients with MDD on medications with high risk for weight gain, especially for patients taking antipsychotics. Concurrent treatment with bupropion does not appear to mitigate the weight gain risk.

The organism's energy requirements for homeostatic balance are covered by the redox mechanisms. Yet in case of psychologically traumatic stress, allostatic regulations activate both pro-oxidant and antioxidant molecules as well as respective components of the inflammatory system. Thus a new setpoint of dynamic interactions among redox elements is reached. Similarly, a multifaceted interplay between redox and inflammatory fields is activated with the mediation of major effector systems such as the immune system, Hypothalamic-Pituitary-Adrenal axis, kynurenine, and the glycaemic regulatory one. In case of sustained and/or intense traumatic stress the prophylactic antioxidant components are inadequate to provide the organism with neuroprotection finally culminating in Oxidative Stress and subsequently to cellular apoptosis. In parallel multiple inflammatory systems trigger and/or are triggered by the redox systems in tight fashion so that the causation sequence appears obscure. This exhaustive review aims at the comprehension of the interaction among components of the redox system as well as to the collection of disperse findings relative to the redox-inflammatory interplay in the context of traumatic stress so that new research strategies could be developed.