Search Results (190)

Introduction: Sex-specific differences in psychopharmacological treatment have gained increasing attention in adults, with studies showing that women often have higher serum concentrations of psychotropic drugs due to biological differences. However, despite recognition of these differences in adults, reference ranges for therapeutic drug monitoring (TDM) in general, but even more sex-specific therapeutic windows for psychotropic drugs, are lacking in children and adolescents, who may metabolize and respond to medications differently. Aim: The study aimed to investigate sex-specific differences in antidepressant (AD) and antipsychotic (AP) -treatment outcomes, and pharmacokinetics in childhood/adolescence. In particular, we examined differences in AD and AP serum levels and clinical effects, including adverse drug effects (ADEs) and therapeutic effectiveness. Methods: This study is part of the multicenter “TDM-VIGIL” pharmacovigilance project, which prospectively followed patients aged 6–18 years treated with AD and AP across 18 child psychiatric centers in German-speaking countries from 2014 to 2018. Clinical data, including drug concentrations (AD: fluoxetine, mirtazapine, (es)citalopram, sertraline; AP: aripiprazole, quetiapine, olanzapine, risperidone), were collected using an internet-based registry, and treatment outcomes and ADEs were assessed during routine visits. Statistical analyses were performed to examine sex differences in pharmacokinetics and clinical responses, adjusting for age, weight, and other confounders. Results: A total of 705 patients (66.5% girls, 24.7% <14 years, mean age of 14.6 years) were included. Female patients were slightly older, had lower body weight, and were more often diagnosed with depression and anorexia nervosa, while boys were more frequently diagnosed with hyperkinetic disorders and atypical autism. We found no sex differences in the serum concentrations of investigated drugs when adjusted for age and weight. In fluoxetine treatment in patients diagnosed with mood (affective) disorders, female sex was associated with the probability for very good therapy response (p = 0.04), as well as with moderate treatment response (p = 0.02) compared to no treatment response. Discussion: Our findings suggest that sex may not affect serum levels of investigated AD and AP in children/adolescents. However, treatment outcome of fluoxetine was associated with sex, with higher probability for a better outcome in female patients diagnosed with mood (affective) disorders. Full article

Background/Objectives: Long-acting injectable antipsychotics (LAIs) represent a significant advancement in the treatment of schizophrenia (SCZ), particularly for improving adherence and long-term outcomes. This study aimed to assess the clinical outcomes of patients receiving atypical LAIs compared to those on various oral antipsychotics over a one-year follow-up in a naturalistic setting. Methods: Sixty patients with SCZ were subdivided in two groups, those receiving LAIs (n = 25) and those receiving oral antipsychotics (n = 35). The groups were comparable for age, gender, educational attainment, employment status, marital status, smoking habits, and baseline SCZ severity, with no differences in baseline chlorpromazine equivalent dosages. Results: Over the follow-up period, patients in the LAI group discontinued treatment less frequently (χ² = 4.72, p = 0.030), showed fewer suicide attempts (χ² = 5.63, p = 0.018), fewer hospitalizations (χ² = 4.95, p = 0.026), and fewer relapses (χ² = 6.61, p = 0.010). Significant differences also emerged on the Drug Attitude Inventory (DAI-10) scores (F = 8.76, p = 0.005) and Body Mass Index (BMI) values (F = 8.32, p = 0.007), with the LAI group showing more favorable outcomes. Conclusions: LAIs, compared to oral antipsychotics, may promote treatment adherence, as shown by decreased hospitalization; furthermore, their use is related with better outcomes, like fewer relapses and less suicide attempts in individuals with SCZ in real-world settings. Full article

Background and Objectives: Schizophrenia is a disabling psychiatric condition, affecting around 1% of people worldwide. It has been ranked among the ten most disabling conditions globally. Alongside the psychological and social burdens imposed on individuals suffering from this disease, there are also serious complications regarding the physical health of these patients. Pneumonia is a significant cause of death in patients with schizophrenia. This group of patients also has a higher risk of developing pneumonia and all-cause mortality compared to those without schizophrenia, along with an increased overall mortality rate. A retrospective study revealed that advanced age, underweight, smoking, and the use of high-dose atypical antipsychotics increase the risk of pneumonia-related mortality in hospitalized patients. Our study aims to examine differences in factors associated with pneumonia in hospitalized patients with schizophrenia, before and after the COVID-19 pandemic, as well as to identify potential changes in clinical characteristics and outcomes. Materials and Methods: This is an observational, retrospective analysis, based on the review of medical records of psychiatric inpatients diagnosed with schizophrenia according to the DSM-5 criteria. Patients were selected according to the following criteria: both schizophrenia and pneumonia diagnoses, hospitalized in Spitalul Clinic de Psihiatrie si Neurologie Brasov during 1 March 2018–1 March 2020, and 1 March 2022–1 March 2024, respectively. Results: A total of 27 patients met the inclusion criteria; 13 patients (48%) were in the pre-pandemic group and 14 patients (52%) in the post-pandemic group. Contrary to other reports, our results showed relatively low pneumonia rates in hospitalized schizophrenia patients (1.02% pre-pandemic and 1.63% post-pandemic), and rates were higher in female patients (61.54% pre-pandemic and 71.43% post-pandemic). Post-pandemic, most cases (42.86%) were registered during summer, in a schizophrenia population with mostly urban residence and with lower smoking rates than the pre-pandemic group. Physical restraints were, however, more frequently utilized in the post-pandemic group. Conclusions: Pneumonia risk factors might register a change in the post-pandemic years. Polypharmacy and physical restraints are probably underestimated risk factors for pneumonia in schizophrenia patients, while a multidisciplinary approach and preventive measures might exert a protective role. Full article

Introduction: Delirium is a common and debilitating clinical complication among ICU patients. Despite the prevalence of this condition, there are insufficient data to support or refute the routine use of atypical antipsychotics since the existing evidence remains sparse and inconclusive. The objective of the present study was to evaluate whether pre-ICU administration of the atypical antipsychotic olanzapine is associated with a differential time to delirium resolution relative to the control condition. Methods: In this emulated clinical trial, we utilized the MIMIC-IV v3.1 database, which contains deidentified health records from approximately 65,000 ICU patients, to derive a cohort of patients with a positive delirium screening within 24 h of ICU admission. We exluded patients who received any antipsychotic other than olanzapine prior to ICU admission. We performed propensity score matching using logistic regression and nearest-neighbor matching (1:1, caliper = 0.2) to balance covariates between the olanzapine and control groups. The primary outcome was time to delirium resolution, defined as the first negative delirium assessment. A Cox proportional hazards model, adjusted for multiple covariates and incorporating age as a time-dependent variable, was used to examine the association between olanzapine use and delirium resolution. Interaction terms were included to evaluate effect modification by age and gender. Results: A total of 5070 patients with a positive delirium screening within 24 h and no exposure to other antipsychotics met the eligibility criteria; 421 olanzapine users were matched to 421 controls using propensity score matching. Covariate balance was achieved (all standardized mean differences < 0.1), and no multicollinearity was detected (all VIFs < 2). Pre-ICU olanzapine use was associated with a 27% decrease in the likelihood of delirium resolution (HR = 0.73; 95% CI: 0.63–0.86; p < 0.001). A significant interaction with age indicated that the negative impact of olanzapine on delirium resolution increased with advancing age (HR = 1.0024 per unit of age × log(time), p = 0.023), translating to a 2.4% increase in the risk of prolonged delirium resolution for every 10-year increase in age per log(time). There was no modification of the association according to gender. Discussion: The negative effect of olanzapine on ICU delirium resolution, particularly among the elderly, presented in this study is in line with the results of our earlier study showing a negative effect (i.e., prolonged ICU stay) among patients receiving quetiapine relative to both control and haloperidol conditions. Distinctly strong anticholinergic effects of both olanzapine and quetiapine relative to the other antipsychotic agents may be driving the identified negative outcomes. Conclusions: Results of this emulated clinical trial do not support the use of olanzapine for the treatment of ICU delirium because the agent prolongs time to resolution of the condition. Full article

Background/Objectives: Oppositional defiant disorder (ODD) and conduct disorder (CD) are important behavior disorders in children and adolescents, often linked with long-term psychosocial problems. Antipsychotics are frequently prescribed to manage severe symptoms and improve behavior, but their efficacy in this population is still unclear and a lot of physicians are remittent in prescribing them. This systematic review aims to assess the effectiveness of antipsychotic treatment in reducing symptoms associated with ODD and CD in children and adolescents. Methods: Studies that investigated how effective antipsychotic treatments are for children and teens diagnosed with oppositional defiant disorder (ODD) and conduct disorder (CD) were reviewed. Only studies that met a few main criteria were included: participants were between 5 and 18 years old with an ODD or CD diagnosis; the treatment could be any type of antipsychotic, whether typical or atypical; the accepted study designs were randomized controlled trials (RCTs), cohort studies, systematic reviews with meta-analysis, or observational studies. The outcomes of interest were reductions in aggressive or defiant behaviors, improvements in social functioning, and the occurrence of any adverse effects from the medications. There was no restriction on the language of publication, and studies published from 2000 to 2024 were considered. Studies that focused only on non-antipsychotic drugs or behavioral therapies, as well as case reports, expert opinions, and non-peer-reviewed articles did not meet the inclusion criteria. Results: The review consisted of 13 studies. The results suggest that some antipsychotic drugs—especially atypical antipsychotics—can substantially reduce aggressive and defiant behavior in children and adolescents who have oppositional defiant disorder (ODD) or conduct disorder (CD). Common side effects of these medications include weight gain, sedation, and metabolic problems. Conclusions: Although adverse effects are a concern, the potential of these medications to manage disruptive behaviors should not be overlooked. When used in combination with behavioral therapy and other forms of treatment, antipsychotics can markedly improve the outcomes of these very difficult-to-treat patients. Clinicians who treat these patients need to consider antipsychotics as a serious option. If they do not, they are denying their patients medication that could greatly benefit them. Full article

Background/Objectives: The co-occurrence of Attention-deficit/hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) is very common and worsens adaptive functioning. This systematic review evaluates both pharmacological and non-pharmacological interventions in this underserved population. Methods: Registered on PROSPERO (CRD42024526157), a systematic search was conducted on PubMed, Embase, and Web of Science until 5 April 2025. The review includes (a) pilot studies and RCTs, (b) participants aged <18 years, (c) diagnoses of ASD and ADHD based on DSM-IV/V or ICD-9/10, (d) at least one group receiving any intervention, and (e) publications in English, Italian, Spanish, or German. Newcastle Ottawa Scale tools for non-randomized studies and the Cochrane Risk of Bias Tools for randomized controlled trials were used to assess studies’ quality. Results: A total of 32 studies were included: 87.5% concerning pharmacological treatments. Specifically, methylphenidate (MPH, n = 11), atomoxetine (ATX, n = 11), guanfacina (n = 4), clonidine (n = 1), or atypical antipsychotics (n = 1) were examined. MPH and ATX were most frequently studied, with both showing positive effects in reducing ADHD core symptoms compared to placebo. ATX also reduces stereotyped behaviors and social withdrawal, although more withdrawals due to adverse events (AEs) were reported for ATX than MPH. Four studies (12.5%) examined non-pharmacological interventions, including treatment with virtual reality tools, digital platforms, educational animations, and biomedical protocols; improvements in emotion recognition, behavioral regulation, attention, and social functioning were found. Conclusions: While limited data prevent definitive conclusions, MPH and ATX appear to be relatively safe and effective on hyperactivity-impulsivity symptoms, even in individuals with ASD. Evidence on non-pharmacological treatments is limited, and further studies are needed to better establish their therapeutic potential. Full article

Background: Feeding and Eating Disorders (FEDs) are severe mental health conditions often emerging during childhood or adolescence, with rising prevalence. They are frequently associated with psychiatric and organic comorbidities, including anxiety symptoms and insomnia. Phytotherapy, particularly Passiflora incarnata L. Herba, has been suggested as a potential treatment option for anxiety and insomnia in youth. Methods: this is an observational and retrospective study that includes patients assessed in a third-level Italian Regional Centre for Feeding and Eating Disorders in Children and Adolescents between 1 January 2020 and 31 December 2023. Eligible patients had a confirmed diagnosis of a FED, along with either an anxiety or a sleep disorder. During follow-up, the clinical efficacy of Passiflora incarnata L. Herba was assessed using the Clinical Global Impression–Improvement scale (CGI-I). Comparative analyses were conducted by stratifying the sample based on the target symptoms (sleep disorders/insomnia and anxiety), FED subtype, and whether polytherapy was used. Results: this study includes 94 patients, with most diagnosed with anorexia nervosa (71.3%). Passiflora incarnata L. Herba was administered at a dosage of 200 mg (1–2 tablets for day). It was often combined with selective serotonin reuptake inhibitors (SSRIs) (56.5%), atypical antipsychotics (27.7%), or benzodiazepines (7.4%). Treatment was initiated for anxiety symptoms (75.5%) or insomnia (28.7%). No side effects were reported. Among patients with specific outcome data, 53.3% reported improvements in anxiety symptoms, and 45.4% reported improvements in insomnia. Conclusions: this is the first study to evaluate the use of Passiflora incarnata L. Herba for anxiety and insomnia in children and adolescents with FEDs. Our findings suggest that Passiflora incarnata L. Herba may serve as a well-tolerated adjunctive treatment, showing symptomatic improvement in up to 53% of the patients with data on treatment outcomes. Notably, 53.3% and 45.4% of participants, with specific outcome data, reported reduced anxiety and insomnia symptoms, respectively. Given its excellent safety profile and preliminary efficacy, Passiflora incarnata L. Herba may represent a promising alternative for patients with mild symptoms or for caregivers hesitant about conventional pharmacotherapy. Full article

We tried to synthesize the possibilities of predicting the response to clozapine treatment, which can significantly improve the efficacy of the active substance and reduce adverse reactions, and how the active substance acts at the D1 dopaminergic receptors D2, D3, D4, and D5, muscarinic M1, M2, M3, and M5, and the histamine and alpha 1 adrenergic receptor, as well as how it contributes to increased cerebral blood flow, the effect on ribosomal protein S6 function, or the effect on kynurenine 3-monooxygenase function. Clozapine is one of the most effective antipsychotics, and there is potential to improve performance by combining it with different compounds to limit adverse effects or by augmenting it with other antipsychotics (amisulpride, paliperidone), other active substances with different properties (minocycline, N-acetylcysteine, memantine), or alternative therapies (electroconvulsive therapy, repetitive transcranial magnetic stimulation). There are also significant steps in optimizing clozapine efficacy by predicting treatment response, which could be determined by testing the following: plasma levels of clozapine N-oxide and N-desmethylclozapine, serum levels of neurotrophins and glutamate, genetic testing, the polygenic risk score, morphometry, or even the identification and accurate determination of persistent negative symptoms. Full article

In animal models, ketamine, a non-competitive N-methyl-D-aspartate (NMDA) antagonist, induces schizophrenia-like symptoms, such as positive and negative symptoms, as well as cognitive deficits. In the present study, we evaluated the behavioral responses and the number of EODs (electric organ discharges) of the weakly electric fish Gnathonemus petersii using the novel object recognition task (NORT). We aimed to investigate whether pharmacological modulation of the glutamatergic system would impair cognitive functions by administering the NMDA receptor antagonist ketamine, and whether these impairments could be suppressed by the administration of typical (first-generation) and atypical (second-generation) antipsychotics—clozapine and haloperidol, respectively. G. petersii preferred the familiar object over the novel object in the NORT paradigm. Although no significant differences were observed when exploring the two identical objects during the training session, the fish spent less time, moved a shorter distance, and emitted fewer EODs in the testing phase with the novel object. No direct relationship was detected between the EODs and behavioral responses to the administration of ketamine and typical antipsychotics. Ketamine administered with atypical antipsychotic clozapine disrupted the perception of the original object, where one of the objects was preferred. In the novel object trial, the time spent on the original and new objects was attenuated to the same level. Full article

Pituitary cells are specialized cells located within the pituitary gland, a small, pea-sized gland situated at the base of the brain. Through the use of cellular electrophysiological techniques, the electrical properties of these cells have been revealed. This review paper aims to introduce the ion currents that are known to be functionally expressed in pituitary cells. These currents include a voltage-gated Na⁺ current (I_Na), erg-mediated K⁺ current (I_K(erg)), M-type K⁺ current (I_K(M)), hyperpolarization-activated cation current (I_h), and large-conductance Ca²⁺-activated K⁺ (BK_Ca) channel. The biophysical characteristics of the respective ion current were described. Additionally, we also provide explanations for the effect of various drugs or compounds on each of these currents. GH₃-cell exposure to GV-58 can increase the magnitude of I_Na with a concurrent rise in the inactivation time constant of the current. The presence of esaxerenone, an antagonist of the aldosterone receptor, directly suppresses the magnitude of peak and late I_Na. Risperidone, an atypical antipsychotic agent, is effective at suppressing the I_K(erg) amplitude directly, and di(2-ethylhexyl)-phthalate suppressed I_K(erg). Solifenacin and kynurenic acid can interact with the K_M channel to stimulate I_K(M), while carisbamate and cannabidiol inhibit the I_h amplitude activated by sustained hyperpolarization. Moreover, the presence of either rufinamide or QO-40 can enhance the activity of single BK_Ca channels. To summarize, alterations in ion currents within native pituitary cells or pituitary tumor cells can influence their functional activity, particularly in processes like stimulus–secretion coupling. The effects of small-molecule modulators, as demonstrated here, bear significance in clinical, therapeutic, and toxicological contexts. Full article

Background/Objectives: Montelukast (MLK), a leukotriene receptor antagonist, has been associated with neuropsychiatric side effects. This study aimed to rationally modify MLK’s structure to reduce these risks by optimizing its interactions with dopamine D2 (DRD2) and serotonin 5-HT1A receptors using computational molecular simulation techniques. Methods: A library of MLK derivatives was designed and screened using structural similarity analysis, molecular docking, molecular dynamics (MD) simulations, MM/PBSA binding free energy calculations, and ADME-Tox predictions. Structural similarity analysis, based on Tanimoto coefficient fingerprinting, compared MLK derivatives to known neuropsychiatric drugs. Docking was performed to assess initial receptor binding, followed by 100 ns MD simulations to evaluate binding stability. MM/PBSA calculations quantified binding affinities, while ADME-Tox profiling predicted pharmacokinetic and toxicity risks. Results: Several MLK derivatives showed enhanced DRD2 and 5-HT1A binding. MLK_MOD-42 and MLK_MOD-43 emerged as the most promising candidates, exhibiting MM/PBSA binding free energies of −31.92 ± 2.54 kcal/mol and −27.37 ± 2.22 kcal/mol for DRD2 and −30.22 ± 2.29 kcal/mol and −28.19 ± 2.14 kcal/mol for 5-HT1A, respectively. Structural similarity analysis confirmed that these derivatives share key pharmacophoric features with atypical antipsychotics and anxiolytics. However, off-target interactions were not assessed, which may influence their overall safety profile. ADME-Tox analysis predicted improved oral bioavailability and lower neurotoxicity risks. Conclusions: MLK_MOD-42 and MLK_MOD-43 exhibit optimized receptor interactions and enhanced pharmacokinetics, suggesting potential neuropsychiatric applications. However, their safety and efficacy remain to be validated through in vitro and in vivo studies. Until such validation is performed, these derivatives should be considered as promising candidates with optimized receptor binding rather than confirmed safer alternatives. Full article

Background: Untreated bipolar disorder during pregnancy is associated with poor prenatal care, decreased fetal growth, and an increased risk for postnatal complications, including postpartum psychosis. Although mood stabilizers are first-line therapy, many patients and providers discontinue them in early pregnancy. Antidepressants as monotherapy can increase the risk of mania and rapid cycling, especially in patients with bipolar I, and are not recommended. Objective: This study aims to describe prescribing patterns for the pharmacologic management of bipolar disorder in pregnancy. Methods: This retrospective cohort study included pregnant patients, ≥14 years old, with a documented diagnosis of bipolar disorder and ≥two clinic visits after 1 January 2014, who delivered by 31 October 2017, within our health system. Eligible patients were identified by the ICD-9 and ICD-10 codes for bipolar disorder and their medication profiles. The primary outcome was to describe bipolar disorder treatment regimens at first visit, during pregnancy, and at delivery. Descriptive statistics were used. Results: Of the 214 pregnancies analyzed, 134 (62.6%) used psychiatric medications during pregnancy, with 79/134 (59%) being mood stabilizers. During the initial visit, 61/214 (28.5%) pregnancies were on psychiatric medications, including 30 (49.2%) on mood stabilizers and 16 (26.2%) on antidepressants alone. At delivery, 98/214 (45.8%) pregnancies were on psychiatric medications, with 48/98 (49%) on mood stabilizers and 35/98 (35.7%) on antidepressants without mood stabilizers. Other therapies included benzodiazepines, buspirone, and amphetamines, as monotherapy or combination. Conclusions: Despite having documented bipolar disorder, only 30/214 (14%), 79/214 (36.9%), and 48/214 (22.4%) pregnancies were treated with mood stabilizers at the first visit, during pregnancy, and at delivery, respectively. Unfortunately, justification for discontinuation was not documented. The most commonly prescribed mood stabilizer was lurasidone, followed by lamotrigine. Antidepressant monotherapy persisted throughout pregnancy, demonstrating inappropriate disease management. Full article

Aripiprazole (ARZ) is an atypical antipsychotic drug used to treat a variety of mood and psychotic disorders, such as schizophrenia, bipolar disorder, major depressive disorder, autism, and Tourette’s syndrome. Although ARZ offers significant therapeutic benefits, its poor solubility in water requires the development of delivery systems aimed at improving the solubility and bioavailability of the drug. In this work, cryogels based on two natural products—agar and β-cyclodextrin (CD)—were developed and evaluated as a drug delivery system for ARZ. The cryogels were prepared by cryogenic treatment of aqueous solutions of agar and the β-CD/ARZ complex, followed by thawing. The main characteristics of the material, including gel fraction yield, swelling degree, pore volume, elastic properties, and morphology were studied in detail. The release of ARZ from composite cryogels was assessed in two media resembling the pH in stomach and intestine. The system exhibited a pH-dependent release of ARZ, with a slower rate in acidic media (pH 1.2) than in the neutral phosphate buffer (pH 6.8). Under in vitro conditions, the amount of released ARZ over 48 h reached 33%. Full article

Background and Objectives: Myoclonus is already associated with a wide variety of drugs and systemic conditions. As new components are discovered, more drugs are suspected of causing this disabling abnormal involuntary movement. This systematic review aims to assess the medications associated with drug-induced myoclonus (DIM). Materials and Methods: Two reviewers assessed the PubMed database using the search term “myoclonus”, without language restriction, for articles published between 1955 and 2024. The medications found were divided into classes and sub-classes, and the subclasses were graded according to their level of evidence. Results: From 12,097 results, 1115 were found to be DIM. The subclasses of medications with level A evidence were intravenous anesthetics (etomidate), cephalosporins (ceftazidime, cefepime), fluoroquinolones (ciprofloxacin), selective serotonin reuptake inhibitors (citalopram, escitalopram, paroxetine, sertraline), tricyclic antidepressant (amitriptyline), glutamate antagonist (amantadine), atypical antipsychotics (clozapine, quetiapine), antiseizure medications (carbamazepine, oxcarbazepine, phenytoin, gabapentin, pregabalin, valproate), pure opioid agonist (fentanyl, morphine), bismuth salts, and mood stabilizers (lithium). The single medication with the highest number of reports was etomidate. Drug-induced asterixis is associated with a specific list of medications. The neurotransmitters likely involved in DIM are serotonin, dopamine, gamma-aminobutyric acid (GABA), and glutamate. Conclusions: DIM may be reversible with management that can include drug discontinuation, dose adjustment, and the prescription of a medication used to treat idiopathic myoclonus. Based on the main clinical constellation of symptoms and pathophysiological mechanisms found in this study, DIM can be categorized into three types: type 1 (serotonin syndrome), type 2 (non-serotonin syndrome), and type 3 (unknown). Full article