Search Results (43)

Objectives: The oral route is the most widely used method of administration. However, the bitter taste of drugs is a prevalent issue compromising patient acceptance. This study aimed to develop a palatable amorphous trazodone hydrochloride (TRA) formulation via ion exchange with Amberlite IRP88 resin as the carrier. Methods: TRA-Amberlite IRP88 complexes (TRCs) were prepared using the static exchange method and their physical properties were then characterized. Molecular docking was carried out to elucidate the molecular interaction. Finally, the dissolution profiles and taste of TRCs were evaluated. Results: The Physical characterizations confirmed that TRA was amorphously dispersed in Amberlite IRP88. Importantly, the in vivo taste masking study suggested that the bitterness of TRA was effectively masked. The reason was that the dissociation of TRCs was suppressed in the saliva, resulting in reduced dissolution in the oral cavity. Conclusion: this study suggests that amorphization is effective in masking the bitterness of drugs and provides guidance for the development of palatable oral formulations. Full article

Cholesterol homeostasis is necessary for normal vertebrate development. The disruption of cholesterol homeostasis can cause abnormal body and nervous system development and lead to dysfunctional behavior and increased mortality. Commonly prescribed psychopharmaceuticals can alter cholesterol synthesis and may disrupt early vertebrate development. A high-throughput vertebrate zebrafish model system was used to test the hypothesis that exposure to psychopharmaceutical medications alters cholesterol biosynthesis and disrupts gene transcription, early whole-body and brain development, and nervous system function, resulting in abnormal behavior. Exposure to cariprazine, aripiprazole, trazodone, and AY9944 increased 7-dehydrocholesterol levels compared to vehicle-treated zebrafish. Significant differences in disease-associated gene expression, brain structure, and functional behaviors were observed in psychopharmaceutical and AY9944-treated zebrafish compared to controls. These data reveal that the high-throughput zebrafish model system can discern psychopharmaceutical effects on cholesterol synthesis, gene transcription, and key features of early vertebrate development that influences behavior. Full article

This review concentrates on the application of carbon-based materials in the development and fabrication of voltammetric sensors of antidepressant drugs used in the treatment of moderate to severe depression, anxiety disorders, personality disorders, and various phobias. Voltammetric techniques offer outstanding sensitivity and selectivity, accuracy, low detection limit, high reproducibility, instrumental simplicity, cost-effectiveness, and short time of direct determination of antidepressant drugs in pharmaceutical and clinical samples. Moreover, the combination of voltammetric approaches with the unique characteristics of carbon and its derivatives has led to the development of powerful electrochemical sensing tools for detecting antidepressant drugs, which are highly desirable in healthcare, environmental monitoring, and the pharmaceutical industry. In this review, carbon-based materials, such as glassy carbon and boron-doped diamond, and a wide spectrum of carbon nanoparticles, including graphene, graphene oxides, reduced graphene oxides, single-walled carbon nanotubes, and multi-walled carbon nanotubes were described in terms of the sensing performance of agomelatine, alprazolam, amitriptyline, aripiprazole, carbamazepine, citalopram, clomipramine, clozapine, clonazepam, desipramine, desvenlafaxine, doxepin, duloxetine, flunitrazepam, fluoxetine, fluvoxamine, imipramine, nifedipine, olanzapine, opipramol, paroxetine, quetiapine, serotonin, sertraline, sulpiride, thioridazine, trazodone, venlafaxine, and vortioxetine. Full article

The objective of this study was to evaluate the effects of trazodone as part of premedication in routine surgical procedures. A prospective, randomized, double-blinded clinical study was conducted on 16 adult female dogs undergoing elective ovariectomy. Behavioral responses were assessed after oral administration of trazodone (5 mg/kg) in eight dogs and compared with a control group (n = 8). Sedation levels at the time of induction and the required dose of propofol were recorded. Additionally, intraoperative fentanyl IV boluses (2.5 µg/kg) administered in response to surgical pain, along with heart rate (HR) and non-invasive arterial pressure (NIAP), were compared between groups. Dogs receiving trazodone exhibited significantly lower stress scores on the Clinic Dog Stress Scale (CDSS) and fewer episodes of vomiting after premedication, and they required lower doses of both propofol and intraoperative analgesia. These findings suggest that oral trazodone administration two hours before hospital arrival may help reduce preoperative stress in dogs undergoing elective ovariectomy. However, further studies with larger sample sizes are needed to confirm these results and fully evaluate the role of trazodone in preoperative protocols. Full article

Background: Hyponatremia is a common electrolyte disorder in older adults that can lead to poor clinical outcomes and increased mortality. This study aims to evaluate the interrelationship between hyponatremia and geriatric syndromes and drugs in older adults. Methods: This study included 1100 elderly patients admitted to a geriatric clinic. Patient records were used to obtain demographic information, comorbidities, geriatric syndromes, medications, laboratory results, and comprehensive geriatric assessment parameters. Results: The prevalence of hyponatremia was 23.9% in this study (mean age ± SD was 75.59 ± 8.13 years). The frequency of polypharmacy, dementia, falls, malnutrition and risk of malnutrition, frailty, probable sarcopenia, hypertension, cerebrovascular disease, and congestive heart failure was higher, and patients were older in the hyponatremia group (p < 0.05) than in the normonatremia group. After the adjustment of covariates, hyponatremia was shown to be related to drugs including escitalopram (odds ratio [OR]: 1.82, 95% confidence interval [CI]: 1.20–2.76), trazodone (OR: 2.27, 95% CI: 1.26–4.10), renin angiotensin aldosterone system (RAAS) inhibitors (OR: 1.71, 95% CI: 1.18–2.47), hydrochlorothiazide (OR: 1.83, 95% CI: 1.28–2.62), and opioids (OR: 4.46, 95% CI: 1.24–16.02) (p < 0.05). Polypharmacy, falls, and malnutrition with risk of malnutrition were still significantly associated with increased hyponatremia risk even after adjustment for age, sex, and comorbidity burden (p < 0.05). Conclusions: Hyponatremia seems to be associated with certain geriatric syndromes, as well as the use of some antidepressants and cardiovascular drugs in older adults. Malnourished older adults taking RAAS inhibitors, diuretics, opioids, and antidepressants may be at a higher risk of developing hyponatremia. They should be closely monitored, especially if they are taking multiple medications. Full article

Depression persists as one of the illnesses described relentlessly through the centuries because it affects a large group of people. Background/Objectives: The treatment of depression consists of various therapeutic agents, among which selective serotonin reuptake inhibitors (SSRIs) are elective. As polypharmacy tends to become the norm in modern days, the study of the real-life occurrence of drug–drug interactions is imperative. The aim of this study was the evaluation of drug–drug interactions (DDIs) between antidepressant medicines, namely SSRIs (each representative) versus eleven representatives from other antidepressant classes. Methods: Based on the spontaneous safety reports (ICSRs) uploaded to EudraVigilance until the end of July 2024, the descriptive and the disproportionality analyses were performed, and results were interpreted in the context of pharmacologic variability. Results: SSRIs were the focus of 137,369 ICSRs while for the other antidepressants, namely amitriptyline, clomipramine, duloxetine, venlafaxine, mirtazapine, bupropion, trazodone, tianeptine, agomelatine, brexpiprazole, and esketamine, a total of 155,458 reports were registered. The most notable differences appeared in psychiatric adverse drug reactions. Except fluvoxamine (n = 463), the remaining SSRIs had a higher number of DDIs reported (n = 1049 for escitalopram and n = 1549 for sertraline) compared to other antidepressants. However, similar numbers of DDIs were reported for duloxetine (n = 1252) and venlafaxine (n = 1513). Sertraline unspecified DDIs were reported with a higher probability compared to all other drugs (e.g., esketamine ROR: 9.37, 95% CI: 5.17–16.96, tianeptine ROR: 4.08, 95% CI: 2.49–6.69, etc.). Conclusions: SSRIs, although known to influence various cytochrome P450 isoenzymes, have not shown higher inhibitory interactions compared to any of the drugs selected as reference. Sertraline appears in more reports concerning DDIs than the other antidepressants. Still, further real world studies related to the DDIs of SSRIs are needed to complete the relevant knowledge level. Full article

Creativity and the production of artwork can have an impact on the course and treatment of comorbid severe mental illness and neurodegeneration. We report on a 70-year-old male patient with highly original artistic behavior, who suffered from lifelong recurrent major depression and subsequently developed symptoms of progressive bulbar palsy (PBP). In the context of a systematic literature review, we detail the patient’s personal and artistic biographies and portray artwork from his artistic portfolio together with his disease history, clinical examination, psychopathological and neuropsychological evaluations, blood and cerebrospinal fluid analyses, neuroimaging, neurophysiological testing, and psychotherapeutic treatment. The patient’s 1–2-year history of primarily bulbar motor symptoms and signs aligned with electromyography, showing widespread signs of continuing denervation/chronic neurogenic changes. Slight impairments in semantic fluency, executive control, and visuoconstructive abilities were observed in neuropsychological testing, in conjunction with right-sided medial temporal lobe atrophy in an MRI. He was prescribed medication, including extended-release venlafaxine, trazodone, pramipexole, and zolpidem, and took his medication regularly, usually at high doses. For most of his life, the patient had attributed professional “success” and artistic output to, at times, excessive alcohol consumption. Later, however, his interest in creative work continued despite alcohol reduction and cessation. Psychotherapy grounded him in reality via goal-centered behaviors, making him realize that his physical and mental ailments rather hindered his creative output. In summary, creative behavior can be utilized in the treatment of patients with psychiatric conditions (affective or addictive disorders) and/or neurodegenerative diseases. In the reported case, specific psychopharmacology and psychotherapy that address goal-directed self-efficacy experiences of reality were critical to the patient’s treatment. Full article

Objective: Chloroquine (CQ) and hydroxychloroquine (HCQ) were used as off-label treatments for SARS-CoV-2 infection during the first pandemic waves. The urgency of combatting COVID-19 led to the dissemination of medical recommendations with a scarce awareness of possible drug–drug interactions. This issue primarily concerned people already taking multiple medications, such as older individuals. We estimated the prevalence of drug interactions with CQ or HCQ in COVID-19 inpatients during the first pandemic waves and their possible association with hospitalization-related outcomes. Methods: This study considers 487 patients aged ≥60, hospitalized for COVID-19 from March to December 2020, and treated with CQ or HCQ. Data on acute and chronic therapies and hospitalization length and outcomes were derived from medical records. The presence of drugs potentially interacting with CQ and HCQ was identified based on published literature and drug databases. Results: In our sample (mean age 77.1 years, 47.8% females), 255 (52.4%) patients presented with one drug interaction with CQ or HCQ, and 114 (23.4%) had more than two interactions. The most frequent drugs potentially interacting with CQ or HCQ were lopinavir/ritonavir (50.4%), azithromycin (47.2%), tocilizumab (15.4%), levofloxacin (8.7%), clarithromycin (6.0%), amlodipine (3.3%), and trazodone (2.4%). No substantial differences in the duration and outcomes of the hospitalization emerged as a function of the presence of drug–drug interactions. Conclusions: Many older patients prescribed with CQ or HCQ, which have lately proved ineffective against COVID-19, were exposed to the risk of drug–drug interaction. This underlines that medical recommendations should undergo careful peer review before being widely disseminated, even in emergencies like a pandemic. Full article

An ultra-performance liquid chromatography with photodiode array (UPLC-PDA) UV detection method was developed here for the first time for simple, rapid, selective and sensitive quantification of the commonly prescribed selective cyclooxygenase-2 (COX-2) inhibitor etoricoxib in low plasma volumes (50 μL). The method includes protein precipitation followed by liquid–liquid extraction, evaporation and reconstitution. A gradient mobile phase of 75:25 going to 55:45 (v/v) water:acetonitrile (1 mL/min flow rate) was applied. Total run time was 8 min, representing a significant improvement relative to previous reports. Excellent linearity (r² = 1) was obtained over a wide (0.1–12 µg/mL) etoricoxib concentration range. Short retention times for etoricoxib (4.9 min) and the internal standard trazodone (6.4 min), as well as high stability, recovery, accuracy, precision and reproducibility, and low etoricoxib LOD (20 ng/mL) and LOQ (100 ng/mL), were achieved. Finally, the method was successfully applied to a pharmacokinetic study (single 20 mg/kg orally administered etoricoxib mini-capsule) in rats. In conclusion, the advantages demonstrated in this work make this analytical method both time- and cost-efficient for drug monitoring in pre-clinical/clinical settings. Full article

Background: Primary Stabbing Headache (PSH) is characterized by brief, focal, and paroxysmal pain (“stab”), occurring sporadically or in clusters. Data on pediatric cases are poor. Methods: We performed a comprehensive literature review by searching PubMed, Cochrane, and Embase in order to collect pediatric case reports and case series of PSH. Results: A total of 12 out of 162 articles assessed for eligibility were finally included. The prevalence of PSH and probable PSH varies from 2.5 to 10% among children with primary headaches and it is higher among children aged less than 6 years old. The mean age of onset is between 7 and 11 years of age. Attack duration greatly varies, ranging from a few seconds to several minutes. The intensity of pain is usually from moderate to severe. Associated symptoms are infrequent but may be observed (mainly photophobia, vertigo, nausea, and vomiting). Neuroradiological findings are usually unremarkable; EEG may show sporadic epileptiform abnormalities (up to 30% of cases). Preventive therapy is anecdotal, including treatment with indomethacin, trazodone, valproate, and amitriptyline. Conclusion: PSH is a common but still underdiagnosed entity among children with primary headaches; further and larger cohort studies are needed to better assess, in particular, prognosis and response to therapy. Full article

This article discusses a new method for monitoring drug concentrations in blood samples from patients with mood disorders. The method uses solid-phase microextraction to extract analytes directly from blood samples. It has been adapted to identify the most commonly used drugs in mood disorders, including amitriptyline, citalopram, fluoxetine, paroxetine, sertraline, trazodone, duloxetine, venlafaxine, lamotrigine, quetiapine, olanzapine, and mirtazapine. The analysis is carried out using high-performance liquid chromatography coupled with mass spectroscopy. The proposed DI-SPME/LC-MS method allows for a simple and quick screening analysis while minimizing the volume of the tested sample and solvent, in line with the principles of green analytical chemistry. The method was used to analyze 38 blood samples taken from patients with mood disorders, and drug concentrations were determined and compared with therapeutic and toxic dose ranges. This allowed for better control of the course of treatment. Full article

The concurrent use of several medications is a common practice in the treatment of complex psychiatric conditions. One such commonly used combination is aripiprazole (ARI), an antipsychotic, and trazodone (TRZ), an antidepressant. In addition to their effects on dopamine and serotonin systems, both of these compounds are inhibitors of the 7-dehydrocholesterol reductase (DHCR7) enzyme. To evaluate the systemic and nervous system distribution of ARI and TRZ and their effects on cholesterol biosynthesis, adult mice were treated with both ARI and TRZ for 21 days. The parent drugs, their metabolites, and sterols were analyzed in the brain and various organs of mice using LC-MS/MS. The analyses revealed that ARI, TRZ, and their metabolites were readily detectable in the brain and organs, leading to changes in the sterol profile. The levels of medications, their metabolites, and sterols differed across tissues with notable sex differences. Female mice showed higher turnover of ARI and more cholesterol clearance in the brain, with several post-lanosterol intermediates significantly altered. In addition to interfering with sterol biosynthesis, ARI and TRZ exposure led to decreased ionized calcium-binding adaptor molecule 1 (IBA1) and increased DHCR7 protein expression in the cortex. Changes in sterol profile have been also identified in the spleen, liver, and serum, underscoring the systemic effect of ARI and TRZ on sterol biosynthesis. Long-term use of concurrent ARI and TRZ warrants further studies to fully evaluate the lasting consequences of altered sterol biosynthesis on the whole body. Full article

About 30% of major depression disorder patients fail to achieve remission, hence being diagnosed with treatment-resistant major depression (TRD). Opium had been largely used effectively to treat depression for centuries, but when other medications were introduced, its use was discounted due to addiction and other hazards. In a series of previous studies, we evaluated the antinociceptive effects of eight antidepressant medications and their interaction with the opioid system. Mice were tested with a hotplate or tail-flick after being injected with different doses of mianserin, mirtazapine, trazodone, venlafaxine, reboxetine, moclobemide, fluoxetine, or fluvoxamine to determine the effect of each drug in eliciting antinociception. When naloxone inhibited the antinociceptive effect, we further examined the effect of the specific opioid antagonists of each antidepressant drug. Mianserin and mirtazapine (separately) induced dose-dependent antinociception, each one yielding a biphasic dose-response curve, and they were antagonized by naloxone. Trazodone and venlafaxine (separately) induced a dose-dependent antinociceptive effect, antagonized by naloxone. Reboxetine induced a weak antinociceptive effect with no significant opioid involvement, while moclobemide, fluoxetine, and fluvoxamine had no opioid-involved antinociceptive effects. Controlled clinical studies are needed to establish the efficacy of the augmentation of opiate antidepressants in persons with treatment-resistant depression and the optimal dosage of drugs prescribed. Full article

Mitochondrial dysfunction is involved in the pathophysiology of psychiatric and neurodegenerative disorders and can be used as a modulator and/or predictor of treatment responsiveness. Understanding the mitochondrial effects of antidepressants is important to connect mitochondria with their therapeutic and/or adverse effects. Pig brain-isolated mitochondria were used to evaluate antidepressant-induced changes in the activity of electron transport chain (ETC) complexes, monoamine oxidase (MAO), mitochondrial respiratory rate, and ATP. Bupropion, escitalopram, fluvoxamine, sertraline, paroxetine, and trazodone were tested. All tested antidepressants showed significant inhibition of complex I and IV activities at high concentrations (50 and 100 µmol/L); complex II + III activity was reduced by all antidepressants except bupropion. Complex I-linked respiration was reduced by escitalopram >> trazodone >> sertraline. Complex II-linked respiration was reduced only by bupropion. Significant positive correlations were confirmed between complex I-linked respiration and the activities of individual ETC complexes. MAO activity was inhibited by all tested antidepressants, with SSRIs causing a greater effect than trazodone and bupropion. The results indicate a probable association between the adverse effects of high doses of antidepressants and drug-induced changes in the activity of ETC complexes and the respiratory rate of mitochondria. In contrast, MAO inhibition could be linked to the antidepressant, procognitive, and neuroprotective effects of the tested antidepressants. Full article

Insomnia is the most prevalent sleep disorder, affecting millions worldwide and taking a heavy toll on patient health with significant social and economic impact. Even though there are multiple different types of insomnia medications and behavioral therapies, there are still many individuals for whom treatment remains ineffective. The objective of this retrospective study was to analyze the effectiveness of daridorexant in a cohort of chronic insomnia patients largely transitioned from GABA-A positive allosteric modulators (benzodiazepines, zolpidem or eszopiclone) or other frequently prescribed insomnia medications (including trazodone, atypical antipsychotics or tricyclic antidepressants). A total of 86 patients were treated in the course of ordinary practice and the primary analytic endpoint was the change in Insomnia Severity Index (ISI) score following ≥ 30 nights of treatment with daridorexant. Results from 80 of the 86 patients with full data (65% female, mean age 53.5 years, 18.8% with comorbid obstructive sleep apnea, 91.3% transitioned from a different medication) showed a mean improvement in ISI score of 7.0 ± 0.54 points (SEM) (p < 0.0001) from 18.0 to 11.0. Overall, 78% of the cohort demonstrated a clinically meaningful improvement as defined by at least a six-point drop in ISI. Total sleep time increased by 54 ± 1.0 min (SEM) (p < 0.0001) from 6.0 h to 6.9 h. Mean sleep latency decreased by 23.9 ± 2.4 min (SEM) (p < 0.0001) from 58.8 min to 34.9 min. Wake after sleep onset decreased by 31.6 ± 3.2 min (SEM) (p < 0.001) from 42.8 min to 11.3 min. Sleep efficiency improved by 10.5 ± 1.1% (SEM) (p < 0.0001) from 79.3% to 89.8%. No significant adverse events were noted during the study duration. Keeping in mind this study’s limitations, these data suggest that for insomnia patients with an incomplete response to current therapy, switching to daridorexant is safe and may be an effective alternative treatment. Full article