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Cureus Apr 2024Hyponatremia, a common electrolyte disorder, usually has a benign clinical course. However, patients with the syndrome of inappropriate antidiuretic hormone secretion...
Hyponatremia, a common electrolyte disorder, usually has a benign clinical course. However, patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) can suffer unfavorable outcomes, including mortality. Atypical antipsychotics, which are among the drugs associated with SIADH, also cause tardive dyskinesia, a condition that physicians can now effectively manage with the recently approved agent - valbenazine. We herein report a case of severe hyponatremia due to SIADH in a 58-year-old man who developed hyponatremia-induced generalized seizures six weeks after valbenazine was added to his regimen to mitigate olanzapine-associated tardive dyskinesia. His electrolyte derangement and clinical course improved following prompt recognition and treatment of SIADH. The temporal association between the commencement of valbenazine and the onset of SIADH suggests a possible but previously unreported link between valbenazine and the development of SIADH. Awareness of this uncommon association is relevant to patient safety.
PubMed: 38765393
DOI: 10.7759/cureus.58493 -
Environmental Toxicology and... Jun 2024Pharmaceuticals released from municipal effluents discharges pose a risk to aquatic organisms. The toxicity of 5 pharmaceuticals with distinct therapeutic actions were...
Pharmaceuticals released from municipal effluents discharges pose a risk to aquatic organisms. The toxicity of 5 pharmaceuticals with distinct therapeutic actions were assessed in rainbow trout: olanzapine (antipsychotic), erythromycin (antibiotic), mycophenoate (immunosuppression), pinaverium (anti-inflammatory) and trazodone (sedative). Juveniles were exposed to these drugs for 96 h at concentrations between 64 µg/L up to 40 mg/L to reach lethality. Survival was determined and a suite of biomarkers was analyzed for drug biotransformation, oxidative stress/damage and metabolic activity at sublethal concentrations. The data revealed the following toxicity: olanzapine >trazodone>mycophenolate>pinaverium∼erythromycin based on mortality. The data also revealed that toxicity was associated to mass, pKa and hydrophobicity and the following sublethal effects: GST, LPO and DNA strand breaks. Pharmaceuticals with lower molecular weight, physiological pKa, moderate hydrophobicity, low biotransformation and DNA strand breaks were generally more toxic to fish. However, this should be considered as a general guide in identifying toxic pharmaceuticals in non-target organisms.
Topics: Animals; Oncorhynchus mykiss; Water Pollutants, Chemical; Biomarkers; Erythromycin; Trazodone; Olanzapine; Glutathione Transferase; Benzodiazepines; Oxidative Stress
PubMed: 38763437
DOI: 10.1016/j.etap.2024.104472 -
Prague Medical Report 2024Second-generation antipsychotics (SGAs), also known as atypical antipsychotics, are a newer class of antipsychotic drugs used to treat schizophrenia, bipolar disorder,... (Review)
Review
Second-generation antipsychotics (SGAs), also known as atypical antipsychotics, are a newer class of antipsychotic drugs used to treat schizophrenia, bipolar disorder, and related psychiatric conditions. The plasma concentration of antipsychotic drugs is a valid measure of the drug at its primary target structure in the brain, and therefore determines the efficacy and safety of these drugs. However, despite the well-known high variability in pharmacokinetics of these substances, psychiatric medication is usually administered in uniform dosage schedules. Therapeutic drug monitoring (TDM), as the specific method that can help personalised medicine in dose adjustment according to the characteristics of the individual patient, minimizing the risk of toxicity, monitoring adherence, and increasing cost-effectiveness in the treatment, thus seems to be an elegant tool to solve this problem. Non-response to therapeutic doses, uncertain adherence to medication, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM of SGAs. This review aims to summarize an overview of the current knowledge and evidence of the possibilities to tailor the dosage of selected SGAs using TDM, including the necessary pharmacokinetic parameters for personalised pharmacotherapy.
Topics: Humans; Drug Monitoring; Antipsychotic Agents; Schizophrenia
PubMed: 38761044
DOI: 10.14712/23362936.2024.10 -
Molecular Neurobiology May 2024Schizophrenia (SCZ) is a complex, severe psychotic disorder that is highly persistent. Patients often cannot control their emotions and have delusions of victimization,...
Schizophrenia (SCZ) is a complex, severe psychotic disorder that is highly persistent. Patients often cannot control their emotions and have delusions of victimization, world-weariness, and even suicide. Therefore, safer and more effective drugs are urgently needed. Rannasangpei (RNSP) from "the four medicine tantras" was used as a neuroprotective agent. The objective of this study was to investigate the effect and mechanism of RNSP on MK-801-induced SCZ in mice. Fifty C57BL/6J mice were randomly divided into a normal group, a model group, an RNSP group, a crocin (CRO) group, and an olanzapine (OLA) group, except for the normal group. The remaining mice were used to establish the MK-801-induced SCZ model. Changes in positive symptoms and cognitive impairment in mice before and after drug intervention were assessed by using the prepulse inhibition (PPI) test, Y-maze test (YMT), and open-field test (OFT). Intragastric administration of RNSP alleviated the symptoms of SCZ in SCZ mice, as demonstrated by the PPI, YMT, and OFT results. Compared with the model group, the first-line antipsychotic olanzapine reversed the anxiety-like phenotypes, hypermotility, and PPI deficits in the SCZ model mice. Further analysis revealed that RNSP reduced oxidative stress in SCZ model mice, as evidenced by increased superoxide dismutase (SOD) levels and decreased malondialdehyde (MDA) levels in the hippocampus, cortex, and blood of SCZ model mice. In our study, RNSP treatment restored the expression of brain-derived neurotrophic factor (BDNF), dopamine D2 receptor, p-Trkb, Akt/p-Akt, and doublecortin and inhibited the expression of IBA1 and Bax in the hippocampus of SCZ model mice. The polymerase chain reaction data indicated that RNSP treatment increased the expression of Bcl-2 and TGF-β and decreased the expression of Bax, IL-1β, and TNF-α in the brains of the model mice. Our results are the first to show that RNSP reverses SCZ-like behaviors in rodents (both positive symptoms and cognitive deficits) by reducing oxidative stress and activating the BDNF-TrkB/Akt pathway, suggesting that RNSP is a novel approach for treating SCZ.
PubMed: 38753130
DOI: 10.1007/s12035-024-04213-5 -
Therapeutic Advances in... 2024Clozapine, renowned for its efficacy in treatment-resistant schizophrenia, is associated with rare yet potentially severe side effects, including hematological...
Clozapine, renowned for its efficacy in treatment-resistant schizophrenia, is associated with rare yet potentially severe side effects, including hematological disorders, myocarditis, seizures and gastrointestinal obstruction. Dermatological adverse effects, though less serious, can profoundly impact patients' quality of life. We present the first reported case of cholinergic urticaria induced by clozapine, in a 25-year-old male with treatment-resistant schizophrenia. Four months into clozapine therapy, the patient developed intensely pruritic erythematous lesions triggered by sweating, significantly impairing his daily activities. Despite attempts at management, including dose reduction and antihistamine therapy, the urticaria persisted. However, a favorable outcome was achieved upon switching to quetiapine. This case underscores the importance of recognizing and managing treatment-related adverse effects, even when they arise late in treatment, and highlights the need for individualized therapeutic approaches.We discuss potential mechanisms underlying clozapine-induced cholinergic urticaria and emphasize the significance of patient-centered care in optimizing treatment outcomes in schizophrenia.
PubMed: 38745850
DOI: 10.1177/20451253241241056 -
Frontiers in Psychiatry 2024This study aims to explore the gender differences in cognitive improvements after two months of atypical antipsychotic treatment in first episode schizophrenia (FES).
AIMS
This study aims to explore the gender differences in cognitive improvements after two months of atypical antipsychotic treatment in first episode schizophrenia (FES).
METHODS
82 patients with FES, including 50 male patients and 32 female patients, were enrolled in the present study. Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) were respectively conducted to evaluate the clinical symptoms and cognitive function of patients with FES at baseline and after treatment. Repeated measure ANOVA was performed to compare gender differences in cognitive domains scores between baseline and 2-month follow-up. Stepwise liner regression model was performed to explore the effect factors of cognitive improvements in patients.
RESULTS
There was no significant difference in age of onset, education years, PANSS scores, duration of untreated psychosis and Olanzapine equivalent doses between male and female patients (all p > 0.05). In the comparisons of cognition function, male patients exhibited better performance in social cognition compared with female patients at baseline (t = 3.20, < 0.05). After treatment, improvements of attention/vigilance and working memory were both found in male patients and female patients (attention/vigilance, F = 11.867, < 0.05; working memory, F = 18.265, < 0.05). In addition, improvement of speed of information processing was only found in female patients (F = 11.65, < 0.01). Significant interaction between time and gender was found in speed information of processing (F = 4.140, = 0.045). Stepwise liner regression model revealed that improvements of negative symptoms promote improvements of cognitive function in female patients (all < 0.05).
CONCLUSIONS
Our findings revealed gender differences of cognitive improvements in patients with FES after 2-month treatment. It provides new evidence for gender differences in cognitive symptoms of schizophrenia, and also provides preliminary clues for further individualized cognitive intervention strategies.
PubMed: 38742135
DOI: 10.3389/fpsyt.2024.1369532 -
Biochimica Et Biophysica Acta.... Jun 2024Olanzapine (OLA) is a highly obesogenic second-generation antipsychotic (SGA). Recently we demonstrated that, contrarily to OLA oral treatment, intraperitoneal (i.p.)...
Olanzapine (OLA) is a highly obesogenic second-generation antipsychotic (SGA). Recently we demonstrated that, contrarily to OLA oral treatment, intraperitoneal (i.p.) administration resulted in weight loss and absence of hepatic steatosis in wild-type (WT) and protein tyrosine phosphatase 1B (PTP1B)-deficient (KO) male mice. This protection relied on two central-peripheral axes connecting hypothalamic AMPK with brown/inguinal white adipose tissue (BAT/iWAT) uncoupling protein-1 (UCP-1) and hypothalamic JNK with hepatic fatty acid synthase (FAS). Herein, we addressed OLA i.p. treatment effects in WT and PTP1B-KO female mice. Contrarily to our previous results in WT females receiving OLA orally, the i.p. treatment did not induce weight gain or hyperphagia. Molecularly, in females OLA failed to diminish hypothalamic phospho-AMPK or elevate BAT UCP-1 and energy expenditure (EE) despite the preservation of iWAT browning. Conversely, OLA i.p. treatment in ovariectomized mice reduced hypothalamic phospho-AMPK, increased BAT/iWAT UCP-1 and EE, and induced weight loss as occurred in males. Pretreatment of hypothalamic neurons with 17β-estradiol (E) abolished OLA effects on AMPK. Moreover, neither hypothalamic JNK activation nor hepatic FAS upregulation were found in WT and PTP1B-KO females receiving OLA via i.p. Importantly, this axis was reestablished upon ovariectomy. In this line, E prevented OLA-induced phospho-JNK in hypothalamic neurons. These results support the role of estrogens in sex-related dimorphism in OLA treatment. This study evidenced the benefit of OLA i.p. administration in preventing its obesogenic effects in female mice that could offer clinical value.
Topics: Animals; Female; Adipose Tissue, Brown; Hypothalamus; Mice; Liver; Estrogens; Olanzapine; Mice, Knockout; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Uncoupling Protein 1; Male; Energy Metabolism; Injections, Intraperitoneal; Adipose Tissue, White; Mice, Inbred C57BL; Estradiol; Ovariectomy
PubMed: 38733774
DOI: 10.1016/j.bbadis.2024.167227 -
Cancers Apr 2024Despite a better understanding of the mechanisms causing cancer cachexia (CC) and development of promising pharmacologic and supportive care interventions, CC persists... (Review)
Review
Despite a better understanding of the mechanisms causing cancer cachexia (CC) and development of promising pharmacologic and supportive care interventions, CC persists as an underdiagnosed and undertreated condition. CC contributes to fatigue, poor quality of life, functional impairment, increases treatment related toxicity, and reduces survival. The core elements of CC such as weight loss and poor appetite should be identified early. Currently, addressing contributing conditions (hypothyroidism, hypogonadism, and adrenal insufficiency), managing nutrition impact symptoms leading to decreased oral intake (nausea, constipation, dysgeusia, stomatitis, mucositis, pain, fatigue, depressed mood, or anxiety), and the addition of pharmacologic agents when appropriate (progesterone analog, corticosteroids, and olanzapine) is recommended. In Japan, the clinical practice has changed based on the availability of Anamorelin, a ghrelin receptor agonist that improved lean body mass, weight, and appetite-related quality of life (QoL) compared to a placebo, in phase III trials. Other promising therapeutic agents currently in trials include Espindolol, a non-selective β blocker and a monoclonal antibody to GDF-15. In the future, a single therapeutic agent or perhaps multiple medications targeting the various mechanisms of CC may prove to be an effective strategy. Ideally, these medications should be incorporated into a multimodal interdisciplinary approach that includes exercise and nutrition.
PubMed: 38730648
DOI: 10.3390/cancers16091696 -
The Primary Care Companion For CNS... May 2024To examine the complexities of psychotropic medication prescription in home-based palliative care for oncology patients. A retrospective analysis of 125 medical...
To examine the complexities of psychotropic medication prescription in home-based palliative care for oncology patients. A retrospective analysis of 125 medical records of patients receiving palliative home care for cancer was conducted at a tertiary hospital, with a specific focus on the prescription patterns of psychotropic medications. The data were collected in September 2023. Among 125 cases, the mean age was 64.4 ± 14.9 years, with 50.4% females. Breast cancer (14.4%) and lung cancer (13.6%) were the most common diagnoses. Psychotropic medication was administered to 35.2% of patients. Treatment was initiated by palliative care doctors in 75% of cases, while psychiatrists handled 25%. Medication selection was predominantly symptom driven (63%), with anxiety prompting benzodiazepine prescriptions in 50% of cases, depression resulting in antidepressant use in 22%, and psychosis leading to antipsychotic treatment in 18%. Specific diagnoses were the target in only 36% of prescriptions, with delirium (27%) being the most prevalent, followed by depression and bipolar disorder. Benzodiazepines were the most commonly prescribed class of medications (56.8%), with clonazepam being the most prevalent (40.9%), followed by alprazolam and lorazepam (15.9%). Atypical antipsychotics made up 43.1% of prescriptions, with quetiapine being the most frequently prescribed (34%), along with olanzapine and risperidone (11%). Antidepressants accounted for 31.8% of prescriptions, including selective serotonin reuptake inhibitors at 18% and mirtazapine and amitriptyline at 6% each. Haloperidol, a typical antipsychotic, was prescribed in 13.6% of cases. Polypharmacy was observed in 35.6% of patients. In palliative home care, psychotropic medications are frequently prescribed by palliative doctors primarily for symptom management, with limited psychiatric consultations and challenges in accessing psychological evaluations. Collaborative efforts among regional or institutional medical bodies, including psychiatrists, psychologists, palliative doctors, and social workers, are needed to establish ethical guidelines for appropriate and effective psychotropic prescription. .
Topics: Humans; Female; Male; Middle Aged; Palliative Care; Retrospective Studies; Psychotropic Drugs; Aged; Home Care Services; Neoplasms; Drug Prescriptions; Adult; Aged, 80 and over; Practice Patterns, Physicians'
PubMed: 38728674
DOI: 10.4088/PCC.23m03668 -
Journal of the European Academy of... May 2024Data remain scarce for the first-line antipsychotic choice in treating delusional infestation (DI).
BACKGROUND
Data remain scarce for the first-line antipsychotic choice in treating delusional infestation (DI).
OBJECTIVES
We evaluated the treatment responses associated with different antipsychotics in DI patients.
METHODS
We undertook a multicentre, retrospective observational study using anonymised electronic patient records from two hospitals in the United Kingdom from 1 January 2011 to 1 January 2023. Eligible participants were adults (≥18 years) diagnosed with DI treated with an antipsychotic, and had both an assigned baseline and follow-up Clinical Global Impression Scale (CGI-S) score. The CGI-S is a validated psychiatric research tool. Participants were excluded if they had known limited or non-adherence to an antipsychotic, or if no CGI-S scores were present at follow-up. First clinic visits before the initiation of an antipsychotic were assigned as the baseline CGI-S score. The last available CGI-S score before the patient either changed antipsychotic or left the clinic for any reason was used to assign follow-up CGI-S scores. The primary outcome was the response to each individual antipsychotic treatment, measured by the difference in the baseline and last available follow-up CGI-S scores. Differences in CGI-S changes between antipsychotic episodes were tested by analysis of variance (ANOVA).
RESULTS
In total, 414 patient records were analysed, and data were extracted. The mean age was 61.8 years (SD 14.1). One hundred seventy (41%) of 414 patients were men and 244 (59%) were women. In total, 156 (38%) of 414 patients were eligible, yielding a total of 315 antipsychotic prescribing episodes. The ANOVA, ranking in order of treatment response, showed that the highest mean score (expressing highest treatment response) was observed in amisulpride (31 [67%] of 46) and risperidone (95 [57%] of 167), followed by some distance by quetiapine (9 [36%] of 25), aripiprazole (13 [28%] of 46) and olanzapine (7 [25%] of 28).
CONCLUSIONS
Amisulpride and risperidone were associated with a higher treatment response than quetiapine, aripiprazole and olanzapine. Amisulpride and risperidone should therefore be considered the first-line treatment options in DI patients.
PubMed: 38727630
DOI: 10.1111/jdv.20081