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Medicine Jun 2024Chaihu-Shugan-San (CSS), a Traditional Chinese Medicine formula, has been widely used for treating depression since the Ming Dynasty, as recorded in Jingyue Quanshu, but... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chaihu-Shugan-San (CSS), a Traditional Chinese Medicine formula, has been widely used for treating depression since the Ming Dynasty, as recorded in Jingyue Quanshu, but its effectiveness and safety lack comprehensive and objective evaluation. Based on our meta-analysis, we aimed to adequately evaluate the efficacy and risk of CSS by considering the latest clinical literature.
METHODS
Multiple databases, including PubMed, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure, Chongqing VIP, and Wanfang, were used to collect clinical data. The quality of the included clinical studies was assessed using the Cochrane Risk of Bias Tool, and the data were meta-analyzed using Review Manager 5.0 and Stata 17. The data were obtained from a genome-wide association study, and Mendelian randomization (MR) was performed using R Software 4.3.2 with the TwoSampleMR and MR Pleiotropy RESidual Sum and Outlier packages.
RESULTS
A total of 15 studies with 1034 patients and 6 antidepressant drugs were included in this work. Meta-analyses revealed that drug combinations of CSS and antidepressants significantly improved depressive symptoms (weighted mean difference = -4.21; 95% confidence interval [CI]: -5.62--2.81), increased the effective rate (odds ratio [OR] = 3.82; 95% CI: 2.44-6.83), and reduced side effects (OR = -3.55; 95% CI: -5.66--1.43) compared with antidepressant monotherapy. Additionally, compared with antidepressant monotherapy, CSS alone exhibited fewer side effects (95% CI:-9.25--6.95). Like antidepressants, CSS also improved depressive symptoms (weighted mean difference = -0.05; 95% CI: -0.63--0.52) and increased the effective rate (OR = 1.07; 95% CI: 0.52-2.20). Additionally, MR was used to evaluate the safety of traditional antidepressants, as there was a causal association between amitriptyline and body mass index.
CONCLUSION
This analysis demonstrated that compared with traditional antidepressants, CSS combined with antidepressants was more effective and safer for treating depressed patients. MR showed that a causal relationship may exist between amitriptyline and body mass index. Therefore, clinicians should carefully consider the advantages and potential drawbacks of Traditional Chinese Medicine and classic drugs to serve patients better.
Topics: Humans; Antidepressive Agents; Depression; Plant Extracts; Drugs, Chinese Herbal; Treatment Outcome
PubMed: 38941409
DOI: 10.1097/MD.0000000000038668 -
Purinergic Signalling Sep 2023Some non-adenosinergic drugs are reported to also act through adenosine receptors (ARs). We used mouse hypothermia, which can be induced by agonism at any of the four...
Some non-adenosinergic drugs are reported to also act through adenosine receptors (ARs). We used mouse hypothermia, which can be induced by agonism at any of the four ARs, as an in vivo screen for adenosinergic effects. An AR contribution was identified when a drug caused hypothermia in wild type mice that was diminished in mice lacking all four ARs (quadruple knockout, QKO). Alternatively, an adenosinergic effect was identified if a drug potentiated adenosine-induced hypothermia. Four drugs (dipyridamole, nimodipine, cilostazol, cyclosporin A) increased the hypothermia caused by adenosine. Dipyridamole and nimodipine probably achieved this by inhibition of adenosine clearance via ENT1. Two drugs (cannabidiol, canrenoate) did not cause hypothermia in wild type mice. Four other drugs (nifedipine, ranolazine, ketamine, ethanol) caused hypothermia, but the hypothermia was unchanged in QKO mice indicating non-adenosinergic mechanisms. Zinc chloride caused hypothermia and hypoactivity; the hypoactivity was blunted in the QKO mice. Interestingly, the antidepressant amitriptyline caused hypothermia in wild type mice that was amplified in the QKO mice. Thus, we have identified adenosine-related effects for some drugs, while other candidates do not affect adenosine signaling by this in vivo assay. The adenosine-modulating drugs could be considered for repurposing based on predicted effects on AR activation.
Topics: Mice; Animals; Adenosine; Hypothermia; Nimodipine; Receptors, Purinergic P1; Dipyridamole
PubMed: 36781825
DOI: 10.1007/s11302-023-09924-3 -
Journal of Medical Case Reports Sep 2023Acute presentations of acquired exotropia or divergent alignment of either or both eyes are commonly observed following intracranial vascular events, trauma, orbital,...
BACKGROUND
Acute presentations of acquired exotropia or divergent alignment of either or both eyes are commonly observed following intracranial vascular events, trauma, orbital, and endoscopic sinus surgeries.
CASE PRESENTATION
The reported case is about a 16-year-old previously healthy Tamil female who presented to the emergency department with a few hours of reduced responsiveness. With the only clue in the history being about a family conflict the previous day, the examination revealed a noticeable exotropia along with a constellation of anticholinergic findings: a low Glasgow Coma Score, mydriasis, tachycardia, floppy limbs, exaggerated reflexes, and a palpable urinary bladder. Amitriptyline overdose leading to significant neurological involvement was suspected, and she was immediately offered urine alkalinization. Resources for urine and blood toxicological studies were not available. The patient gained consciousness 24 hours later and confirmed an overdose of ten amitriptyline tablets. Exotropia, a unique manifestation of this patient's neurotoxicity, spontaneously resolved in 36 hours.
DISCUSSION AND CONCLUSIONS
The reported case is about an uncommon clinical finding of exotropia seen in a common toxicological emergency: acute amitriptyline overdose. The importance of having a wide knowledge of various clinical presentations of drug toxicities is highlighted here, as any delay in diagnosis or initiation of life-saving measures could have resulted in fatal consequences.
Topics: Female; Humans; Adolescent; Exotropia; Amitriptyline; India; Eye; Cognition; Drug Overdose
PubMed: 37679834
DOI: 10.1186/s13256-023-04057-y -
Oman Medical Journal Nov 2023This study sought to determine the confidence level of mental health practitioners in Oman regarding the use of antidepressants during pregnancy and breastfeeding,...
OBJECTIVES
This study sought to determine the confidence level of mental health practitioners in Oman regarding the use of antidepressants during pregnancy and breastfeeding, assess their knowledge and need for further training in this area, and examine their current prescribing patterns and preferences.
METHODS
A questionnaire-based survey was conducted from May to June 2017 among all practitioners in the psychiatry specialty, including medical officers authorized to prescribe medications, at the Behavioral Medicine Department of Sultan Qaboos University Hospital and Al Masarra Hospital.
RESULTS
Forty-two practitioners (response rate = 89.4%) responded to the questionnaire. Of them, 10 (23.8%) had no experience, while 30 (71.4%) had experience in prescribing antidepressants during both pregnancy and breastfeeding periods. Twenty-seven (64.3%) respondents felt that they were confident in prescribing antidepressants for women during their perinatal period, while 30.0% were neutral. Moreover, 35 (83.3%) participants expressed the need for more training in this area. Furthermore, 34 (81.0%) believed that more training in perinatal psychiatry should be included in the psychiatry curriculum. There was no consistent prescribing pattern (either prescribing or avoiding) among our participating practitioners during the first trimester of pregnancy and breastfeeding periods. The drug of choice in the first trimester of pregnancy was fluoxetine preferred by approximately 85.0% of the practitioners, but avoided by 10.0% of practitioners in the same period. This was followed by amitriptyline (50.0% vs. 23.0%), sertraline (50.0% vs. 9.0%), imipramine (28.0% vs. 84.0%). During breastfeeding, the drug of choice for approximately 74.0% of the practitioners was paroxetine, but avoided by 15.0% of practitioners. This was followed by sertraline (50.0% vs. 8.0%). The most common reasons for prescription during pregnancy were safety, evidence-based practice, and low teratogenicity. For breastfeeding, the main reasons for prescription were low levels of the drug in breast milk, safety, and evidence-based practice. On the other hand, high teratogenicity, neonatal side effects, limited data, and lack of evidence were among the most common reasons behind avoiding prescribing during pregnancy, while high levels of breast milk, neonatal side effects, limited evidence, and safety concerns were the most common reasons during the breastfeeding period.
CONCLUSIONS
There was inconsistency among mental health practitioners in making prescription decisions and in their prescribing patterns.
PubMed: 38264515
DOI: 10.5001/omj.2023.123 -
Cureus Oct 2023Background Patients staying in acute rehabilitation often use large amounts of opioids during their stay. There are a number of reasons for this increased opioid...
Background Patients staying in acute rehabilitation often use large amounts of opioids during their stay. There are a number of reasons for this increased opioid exposure, including but not limited to daily exercises with physical and occupational therapists, increased demand on a healing body, and use of previously atrophying musculature. Some physiatrists have noticed that patients who concurrently are prescribed medications such as Robaxin seem to require fewer opioids during their stay in acute rehabilitation. This study aimed to determine the association between non-opioid analgesic use and total opioid load, as measured using morphine milligram equivalents (MMEs), during inpatient rehabilitation for traumatic brain injury. Methodology A retrospective study of individuals with a diagnosis of traumatic brain injury admitted to an acute inpatient rehabilitation program was performed. Non-opioid medications that were reviewed in the study included acetaminophen, amitriptyline, baclofen, diclofenac, gabapentin, ibuprofen, lidocaine, methocarbamol, nortriptyline, and pregabalin. Five of the most-used non-opioid medications (acetaminophen, diclofenac, gabapentin, lidocaine, and methocarbamol) were statistically analyzed using regression and analysis of variance to evaluate for any significant variables. Results Results showed that the average daily dose of acetaminophen has a significant effect on the average daily MME and that the average daily dose of gabapentin and methocarbamol each have a significant effect on the change of daily MME usage from admission to discharge from acute rehab (ΔMME). Results also showed that the mere presence of methocarbamol (regardless of daily or total dosage) had a significant effect on the ΔMME. Conclusions Based on these findings, physicians may want to consider prescribing acetaminophen, gabapentin, or methocarbamol for patients admitted for inpatient rehabilitation following traumatic brain injury who require high amounts of opioids.
PubMed: 37954704
DOI: 10.7759/cureus.46872 -
Environmental Toxicology and... Mar 2024Interaction of nanoplastics (NPls) with other environmental contaminants could affect their uptake by the organisms and their toxicity. Thus, the present study aims to...
Interaction of nanoplastics (NPls) with other environmental contaminants could affect their uptake by the organisms and their toxicity. Thus, the present study aims to investigate the polystyrene NPls (44 nm) interaction with the antidepressant amitriptyline (AMI) and its toxicity to Danio rerio embryos. A similar toxicological profile for NPls + AMI exposure was found for most of the evaluated endpoints, comparing with AMI single exposure, showing that the presence of NPls did not modulate the AMI toxicity. However, the behavioral assessment showed a different pattern with hypoactivity for the NPls + AMI exposure (NPls - hyperactivity; AMI - no effect). Interaction effects between NPls and AMI were also found in the protein contents (antagonism) and in the total glutathione content (synergism). This study highlights the complexity and unpredictability of NPls interaction with pharmaceuticals, important for an accurate environmental risk assessment and for the developing of effective strategies and interventions against plastic pollution.
Topics: Animals; Amitriptyline; Zebrafish; Microplastics; Water Pollutants, Chemical; Polystyrenes
PubMed: 38244879
DOI: 10.1016/j.etap.2024.104372 -
Polymers Oct 2023N-butyl-N-methyl-1-phenylpyrrole[1,2-a] pyrazine-3-carboxamide (GML-3) is a potential candidate for combination drug therapy due to its anxiolytic and antidepressant...
Modeling of the Aqueous Solubility of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a] pyrazine-3-carboxamide: From Micronization to Creation of Amorphous-Crystalline Composites with a Polymer.
N-butyl-N-methyl-1-phenylpyrrole[1,2-a] pyrazine-3-carboxamide (GML-3) is a potential candidate for combination drug therapy due to its anxiolytic and antidepressant activity. The anxiolytic activity of GML-3 is comparable to diazepam. The antidepressant activity of GML-3 is comparable to amitriptyline. GML-3 is an 18 kDa mitochondrial translocator protein (TSPO) ligand and is devoid of most of the side effects of diazepam, which makes the research on the creation of drugs based on it promising. However, its low water solubility and tendency to agglomerate prevented its release. This research aimed to study the effect of dry grinding, the rapid expansion of a supercritical solution (RESS), and the eutectic mixture (composite) of GML-3 with polyvinylpyrrolidone (PVP) on the particle size, dissolution rate, and lattice retention of GML-3. The use of supercritical CO in the RESS method was promising in terms of particle size reduction, resulting in a reduction in the particle size of GML-3 to 20-40 nm with a 430-fold increase in dissolution rate. However, in addition to particle size reduction after RESS, GML-3 began to show signs of a polymorphism phenomenon, which was also studied in this article. It was found that coarse grinding reduced particle size by a factor of 2 but did not significantly affect solubility or crystal structure. Co-milling with the polymer made it possible to level the effect of the appearance of a residual electrostatic charge on the particles, as in the case of grinding, and the increased solubility in the resulting mechanical mixtures of GML-3 with the polymer may also indicate the dissolving properties of polymers (an increase in 400-800 times). The best result in terms of GML-3 solubility was demonstrated by the resulting GML-3:PVP composite at a ratio of 1:4, which made it possible to achieve a solubility of about 80% active pharmaceutical ingredient (API) within an hour with an increase in the dissolution rate by 1600 times. Thus, the creation of composites is the most effective method for improving the solubility of GML-3, superior to micronization.
PubMed: 37896380
DOI: 10.3390/polym15204136 -
Cureus Aug 2023The author reports a 19-year-old woman suffering from repeated episodes of non-bloody vomiting for 18 months. All routine and special investigations were normal. She was...
The author reports a 19-year-old woman suffering from repeated episodes of non-bloody vomiting for 18 months. All routine and special investigations were normal. She was labeled as a case of cyclic vomiting syndrome (CVS), and she developed insomnia after the initiation of amitriptyline as a prophylactic treatment. The case was reported to increase awareness regarding the importance of monitoring medication side effects among clinicians when using different classes of medications to treat CVS.
PubMed: 37692726
DOI: 10.7759/cureus.43249 -
Molecules (Basel, Switzerland) Jan 2024This article discusses a new method for monitoring drug concentrations in blood samples from patients with mood disorders. The method uses solid-phase microextraction to...
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.
Topics: Humans; Solid Phase Microextraction; Mood Disorders; Drug Monitoring; Immersion; Fluoxetine
PubMed: 38338419
DOI: 10.3390/molecules29030676 -
Chemosphere Sep 2023Sludge is one of the most problematic residues generated during wastewater treatment. Herein, we validate a single-step, sensitive procedure for the determination of a...
Sludge is one of the most problematic residues generated during wastewater treatment. Herein, we validate a single-step, sensitive procedure for the determination of a selection of 46 basic micro-pollutants, either used as pharmaceuticals or pesticides, in sludge from municipal sewage treatment plants (STPs), using liquid chromatography tandem mass spectrometry as determination technique. The proposed method permitted to achieve accurate recoveries (values from 70% to 120%, for samples spiked at different concentration levels) using solvent-based calibration standards. This feature, combined with limits of quantification lower than 5 ng g (dry weight), allowed the rapid and sensitive quantification of target compounds in freeze-dried sludge samples. Out of 46 investigated pollutants, 33 species showed detection frequencies above 85% in a group of 48 sludge samples, obtained from 45 STPs located in the Northwest of Spain. The assessment of eco-toxicological risks associated to sludge disposal as fertilizer in agriculture and/or forestry, considering average concentrations found in sludge samples, highlighted eight pollutants (sertraline, venlafaxine, N-desethyl amiodarone, amiodarone, norsertraline, trazodone, amitriptyline and ketoconazole) representing an environmental hazard based on ratios between predicted soil levels and non-effect concentrations estimated using the equilibrium partition method.
Topics: Sewage; Environmental Pollutants; Spain; Amiodarone; Water Purification; Risk Assessment; Water Pollutants, Chemical
PubMed: 37268235
DOI: 10.1016/j.chemosphere.2023.139094