-
World Psychiatry : Official Journal of... Jun 2024Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative...
Real-world effectiveness of antidepressants, antipsychotics and their combinations in the maintenance treatment of psychotic depression. Evidence from within-subject analyses of two nationwide cohorts.
Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative effectiveness of medications used in its maintenance treatment. The objective of this study was to investigate the comparative effectiveness of specific antipsychotics and antidepressants, and their combinations, on the risk of psychiatric hospitalization among persons with PD in routine care. Persons aged 16-65 years with a first-time diagnosis of PD were identified from Finnish (years 2000-2018) and Swedish (years 2006-2021) nationwide registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. The main exposures were specific antipsychotics and antidepressants, and the main outcome measure was psychiatric hospitalization as a marker of severe relapse. The risk of hospitalization associated with periods of use vs. non-use of medications (expressed as adjusted hazard ratio, aHR) was assessed by a within-individual design, using each individual as his/her own control, and analyzed with stratified Cox models. The two national cohorts were first analyzed separately, and then combined using a fixed-effect meta-analysis. The Finnish cohort included 19,330 persons (mean age: 39.8±14.7 years; 57.9% women) and the Swedish cohort 13,684 persons (mean age: 41.3±14.0 years; 53.5% women). Individual antidepressants associated with a decreased risk of relapse vs. non-use of antidepressants were bupropion (aHR=0.73, 95% CI: 0.63-0.85), vortioxetine (aHR=0.78, 95% CI: 0.63-0.96) and venlafaxine (aHR=0.92, 95% CI: 0.86-0.98). Any long-acting injectable antipsychotic (LAI) (aHR=0.60, 95% CI: 0.45-0.80) and clozapine (aHR=0.72, 95% CI: 0.57-0.91) were associated with a decreased risk of relapse vs. non-use of antipsychotics. Among monotherapies, only vortioxetine (aHR=0.67, 95% CI: 0.47-0.95) and bupropion (aHR=0.71, 95% CI: 0.56-0.89) were associated with a significantly decreased risk of relapse vs. non-use of both antidepressants and antipsychotics. In an exploratory analysis of antidepressant-antipsychotic combinations, a decreased relapse risk was found for amitriptyline-olanzapine (aHR=0.45, 95% CI: 0.28-0.71), sertraline-quetiapine (aHR=0.79, 95% CI: 0.67-0.93) and venlafaxine-quetiapine (aHR=0.82, 95% CI: 0.73-0.91) vs. non-use of antidepressants and antipsychotics. Benzodiazepines and related drugs (aHR=1.29, 95% CI: 1.24-1.34) and mirtazapine (aHR=1.17, 95% CI: 1.07-1.29) were associated with an increased risk of relapse. These data indicate that, in the maintenance treatment of PD, bupropion, vortioxetine, venlafaxine, any LAI, clozapine, and only few specific antidepressant-antipsychotic combinations are associated with a decreased risk of relapse. These findings challenge the current recommendation by treatment guidelines to combine an antipsychotic with an antidepressant (without further specification) as standard treatment in PD.
PubMed: 38727044
DOI: 10.1002/wps.21205 -
Journal of Pain Research 2023Chemotherapy-induced peripheral neurotoxicity (CIPN) affects nearly 70% of cancer patients after chemotherapy, causing sensory, motor, autonomic dysfunction, and...
INTRODUCTION
Chemotherapy-induced peripheral neurotoxicity (CIPN) affects nearly 70% of cancer patients after chemotherapy, causing sensory, motor, autonomic dysfunction, and neuropathic pain. The Desirability of Outcome Ranking (DOOR) framework is proposed as a better way to assess preventive or therapeutic interventions for CIPN.
METHODS
A survey was conducted among Italian healthcare professionals and researchers affiliated to the Italian Chapter of the International Association for the Study of Pain (AISD) to identify the most important outcomes in clinical management and research.
RESULTS
Among the 73 respondents, 61 qualified for the survey, with an overall response rate of 1.2%. The vast majority were physicians (77%), most of whom were anesthesiologists (47.5%). The results showed that pain, survival, sensory impairment, motor impairment, and quality of life were consistently ranked as the most important outcomes, but there was significant disagreement in the outcomes relative ranking, making it difficult to develop a DOOR algorithm. The study also revealed that clinicians commonly use structured interviews to evaluate patients with CIPN, and the most prescribed drugs or supplements were palmitoylethanolamide, pregabalin, gabapentin and alpha lipoic acid as preventive agents and pregabalin, palmitoylethanolamide, duloxetine, gabapentin, and amitriptyline as therapeutic agents. However, many of these drugs have not been clinically proven to be effective for CIPN.
DISCUSSION
This study suggests that the implementation of a DOOR framework for CIPN using healthcare professionals is more difficult than expected, given the significant disagreement in our respondents' ranking of outcomes. Our work provides interesting topics for future research in CIPN, but its limitations include a small sample size, a low response rate, and a possible selection bias.
PubMed: 37790191
DOI: 10.2147/JPR.S414389 -
The Journal of Pharmacology and... Jan 2024Inflammatory pain is caused by tissue hypersensitization and is a component of rheumatic diseases, frequently causing chronic pain. Current guidelines use a multimodal...
Assessing Dose- and Sex-Dependent Antinociceptive Effects of Cannabidiol and Amitriptyline, Alone and in Combination, and Exploring Mechanism of Action Involving Serotonin 1A Receptors.
Inflammatory pain is caused by tissue hypersensitization and is a component of rheumatic diseases, frequently causing chronic pain. Current guidelines use a multimodal approach to pain and sociocultural changes have renewed interest in cannabinoid use, particularly cannabidiol (CBD), for pain. The tricyclic antidepressant amitriptyline (AT) is approved for use in pain-related syndromes, alone and within a multimodal approach. Therefore, we investigated sex- and dose-dependent effects of CBD and AT antinociception in the 2.5% formalin inflammatory pain model. Male and female C57BL/6J mice were pretreated with either vehicle, CBD (0.3-100 mg/kg), or AT (0.1-30 mg/kg) prior to formalin testing. In the acute phase, CBD induced antinociception after administration of 30-100 mg/kg in males and 100 mg/kg in females and in the inflammatory phase at doses of 2.5-100 mg/kg in males and 10-100 mg/kg in females. In the acute phase, AT induced antinociception at 10 mg/kg for all mice, and at 0.3 mg/kg in males and 3 mg/kg in female mice in the inflammatory phase. Combining the calculated median effective doses of CBD and AT produced additive effects for all mice in the acute phase and for males only in the inflammatory phase. Use of selective serotonin 1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1 piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY-100635) maleate (0.1 mg/kg) before co-administration of CBD and AT reversed antinociception in the acute and partially reversed antinociception in the inflammatory phase. Administration of AT was found to enhance cannabinoid receptor type 1mRNA expression only in female mice. These results suggest a role for serotonin and sex in mediating cannabidiol and amitriptyline-induced antinociception in inflammatory pain. SIGNIFICANCE STATEMENT: Inflammatory pain is an important component of both acute and chronic pain. We have found that cannabidiol (CBD) and amitriptyline (AT) show dose-dependent, and that AT additionally shows sex-dependent, antinociceptive effects in an inflammatory pain model. Additionally, the combination of CBD and AT was found to have enhanced antinociceptive effects that is partially reliant of serotonin 1A receptors and supports the use of CBD within a multimodal approach to pain.
Topics: Mice; Male; Female; Animals; Cannabidiol; Serotonin; Amitriptyline; Chronic Pain; Receptor, Serotonin, 5-HT1A; Mice, Inbred C57BL; Serotonin Antagonists; Analgesics; Formaldehyde
PubMed: 38129125
DOI: 10.1124/jpet.123.001855 -
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 -
Frontiers in Pharmacology 2024Amidst rising global burden of depression and the associated challenges with conventional antidepressant therapies, there is a growing interest in exploring the...
Amidst rising global burden of depression and the associated challenges with conventional antidepressant therapies, there is a growing interest in exploring the efficacy and safety of alternative treatments. This study uses a Bayesian network meta-analysis to rigorously evaluate the therapeutic potential of Chinese herbal medicines in the treatment of depression, focusing on their comparative efficacy and safety against standard pharmacological interventions. Five databases (PubMed, Wanfang Data, EMBASE, CNKI, and the Cochrane Library) and grey literature were searched from inception to end of July 2023 to identify studies that assessed the efficacy and safety of Chinese herbal medicines in treating depression. The response rate, Hamilton Depression Scale (HAMD) scores, and rates of adverse events were assessed through both direct and indirect comparisons. Data extraction and risk of bias assessment were meticulously performed. Statistical analysis used Markov chain Monte Carlo methods, with effect size estimates provided as odd ratios and their 95% confidence intervals. A total of 198 RCTs involving 8,923 patients were analyzed, assessing 17 Chinese herbal medicines. Surface Under the Cumulative Ranking results indicated that the top three treatments with the best response rate were possibly , , and ; the top three treatments on the reduction of HAMD scores were , , and ; and the top three treatments with the lowest adverse effects rates were , , and . Interestingly, commonly used synthetic drugs such as , , , , , and , not only appeared to be less effective than specific Chinese herbal medicines (, , , , and ), but they were also related to substantially higher risk of adverse events. Our findings elucidate the promising therapeutic potential of Chinese herbal medicines as viable alternatives in the treatment of depression, with certain herbs demonstrating enhanced efficacy and safety profiles. The outcomes of this study advocate for the integration of these alternative modalities into contemporary depression management paradigms. However, it underscores the necessity for larger, methodologically robust trials to further validate and refine these preliminary findings. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023452109.
PubMed: 38633609
DOI: 10.3389/fphar.2024.1295564 -
The Science of the Total Environment Dec 2023This study utilizes wastewater-based epidemiology (WBE) to evaluate spatiotemporal changes in the consumption of antidepressants before and during the COVID-19 pandemic...
This study utilizes wastewater-based epidemiology (WBE) to evaluate spatiotemporal changes in the consumption of antidepressants before and during the COVID-19 pandemic in Slovenia. Composite 24-h influent wastewater samples (n = 210) were collected from six wastewater treatment plants between summer 2019 and spring 2021. The samples were extracted using 96-well solid-phase extraction and analysed by liquid chromatography-tandem mass spectrometry. The measured concentrations of target antidepressant biomarkers were then converted to population-normalised mass loads (PNMLs), taking into account flow rate and catchment population. Ten biomarkers, including amitriptyline, bupropion, bupropion-OH, citalopram, norcitalopram, normirtazapine, venlafaxine, O-desmethylvenlafaxine, trazodone, and moclobemide, were above the lower limit of quantification and were included in the spatiotemporal temporal assessment. The highest PNMLs were detected for O-desmethylvenlafaxine (mean ± SD: 82.1 ± 21.2 mg/day/1000 inhabitants) and venlafaxine (38.0 ± 10.6 mg/day/1000 inhabitants), followed by citalopram (27.0 ± 10.7 mg/day/1000 inhabitants). In addition, the mean metabolite/parent compound ratios were comparable with other WBE studies indicating consumption rather than direct disposal. Overall, the results indicated significant spatiotemporal variations depending on the location, and the PNMLs of most biomarkers increased during the first wave of the COVID-19 pandemic (spring of 2020). However, no clear spatial patterns were revealed related to the pandemic.
PubMed: 37640073
DOI: 10.1016/j.scitotenv.2023.166586 -
Frontiers in Neurology 2024Vestibular migraine (VM) is a newly defined clinical condition. Several vestibular abnormalities have been reported in patients with VM. However, to date, no specific...
INTRODUCTION
Vestibular migraine (VM) is a newly defined clinical condition. Several vestibular abnormalities have been reported in patients with VM. However, to date, no specific vestibular examinations are used to define VM. Therefore, the utility of vestibular examinations is limited. Currently, the role of vestibular examination has not been clearly defined. We speculated that the results of vestibular examinations could predict the prognosis of VM. We investigated the relationship between the vestibular examination results and clinical outcomes in patients with VM.
METHODS
This study included 25 patients with VM. Vestibular examinations, including the video head impulse test (V-HIT), cervical and ocular vestibular evoked myogenic potential (c-VEMP and o-VEMP), posturography, and several questionnaires, including the Dizziness Handicap Inventory (DHI), were conducted at the initial evaluation. Lifestyle modifications for VM and conventional pharmacological prophylactic treatments, including lomerizine, amitriptyline, and valproic acid, were performed. After 4 weeks of treatment, clinical improvements were evaluated using the Clinical Global Improvement Scale (CGI-s). The relationships among the CGI-S score, several clinical variables, and the results of several vestibular examinations were evaluated. Each patient was further classified into two subgroups according to treatment outcomes concerning vertigo and headache: CGI-S score from 0 to 2 (good response [GR]) and CGI-S score > 3 (poor response [PR]).
RESULTS
Overall, after treatment, most of the patients had improved dizziness and headache, and the CGI-s was 2.7 ± 1.3. There were 12 GRs, and 13 had PRs. Thus, neither V-HIT nor posturography predicted the prognosis. For c-VEMP, patients with GRs had significantly small AR concerning PR (19.2 ± 12.8 and 62.5 ± 42.5, respectively, [ < 0.01]). There were five normal, six unilateral, and 14 bilateral no response in 500hz o-VEMP. CGI-s of normal, unilateral, and bilateral no response was 1.4 ± 0.5, 2.8 ± 1.3, and 3.1 ± 1.2, respectively. There was a statistically significant difference between the normal and bilateral non-response o-VEMP groups ( < 0.05).
CONCLUSION
Patients with VM had improvements in both headache and vertigo through a combination of lifestyle changes and prophylactic medications. Vestibular examinations, especially o- or c-VEMP, are beneficial for predicting the treatment outcomes of VM. The pathophysiology of VM is closely related to vestibular abnormalities, particularly the otolith-related pathways.
PubMed: 38660093
DOI: 10.3389/fneur.2024.1370940 -
Catchment area, fate, and environmental risks investigation of micropollutants in Danish wastewater.Environmental Science and Pollution... Dec 2023This study aimed to investigate the spatial distribution of micropollutants in wastewater related to catchment area, and their environmental risks and fate. About 24-h...
This study aimed to investigate the spatial distribution of micropollutants in wastewater related to catchment area, and their environmental risks and fate. About 24-h flow proportional effluent (n = 26) wastewater samples were collected from eight WWTPs across Denmark. From five of these WWTPs corresponding influent samples (n = 20) were collected. Samples were enriched by multi-layer solid phase and analysed by liquid chromatography-high-resolution mass spectrometry and comprehensive two-dimensional gas chromatography with high-resolution mass spectrometry detection. We detected and quantified 79 micropollutants from a list of 291 micropollutants in at least one influent or effluent wastewater sample. From this we found that 54 micropollutants decreased in concentrations during wastewater treatment, while O-desmethylvenlafaxine, carbamazepine, amitriptyline, benzothiazole, terbutryn, and citalopram increased in concentrations through the WWTP.The toxicity of effluent wastewater samples was assessed by EC50 using Raphidocelis subcapitata (R. subcapitata) and LC50 using the crustacean Daphnia magna (D. Magna), for which six micropollutants were detected above the predicted no-effect concentration. Our study demonstrates that catchment area influences the micropollutant composition of wastewater. Out of 19 pharmaceuticals, the measured concentration in influent wastewater was predicted within a factor of 10 from sale numbers and human excretion, which demonstrates the strong influence of catchment area on micropollutant composition.
Topics: Humans; Wastewater; Waste Disposal, Fluid; Water Pollutants, Chemical; Environmental Monitoring; Denmark
PubMed: 37950122
DOI: 10.1007/s11356-023-30331-z -
The Acid Sphingomyelinase Inhibitor Amitriptyline Ameliorates TNF-α-Induced Endothelial Dysfunction.Cardiovascular Drugs and Therapy Feb 2024Inflammation associated endothelial cell (EC) dysfunction is key to atherosclerotic disease. Recent studies have demonstrated a protective role of amitriptyline in...
PURPOSE
Inflammation associated endothelial cell (EC) dysfunction is key to atherosclerotic disease. Recent studies have demonstrated a protective role of amitriptyline in cardiomyocytes induced by hypoxia/reoxygenation. However, the mechanism by which amitriptyline regulates the inflammatory reaction in ECs remains unknown. Thus, the aim of this study was to investigate whether amitriptyline protects against inflammation in TNF-α-treated ECs.
METHODS
HUVECs were incubated with amitriptyline (2.5 μM) or TNF-α (20 ng/ml) for 24 h. EdU, tube formation, transwell, DHE fluorescence staining, and monocyte adhesion assays were performed to investigate endothelial function. Thoracic aortas were isolated from mice, and vascular tone was measured with a wire myograph system. The levels of ICAM-1, VCAM-1, MCP-1, phosphorylated MAPK and NF-κB were detected using western blotting.
RESULTS
Amitriptyline increased the phosphorylation of nitric oxide synthase (eNOS) and the release of NO. Amitriptyline significantly inhibited TNF-α-induced increases in ASMase activity and the release of ceramide and downregulated TNF-α-induced expression of proinflammatory proteins, including ICAM-1, VCAM-1, and MCP-1 in ECs, as well as the secretion of sICAM-1 and sVCAM-1. TNF-α treatment obviously increased monocyte adhesion and ROS production and impaired HUVEC proliferation, migration and tube formation, while amitriptyline rescued proliferation, migration, and tube formation and decreased monocyte adhesion and ROS production. Additionally, we demonstrated that amitriptyline suppressed TNF-α-induced MAPK phosphorylation as well as the activity of NF-κB in HUVECs. The results showed that the relaxation response of aortic rings to acetylcholine in the WT-TNF-α group was much lower than that in the WT group, and the sensitivity of aortic rings to acetylcholine in the WT-TNF-α group and WT-AMI-TNF-α group was significantly higher than that in the WT-TNF-α group.
CONCLUSION
These results suggest that amitriptyline reduces endothelial inflammation, consequently improving vascular endothelial function. Thus, the identification of amitriptyline as a potential strategy to improve endothelial function is important for preventing vascular diseases.
Topics: Animals; Mice; Humans; NF-kappa B; Intercellular Adhesion Molecule-1; Tumor Necrosis Factor-alpha; Human Umbilical Vein Endothelial Cells; Amitriptyline; Reactive Oxygen Species; Vascular Cell Adhesion Molecule-1; Sphingomyelin Phosphodiesterase; Acetylcholine; Inflammation; Vascular Diseases
PubMed: 36103099
DOI: 10.1007/s10557-022-07378-0 -
Medicina (Kaunas, Lithuania) Aug 2023: Sensory ganglionopathy is a rare neurological disorder caused by degeneration of the neurons composing the dorsal root ganglia. It manifests as various sensory...
: Sensory ganglionopathy is a rare neurological disorder caused by degeneration of the neurons composing the dorsal root ganglia. It manifests as various sensory disturbances in the trunk, proximal limbs, face, or mouth in a patchy and asymmetrical pattern. Harlequin syndrome is characterized by unilateral flushing and sweating of the face, neck, and upper chest, concurrent with contralateral anhidrosis. Here, we present and discuss a clinical case of sarcoidosis-associated ganglionopathy and Harlequin syndrome. : A 31-year-old woman complained of burning pain in the right side of the upper chest and the feet. She also experienced episodes of intense flushing and sweating on the right side of her face, neck, and upper chest. Three years before these symptoms began, the patient was diagnosed with pulmonary sarcoidosis. On neurological examination, sensory disturbances were present. In the trunk, the patient reported pronounced hyperalgesia and allodynia in the upper part of the right chest and some patches on the right side of the upper back. In the extremities, hypoalgesia in the tips of the fingers and hyperalgesia in the feet were noted. An extensive diagnostic workup was performed to eliminate other possible causes of these disorders. A broad range of possible metabolic, immunological, and structural causes were ruled out. Thus, the final clinical diagnosis of sarcoidosis-induced sensory ganglionopathy, small-fiber neuropathy, and Harlequin syndrome was made. Initially, the patient was treated with pregabalin and amitriptyline, but the effect was inadequate for the ganglionopathy-induced pain. Therefore, therapeutic plasma exchange as an immune-modulating treatment was selected, leading to partial pain relief. : This case report demonstrates the possible autoimmune origin of both sensory ganglionopathy and Harlequin syndrome. It suggests that an autoimmune etiology for these disorders should be considered and the diagnostic workup should include screening for the most common autoimmune conditions.
Topics: Humans; Female; Adult; Hypohidrosis; Hyperalgesia; Sarcoidosis; Pain; Fingers
PubMed: 37629785
DOI: 10.3390/medicina59081495