-
Environmental Monitoring and Assessment Mar 2024Defining the environmental occurrence and distribution of chemicals of emerging concern (CECs), including pharmaceuticals and personal care products (PPCPs) in coastal...
Defining the environmental occurrence and distribution of chemicals of emerging concern (CECs), including pharmaceuticals and personal care products (PPCPs) in coastal aquatic systems, is often difficult and complex. In this study, 70 compounds representing several classes of pharmaceuticals, including antibiotics, anti-inflammatories, insect repellant, antibacterial, antidepressants, chemotherapy drugs, and X-ray contrast media compounds, were found in dreissenid mussel (zebra/quagga; Dreissena spp.) tissue samples. Overall concentration and detection frequencies varied significantly among sampling locations, site land-use categories, and sites sampled proximate and downstream of point source discharge. Verapamil, triclocarban, etoposide, citalopram, diphenhydramine, sertraline, amitriptyline, and DEET (N,N-diethyl-meta-toluamide) comprised the most ubiquitous PPCPs (> 50%) detected in dreissenid mussels. Among those compounds quantified in mussel tissue, sertraline, metformin, methylprednisolone, hydrocortisone, 1,7-dimethylxanthine, theophylline, zidovudine, prednisone, clonidine, 2-hydroxy-ibuprofen, iopamidol, and melphalan were detected at concentrations up to 475 ng/g (wet weight). Antihypertensives, antibiotics, and antidepressants accounted for the majority of the compounds quantified in mussel tissue. The results showed that PPCPs quantified in dreissenid mussels are occurring as complex mixtures, with 4 to 28 compounds detected at one or more sampling locations. The magnitude and composition of PPCPs detected were highest for sites not influenced by either WWTP or CSO discharge (i.e., non-WWTPs), strongly supporting non-point sources as important drivers and pathways for PPCPs detected in this study. As these compounds are detected at inshore and offshore locations, the findings of this study indicate that their persistence and potential risks are largely unknown, thus warranting further assessment and prioritization of these emerging contaminants in the Great Lakes Basin.
Topics: Animals; Sertraline; Lakes; Environmental Monitoring; Bivalvia; Anti-Bacterial Agents; Etoposide; Cosmetics; Antidepressive Agents; Pharmaceutical Preparations
PubMed: 38438687
DOI: 10.1007/s10661-023-12119-3 -
Southern Medical Journal Mar 2024
Topics: Humans; Fibromyalgia; Amitriptyline; Tongue
PubMed: 38428940
DOI: 10.14423/SMJ.0000000000001645 -
Life (Basel, Switzerland) Feb 2024Primary Stabbing Headache (PSH) is characterized by brief, focal, and paroxysmal pain ("stab"), occurring sporadically or in clusters. Data on pediatric cases are poor. (Review)
Review
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.
PubMed: 38398725
DOI: 10.3390/life14020216 -
Medicine Feb 2024Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination, inflammation, neuronal loss, and gliosis (scarring). Our object to review MS pathophysiology... (Review)
Review
Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination, inflammation, neuronal loss, and gliosis (scarring). Our object to review MS pathophysiology causes and treatment. A Narrative Review article was conducted by searching on Google scholar, PubMed, Research Gate about relevant keywords we exclude any unique cases and case reports. The destruction of myelinated axons in the central nervous system reserves this brunt. This destruction is generated by immunogenic T cells that produce cytokines, copying a proinflammatory T helper cells1-mediated response. Autoreactive cluster of differentiation 4 + cells, particularly the T helper cells1 subtype, are activated outside the system after viral infections. T-helper cells (cluster of differentiation 4+) are the leading initiators of MS myelin destruction. The treatment plan for individuals with MS includes managing acute episodes, using disease-modifying agents to decrease MS biological function of MS, and providing symptom relief. Management of spasticity requires physiotherapy, prescription of initial drugs such as baclofen or gabapentin, secondary drug options such as tizanidine or dantrolene, and third-line treatment such as benzodiazepines. To treat urinary incontinence some options include anticholinergic medications such as oxybutynin hydrochloride, tricyclic antidepressants (such as amitriptyline), and intermittent self-catheterization. When it comes to bowel problems, one can try to implement stool softeners and consume a high roughage diet. The review takes about MS causes Pathophysiology and examines current treatment strategies, emphasizing the advancements in disease-modifying therapies and symptomatic treatments. This comprehensive analysis enhances the understanding of MS and underscores the ongoing need for research to develop more effective treatments.
Topics: Humans; Multiple Sclerosis; Treatment Outcome; Chronic Disease; Muscle Spasticity
PubMed: 38394496
DOI: 10.1097/MD.0000000000037297 -
Acta Psychiatrica Scandinavica May 2024Long-term studies comparing nonresponse to antidepressants for major depressive disorder (MDD) are lacking. (Comparative Study)
Comparative Study
Comparative responses to 17 different antidepressants in major depressive disorder: Results from a 2-year long-term nation-wide population-based study emulating a randomized trial.
BACKGROUND
Long-term studies comparing nonresponse to antidepressants for major depressive disorder (MDD) are lacking.
AIMS
To present systematic population-based nation-wide register data on comparative 2-year non-response within six antidepressant drug classes and 17 different antidepressants in patients with MDD.
METHOD
The study included all 106,920 patients in Denmark with a first main index diagnosis of MDD at a psychiatric hospital inpatient or outpatient contact and who subsequently had a purchase of an antidepressant in the period from 1995 to 2018. Non-response to first antidepressant within a 2-year study period was defined as switch to or add-on of another antidepressant, antipsychotic medication, lithium, or hospitalization. Analyses emulated a targeted trial in populations standardized according to age, sex, socioeconomic status, and comorbidity with psychiatric and physical disorders.
RESULTS
Compared with sertraline, there was no difference for citalopram (RR: 1.00 [95% CI: 0.98-1.02]) but fluoxetine (1.13 [95% CI: 1.10-1.17]), paroxetine (1.06 [95% CI: 1.01-1.10]) and escitalopram (1.22 [95% CI: 1.18-1.25]) were associated with higher risk ratio of non-responses. Within selective noradrenaline reuptake inhibitors, sertraline outperformed reboxetine; within serotonin-norepinephrine reuptake inhibitors, venlafaxine outperformed duloxetine; within noradrenergic and specific serotonergic antidepressants, mirtazapine outperformed mianserin and within the class of other antidepressants, sertraline outperformed agomelatine and vortioxetine. Within tricyclic antidepressants, compared to amitriptyline, nortriptyline, dosulepin, and clomipramine had higher non-response, whereas there was no difference for imipramine.
CONCLUSIONS
These analyses emulating a randomized trial of "real world" observational register-based data show that 2-year long-term non-responses to some antidepressants within six different drug classes are increased over others.
Topics: Humans; Antidepressive Agents; Depressive Disorder, Major; Fluoxetine; Selective Serotonin Reuptake Inhibitors; Sertraline
PubMed: 38379028
DOI: 10.1111/acps.13673 -
Environmental Science and Pollution... Mar 2024The uptake, translocation, and metabolization of four widely used drugs, amitriptyline, orphenadrine, lidocaine, and tramadol, were investigated in a laboratory study....
The uptake, translocation, and metabolization of four widely used drugs, amitriptyline, orphenadrine, lidocaine, and tramadol, were investigated in a laboratory study. Cress (Lepidium sativum L.) and pea (Pisum sativum L.) were employed as model plants. These plants were grown in tap water containing the selected pharmaceuticals at concentrations ranging from 0.010 to 10 mg L, whereby the latter concentration was employed for the (tentative) identification of drug-related metabolites formed within the plant. Thereby, mainly phase I metabolites were detected. Time-resolved uptake studies, with sampling after 1, 2, 4, 8, and 16 days, revealed that all four pharmaceuticals were taken up by the roots and further relocated to plant stem and leaves. Also in these studies, the corresponding phase I metabolites could be detected, and their translocation from root to stem (pea only) and finally leaves could be investigated.
Topics: Amitriptyline; Pisum sativum; Brassicaceae; Orphenadrine; Tramadol; Lidocaine; Plants; Vegetables; Pharmaceutical Preparations; Plant Roots
PubMed: 38363510
DOI: 10.1007/s11356-024-32379-x -
The Lancet. Psychiatry Mar 2024There are no recommendations based on the efficacy of specific drugs for the treatment of psychotic depression. To address this evidence gap, we did a network... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are no recommendations based on the efficacy of specific drugs for the treatment of psychotic depression. To address this evidence gap, we did a network meta-analysis to assess and compare the efficacy and safety of pharmacological treatments for psychotic depression.
METHODS
In this systematic review and network meta-analysis, we searched ClinicalTrials.gov, CENTRAL, Embase, PsycINFO, PubMed, Scopus, and Web of Science from inception to Nov 23, 2023 for randomised controlled trials published in any language that assessed pharmacological treatments for individuals of any age with a diagnosis of a major depressive episode with psychotic features, in the context of major depressive disorder or bipolar disorder in any setting. We excluded continuation or maintenance trials. We screened the study titles and abstracts identified, and we extracted data from relevant studies after full-text review. If full data were not available, we requested data from study authors twice. We analysed treatments for individual drugs (or drug combinations) and by grouping them on the basis of mechanisms of action. The primary outcomes were response rate (ie, the proportion of participants who responded to treatment) and acceptability (ie, the proportion who discontinued treatment for any reason). We calculated risk ratios and did separate frequentist network meta-analyses by using random-effects models. The risk of bias of individual studies was assessed with the Cochrane risk-of-bias tool and the confidence in the evidence with the Confidence-In-Network-Meta-Analysis (CINeMA). This study was registered with PROSPERO, CRD42023392926.
FINDINGS
Of 6313 reports identified, 16 randomised controlled trials were included in the systematic review, and 14 were included in the network meta-analyses. The 16 trials included 1161 people with psychotic depression (mean age 50·5 years [SD 11·4]). 516 (44·4%) participants were female and 422 (36·3%) were male; sex data were not available for the other 223 (19·2%). 489 (42·1%) participants were White, 47 (4·0%) were African American, and 12 (1·0%) were Asian; race or ethnicity data were not available for the other 613 (52·8%). Only the combination of fluoxetine plus olanzapine was associated with a higher proportion of participants with a treatment response compared with placebo (risk ratio 1·91 [95% CI 1·27-2·85]), with no differences in terms of safety outcomes compared with placebo. When treatments were grouped by mechanism of action, the combination of a selective serotonin reuptake inhibitor with a second-generation antipsychotic was associated with a higher proportion of treatment responses than was placebo (1·89 [1·17-3·04]), with no differences in terms of safety outcomes. In head-to-head comparisons of active treatments, a significantly higher proportion of participants had a response to amitriptyline plus perphenazine (3·61 [1·23-10·56]) and amoxapine (3·14 [1·01-9·80]) than to perphenazine, and to fluoxetine plus olanzapine compared with olanzapine alone (1·60 [1·09-2·34]). Venlafaxine, venlafaxine plus quetiapine (2·25 [1·09-4·63]), and imipramine (1·95 [1·01-3·79]) were also associated with a higher proportion of treatment responses overall. In head-to-head comparisons grouped by mechanism of action, antipsychotic plus antidepressant combinations consistently outperformed monotherapies from either drug class in terms of the proportion of participants with treatment responses. Heterogeneity was low. No high-risk instances were identified in the bias assessment for our primary outcomes.
INTERPRETATION
According to the available evidence, the combination of a selective serotonin reuptake inhibitor and a second-generation antipsychotic-and particularly of fluoxetine and olanzapine-could be the optimal treatment choice for psychotic depression. These findings should be taken into account in the development of clinical practice guidelines. However, these conclusions should be interpreted cautiously in view of the low number of included studies and the limitations of these studies.
FUNDING
None.
Topics: Male; Female; Humans; Middle Aged; Depressive Disorder, Major; Fluoxetine; Perphenazine; Network Meta-Analysis; Bipolar Disorder; Venlafaxine Hydrochloride; Selective Serotonin Reuptake Inhibitors; Depression; Antipsychotic Agents; Olanzapine
PubMed: 38360024
DOI: 10.1016/S2215-0366(24)00006-3 -
Best Practice & Research. Clinical... Feb 2024Approaching patients with fibromyalgia (FM) is challenging due to the limited availability of scientifically proven effective therapies. (Review)
Review
INTRODUCTION
Approaching patients with fibromyalgia (FM) is challenging due to the limited availability of scientifically proven effective therapies.
OBJECTIVE
Review the treatments in use for FM and present new knowledge that could benefit these patients. Non-pharmacological interventions are recommended as the first line of treatment: aerobic exercise, cognitive behavioral therapy and patient education, all aimed at improving pain and other symptoms. Additional approaches have been studied, such as, digital health interventions, combined treatments, noninvasive neuromodulation, and others. Concerning pharmacological therapy, the mechanism of action of the medications currently used is to promote pain modulation. Medications approved by Food and Drug Administration are duloxetine, milnacipran and pregabalin. Amitriptyline, cyclobenzaprine, gabapentin and naltrexone are considered for off-label use. Cannabinoids, vitamin D supplementation are still controversial and further research is needed.
CONCLUSION
The combination of therapies, whether old, recent or reformulated, are the most effective strategy for managing symptoms in patients with fibromyalgia.
KEY WORDS
fibromyalgia, treatment, nonpharmacological interventions, pharmacological treatment.
PubMed: 38355316
DOI: 10.1016/j.berh.2024.101933 -
Pharmacopsychiatry Mar 2024CYP2D6 and CYP2C19 functional status as defined by genotype is modulated by phenoconversion (PC) due to pharmacokinetic interactions. As of today, there is no data on...
INTRODUCTION
CYP2D6 and CYP2C19 functional status as defined by genotype is modulated by phenoconversion (PC) due to pharmacokinetic interactions. As of today, there is no data on the effect size of PC for CYP2C19 functional status. The primary aim of this study was to investigate the impact of PC on CYP2C19 functional status.
METHODS
Two patient cohorts (total n=316; 44.2±15.4 years) were investigated for the functional enzyme status of CYP2C19 applying two different correction methods (PC, PC) as well as serum concentration and metabolite-to-parent ratio of venlafaxine, amitriptyline, mirtazapine, sertraline, escitalopram, risperidone, and quetiapine.
RESULTS
There was a decrease in the number of normal metabolizers of CYP2C19 and an increase in the number of poor metabolizers. When controlled for age, sex, and, in the case of amitriptyline, venlafaxine, and risperidone, CYP2D6 functional enzyme status, an association was observed between the CYP2C19 phenotype/functional enzyme status and serum concentration of amitriptyline, sertraline, and escitalopram.
DISCUSSION
PC of CYP2C19 changes phenotypes but does not improve correlations with serum concentrations. However, only a limited number of patients received perturbators of CYP2C19. Studies with large numbers of patients are still lacking, and thus, it cannot be decided if there are minor differences and which method of correction to use. For the time being, PC is relevant in individual patients treated with CYP2C19-affecting drugs, for example, esomeprazole. To ensure adequate serum concentrations in these patients, this study suggests the use of therapeutic drug monitoring.
Topics: Humans; Cytochrome P-450 CYP2D6; Venlafaxine Hydrochloride; Amitriptyline; Pharmacogenetics; Sertraline; Risperidone; Escitalopram; Cytochrome P-450 CYP2C19; Genotype
PubMed: 38354747
DOI: 10.1055/a-2248-6924 -
Psychiatry Research Apr 2024Sleep disturbances in posttraumatic stress disorder (PTSD) are a potential target for improving PTSD severity with pharmacotherapy. TNX-102 SL is a bedtime sublingual... (Randomized Controlled Trial)
Randomized Controlled Trial
A phase 3, randomized, placebo-controlled, trial to evaluate the efficacy and safety of bedtime sublingual cyclobenzaprine (TNX-102 SL) in military-related posttraumatic stress disorder.
Sleep disturbances in posttraumatic stress disorder (PTSD) are a potential target for improving PTSD severity with pharmacotherapy. TNX-102 SL is a bedtime sublingual formulation of cyclobenzaprine with potent binding and antagonist activity at 5-HT, α-adrenergic, H histaminergic, and M muscarinic receptors, which play roles in the pharmacological management of sleep disturbances. This Phase 3 trial evaluated the efficacy and safety of TNX-102 SL in patients with military-related PTSD. Early and sustained improvements in sleep were associated with TNX-102 SL treatment by PROMIS Sleep Disturbance scale and Clinician Administered PTSD Scale (CAPS-5) "sleep disturbance" item, establishing a sleep quality benefit. Primary analysis comparing change from baseline in CAPS-5 total severity between TNX-102 SL and placebo at week 12 was not significant; however, week 4 was associated with an improvement. Secondary analyses showed TNX-102 SL treatment was associated with benefits on the Clinician Global Impression of Improvement at week 4 and the Patient Global Impression of Change at week 12. Time since trauma exposure was a discriminator of CAPS-5 treatment response in the subgroup ≤ 9 years since the index event. This study provides preliminary evidence that TNX-102 SL is well-tolerated and may promote recovery from PTSD by addressing sleep-related symptoms.
Topics: Humans; Stress Disorders, Post-Traumatic; Military Personnel; Sleep; Treatment Outcome; Double-Blind Method; Amitriptyline
PubMed: 38350291
DOI: 10.1016/j.psychres.2024.115764