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European Urology Open Science Oct 2023Radiotherapy of the pelvis is a widely used method for the treatment of malignancies, and local complications including pain following pelvic radiation therapy are... (Review)
Review
The Benefits and Harms of Pharmacological Treatment for Postradiation Pelvic Pain: A Systematic Review by the European Association of Urology Chronic Pelvic Pain Panel with Recommendations for Clinical Practice.
CONTEXT
Radiotherapy of the pelvis is a widely used method for the treatment of malignancies, and local complications including pain following pelvic radiation therapy are acknowledged complications.
OBJECTIVE
The primary objective is to assess the clinical effectiveness and safety of pharmacological therapies on postradiation pelvic pain.
EVIDENCE ACQUISITION
A systematic review of the use of different pharmacological treatments in the management of post-radiation pelvic pain was conducted (PROSPERO-ID: CRD42021249026). Comprehensive searches of EMBASE, Medline, and Cochrane library were performed for publications between January 1980 and April 2021. The primary outcomes were improvement in pain and adverse events following treatment. The secondary outcomes included quality of life, bowel function, and urinary function.
EVIDENCE SYNTHESIS
After screening 1514 abstracts, four randomised controlled trials were identified, enrolling 355 patients with bladder and anorectal subtypes of postradiotherapy chronic pelvic pain (CPP). A narrative synthesis was performed as heterogeneity of included studies precluded a meta-analysis. A single study reported a significant reduction in pain after 6 mo in patients with bladder pain syndrome treated with hyaluronic acid or hyperbaric oxygen. Anorectal pain was reported to be reduced by the application of 4% formalin, but the use of hyperbaric oxygen in postradiotherapy anorectal pain remains controversial. Adverse event reporting was generally poor. Studies looking at medications used routinely in guidelines for neuropathic pain, such as gabapentin, pregabalin, amitriptyline, and duloxetine, were absent or of poor quality when it came to postradiation pelvic pain.
CONCLUSIONS
Beneficial effects of hyperbaric oxygen or formalin on pain, quality of life, and functional symptoms were seen in patients with certain CPP subtypes, but the current evidence level is too weak to allow recommendations about the use of any pharmacological treatment for postradiation pelvic pain.
PATIENT SUMMARY
Different pharmacological treatments are used to treat pain after radiotherapy, but current studies are of insufficient quality to determine whether these should be recommended and many chronic pelvic pain subtypes are not covered. Further research is needed.
PubMed: 37711669
DOI: 10.1016/j.euros.2023.08.009 -
Brain, Behavior, & Immunity - Health Jan 2021Amitriptyline is prescribed to reduce the intensity of chronic neuropathic pain. There is a paucity of validated evidence in humans regarding amitriptyline's mechanism...
Examination and characterisation of the effect of amitriptyline therapy for chronic neuropathic pain on neuropeptide and proteomic constituents of human cerebrospinal fluid.
INTRODUCTION
Amitriptyline is prescribed to reduce the intensity of chronic neuropathic pain. There is a paucity of validated evidence in humans regarding amitriptyline's mechanism of action. We examined the effect of amitriptyline therapy on cerebrospinal fluid (CSF) neuropeptides and proteome in patients with chronic neuropathic pain to identify potential mechanisms of action of amitriptyline.
METHODS
Patients with lumbar radicular neuropathic pain were selected for inclusion with clinical and radiological signs and a >50% reduction in pain in response to a selective nerve root block. Baseline (pre-treatment) and 8-week (post-treatment) pain scores with demographics were recorded. CSF samples were taken at baseline (pre-treatment) and 8 weeks after amitriptyline treatment (post-treatment). Proteome analysis was performed using mass spectrometry and secreted cytokines, chemokines and neurotrophins were measured by enzyme-linked immunosorbent assay (ELISA).
RESULTS
A total of 9/16 patients experienced a >30% reduction in pain after treatment with amitriptyline and GO analysis demonstrated that the greatest modulatory effect was on immune system processes. KEGG analysis also identified a reduction in PI3K-Akt and MAPK signalling pathways in responders but not in non-responders. There was also a significant decrease in the chemokine eotaxin-1 (p = 0.02) and a significant increase in the neurotrophin VEGF-A (p = 0.04) in responders.
CONCLUSION
The CSF secretome and proteome was modulated in responders to amitriptyline verifying many pre-clinical and models. The predominant features were immunomodulation with a reduction in pro-inflammatory pathways of neuronal-glia communications and evidence of a neurotrophic effect.
PubMed: 34589721
DOI: 10.1016/j.bbih.2020.100184 -
Translational Psychiatry Feb 2021Antidepressant medications are known to modulate the central nervous system, and gut microbiota can play a role in depression via microbiota-gut-brain axis. But the...
Antidepressant medications are known to modulate the central nervous system, and gut microbiota can play a role in depression via microbiota-gut-brain axis. But the impact of antidepressants on gut microbiota function and composition remains poorly understood. Thus this study assessed the effect of serotonin reuptake inhibitor antidepressant fluoxetine (Flu) and tricyclic antidepressant amitriptyline (Ami) administration on gut microbiota composition, diversity, and species abundance, along with microbial function in a chronic unpredictable mild stress (CUMS)-induced depression rat model. Oral administration of Ami and Flu significantly altered the overall gut microbiota profile of CUMS-induced rats, as assessed using the permutational multivariate analysis of variance test. At the phylum level, 6-week of antidepressant treatment led to a decreased Firmicutes/Bacteroidetes ratio due to an enhanced Bacteroidetes and reduced Firmicutes relative abundance. Flu was more potent than Ami at altering the Firmicutes and Bacteroidetes levels in the CUMS rats. At the family level, both antidepressants significantly increased the abundance of Porphyromonadaceae. However, an increased Bacteroidaceae level was significantly associated with Ami, not Flu treatment. Furthermore, at the genus level, an increase in the relative abundance of Parabacteroides, Butyricimonas, and Alistipes was observed following Ami and Flu treatment. Subsequent metagenomics and bioinformatics analysis further indicated that Ami and Flu likely also modulated metabolic pathways, such as those involved in carbohydrate metabolism, membrane transport, and signal transduction. Additionally, both antidepressants affected antibiotic resistome, such as for aminoglycoside (aph3iiiA), multidrug (mdtK, mdtP, mdtH, mdtG, acrA), and tetracycline (tetM) resistance in CUMS rats. These data clearly illustrated the direct impact of oral administration of Flu and Ami on the gut microbiome, thus set up the foundation to reveal more insights on the therapeutic function of the antidepressants and their overall contribution to host health.
Topics: Amitriptyline; Animals; Antidepressive Agents; Fluoxetine; Gastrointestinal Microbiome; Rats; Stress, Psychological
PubMed: 33602895
DOI: 10.1038/s41398-021-01254-5 -
Molecules (Basel, Switzerland) Oct 2022Mental disorders have a poor clinical prognosis and account for approximately 8% of the global burden of disease. Some examples of mental disorders are anxiety and...
Mental disorders have a poor clinical prognosis and account for approximately 8% of the global burden of disease. Some examples of mental disorders are anxiety and depression. Conventional antidepressants have limited efficacy in patients because their pharmacological effects wear off, and side effects increase with prolonged use. It is claimed that herbal medicine's antioxidant capacity helps regulate people's mood and provide a more substantial pharmacological effect. With this background, the purpose of this study is to investigate the effect of rutin on reserpine-induced anxiety and depression in rats. The animals were divided into groups of six rats each: normal control (water), a depression model, a rutin-treated rat model, and an amitriptyline-treated rat model. According to the results, 14 days of treatment with rutin, once daily, showed a modest antidepressant effect. This effect was mediated by increased serotonin, norepinephrine, and dopamine levels in cortical and hippocampal regions. The antioxidant and vasodilator properties of rutin may contribute to its antidepressant properties. According to this study, rutin has shown antidepressant effects by reducing antioxidant activity and acetylcholinesterase.
Topics: Animals; Rats; Reserpine; Depression; Rutin; Serotonin; Acetylcholinesterase; Antioxidants; Antidepressive Agents; Anxiety
PubMed: 36364141
DOI: 10.3390/molecules27217313 -
World Journal of Psychiatry Apr 2021Serotonin syndrome (SS) is an underdiagnosed drug-induced clinical syndrome resulting from the excess intrasynaptic concentration of serotonin. Very limited information...
BACKGROUND
Serotonin syndrome (SS) is an underdiagnosed drug-induced clinical syndrome resulting from the excess intrasynaptic concentration of serotonin. Very limited information is available about chronic SS.
AIM
To evaluate the epidemiological, clinical, and other aspects of the insidious onset SS.
METHODS
We retrospectively evaluated 14 consecutive adult patients (> 18 years) who had complaints for more than 6 wk at the time of consultation and met the Hunter criteria for SS.
RESULTS
The mean age was 41.1 years (range: 21-61 years), with a male preponderance (64%). Although tremors were observed in all patients, this was a presenting complaint in only 43% of patients. Generalized body pain, insomnia, and restlessness were common presenting features (50% each). Other common clinical features were stiffness of the limbs (43%), diaphoresis (43%), gait disturbances (36%), bowel disturbances (36%), dizziness (29%), sexual dysfunctions (21%), incoordination (14%), and fatigue (14%) The mean duration of symptoms before the diagnosis of SS was 13.5 ± 5.8 wk (range: 6-24 wk). Amitriptyline was the most common drug ( = 6, 43%), followed by tramadol ( = 5, 36%) and sodium valproate ( = 5, 36%). All patients received cyproheptadine, a 5- hydroxytryptamine2A antagonist, as treatment and noted an excellent response over the course of 4-14 d.
CONCLUSION
This study represents the largest study on chronic SS. We suggest that patients receiving serotonergic drugs should be physically examined for the presence of SS upon the development of new symptoms.
PubMed: 33889537
DOI: 10.5498/wjp.v11.i4.124 -
Journal of Pain Research 2020Bruxism, specifically sleep bruxism (SB), is a worldwide discussed topic in the literature; however, there is insufficient evidence to define and support a standard... (Review)
Review
Bruxism, specifically sleep bruxism (SB), is a worldwide discussed topic in the literature; however, there is insufficient evidence to define and support a standard approach for the treatment of SB. The purpose of this overview was to map the evidence from systematic reviews (SR), examining the effects of interventions to improve chronic pain related to bruxism. The methodological quality of SRs was assessed using the AMSTAR-2 tool. We conducted a comprehensive literature search in April 2020, in the following databases: Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, LILACS, BBO, and Epistemonikos. Nine SRs with critically low to high methodological quality were included. Considering the main findings, botulinum toxin type A (BTX-A) showed a significant pain and sleep bruxism frequency reduction when compared to placebo or conventional treatment (behavioral therapy, occlusal splints, and drugs), after 6 and 12 months. Occlusal splints combined to muscle massage showed some benefit in pain reduction. There was no difference in pain and bruxism frequency between biofeedback therapy and an inactive control group. Regarding drug therapy, there is no difference when amitriptyline, bromocriptine, clonidine, propranolol, and levodopa were compared to placebo. In conclusion, there is some evidence to support the use of occlusal splints plus massage, and BTX-A to reduce chronic pain related to SB. No evidence was provided to support the recommendation of biofeedback therapy and drug therapy. There is still a need for more methodologically rigorous randomized clinical trials (RCT) to be conducted on the efficacy and safety of different therapies for SB.
PubMed: 33061557
DOI: 10.2147/JPR.S268114 -
Therapeutic Advances in... 2024Tricyclic antidepressants (TCAs) remain widely prescribed for depression and many other conditions. There may be important differences between individual TCA in regard... (Review)
Review
Tricyclic antidepressants (TCAs) remain widely prescribed for depression and many other conditions. There may be important differences between individual TCA in regard to their overdose toxicity and their cardiac toxicity in clinical use. We conducted a systematic review to compare the toxicity of individual TCA in overdose and the risk of serious adverse cardiac events occurring with therapeutic doses. We used the fatal toxicity index (FTI) and case fatality ratio as markers of fatality in overdose, and hazard ratios or odds ratios for the risk of cardiovascular adverse events during normal clinical use. In all, 30 reports of mortality in overdose and 14 observational studies assessing the risk of cardiovascular adverse events in clinical use were included. FTI values were of the same order of magnitude (10-10) for all TCAs except lofepramine. Desipramine appears to be somewhat more likely than other TCAs to lead to death in overdose. Amitriptyline, clomipramine, dothiepin/dosulepin, doxepin, trimipramine and imipramine showed broadly similar toxicity and were usually reported to be less toxic than desipramine. Data on nortriptyline were contradictory. Lofepramine had the lowest risk of death in overdose. The rank order of overdose toxicity was broadly consistent between different FTI definitions and between markers used. With respect to the risk of cardiovascular events at clinically relevant exposure, amitriptyline, nortriptyline and lofepramine were associated with a greater risk of in-use cardiotoxicity. All measures of overdose toxicity were subject to external influences and confounding. The continued use of TCAs in depression and other conditions should be minimized when considering their undoubted toxicity in overdose and possible toxicity in normal clinical use.
PubMed: 38827015
DOI: 10.1177/20451253241243297 -
Alpha Psychiatry Sep 2021The aim of the article is to review systematically current researches investigating the relationship between intrauterine exposure to antidepressants and neonatal... (Review)
Review
The aim of the article is to review systematically current researches investigating the relationship between intrauterine exposure to antidepressants and neonatal hypoglycemia. This paper included studies published in electronic databases from January 2005 to July 2020. The searched keywords were as follows: antidepressants, pregnancy, selective serotonin reuptake inhibitors (SSRIs), citalopram, fluoxetine, paroxetine, escitalopram, sertraline, fluvoxamine, selective serotonin-norepinephrine reuptake inhibitors (SNRIs), venlafaxine, tricyclic antidepressants (TCAs), neonatal outcomes, neonatal hypoglycemia, imipramine, clomipramine, amitriptyline, bupropion, trazodone, and mirtazapine. This review examined 10 relevant studies. The odds ratio/risk ratio reported in the studies were 1.33-1.73 for any antidepressant, 1.30-1.35 for SSRI, 1.42-2.11 for SNRI, and 2.07 for TCAs. The risk of neonatal hypoglycemia in infants exposed to maternal TCAs appears to be slightly higher compared to infants exposed to maternal SSRIs. Data from current studies consistently show that exposure to maternal antidepressants during pregnancy may be related to increased risk of neonatal hypoglycemia in infants.
PubMed: 36447450
DOI: 10.1530/alphapsychiatry.2021.21143