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BMC Anesthesiology Dec 2022To evaluate the effect of duloxetine when added to a multimodal analgesia regimen on posthemorrhoidectomy pain, opioid consumption, and side effects. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
To evaluate the effect of duloxetine when added to a multimodal analgesia regimen on posthemorrhoidectomy pain, opioid consumption, and side effects.
METHODS
Prospective, randomized, double-blind placebo-controlled trial. This study included 62 patients who underwent hemorrhoidectomy. The patients were randomly assigned to receive oral duloxetine 60 mg or placebo 2 h before and 24 h after surgery. The primary outcomes were pain intensity - measured on an 11-point visual analog pain scale - and cumulative morphine consumption at 12, 24, and 48 postoperative hours.
RESULTS
Fifty-two patients completed the study (25 in the duloxetine group and 27 in the placebo group). Pain scores did not differ between duloxetine and placebo: 4.5; 3.0 - 7.0 vs. 5.0; 3.5 - 7.0, p = 0.68 at 12 h, 3.0; 2.0 - 5.0 vs. 3.0; 2.0 - 5.0, p = 0.56 at 24 h, and 2.5; 1.75 - 3.75 vs. 1.5; 0.5 - 3, p = 0.08 at 48 h. Further, cumulative morphine consumption did not differ between the duloxetine and placebo groups: 4; 1.25 - 10.75 mg vs. 7; 1.0 - 12.0 mg, p = 0.68 at 12 h, 9.5; 2.0 - 17.5 mg vs. 8.0; 4.0 - 18.0 mg; p = 0.80 at 24 h, and 11.0; 2.0 - 27.0 mg vs. 10; 4.0 - 24.0 mg, p = 0.78 at 48 h. Side effects did not differ between the groups.
CONCLUSIONS
Compared with placebo, duloxetine did not decrease pain intensity or morphine consumption during the first 48 h postoperatively.
TRIAL REGISTRATION
The study was retrospectively registered on the Brazilian Clinical Trials Registry (identifier: RBR-9pdgms, registration date: 08/10/2020).
Topics: Humans; Duloxetine Hydrochloride; Prospective Studies; Pain; Morphine; Analgesia; Drug-Related Side Effects and Adverse Reactions
PubMed: 36457090
DOI: 10.1186/s12871-022-01908-x -
Pain Apr 2023This study investigated the tolerability and preliminary efficacy of duloxetine as an alternative nonopioid therapeutic option for the prevention of persistent...
This study investigated the tolerability and preliminary efficacy of duloxetine as an alternative nonopioid therapeutic option for the prevention of persistent musculoskeletal pain (MSP) among adults presenting to the emergency department with acute MSP after trauma or injury. In this randomized, double-blind, placebo-controlled study, eligible participants (n = 78) were randomized to 2 weeks of a daily dose of one of the following: placebo (n = 27), 30 mg duloxetine (n = 24), or 60 mg duloxetine (n = 27). Tolerability, the primary outcome, was measured by dropout rate and adverse effects. Secondary outcomes assessed drug efficacy as measured by (1) the proportion of participants with moderate to severe pain (numerical rating scale ≥ 4) at 6 weeks (pain persistence); and (2) average pain by group over the six-week study period. We also explored treatment effects by type of trauma (motor vehicle collision [MVC] vs non-MVC). In both intervention groups, duloxetine was well tolerated and there were no serious adverse events. There was a statistically significant difference in pain over time for the 60 mg vs placebo group ( P = 0.03) but not for the 30 mg vs placebo group ( P = 0.51). In both types of analyses, the size of the effect of duloxetine was larger in MVC vs non-MVC injury. Consistent with the role of stress systems in the development of chronic pain after traumatic stress, our data indicate duloxetine may be a treatment option for reducing the transition from acute to persistent MSP. Larger randomized controlled trials are needed to confirm these promising results.
Topics: Adult; Humans; Duloxetine Hydrochloride; Musculoskeletal Pain; Chronic Pain; Acute Pain; Double-Blind Method; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 36375173
DOI: 10.1097/j.pain.0000000000002782 -
The Cochrane Database of Systematic... Oct 2022Although pain is common in osteoarthritis, most people fail to achieve adequate analgesia. Increasing acknowledgement of the contribution of pain sensitisation has... (Review)
Review
BACKGROUND
Although pain is common in osteoarthritis, most people fail to achieve adequate analgesia. Increasing acknowledgement of the contribution of pain sensitisation has resulted in the investigation of medications affecting pain processing with central effects. Antidepressants contribute to pain management in other conditions where pain sensitisation is present.
OBJECTIVES
To assess the benefits and harms of antidepressants for the treatment of symptomatic knee and hip osteoarthritis in adults.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search was January 2021.
SELECTION CRITERIA
We included randomised controlled trials of adults with osteoarthritis that compared use of antidepressants to placebo or alternative comparator. We included trials that focused on efficacy (pain and function), treatment-related adverse effects and had documentation regarding discontinuation of participants. We excluded trials of less than six weeks of duration or had participants with concurrent mental health disorders.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Major outcomes were pain; responder rate; physical function; quality of life; and proportion of participants who withdrew due to adverse events, experienced any adverse events or had serious adverse events. Minor outcomes were proportion meeting the OARSI (Osteoarthritis Research Society International) Response Criteria, radiographic joint structure changes and proportion of participants who dropped out of the study for any reason. We used GRADE to assess certainty of evidence.
MAIN RESULTS
Nine trials (2122 participants) met the inclusion criteria. Seven trials examined only knee osteoarthritis. Two also included participants with hip osteoarthritis. All trials compared antidepressants to placebo, with or without non-steroidal anti-inflammatory drugs. Trial sizes were 36 to 388 participants. Most participants were female, with mean ages of 54.5 to 65.9 years. Trial durations were 8 to 16 weeks. Six trials examined duloxetine. We combined data from nine trials in meta-analyses for knee and hip osteoarthritis. One trial was at low risk of bias in all domains. Five trials were at risk of attrition and reporting bias. High-certainty evidence found that antidepressants resulted in a clinically unimportant improvement in pain compared to placebo. Mean reduction in pain (0 to 10 scale, 0 = no pain) was 1.7 points with placebo and 2.3 points with antidepressants (mean difference (MD) -0.59, 95% confidence interval (CI) -0.88 to -0.31; 9 trials, 2122 participants). Clinical response was defined as achieving a 50% or greater reduction in 24-hour mean pain. High-certainty evidence demonstrated that 45% of participants receiving antidepressants had a clinical response compared to 28.6% receiving placebo (RR 1.55, 95% CI 1.32 to 1.82; 6 RCTs, 1904 participants). This corresponded to an absolute improvement in pain of 16% more responders with antidepressants (8.9% more to 26% more) and a number needed to treat for an additional beneficial effect (NNTB) of 6 (95% CI 4 to 11). High-certainty evidence showed that the mean improvement in function (on 0 to 100 Western Ontario and McMaster Universities Arthritis Index, 0 = best function) was 10.51 points with placebo and 16.16 points with antidepressants (MD -5.65 points, 95% CI -7.08 to -4.23; 6 RCTs, 1909 participants). This demonstrates a small, clinically unimportant response. Moderate-certainty evidence (downgraded for imprecision) showed that quality of life measured using the EuroQol 5-Dimension scale (-0.11 to 1.0, 1.0 = perfect health) improved by 0.07 points with placebo and 0.11 points with antidepressants (MD 0.04, 95% CI 0.01 to 0.07; 3 RCTs, 815 participants). This is clinically unimportant. High-certainty evidence showed that total adverse events increased in the antidepressant group (64%) compared to the placebo group (49%) (RR 1.27, 95% CI 1.15 to 1.41; 9 RCTs, 2102 participants). The number needed to treat for an additional harmful outcome (NNTH) was 7 (95% CI 5 to 11). Low-certainty evidence (downgraded twice for imprecision for very low numbers of events) found no evidence of a difference in serious adverse events between groups (RR 0.94, 95% CI 0.46 to 1.94; 9 RCTs, 2101 participants). The NNTH was 1000. Moderate-certainty evidence (downgraded for imprecision) showed that 11% of participants receiving antidepressants withdrew from trials due to an adverse event compared to 5% receiving placebo (RR 2.15, 95% CI 1.56 to 2.97; 6 RCTs, 1977 participants). The NNTH was 17 (95% CI 10 to 35).
AUTHORS' CONCLUSIONS
There is high-certainty evidence that use of antidepressants for knee osteoarthritis leads to a non-clinically important improvement in mean pain and function. However, a small number of people will have a 50% or greater important improvement in pain and function. This finding was consistent across all trials. Pain in osteoarthritis may be due to a variety of causes that differ between individuals. It may be that the cause of pain that responds to this therapy is only present in a small number of people. There is moderate-certainty evidence that antidepressants have a small positive effect on quality of life with heterogeneity between trials. High-certainty evidence indicates antidepressants result in more adverse events and moderate-certainty evidence indicates more withdrawal due to adverse events. There was little to no difference in serious adverse events (low-certainty evidence due to low numbers of events). This suggests that if antidepressants were being considered, there needs to be careful patient selection to optimise clinical benefit given the known propensity for adverse events with antidepressant use. Future trials should include alternative antidepressant agents or phenotyping of pain in people with osteoarthritis, or both.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Duloxetine Hydrochloride; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 36269595
DOI: 10.1002/14651858.CD012157.pub2 -
Health Technology Assessment... Oct 2022The mainstay of treatment for diabetic peripheral neuropathic pain is pharmacotherapy, but the current National Institute for Health and Care Excellence guideline is not... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The mainstay of treatment for diabetic peripheral neuropathic pain is pharmacotherapy, but the current National Institute for Health and Care Excellence guideline is not based on robust evidence, as the treatments and their combinations have not been directly compared.
OBJECTIVES
To determine the most clinically beneficial, cost-effective and tolerated treatment pathway for diabetic peripheral neuropathic pain.
DESIGN
A randomised crossover trial with health economic analysis.
SETTING
Twenty-one secondary care centres in the UK.
PARTICIPANTS
Adults with diabetic peripheral neuropathic pain with a 7-day average self-rated pain score of ≥ 4 points (Numeric Rating Scale 0-10).
INTERVENTIONS
Participants were randomised to three commonly used treatment pathways: (1) amitriptyline supplemented with pregabalin, (2) duloxetine supplemented with pregabalin and (3) pregabalin supplemented with amitriptyline. Participants and research teams were blinded to treatment allocation, using over-encapsulated capsules and matching placebos. Site pharmacists were unblinded.
OUTCOMES
The primary outcome was the difference in 7-day average 24-hour Numeric Rating Scale score between pathways, measured during the final week of each pathway. Secondary end points included 7-day average daily Numeric Rating Scale pain score at week 6 between monotherapies, quality of life (Short Form questionnaire-36 items), Hospital Anxiety and Depression Scale score, the proportion of patients achieving 30% and 50% pain reduction, Brief Pain Inventory - Modified Short Form items scores, Insomnia Severity Index score, Neuropathic Pain Symptom Inventory score, tolerability (scale 0-10), Patient Global Impression of Change score at week 16 and patients' preferred treatment pathway at week 50. Adverse events and serious adverse events were recorded. A within-trial cost-utility analysis was carried out to compare treatment pathways using incremental costs per quality-adjusted life-years from an NHS and social care perspective.
RESULTS
A total of 140 participants were randomised from 13 UK centres, 130 of whom were included in the analyses. Pain score at week 16 was similar between the arms, with a mean difference of -0.1 points (98.3% confidence interval -0.5 to 0.3 points) for duloxetine supplemented with pregabalin compared with amitriptyline supplemented with pregabalin, a mean difference of -0.1 points (98.3% confidence interval -0.5 to 0.3 points) for pregabalin supplemented with amitriptyline compared with amitriptyline supplemented with pregabalin and a mean difference of 0.0 points (98.3% confidence interval -0.4 to 0.4 points) for pregabalin supplemented with amitriptyline compared with duloxetine supplemented with pregabalin. Results for tolerability, discontinuation and quality of life were similar. The adverse events were predictable for each drug. Combination therapy (weeks 6-16) was associated with a further reduction in Numeric Rating Scale pain score (mean 1.0 points, 98.3% confidence interval 0.6 to 1.3 points) compared with those who remained on monotherapy (mean 0.2 points, 98.3% confidence interval -0.1 to 0.5 points). The pregabalin supplemented with amitriptyline pathway had the fewest monotherapy discontinuations due to treatment-emergent adverse events and was most commonly preferred (most commonly preferred by participants: amitriptyline supplemented with pregabalin, 24%; duloxetine supplemented with pregabalin, 33%; pregabalin supplemented with amitriptyline, 43%; = 0.26). No single pathway was superior in cost-effectiveness. The incremental gains in quality-adjusted life-years were small for each pathway comparison [amitriptyline supplemented with pregabalin compared with duloxetine supplemented with pregabalin -0.002 (95% confidence interval -0.011 to 0.007) quality-adjusted life-years, amitriptyline supplemented with pregabalin compared with pregabalin supplemented with amitriptyline -0.006 (95% confidence interval -0.002 to 0.014) quality-adjusted life-years and duloxetine supplemented with pregabalin compared with pregabalin supplemented with amitriptyline 0.007 (95% confidence interval 0.0002 to 0.015) quality-adjusted life-years] and incremental costs over 16 weeks were similar [amitriptyline supplemented with pregabalin compared with duloxetine supplemented with pregabalin -£113 (95% confidence interval -£381 to £90), amitriptyline supplemented with pregabalin compared with pregabalin supplemented with amitriptyline £155 (95% confidence interval -£37 to £625) and duloxetine supplemented with pregabalin compared with pregabalin supplemented with amitriptyline £141 (95% confidence interval -£13 to £398)].
LIMITATIONS
Although there was no placebo arm, there is strong evidence for the use of each study medication from randomised placebo-controlled trials. The addition of a placebo arm would have increased the duration of this already long and demanding trial and it was not felt to be ethically justifiable.
FUTURE WORK
Future research should explore (1) variations in diabetic peripheral neuropathic pain management at the practice level, (2) how OPTION-DM (Optimal Pathway for TreatIng neurOpathic paiN in Diabetes Mellitus) trial findings can be best implemented, (3) why some patients respond to a particular drug and others do not and (4) what options there are for further treatments for those patients on combination treatment with inadequate pain relief.
CONCLUSIONS
The three treatment pathways appear to give comparable patient outcomes at similar costs, suggesting that the optimal treatment may depend on patients' preference in terms of side effects.
TRIAL REGISTRATION
The trial is registered as ISRCTN17545443 and EudraCT 2016-003146-89.
FUNDING
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme, and will be published in full in ; Vol. 26, No. 39. See the NIHR Journals Library website for further project information.
Topics: Adult; Humans; Pregabalin; Duloxetine Hydrochloride; Amitriptyline; Quality of Life; Neuralgia; Cost-Benefit Analysis; Diabetes Mellitus
PubMed: 36259684
DOI: 10.3310/RXUO6757 -
Arquivos de Neuro-psiquiatria Sep 2022Migraine affects 1 billion people worldwide and > 30 million Brazilians; besides, it is an underdiagnosed and undertreated disorder.
BACKGROUND
Migraine affects 1 billion people worldwide and > 30 million Brazilians; besides, it is an underdiagnosed and undertreated disorder.
OBJECTIVE
The need to disseminate knowledge about the prophylactic treatment of migraine is known, so the Brazilian Headache Society (SBCe, in the Portuguese acronym) appointed a committee of authors with the objective of establishing a consensus with recommendations on the prophylactic treatment of episodic migraine based on articles from the world literature as well as from personal experience.
METHODS
Meetings were held entirely online, with the participation of 12 groups that reviewed and wrote about the pharmacological categories of drugs and, at the end, met to read and finish the document. The drug classes studied in part II of this Consensus were: antihypertensives, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, calcium channel blockers, other drugs, and rational polytherapy.
RESULTS
From this list of drugs, only candesartan has been established as effective in controlling episodic migraine. Flunarizine, venlafaxine, duloxetine, and pizotifen were defined as likely to be effective, while lisinopril, enalapril, escitalopram, fluvoxamine, quetiapine, atorvastatin, simvastatin, cyproheptadine, and melatonin were possibly effective in prophylaxis of the disease.
CONCLUSIONS
Despite an effort by the scientific community to find really effective drugs in the treatment of migraine, given the large number of drugs tested for this purpose, we still have few therapeutic options.
Topics: Humans; Brazil; Consensus; Migraine Disorders; Venlafaxine Hydrochloride; Headache
PubMed: 36257618
DOI: 10.1055/s-0042-1755320 -
Molecular Psychiatry Jan 2023A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to... (Meta-Analysis)
Meta-Analysis
A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to treat adults with major depressive disorder (MDD) in the maintenance phase. This study searched the PubMed, Cochrane Library, and Embase databases and included only double-blind, randomized, placebo-controlled trials with an enrichment design: patients were stabilized on the antidepressant of interest during the open-label study and then randomized to receive the same antidepressant or placebo. The outcomes were the 6-month relapse rate (primary outcome, efficacy), all-cause discontinuation (acceptability), discontinuation due to adverse events (tolerability), and the incidence of individual adverse events. The risk ratio with a 95% credible interval was calculated. The meta-analysis comprised 34 studies (n = 9384, mean age = 43.80 years, and %females = 68.10%) on 20 antidepressants (agomelatine, amitriptyline, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, vilazodone, and vortioxetine) and a placebo. In terms of the 6-month relapse rate, amitriptyline, citalopram, desvenlafaxine, duloxetine, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, and vortioxetine outperformed placebo. Compared to placebo, desvenlafaxine, paroxetine, sertraline, venlafaxine, and vortioxetine had lower all-cause discontinuation; however, sertraline had a higher discontinuation rate due to adverse events. Compared to placebo, venlafaxine was associated with a lower incidence of dizziness, while desvenlafaxine, sertraline, and vortioxetine were associated with a higher incidence of nausea/vomiting. In conclusion, desvenlafaxine, paroxetine, venlafaxine, and vortioxetine had reasonable efficacy, acceptability, and tolerability in the treatment of adults with stable MDD.
Topics: Female; Humans; Adult; Depressive Disorder, Major; Duloxetine Hydrochloride; Sertraline; Citalopram; Venlafaxine Hydrochloride; Vortioxetine; Fluoxetine; Paroxetine; Mirtazapine; Amitriptyline; Desvenlafaxine Succinate; Fluvoxamine; Reboxetine; Network Meta-Analysis; Antidepressive Agents; Randomized Controlled Trials as Topic
PubMed: 36253442
DOI: 10.1038/s41380-022-01824-z -
Pain Research & Management 2022There is no approved drug for fibromyalgia syndrome (FMS) in Europe. In the German S3 guideline, amitriptyline, duloxetine, and pregabalin are recommended for temporary...
There is no approved drug for fibromyalgia syndrome (FMS) in Europe. In the German S3 guideline, amitriptyline, duloxetine, and pregabalin are recommended for temporary use. The aim of this study was to cross-sectionally investigate the current practice of medication in FMS patients in Germany. We systematically interviewed 156 patients with FMS, while they were participating in a larger study. The patients had been stratified into subgroups with and without a decrease in intraepidermal nerve fiber density. The drugs most commonly used to treat FMS pain were nonsteroidal anti-inflammatory drugs (NSAIDs) (41.0% of all patients), metamizole (22.4%), and amitriptyline (12.8%). The most frequent analgesic treatment regimen was "on demand" (53.9%), during pain attacks, while 35.1% of the drugs were administered daily and the remaining in other regimens. Median pain relief as self-rated by the patients on a numerical rating scale (0-10) was 2 points for NSAIDS, 2 for metamizole, and 1 for amitriptyline. Drugs that were discontinued due to lack of efficacy rather than side effects were acetaminophen, flupirtine, and selective serotonin reuptake inhibitors. Reduction in pain severity was best achieved by NSAIDs and metamizole. Our hypothesis that a decrease in intraepidermal nerve fiber density might represent a neuropathic subtype of FMS, which would be associated with better effectiveness of drugs targeting neuropathic pain, could not be confirmed in this cohort. Many FMS patients take "on-demand" medication that is not in line with current guidelines. More randomized clinical trials are needed to assess drug effects in FMS subgroups.
Topics: Acetaminophen; Amitriptyline; Analgesics; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Cross-Sectional Studies; Dipyrone; Duloxetine Hydrochloride; Fibromyalgia; Humans; Neuralgia; Pregabalin; Selective Serotonin Reuptake Inhibitors
PubMed: 36247103
DOI: 10.1155/2022/1217717 -
PloS One 2022To evaluate the efficacy and safety of different antidepressants and anticonvulsants in the treatment of central poststroke pain (CPSP) by network meta-analysis and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of different antidepressants and anticonvulsants in the treatment of central poststroke pain (CPSP) by network meta-analysis and provide an evidence-based foundation for clinical practice.
METHODS
PubMed, Cochrane Library, EMBASE, CNKI, APA PsycINFO, Wanfang, VIP and other databases were searched by computer to find clinical randomized controlled studies (RCTs) on drug treatment of CPSP. The retrieval time limit was from the establishment of each database to July 2022. The quality of the included RCTs was evaluated using the bias risk assessment tool recommended by Cochrane. Stata 14.0 was used for network meta-analysis.
RESULTS
A total of 13 RCTs, 1040 patients and 9 drugs were finally included. The results of the network meta-analysis showed that the effectiveness ranking as rated by the visual analog scale (VAS) was gabapentin > pregabalin > fluoxetine > lamotrigine > duloxetine > serqulin > amitriptyline > carbamazepine > vitamin B. Ranking according to the numerical rating scale (NRS) was pregabalin > gabapentin > carbamazepine. Ranking derived from the Hamilton depression scale (HAMD) was pregabalin > duloxetine > gabapentin > amitriptyline.
CONCLUSION
All nine drugs can relieve the pain of CPSP patients to different degrees; among them pregabalin and gabapentin have the most significant effect, and gabapentin and pregabalin also have the most adverse reactions. In the future, more multicenter, large sample, double-blind clinical randomized controlled trials need to be carried out to supplement and demonstrate the results of this study.
Topics: Amitriptyline; Anticonvulsants; Antidepressive Agents; Carbamazepine; Duloxetine Hydrochloride; Fluoxetine; Gabapentin; Humans; Lamotrigine; Multicenter Studies as Topic; Network Meta-Analysis; Neuralgia; Pregabalin; Randomized Controlled Trials as Topic; Vitamins
PubMed: 36227855
DOI: 10.1371/journal.pone.0276012 -
Drug Discoveries & Therapeutics Nov 2022The purpose of this study is to compare the efficacy and safety of pharmacotherapies for chronic pain due to osteoarthritis (OA) between a group with duloxetine (DLX)...
Comparison of efficacy and safety in the combination therapies of duloxetine and S-flurbiprofen plaster, and of duloxetine and conventional NSAIDs for chronic pain in patients with osteoarthritis (OASIS DUAL study).
The purpose of this study is to compare the efficacy and safety of pharmacotherapies for chronic pain due to osteoarthritis (OA) between a group with duloxetine (DLX) and S-flurbiprofen plaster (SFPP) (the SFPP group) and a group with DLX and conventional non-steroidal anti-inflammatory drugs (NSAIDs) (the control group). The subjects were 49 patients (17 men and 32 women). The evaluation of factors associated with treatment termination due to symptoms improvement showed that significantly more women terminated treatment than did men, and significantly more members of the SFPP group terminated treatment than did members of the control group. The visual analogue scale (VAS) score in the SFPP group was significantly improved from 6.6 ± 1.7 before treatment to 3.6 ± 2.1 one month later and showed significant difference until nine months later. The VAS score in the control group was significantly improved from 6.7 ± 1.9 to 4.1 ± 2.8 one month later. The VAS score improvement rate was significantly higher in the SFPP group than in the control group, suggesting that the DLX-SFPP combination had higher efficacy than the DLX-conventional NSAIDs combination. The incidence of adverse drug reactions was 55% in the SFPP group, which is not significantly different from 50% incidence in the control group. The treatment discontinuation rate due to adverse drug reactions, however, was 60% in the control group and 19% in the SFPP group. It was suggested that the efficacy and safety of the DLX-SFPP combination for chronic pain due to OA are equal to or higher than that of the DLX-conventional NSAIDs combination.
Topics: Humans; Male; Female; Flurbiprofen; Duloxetine Hydrochloride; Chronic Pain; Anti-Inflammatory Agents, Non-Steroidal; Osteoarthritis; Drug-Related Side Effects and Adverse Reactions; Treatment Outcome
PubMed: 36223938
DOI: 10.5582/ddt.2022.01052 -
Chemphyschem : a European Journal of... Feb 2023Crystallographic disorder, whether static or dynamic, can be detrimental to the physical and chemical stability, ease of crystallization and dissolution rate of an...
Crystallographic disorder, whether static or dynamic, can be detrimental to the physical and chemical stability, ease of crystallization and dissolution rate of an active pharmaceutical ingredient. Disorder can result in a loss of manufacturing control leading to batch-to-batch variability and can lengthen the process of structural characterization. The range of NMR active nuclei makes solid-state NMR a unique technique for gaining nucleus-specific information about crystallographic disorder. Here, we explore the use of high-field Cl solid-state NMR at 23.5 T to characterize both static and dynamic crystallographic disorder: specifically, dynamic disorder occurring in duloxetine hydrochloride (1), static disorder in promethazine hydrochloride (2), and trifluoperazine dihydrochloride (3). In all structures, the presence of crystallographic disorder was confirmed by C cross-polarization magic-angle spinning (CPMAS) NMR and supported by GIPAW-DFT calculations, and in the case of 3, H solid-state NMR provided additional confirmation. Applying Cl solid-state NMR to these compounds, we show that higher magnetic fields are beneficial for resolving the crystallographic disorder in 1 and 3, while broad spectral features were observed in 2 even at higher fields. Combining the data obtained from H, C, and Cl NMR, we show that 3 exhibits a unique case of disorder involving the N-H hydrogen positions of the piperazinium ring, driving the chloride anions to occupy three distinct sites.
Topics: Humans; Chlorides; Magnetic Resonance Spectroscopy; Magnetic Resonance Imaging; Pharmaceutical Preparations
PubMed: 36195553
DOI: 10.1002/cphc.202200558