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ClinicoEconomics and Outcomes Research... 2023To demonstrate a need for improved health insurance coverage for anti-obesity medications (AOMs) by comparing clinical and economic benefits of obesity treatments to...
PURPOSE
To demonstrate a need for improved health insurance coverage for anti-obesity medications (AOMs) by comparing clinical and economic benefits of obesity treatments to covered medications for selected therapeutic areas.
METHODS
Using a grey literature search, we identified and prioritized therapeutic areas and treatment analogues for comparison to obesity. A targeted literature review identified clinical and economic outcomes research across the therapeutic area analogues. Associated comorbidities, clinical evidence, indirect costs (ie, absenteeism and productivity loss), and direct medical costs were evaluated to determine the relative value of treating obesity.
RESULTS
Four therapeutic areas/treatment analogues were selected for comparison to obesity: smoking cessation (varenicline), daytime sleepiness (modafinil), migraines (erenumab), and fibromyalgia (pregabalin). Obesity was associated with 17 comorbidities, more than migraine (9), smoking (8), daytime sleepiness (5), and fibromyalgia (2). Economic burden was greatest for obesity, followed by smoking, with yearly indirect and direct medical costs totaling $676 and $345 billion, respectively. AOMs resulted in cost savings of $2586 in direct medical costs per patient per year (PPPY), greater than that for varenicline at $930 PPPY, modafinil at $1045 PPPY, and erenumab at $468 PPPY; pregabalin utilization increased costs by $924 PPPY. AOMs were covered by 10-16% of United States health insurance plans, compared to 45-59% for the four comparators.
CONCLUSION
Compared to four therapeutic analogues, obesity represented the highest economic burden and was associated with more comorbidities. AOMs provide greater cost savings compared to selected analogues. However, AOMs have limited formulary coverage. Improved coverage of AOMs may increase access to these treatments and may help address the clinical and economic burden associated with obesity and its comorbidities.
PubMed: 36726966
DOI: 10.2147/CEOR.S392276 -
The Cochrane Database of Systematic... Jan 2023Fatigue is the most commonly reported symptom in people with advanced cancer. Cancer-related fatigue (CRF) is pervasive and debilitating, and can greatly impact quality... (Review)
Review
BACKGROUND
Fatigue is the most commonly reported symptom in people with advanced cancer. Cancer-related fatigue (CRF) is pervasive and debilitating, and can greatly impact quality of life (QoL). CRF has a highly variable clinical presentation, likely due to a complex interaction of multiple factors. Corticosteroids are commonly used to improve CRF, but the benefits are unclear and there are significant adverse effects associated with long-term use. With the increasing survival of people with metastatic cancer, the long-term effects of medications are becoming increasingly relevant. Since the impact of CRF can be immensely debilitating and can negatively affect QoL, its treatment warrants further review.
OBJECTIVES
To determine the benefits and harms of corticosteroids compared with placebo or an active comparator in adults with advanced cancer and CRF.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, Science Citation Index (ISI Web of Science), LILACS, and two clinical trial registries from inception to 18 July 2022. SELECTION CRITERIA: We included randomised controlled trials in adults aged ≥18 years. We included participants with advanced cancer who were suffering from CRF. We included trials that randomised participants to corticosteroids at any dose, by any route, administered for the relief of CRF; compared to placebo or an active comparator, including supportive care or non-pharmacological treatments.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed titles identified by the search strategy; two review authors assessed risk of bias; and two extracted data. We extracted the primary outcome of participant-reported fatigue relief using validated scales and secondary outcomes of adverse events, serious adverse events and QoL. We calculated the risk ratio with 95% confidence intervals (CIs) between groups for dichotomous outcomes. We measured arithmetic mean and standard deviation, and reported the mean difference (MD) with 95% CI between groups for continuous outcomes. We used standardised mean difference (SMD) with 95% CIs when an outcome was measured with different instruments measuring the same construct. We used a random-effects model to meta-analyse the outcome data. We rated the certainty of the evidence using GRADE and created two summary of findings tables. MAIN RESULTS: We included four studies with 297 enroled participants; data were available for only 239 participants. Three studies compared corticosteroid (equivalent ≤ 8 mg dexamethasone) to placebo. One study compared corticosteroid (dexamethasone 4 mg) to an active comparator (modafinil 100 mg). There were insufficient data to evaluate subgroups, such as dose and duration of treatment. One study had a high risk of performance and detection bias due to lack of blinding, and one study had a high risk of attrition bias. Otherwise, we assessed risks of bias as low or unclear. Comparison 1: corticosteroids compared with placebo Participant-reported fatigue relief The was no clear difference between corticosteroids and placebo (SMD -0.46, 95% CI -1.07 to 0.14; 3 RCTs, 165 participants, very low-certainty evidence) for relief of fatigue at one week of the intervention. We downgraded the certainty of the evidence three times for study limitations due to unclear risk of bias, imprecision, and inconsistency. Adverse events There was no clear difference in the occurrence of adverse events between groups, but the evidence is very uncertain (3 RCTs, 165 participants; very low-certainty evidence). Serious adverse events There was no clear difference in the occurrence of serious adverse events between groups, but the evidence is very uncertain (2 RCTs, 118 participants; very low-certainty evidence). Quality of lIfe One study reported QoL at one week using the Edmonton Symptom Assessment System (ESAS) well-being, and found no clear difference in QoL between groups (MD -0.58, 95% CI -1.93 to 0.77). Another study measured QoL using the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs (QoL-ACD), and found no clear difference between groups. There was no clear difference between groups for either study, but the evidence is very uncertain (2 RCTs, 118 participants; very low-certainty evidence). Comparison 2: corticosteroids compared with active comparator (modafinil) Participant-reported fatigue relief There was improvement in fatigue from baseline to two weeks in both groups (modafinil MD 10.15, 95% CI 7.43 to 12.87; dexamethasone MD 9.21, 95% CI 6.73 to 11.69), however no clear difference between the two groups (MD -0.94, 95% CI -4.49 to 2.61; 1 RCT, 73 participants, very low-certainty evidence). We downgraded the certainty of the evidence three times for very serious study limitations and imprecision. Adverse events There was no clear difference in the occurrence of adverse events between groups, but the evidence is very uncertain (1 RCT, 73 participants; very low-certainty evidence). Serious adverse events There were no serious adverse events reported in either group (1 RCT, 73 participants; very low-certainty evidence). Quality of lIfe One study measured QoL at two weeks, using the ESAS-well-being. There was marked improvement in QoL from baseline in both groups (modafinil MD -2.43, 95% CI -2.88 to -1.98; dexamethasone MD -2.16, 95% CI -2.68 to -1.64), however no clear difference between the two groups (MD 0.27, 95% CI -0.39 to 0.93; 1 RCT, 73 participants, very low-certainty evidence).
AUTHORS' CONCLUSIONS
There is insufficient evidence to support or refute the use of systemic corticosteroids in adults with cancer and CRF. We included four small studies that provided very low-certainty of evidence for the efficacy of corticosteroids in the management of CRF. Further high-quality randomised controlled trials with larger sample sizes are required to determine the effectiveness of corticosteroids in this setting.
Topics: Humans; Adult; Adolescent; Quality of Life; Modafinil; Adrenal Cortex Hormones; Neoplasms; Dexamethasone; Fatigue
PubMed: 36688471
DOI: 10.1002/14651858.CD013782.pub2 -
Epidemiologia (Basel, Switzerland) Dec 2022(1) Objective: We performed a systematic review to explore the prevalence of intravenous (IV) rehydration therapy in hospital settings, and we assessed it by patient... (Review)
Review
(1) Objective: We performed a systematic review to explore the prevalence of intravenous (IV) rehydration therapy in hospital settings, and we assessed it by patient groups and populations. (2) Methods: A systematic review of major databases and grey literature was undertaken from inception to 28 March 2022. Studies reporting prevalence of IV rehydration therapy in a hospital setting were identified. The data were synthesised in a narrative approach. (3) Results: Overall, 29 papers met the inclusion criteria. The prevalence of IV rehydration therapy in paediatric patients ranged from 4.5% (hospitalised with diarrhoea and dehydration) to 100% (admitted to the emergency department with mild to moderate dehydration caused by viral gastroenteritis), and in adults this ranged from 1.5% (had single substance ingestion of modafinil) to 100% (hospitalised with hypercalcemia). The most common indication for IV rehydration therapy in paediatric patients was dehydration due to fluid loss from the gastrointestinal tract. Other causes included malnutrition, neuromuscular disease, bronchiolitis, and influenza. In adults, indications for IV rehydration therapy were much more diverse: fever, diarrhoea, drug intoxication, hypercalcemia, cancer, and postural tachycardia syndrome; (4) Conclusions: This systematic review showed that IV rehydration therapy in paediatric patients is often used to treat dehydration and diarrhoea, while in adults it has a broader spectrum of use. While IV rehydration therapy is important in correcting fluid problems and electrolyte status, the maintenance fluid prescribing practices vary considerably, and guidelines are scarce.
PubMed: 36648776
DOI: 10.3390/epidemiologia4010002 -
Journal of Fluorescence May 2023The neuro-stimulant anti-narcoleptic drug as modafinil (MOD) is used to treatment neurological conditions caused by COVID-19. MOD was used to treatment narcolepsy,...
Rapid One-Pot Microwave Assisted Green Synthesis Nitrogen Doped Carbon Quantum Dots as Fluorescent Precursor for Estimation of Modafinil as Post-Covid Neurological Drug in Human Plasma with Greenness Assessments.
The neuro-stimulant anti-narcoleptic drug as modafinil (MOD) is used to treatment neurological conditions caused by COVID-19. MOD was used to treatment narcolepsy, shift-work sleep disorder, and obstructive sleep apnea-related sleepiness. So, an innovative, quick, economical, selective, and ecologically friendly procedure was carried out. A highly sensitive N@CQDs technique was created from green Eruca sativa leaves in about 4 min using microwave synthesis at 700 w. The quantum yield of the synthesized N@CQDs was found to be 41.39%. By increasing the concentration of MOD, the quantum dots' fluorescence intensity was gradually quenched. After being excited at 445 nm, the fluorescence reading was recorded at 515 nm. The linear range was found to be in the range 50 - 700 ng mL with lower limit of quantitation (LOQ) equal to 45.00 ng mL. The current method was fully validated and bio analytically according to (US-FDA and ICH) guidelines. Full characterization of the N@CQDs has been conducted by high resolution transmission electron microscope (HRTEM), Zeta potential measurement, fluorescence, UV-VIS, and FTIR spectroscopy. Various experimental variables including pH, QDs concentration and the reaction time were optimized. The proposed study is simply implemented for the therapeutic drug monitoring system (TDMS) and various clinical laboratories for further pharmacokinetic research.
Topics: Humans; Quantum Dots; Modafinil; Carbon; Nitrogen; Microwaves; COVID-19; Fluorescent Dyes
PubMed: 36576682
DOI: 10.1007/s10895-022-03128-5 -
Neuropsychiatric Disease and Treatment 2022Bipolar disorder (BD) is a chronic mental illness impacting 1-2% of the population worldwide and causing high rates of functional impairment. Patients with BD spend most... (Review)
Review
INTRODUCTION
Bipolar disorder (BD) is a chronic mental illness impacting 1-2% of the population worldwide and causing high rates of functional impairment. Patients with BD spend most of their time in depressive episodes and up to one-third of patients do not respond to adequate doses of medications. Although no consensus exists for definition of treatment-resistant bipolar depression (TRBD), failure of symptoms improvement despite an adequate trial of two therapeutic agents is a common theme of TRBD. In this paper, we review the evidence base of therapeutic interventions, challenges, and potential future directions for TRBD.
METHODS
We conducted a literature search for randomized controlled trials on PubMed for the treatment of TRBD and ongoing trials for the treatment of TRBD/bipolar depression on clinicaltrials.gov.
RESULTS
Several therapeutic agents have been investigated for TRBD. Adjunctive pramipexole and modafinil have data supporting short-term efficacy in TRBD, along with limited data for racemic intravenous ketamine. Celecoxib augmentation of escitalopram and treatment with metformin in patients with insulin resistance showed promising results. Right unilateral electroconvulsive therapy displayed statistically significant response rate and improvement, but not remission compared to pharmacotherapy. Trials for transcranial magnetic stimulation (TMS) have failed to show a significant difference from sham treatment in TRBD.
FUTURE TRENDS
Pharmacological treatments with novel mechanisms of actions like brexpiprazole and vortioxetine are being investigated following successes in unipolar depression. Modified TMS protocols such as accelerated TMS are under investigation. Innovative approaches like psychedelic-assisted psychotherapy, interleukin-2, fecal microbiota transplantation and multipotent stromal cells are being studied.
CONCLUSION
Evidence on current treatment modalities for TRBD is limited with low efficacy. More research is needed for successful treatment of TRBD. Effective therapies and innovative approaches to treatment are being investigated and could show promise.
PubMed: 36561896
DOI: 10.2147/NDT.S273503 -
Neurotherapeutics : the Journal of the... Mar 2023Wake-promoting agents are used for the management of excessive daytime sleepiness caused by narcolepsy. Clinical and preclinical data suggests that solriamfetol, a novel...
Wake-promoting agents are used for the management of excessive daytime sleepiness caused by narcolepsy. Clinical and preclinical data suggests that solriamfetol, a novel dopamine and norepinephrine reuptake inhibitor, is a promising therapeutic option for excessive daytime sleepiness. We provide the first head-to-head comparison of in vivo efficacy between modafinil and solriamfetol in narcoleptic mice. Both compounds induced potent wake-promoting effects in littermate wild-type and orexin-tTA; TetO-DTA mice when dosed at active and resting phases. However, neither modafinil nor solriamfetol alleviated cataplexy. Remarkably, modafinil significantly induced locomotor activity but solriamfetol had small effects. Awake electroencephalogram profiles revealed that modafinil augmented theta oscillation in a dose-dependent manner, but, on the contrary, the response to solriamfetol was blunted, reflecting the differences in their neurochemical properties and anxiogenic effects. Drug-induced anxiety-related behaviors were evaluated at equipotent wake-promoting doses in WT and DTA mice using the elevated plus maze and forced swim tests. Importantly, 100 mg/kg of modafinil significantly produced anxiety-related behaviors in WT mice, whereas 150 mg/kg of solriamfetol did not have anxiogenic effects. On the other hand, DTA mice exhibited trait anxiety and altered drug responses. Our results suggest that solriamfetol potently promotes wakefulness without psychomotor effects and without inducing anxiety-related behaviors.
Topics: Mice; Animals; Modafinil; Narcolepsy; Disorders of Excessive Somnolence; Arousal; Anxiety
PubMed: 36544071
DOI: 10.1007/s13311-022-01328-2 -
Maedica Sep 2022Antidepressants are the most common treatment for major depression. Also, psychotherapy is used for the treatment of depression. Tricyclic antidepressants are among the...
Antidepressants are the most common treatment for major depression. Also, psychotherapy is used for the treatment of depression. Tricyclic antidepressants are among the most frequently used medications to treat depression, with many known side effects. Therefore, checking and replacing other suitable drugs is essential in order to reduce side effects. Thus, the present study aimed to compare the efficacy of Modafinil and Citalopram in the treatment of patients with major depressive disorder. This interventional study was performed in 2019 on 30 people aged 18 to 65 years who had been diagnosed with a major depressive disorder based on DSM-5 criteria as well as the Hamilton Depression Rating Scale (HDRS), on which they got a score above 25. Subjects were randomly divided into two groups: the first group received Modafinil tablets (200 mg once daily, in the morning) and the second group Citalopram (20-40 mg/day). A Chi-square test was used to analyze the qualitative findings, and an independent t-test was used to compare quantitative data. The results showed that changes in HDRS score were significant over time (P <0.05). The mean difference in HDRS scores was significant in all stages among the study subjects (P <0.05). However, there were no significant differences in HDRS scores between groups in terms of gender, age, marital status, education, occupation, and economic status, either before treatment or three and six weeks after treatment. This was the first comparative study of Modafinil and Citalopram efficacy in treating patients with major depressive disorder. Larger-scale, longer-term clinical trials, including long-term discontinuation trials and placebo-controlled parallel treatment studies, are further necessary. Also, a larger sample size with a placebo comparison is recommended.
PubMed: 36540578
DOI: 10.26574/maedica.2022.17.3.607 -
Journal of Psychopharmacology (Oxford,... Feb 2023Fatigue remains an important factor in major aviation accidents. Stimulants may counteract fatigue's adverse effects, with modafinil as a promising alternative to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Fatigue remains an important factor in major aviation accidents. Stimulants may counteract fatigue's adverse effects, with modafinil as a promising alternative to caffeine. However, the effect of a single dose of modafinil after a limited period of sleep deprivation remains unknown.
AIMS
This study aims to determine the effect of 200 mg modafinil on vigilance during a limited period of sleep deprivation compared to 300 mg caffeine and placebo.
METHODS
Thirty-two volunteers of the Royal Netherlands Air Force (RNLAF) were double-blindly administered modafinil, caffeine, and placebo on three non-consecutive trial days after being awake for median 17 h. Afterwards, subjects completed six series of the Vigilance and Tracking test (VigTrack), psychomotor vigilance task (PVT), and Stanford Sleepiness Scale (SSS), yielding six primary endpoints.
RESULTS
This study revealed statistically significant effects of caffeine and modafinil compared with placebo on all endpoints, except for VigTrack mean tracking error. PVT results were less impaired 2 h after administration, followed by VigTrack parameters and SSS scores 2 h thereafter. Compared with caffeine, modafinil significantly improved PVT and SSS scores at 8 h after administration.
CONCLUSIONS
The present study demonstrates that 200 mg modafinil and 300 mg caffeine significantly decrease the effects of a limited period of sleep deprivation on vigilance compared with placebo. Although PVT parameters already improved 2 h after administration, the most notable effects occurred 2-4 h later. Modafinil seems to be effective longer than caffeine, which is consistent with its longer half-life.
Topics: Humans; Modafinil; Caffeine; Wakefulness; Sleep Deprivation; Benzhydryl Compounds; Psychomotor Performance; Central Nervous System Stimulants; Fatigue; Sleepiness; Double-Blind Method
PubMed: 36515156
DOI: 10.1177/02698811221142568 -
The Journal of Pharmacology and... Mar 2023Although there are no Food and Drug Administration-approved treatments for cocaine use disorder, several modafinil analogs have demonstrated promise in reducing cocaine...
Although there are no Food and Drug Administration-approved treatments for cocaine use disorder, several modafinil analogs have demonstrated promise in reducing cocaine self-administration and reinstatement in rats. Furthermore, the range of dopamine transporter (DAT) compounds provides an opportunity to develop pharmacotherapeutics without abuse liability. This study extended the comparison of JJC8-088 and JJC8-091, the former compound having higher DAT affinity and predicted abuse liability, to rhesus monkeys using a concurrent cocaine versus food schedule of reinforcement. First, binding to striatal DAT was examined in cocaine-naïve monkey tissue. Next, intravenous pharmacokinetics of both JJC compounds were evaluated in cocaine-experienced male monkeys ( = 3/drug). In behavioral studies, acute and chronic administration of both compounds were evaluated in these same monkeys responding under a concurrent food versus cocaine (0 and 0.003-0.1 mg/kg per injection) schedule of reinforcement. In nonhuman primate striatum, JJC8-088 had higher DAT affinity compared with JJC8-091 (14.4 ± 9 versus 2730 ± 1270 nM, respectively). Both JJC compounds had favorable plasma pharmacokinetics for behavioral assessments, with half-lives of 1.1 hours and 3.5 hours for JJC8-088 (0.7 mg/kg, i.v.) and JJC8-091 (1.9 mg/kg, i.v.), respectively. Acute treatment with both compounds shifted the cocaine dose-response curve to the left. Chronic treatment with JJC8-088 decreased cocaine choice in two of the three monkeys, whereas JJC8-091 only modestly reduced cocaine allocation in one monkey. Differences in affinities of JJC8-091 DAT binding in monkeys compared with rats may account for the poor rodent-to-monkey translation. Future studies should evaluate atypical DAT blockers in combination with behavioral interventions that may further decrease cocaine choice. SIGNIFICANCE STATEMENT: Cocaine use disorder (CUD) remains a significant public health problem with no Food and Drug Administration-approved treatments. The ability of drugs that act in the brain in a similar manner to cocaine, but with lower abuse liability, has clinical implications for a treatment of CUD.
Topics: Male; Rats; Animals; Cocaine; Dopamine Plasma Membrane Transport Proteins; Macaca mulatta; Dopamine Uptake Inhibitors; Self Administration; Dose-Response Relationship, Drug
PubMed: 36507847
DOI: 10.1124/jpet.122.001363