-
JAMA Internal Medicine Feb 2021This cohort study uses data from the US Provigil/Nuvigil Pregnancy Registry to assess prevalence of fetal major congenital malformations after exposure to modafinil and...
This cohort study uses data from the US Provigil/Nuvigil Pregnancy Registry to assess prevalence of fetal major congenital malformations after exposure to modafinil and armodafinil during pregnancy.
Topics: Abnormalities, Drug-Induced; Female; Humans; Modafinil; Narcolepsy; Pregnancy; Registries; United States; Wakefulness-Promoting Agents
PubMed: 33074297
DOI: 10.1001/jamainternmed.2020.4009 -
JCO Oncology Practice Feb 2022The financial toxicity of anticancer drugs is well-documented, but little is known about the costs of drugs used to manage cancer-associated symptoms. (Review)
Review
PURPOSE
The financial toxicity of anticancer drugs is well-documented, but little is known about the costs of drugs used to manage cancer-associated symptoms.
METHODS
We reviewed relevant guidelines and compiled drugs used to manage seven cancer-associated symptoms (anorexia and cachexia, chemotherapy-induced peripheral neuropathy, constipation, diarrhea, exocrine pancreatic insufficiency, cancer-associated fatigue, and chemotherapy-induced nausea and vomiting). Using GoodRx website, we identified the retail price (cash price at retail pharmacies) and lowest price (discounted, best-case scenario of out-of-pocket costs) for patients without insurance for each drug or formulation for a typical fill. We describe lowest prices here.
RESULTS
For anorexia and cachexia, costs ranged from $5 US dollars (USD; generic olanzapine or mirtazapine tablets) to $1,156 USD (brand-name dronabinol solution) and varied widely by formulation of the same drug or dosage: for olanzapine 5 mg, $5 USD (generic tablet) to $239 USD (brand-name orally disintegrating tablet). For chemotherapy-induced peripheral neuropathy, costs of duloxetine varied from $12 USD (generic) to $529 USD (brand-name). For constipation, the cost of sennosides or polyethylene glycol was <$15 USD, whereas newer agents such as methylnaltrexone were expensive ($1,001 USD). For diarrhea, the cost of generic loperamide or diphenoxylate-atropine tablets was <$15 USD. For exocrine pancreatic insufficiency, only brand-name formulations were available, range of cost, $1,072 USD-$1,514 USD. For cancer-associated fatigue, the cost of generic dexamethasone or dexmethylphenidate was <$15 USD, whereas brand-name modafinil was more costly ($1,284 USD). For a 4-drug nausea and vomiting prophylaxis regimen, costs ranged from $181 USD to $1,430 USD.
CONCLUSION
We highlight the high costs of many symptom control drugs and the wide variation in the costs of these drugs. These findings can guide patient-clinician discussions about cost-effectively managing symptoms, while promoting the use of less expensive formulations when possible.
Topics: Antineoplastic Agents; Drug Costs; Drugs, Generic; Financial Stress; Humans; Neoplasms; Pharmacies
PubMed: 34558297
DOI: 10.1200/OP.21.00466 -
Cancer Medicine May 2023Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including... (Review)
Review
BACKGROUND
Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including quality of life and survival. This systematic review aimed to identify and describe interventions used to ameliorate (improve) or prevent cognitive impairments in adults with brain tumours.
METHODS
We performed a literature search of the Ovid MEDLINE, PsychINFO and PsycTESTS databases from commencement until September 2021.
RESULTS
In total, 9998 articles were identified by the search strategy; an additional 14 articles were identified through other sources. Of these, 35 randomised and nonrandomised studies were deemed to meet the inclusion/exclusion criteria of our review and were subsequently included for evaluation. A range of interventions were associated with positive effects on cognition, including pharmacological agents such as memantine, donepezil, methylphenidate, modafinil, ginkgo biloba and shenqi fuzheng, and nonpharmacological interventions such as general and cognitive rehabilitation, working memory training, Goal Management Training, aerobic exercise, virtual reality training combined with computer-assisted cognitive rehabilitation, hyperbaric oxygen therapy and semantic strategy training. However, most identified studies had a number of methodological limitations and were judged to be at moderate-to-high risk of bias. In addition, it remains unclear whether and to what extent the identified interventions lead to durable cognitive benefits after cessation of the intervention.
CONCLUSION
The 35 studies identified in this systematic review have indicated potential cognitive benefits for a number of pharmacological and nonpharmacological interventions in patients with brain tumours. Study limitations were identified and further studies should focus on improved study reporting, methods to reduce bias and minimise participant drop-out and withdrawal where possible, and consider standardisation of methods and interventions across studies. Greater collaboration between centres could result in larger studies with standardised methods and outcome measures, and should be a focus of future research in the field.
Topics: Adult; Humans; Quality of Life; Cognitive Dysfunction; Cognition; Cognition Disorders; Brain Neoplasms
PubMed: 36880363
DOI: 10.1002/cam4.5760 -
Metabolites Jun 2022Armodafinil, the R enantiomer of modafinil, was approved in 2007 by the US Food and Drug Administration as a wake-promoting agent for excessive sleepiness treatment. Due...
Armodafinil, the R enantiomer of modafinil, was approved in 2007 by the US Food and Drug Administration as a wake-promoting agent for excessive sleepiness treatment. Due to its abuse by students and athletes, there is a need of its quantification. Quantitative analysis by liquid chromatography-mass spectrometry, however, though very common and sensitive, frequently cannot be performed without isotopically labeled standards which usually have to be specially synthesized. Here we reported our investigation on the preparation of deuterated standard of armodafinil based on the simple and inexpensive hydrogen-deuterium exchange reaction at the carbon centers. The obtained results clearly indicate the possibility of introduction of three deuterons into the armodafinil molecule. The introduced deuterons do not undergo back exchange under neutral and acidic conditions. Moreover, the deuterated and non-deuterated armodafinil isotopologues revealed co-elution during the chromatographic analysis. The ability to control the degree of deuteration using different reaction conditions was determined. The proposed method of deuterated armodafinil standard preparation is rapid, cost-efficient and may be successfully used in its quantitative analysis by LC-MS.
PubMed: 35888702
DOI: 10.3390/metabo12070578 -
The Cochrane Database of Systematic... Sep 2022Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of... (Review)
Review
BACKGROUND
Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of fatigue in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 4, 2016.
OBJECTIVES
To assess the effectiveness and safety of pharmacological and non-pharmacological interventions for adults with PBT and clinically significant (or high levels) of fatigue.
SEARCH METHODS
For this updated review, we searched CENTRAL, MEDLINE and Embase, and checked the reference lists of included studies in April 2022. We also searched relevant conference proceedings, and ClinicalTrials.gov for ongoing trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that investigated any pharmacological or non-pharmacological intervention in adults with PBT and fatigue, where fatigue was the primary outcome measure. We restricted inclusion specifically to studies that enrolled only participants with clinically significant levels of fatigue to improve the clinical utility of the findings.
DATA COLLECTION AND ANALYSIS
Two review authors (JD, DC) independently evaluated search results for the updated search. Two review authors (JD, SYK) extracted data from selected studies, and carried out a risk of bias assessment. We extracted data on fatigue, mood, cognition, quality of life and adverse events outcomes.
MAIN RESULTS
The original review identified one study and this update identified a further two for inclusion. One study investigated the use of modafinil, one study the use of armodafinil and one study the use of dexamfetamine. We identified three ongoing studies. In the original review, the single eligible trial compared modafinil to placebo for 37 participants with a high- or low-grade PBT. One new study compared two doses of armodafinil (150 mg and 250 mg) to placebo for 297 people with a high-grade glioma. The second new study compared dexamfetamine sulfate to placebo for 46 participants with a low- or high-grade PBT. The evidence was uncertain for both modafinil and dexamfetamine regarding fatigue outcome measures, compared to controls, at study endpoint. Two trials did not reach the planned recruitment target and therefore may not, in practice, have been adequately powered to detect a difference. These trials were at a low risk of bias across most areas. There was an unclear risk of bias related to the use of mean imputation for one study because the investigators did not analyse the impact of imputation on the results and information regarding baseline characteristics and randomisation were not clear. The certainty of the evidence measured using GRADE was very low across all three studies. There was one identified study awaiting classification once data are available, which investigated the feasibility of 'health coaching' for people with a PBT experiencing fatigue. There were three ongoing studies that may be eligible for an update of this review, all investigating a non-pharmacological intervention for fatigue in people with PBT.
AUTHORS' CONCLUSIONS
There is currently insufficient evidence to draw reliable and generalisable conclusions regarding potential effectiveness or harm of any pharmacological or non-pharmacological treatments for fatigue in people with PBT. More research is needed on how best to treat people with brain tumours with high fatigue.
Topics: Adult; Brain Neoplasms; Dextroamphetamine; Fatigue; Glioma; Humans; Modafinil
PubMed: 36094728
DOI: 10.1002/14651858.CD011376.pub3 -
Molecules (Basel, Switzerland) Jul 2023Psychostimulant use disorders (PSUD) affect a growing number of men and women and exert sizable public health and economic burdens on our global society. Notably, there... (Review)
Review
Psychostimulant use disorders (PSUD) affect a growing number of men and women and exert sizable public health and economic burdens on our global society. Notably, there are some sex differences in the onset of dependence, relapse rates, and treatment success with PSUD observed in preclinical and clinical studies. The subtle sex differences observed in the behavioral aspects of PSUD may be associated with differences in the neurochemistry of the dopaminergic system between sexes. Preclinically, psychostimulants have been shown to increase synaptic dopamine (DA) levels and may downregulate the dopamine transporter (DAT). This effect is greatest in females during the high estradiol phase of the estrous cycle. Interestingly, women have been shown to be more likely to begin drug use at younger ages and report higher levels of desire to use cocaine than males. Even though there is currently no FDA-approved medication, modafinil, a DAT inhibitor approved for use in the treatment of narcolepsy and sleep disorders, has shown promise in the treatment of PSUD among specific populations of affected individuals. In this review, we highlight the therapeutic potential of modafinil and other atypical DAT inhibitors focusing on the lack of sex differences in the actions of these agents.
Topics: Female; Humans; Male; Dopamine Uptake Inhibitors; Modafinil; Sex Characteristics; Benzhydryl Compounds; Central Nervous System Stimulants; Cocaine; Dopamine
PubMed: 37446929
DOI: 10.3390/molecules28135270 -
Fa Yi Xue Za Zhi Dec 2021Abuse of pharmaceutical drugs is a major public health and social problem worldwide. Mostly abused drugs mainly include opioids such as morphine, tramadol, methadone and...
Abuse of pharmaceutical drugs is a major public health and social problem worldwide. Mostly abused drugs mainly include opioids such as morphine, tramadol, methadone and fentanyl, sedative-hypnotics such as benzodiazepines and non-benzodiazepines, and central stimulants such as Ritalin (methylphenidate), Adderall (amphetamine and dextroamphetamine) and modafinil. Abuse of pharmaceutical drugs not only causes direct damage to multiple systems of the body, but also significantly increases risks of mental and physical diseases, imposing a heavy burden on individuals, families and society. Therefore, the prevention and control of pharmaceutical drug abuse are of vital importance. The Chinese government has taken strict administration measures for pharmaceutical drugs with abuse risk. However, confronting endless new drugs and changing abuse trends, it is necessary to further strengthen management and prevention of pharmaceutical drugs, monitor the trend of abuse, establish rapid response mechanisms, popularize relevant knowledge, and develop specific therapeutic drugs and intervention means, in order to promote prevention and treatment of pharmaceutical drug abuse.
Topics: Analgesics, Opioid; Central Nervous System Stimulants; Humans; Illicit Drugs; Substance-Related Disorders
PubMed: 35243843
DOI: 10.12116/j.issn.1004-5619.2021.310403 -
Nature and Science of Sleep 2023Narcolepsy is a rare debilitating disorder for which multiple novel pharmacological options have been approved as treatment for the past few years. The current study... (Review)
Review
PURPOSE
Narcolepsy is a rare debilitating disorder for which multiple novel pharmacological options have been approved as treatment for the past few years. The current study systematically updates the comparative efficacy and detailed safety analysis of approved wake-promoting agents in narcolepsy.
METHODS
Randomized controlled trials (RCTs) were searched for diagnosed narcolepsy with approved interventions. Efficacy outcomes included the Maintenance of Wakefulness Test (MWT), Epworth Sleepiness Scale (ESS), Clinical Global Impression of Change (CGI-C), and Patient Global Impression of Change (PGI-C). Safety outcomes including overall adverse event (AE) risk were measured. The study was registered at PROSPERO (CRD 42022334915).
RESULTS
The final analysis included 17 RCTs with five drug treatments: modafinil/armodafinil, sodium oxybate, pitolisant, solriamfetol, and lower-sodium oxybate (LXB). For efficacy measures, interventions included in each outcome were effective compared with placebo. Furthermore, the magnitude of solriamfetol effect on MWT (9.11 minutes; 95% CI=7.05-11.16), ESS (-4.79; 95% CI=-6.56 to -3.01), and PGI-C (9.39; 95% CI= 2.37-37.19), and LXB effect on CGI-C (9.67; 95% CI=2.73-34.26) was greater than that of other treatments included in each outcome compared with placebo. For safety measures, all interventions had an acceptable safety profile with LXB having least risk for overall AEs (0.56; 95% CI=0.20-1.53), serious AEs (0.33; 95% CI=0.09-1.20), AEs leading to treatment discontinuation (0.11; 95% CI=0.01-2.04), and all-cause discontinuation (0.04; 95% CI=0.00-0.67) compared to placebo. Placebo had the lowest risk for exploratory AEs.
CONCLUSION
All approved interventions were effective in controlling the symptoms of narcolepsy at varying degrees with an acceptable safety profile.
PubMed: 37082610
DOI: 10.2147/NSS.S404113 -
Annals of Translational Medicine Jan 2021Cancer-related cognitive impairment (CRCI) refers to a series of cognitive impairment symptoms associated with alternations in brain structure and function, caused by a... (Review)
Review
Cancer-related cognitive impairment (CRCI) refers to a series of cognitive impairment symptoms associated with alternations in brain structure and function, caused by a non-central nervous system malignant tumor and its related treatment. CRCI may present as memory loss, impaired concentration, difficulty in multitasking and word retrieval, and reduced comprehension speed. CRCI has become one of the prevalent factors that compromise the quality of life for cancer survivors. Different treatments, including surgery, chemotherapy, radiotherapy, endocrine therapy, and targeted drugs, may contribute to CRCI. Meanwhile, patients' factors, including emotional challenges and genetic makeup, also contribute to the development of CRCI. The condition can be treated with using stimulants methylphenidate and modafinil, metabolites of nicotine: cotinine, antidepressants of fluoxetine and fluvoxamine, dementia drug of donepezil, and antioxidants ZnSO4, n-acetyl cysteine, propofol, and Chinese herbal of silver leaf medicine. Psychotherapies, including meditation and relaxation, cognitive rehabilitation training, along with physical therapies, including aerobic exercise, resistance training, balance training, yoga, qigong, tai chi electroencephalogram biofeedback, and acupuncture, are also beneficial in alleviating cancer-related cognitive impairment symptoms. In recent years, researchers have focused on factors related to the condition and on the available interventions. However, most research was conducted independently, and no review has yet summarized the latest findings. This review details and discusses the status of related factors and potential treatments for CRCI. We also supply specific recommendations to facilitate future research and integration in this field.
PubMed: 33553365
DOI: 10.21037/atm-20-6443 -
Revista de Neurologia Jun 2023Psychotic disorders are considered chronic mental health issues. Although it has been demonstrated that these disorders can present with a wide range of symptoms,... (Review)
Review
INTRODUCTION
Psychotic disorders are considered chronic mental health issues. Although it has been demonstrated that these disorders can present with a wide range of symptoms, pharmacological treatment is based on the use of typical and atypical antipsychotics, whose main mechanism of action is dopaminergic blockade, limiting their effect to the improvement of positive symptoms, without improving the rest of the symptoms and giving rise to a large number of serious adverse effects. For this reason, new therapeutic targets other than the dopaminergic system are being studied. The main objective of this review is to test whether these psychoactive substances used in clinical practice could provide additional benefits as an adjunctive treatment for people with psychotic disorders.
DEVELOPMENT
For this systematic review, a literature search was conducted in the databases PsycINFO, Medline, Psicodoc, PubMed and Google Scholar. Altogether 28 articles were included in the review. One of the main findings is that cannabidiol is more effective for improving positive symptoms and psychopathology; modafinil, for cognitive symptoms, motor and emotional functioning and quality of life; and ketamine, for negative symptoms. In addition, all the substances showed a good tolerability and safety profile, especially in comparison to antipsychotics.
CONCLUSION
The results obtained open up the possibility of having a guideline for clinicians/health professionals on the use of cannabidiol, modafinil and ketamine as adjunctive treatment for patients with psychotic conditions.
Topics: Humans; Antipsychotic Agents; Modafinil; Ketamine; Cannabidiol; Quality of Life; Psychotic Disorders
PubMed: 37231549
DOI: 10.33588/rn.7611.2023077