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Acta Neurologica Scandinavica Feb 2022To describe the pharmacological treatments (2005-2017) and the healthcare utilization (1997-2016) for patients with narcolepsy in Sweden in order to create a framework... (Observational Study)
Observational Study
OBJECTIVES
To describe the pharmacological treatments (2005-2017) and the healthcare utilization (1997-2016) for patients with narcolepsy in Sweden in order to create a framework for future organizational and economic analyses.
MATERIAL & METHODS
Patients of all ages with a diagnosis of narcolepsy registered in the National Patient Registry in specialist care in Sweden were included and information on treatments for narcolepsy was retrieved from The Swedish Prescribed Drug Register.
RESULTS
We collected 2508 patients with narcolepsy, 43,3% men and 56,7% women and 47,9% were prescribed modafenil, 33,8% metylphenidate and 26,2% amphetamine. In total, 3817 treatments were initiated. Patients treated with amphetamine had a higher mean age. More women than men used modafinil, methylphenidate, amphetamine and antidepressants. The narcolepsy population had more outpatient than inpatient healthcare. Patients treated with sodium oxybate had more outpatient visits than other narcolepsy patients, before and during treatment (p = .00).
CONCLUSIONS
This study gives valuable information on pharmaceutical treatments and healthcare utilization for patients with narcolepsy and can be used to estimate the healthcare cost in the future. Patients with sodium oxybate treatment had more outpatient visits than other patients before and during treatment which may be due to the need to monitor potentially severe side-effects or may indicate that patients with sodium oxybate treatment have a severe disease. The number of included patients was less than expected; however, this may depend on patients escaping our collection of data, which does not contain information from primary care.
Topics: Antidepressive Agents; Female; Humans; Male; Modafinil; Narcolepsy; Sodium Oxybate; Sweden
PubMed: 34611886
DOI: 10.1111/ane.13532 -
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 -
British Journal of Pharmacology Dec 2021Modafinil is a potent eugeroic (wakefulness-promoting) drug that is prescribed to treat narcolepsy and has a low incidence of abuse. Although previous studies have shown...
BACKGROUND AND PURPOSE
Modafinil is a potent eugeroic (wakefulness-promoting) drug that is prescribed to treat narcolepsy and has a low incidence of abuse. Although previous studies have shown that modafinil-induced arousal depends on the dopamine receptors and transporters, the specific part/s of the dopamine transmitter system underlying this mechanism remained unclear. Here, we investigated the role of mesencephalic dopamine neurons in modafinil-evoked arousal.
EXPERIMENTAL APPROACH
A dopamine indicator (dLight1.1) was employed to detect dopamine changes in the nucleus accumbens (NAc) and dorsal striatum. We specifically lesioned mesencephalic dopamine neurons via diphtheria toxin (DTA) in the dopamine transporter (DAT)-Cre mice. Then, the sleep-wake states were recorded to evaluate the effect of modafinil on arousal. Finally, the extent of DTA-induced lesions was determined by immunohistochemistry.
KEY RESULTS
Modafinil promptly increased dopamine levels in the NAc and dorsal striatum in a dose-dependent manner. Lesioning of dopamine neurons in the substantia nigra pars compacta (SNc) or ventral tegmental area (VTA) had no significant effects on physiological sleep-wake cycles. Modafinil at 90 mg·kg increased continuous wakefulness for 355 min in control mice. However, these effects were slightly decreased by 6.7% in the SNc-lesioned mice and were prominently diminished by 32.8% in VTA-lesioned mice. Furthermore, the modafinil-induced arousal was completely blocked in the SNc-VTA-lesioned mice, whereas lesions of the dorsal raphé nucleus had no effect.
CONCLUSION AND IMPLICATIONS
Taken together, our findings indicate that mesencephalic dopamine neurons are essential for modafinil-induced arousal.
Topics: Animals; Arousal; Dopaminergic Neurons; Mice; Modafinil; Ventral Tegmental Area; Wakefulness
PubMed: 34399438
DOI: 10.1111/bph.15660 -
The International Journal of... Feb 2013Bipolar depression represents a high priority research field, due to its pervasiveness, and high economic and personal (suicidality, impaired function, quality of life)... (Review)
Review
Bipolar depression represents a high priority research field, due to its pervasiveness, and high economic and personal (suicidality, impaired function, quality of life) costs, and the limited evidence base to inform therapeutics. Mood stabilizers and second-generation antipsychotics for bipolar depression are commonly only partially effective, and their side-effects may overlap with depressive symptoms such as hypersomnia, daytime drowsiness, fatigue, psychomotor retardation, and weight gain. Moreover, the use of antidepressants in bipolar depression is controversial due to concerns regarding the risks of inefficacy or switching to mood elevation. Stimulants and related compounds such as modafinil and armodafinil have on occasion been used as adjuncts in bipolar depressed patients with encouraging results, but their use is limited by the paucity of systematic evidence of efficacy and safety. The present review aims to provide an updated perspective on the use of stimulants and stimulant-like medications in adult bipolar depression, considering not only recent randomized controlled trials, but also open naturalistic studies, in order to clarify the strengths and limitations of using these agents.
Topics: Adult; Antipsychotic Agents; Benzhydryl Compounds; Bipolar Disorder; Central Nervous System Stimulants; Drug Therapy, Combination; Humans; Methylphenidate; Modafinil
PubMed: 22717304
DOI: 10.1017/S1461145712000326 -
Progress in Neuro-psychopharmacology &... Mar 2018Methamphetamine (METH) and modafinil are psychostimulants with different long-term cognitive profiles: METH is addictive and leads to cognitive decline, whereas...
Repeated methamphetamine and modafinil induce differential cognitive effects and specific histone acetylation and DNA methylation profiles in the mouse medial prefrontal cortex.
Methamphetamine (METH) and modafinil are psychostimulants with different long-term cognitive profiles: METH is addictive and leads to cognitive decline, whereas modafinil has little abuse liability and is a cognitive enhancer. Increasing evidence implicates epigenetic mechanisms of gene regulation behind the lasting changes that drugs of abuse and other psychotropic compounds induce in the brain, like the control of gene expression by histones 3 and 4 tails acetylation (H3ac and H4ac) and DNA cytosine methylation (5-mC). Mice were treated with a seven-day repeated METH, modafinil or vehicle protocol and evaluated in the novel object recognition (NOR) test or sacrificed 4days after last injection for molecular assays. We evaluated total H3ac, H4ac and 5-mC levels in the medial prefrontal cortex (mPFC), H3ac and H4ac promotor enrichment (ChIP) and mRNA expression (RT-PCR) of neurotransmitter systems involved in arousal, wakefulness and cognitive control, like dopaminergic (Drd1 and Drd2), α-adrenergic (Adra1a and Adra1b), orexinergic (Hcrtr1 and Hcrtr2), histaminergic (Hrh1 and Hrh3) and glutamatergic (AMPA Gria1 and NMDA Grin1) receptors. Repeated METH and modafinil treatment elicited different cognitive outcomes in the NOR test, where modafinil-treated mice performed as controls and METH-treated mice showed impaired recognition memory. METH-treated mice also showed i) decreased levels of total H3ac and H4ac, and increased levels of 5-mC, ii) decreased H3ac enrichment at promoters of Drd2, Hcrtr1/2, Hrh1 and Grin1, and increased H4ac enrichment at Drd1, Hrh1 and Grin1, iii) increased mRNA of Drd1a, Grin1 and Gria1. Modafinil-treated mice shared none of these effects and showed increased H3ac enrichment and mRNA expression at Adra1b. Modafinil and METH showed similar effects linked to decreased H3ac in Hrh3, increased H4ac in Hcrtr1, and decreased mRNA expression of Hcrtr2. The specific METH-induced epigenetic and transcriptional changes described here may be related to the long-term cognitive decline effects of the drug and its detrimental effects on mPFC function. The lack of similar epigenetic effects of chronic modafinil administration supports this notion.
Topics: Acetylation; Animals; Central Nervous System Stimulants; Cognition; DNA Methylation; Histones; Male; Memory Disorders; Methamphetamine; Mice, Inbred C57BL; Modafinil; Prefrontal Cortex; Recognition, Psychology
PubMed: 29247759
DOI: 10.1016/j.pnpbp.2017.12.009 -
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 -
The Cochrane Database of Systematic... Apr 2016Fatigue 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.
OBJECTIVES
To assess the effectiveness and safety of pharmacological and non-pharmacological interventions for adults with PBT and high levels of fatigue.
SEARCH METHODS
In March 2016, we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO and CINAHL and checked the reference lists of included studies. We also searched relevant conference proceedings, searched for ongoing trials via ClinicalTrials.gov and contacted major co-operative groups with trials in this area.
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.
DATA COLLECTION AND ANALYSIS
Three review authors (JD, SYK, DC) independently evaluated search results, extracted data from selected studies and carried out a bias risk assessment. We extracted data on fatigue, cognition, mood, quality of life and adverse events outcomes.
MAIN RESULTS
We identified nine studies. We excluded eight of these as they did not restrict participation to people with high fatigue. The single eligible trial investigated the use of modafinil compared to placebo. Although this study found a significant improvement over time in the primary outcome of fatigue, the improvement occurred after both modafinil and placebo with no significant difference in response between the two groups. The included trial did not reach its planned recruitment target and therefore may not, in practice, have been adequately powered to detect a difference. The trial was at a low risk of bias across most areas. There was an unclear risk of bias related to the use of mean imputation because the investigators did not analyse the impact of imputation on the results.
AUTHORS' CONCLUSIONS
There was 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; Benzhydryl Compounds; Brain Neoplasms; Fatigue; Humans; Modafinil; Randomized Controlled Trials as Topic; Wakefulness-Promoting Agents
PubMed: 27074263
DOI: 10.1002/14651858.CD011376.pub2 -
Frontiers in Digital Health 2021To compare the findings from a qualitative and a natural language processing (NLP) based analysis of online patient experience posts on patient experience of the...
To compare the findings from a qualitative and a natural language processing (NLP) based analysis of online patient experience posts on patient experience of the effectiveness and impact of the drug Modafinil. Posts ( = 260) from 5 online social media platforms where posts were publicly available formed the dataset/corpus. Three platforms asked posters to give a numerical rating of Modafinil. Thematic analysis: data was coded and themes generated. Data were categorized into PreModafinil, Acquisition, Dosage, and PostModafinil and compared to identify each poster's own view of whether taking Modafinil was linked to an identifiable outcome. We classified this as positive, mixed, negative, or neutral and compared this with numerical ratings. NLP: Corpus text was speech tagged and keywords and key terms extracted. We identified the following entities: drug names, condition names, symptoms, actions, and side-effects. We searched for simple relationships, collocations, and co-occurrences of entities. To identify causal text, we split the corpus into PreModafinil and PostModafinil and used n-gram analysis. To evaluate sentiment, we calculated the polarity of each post between -1 (negative) and +1 (positive). NLP results were mapped to qualitative results. Posters had used Modafinil for 33 different primary conditions. Eight themes were identified: the reason for taking (condition or symptom), impact of symptoms, acquisition, dosage, side effects, other interventions tried or compared to, effectiveness of Modafinil, and quality of life outcomes. Posters reported perceived effectiveness as follows: 68% positive, 12% mixed, 18% negative. Our classification was consistent with poster ratings. Of the most frequent 100 keywords/keyterms identified by term extraction 88/100 keywords and 84/100 keyterms mapped directly to the eight themes. Seven keyterms indicated negation and temporal states. Sentiment was as follows 72% positive sentiment 4% neutral 24% negative. Matching of sentiment between the qualitative and NLP methods was accurate in 64.2% of posts. If we allow for one category difference matching was accurate in 85% of posts. User generated patient experience is a rich resource for evaluating real world effectiveness, understanding patient perspectives, and identifying research gaps. Both methods successfully identified the entities and topics contained in the posts. In contrast to current evidence, posters with a wide range of other conditions found Modafinil effective. Perceived causality and effectiveness were identified by both methods demonstrating the potential to augment existing knowledge.
PubMed: 34713085
DOI: 10.3389/fdgth.2021.598431 -
Journal of Clinical Sleep Medicine :... Dec 2021Excessive daytime sleepiness associated with obstructive sleep apnea affects 9%-22% of continuous positive airway pressure-treated patients. An indirect treatment... (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVES
Excessive daytime sleepiness associated with obstructive sleep apnea affects 9%-22% of continuous positive airway pressure-treated patients. An indirect treatment comparison meta-analysis was performed to compare efficacy and safety of medications (solriamfetol, modafinil, and armodafinil) approved to treat excessive daytime sleepiness associated with obstructive sleep apnea.
METHODS
Efficacy and safety measures assessed in this indirect treatment comparison included Epworth Sleepiness Scale (ESS), 20-minute Maintenance of Wakefulness Test (MWT20), Clinical Global Impression of Change (CGI-C), Functional Outcomes of Sleep Questionnaire (FOSQ), and incidence of treatment-emergent adverse events (any, serious, or leading to discontinuation).
RESULTS
A systematic literature review identified 6 parallel-arm, placebo-controlled randomized controlled trials that randomized 1,714 total participants to placebo, solriamfetol, modafinil, or armodafinil. In this indirect treatment comparison, all comparators were associated with greater improvements than placebo on the ESS, MWT20, and CGI-C after 4, 8, and 12 weeks of treatment. Relative to comparators and placebo at 12 weeks, solriamfetol at 150 mg or 300 mg had the highest probabilities of improvement in the ESS, MWT20, and CGI-C. Modafinil (200 or 400 mg) and solriamfetol (150 or 300 mg) were associated with greater improvement on the FOSQ than placebo at 12 weeks. Less than 2% of patients using placebo or comparators experienced serious or discontinuation-related treatment-emergent adverse events.
CONCLUSIONS
The results of this indirect treatment comparison show 12 weeks of treatment with solriamfetol, modafinil, and armodafinil resulted in varying levels of improvement on the ESS, MWT20, and CGI-C and similar safety risks in participants with excessive daytime sleepiness associated with obstructive sleep apnea.
CITATION
Ronnebaum S, Bron M, Patel D, et al. Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea. . 2021;17(12):2543-2555.
Topics: Benzhydryl Compounds; Carbamates; Disorders of Excessive Somnolence; Double-Blind Method; Humans; Modafinil; Phenylalanine; Sleep Apnea, Obstructive; Treatment Outcome
PubMed: 34402784
DOI: 10.5664/jcsm.9610 -
Behavioral Neuroscience Apr 2009Modafinil has been shown to promote wakefulness and some studies suggest the drug can improve cognitive function. Because of many similarities, the mechanism of action...
Modafinil has been shown to promote wakefulness and some studies suggest the drug can improve cognitive function. Because of many similarities, the mechanism of action may be comparable to classical psychostimulants, although the exact mechanisms of modafinil's actions in wakefulness and cognitive enhancement are unknown. The current study aims to further examine the effects of modafinil as a cognitive enhancer on hippocampus-dependent memory in mice. A high dose of modafinil (75 mg/kg ip) given before training improved acquisition on a Morris water maze. When given only before testing, modafinil did not affect water maze performance. We also examined modafinil (0.075 to 75 mg/kg) on Pavlovian fear conditioning. A low dose of pretraining modafinil (0.75 mg/kg) enhanced memory of contextual fear conditioning (tested off-drug 1 week later) whereas a high dose (75 mg/kg) disrupted memory. Pretraining modafinil did not affect cued conditioning at any dose tested, and immediate posttraining modafinil had no effect on either cued or contextual fear. These results suggest that modafinil's effects of memory are more selective than amphetamine or cocaine and specific to hippocampus-dependent memory.
Topics: Animals; Behavior, Animal; Benzhydryl Compounds; Conditioning, Classical; Dose-Response Relationship, Drug; Fear; Freezing Reaction, Cataleptic; Maze Learning; Memory, Short-Term; Mice; Mice, Inbred C57BL; Modafinil; Neuroprotective Agents; Reaction Time; Time Factors
PubMed: 19331449
DOI: 10.1037/a0014366