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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 -
Bipolar Disorders Jun 2022Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in... (Review)
Review
Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: A systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force.
BACKGROUND
Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations.
METHODS
The review included RCTs of candidate pro-cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials.
RESULTS
We identified 16 RCTs (N = 859) investigating cognitive remediation (CR; k = 6; N = 311), direct current or repetitive magnetic stimulation (k = 3; N = 127), or pharmacological interventions (k = 7; N = 421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre-screening for objective cognitive impairment, no primary outcome and no information on allocation sequence masking.
CONCLUSIONS
Evidence for pro-cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre-screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real-world functioning, investigate multimodal interventions and include neuroimaging.
Topics: Bipolar Disorder; Cognition; Cognitive Dysfunction; Humans; Lurasidone Hydrochloride; Mood Disorders
PubMed: 35174594
DOI: 10.1111/bdi.13193 -
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 -
European Neuropsychopharmacology : the... Jan 2024Growing evidence suggests an association between inflammatory processes and depressive disorders (DD). DD typically emerge during adolescence. Treatment effects of... (Meta-Analysis)
Meta-Analysis Review
Growing evidence suggests an association between inflammatory processes and depressive disorders (DD). DD typically emerge during adolescence. Treatment effects of agents with anti-inflammatory properties in youth DD have not been systematically reviewed. Here, the existing evidence on the use of anti-inflammatory drugs (including polyunsaturated fatty acids, nonsteroidal anti-inflammatory drugs, cytokine inhibitors, statins, pioglitazone, corticosteroids, and minocycline or modafinil) in children and adolescents with DD was synthesized using meta-analysis. The PROSPERO preregistered search yielded 22 records meeting search criteria. Of these, data from 19 primary studies (n = 1366 subjects) were subjected to meta-analysis. A significant but small effect in favor of anti-inflammatory agents in reducing depressive symptoms in youth with DD was found (SMD = -0.29, 95 % CI = -0.514; -0.063, p = 0.01). Post-hoc analyzes of drug subclasses found a significant effect of omega-3 fatty acids in reducing depressive symptoms. Results underline the importance to consider inflammatory pathways in the supplemental treatment of youth with DD. Further research is warranted, to clarify if anti-inflammatory agents are only effective in a subpopulation of patients (inflammatory biotype of depression in youth) and/or to alleviate specific symptom domains of depression (e.g., cognitive symptoms).
Topics: Child; Humans; Adolescent; Depression; Anti-Inflammatory Agents; Minocycline; Pioglitazone; Fatty Acids, Omega-3
PubMed: 37864981
DOI: 10.1016/j.euroneuro.2023.09.006 -
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 -
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 -
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 -
Journal of Clinical Medicine Oct 2022Narcolepsy is a neurological disease characterized by a core symptom of excessive daytime sleepiness (EDS). Although effective pharmacological interventions for...
Narcolepsy is a neurological disease characterized by a core symptom of excessive daytime sleepiness (EDS). Although effective pharmacological interventions for narcolepsy have been developed, a lack of comparative evidence supporting the relative efficacy among these medications leads to clinical treatment challenge. Therefore, we performed a network meta-analysis to overcome this lack of head-to-head comparisons. Databases were searched systematically for randomized controlled trials that compared pharmacological interventions for narcolepsy. The primary outcomes were changes in the Epworth Sleepiness Scale (ESS) and the Maintenance of Wakefulness Test (MWT). A random-effects frequentist network meta-analysis was conducted. A total of 19 RCTs involving 2504 patients were included. Solriamfetol achieved the highest ranking based on the P-scores, and was superior to pitolisant (MD -2.88, 95% CI -4.89--0.88) and sodium oxybate (MD -2.56, 95% CI -4.62--0.51) for ESS change. Consistently, solriamfetol achieved the highest ranking according to MWT change, and was superior to pitolisant (SMD 0.45, 95% CI 0.02-0.88) and modafinil (SMD 0.42, 95% CI 0.05-0.79). Although solriamfetol demonstrated superior efficacy in EDS improvement, evidence from the clustered ranking plot supported that efficacy-safety profiles of pitolisant, sodium oxybate, and modafinil are more balanced than solriamfetol. Therefore, the choice of medication for EDS in narcolepsy should be made on an individual basis.
PubMed: 36362535
DOI: 10.3390/jcm11216302 -
The Cochrane Database of Systematic... May 2018Despite the high prevalence of apathy in Alzheimer's disease (AD), and its harmful effects, there are currently no therapies proven to treat this symptom. Recently, a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite the high prevalence of apathy in Alzheimer's disease (AD), and its harmful effects, there are currently no therapies proven to treat this symptom. Recently, a number of pharmacological therapies have been investigated as potential treatments for apathy in AD.
OBJECTIVES
Objective 1: To assess the safety and efficacy of pharmacotherapies for the treatment of apathy in Alzheimer's disease (AD).Objective 2: To assess the effect on apathy of pharmacotherapies investigated for other primary outcomes in the treatment of AD.
SEARCH METHODS
We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), MEDLINE, Embase, CINAHL, PsycINFO, LILACS, ClinicalTrials.gov and the World Health Organization (WHO) portal, ICTRP on 17 May 2017.
SELECTION CRITERIA
Eligible studies were double-blind, randomized, placebo-controlled trials (RCTs) investigating apathy as a primary or secondary outcome in people with AD.
DATA COLLECTION AND ANALYSIS
Three review authors extracted data. We assessed the risks of bias of included studies using Cochrane methods, and the overall quality of evidence for each outcome using GRADE methods. We calculated mean difference (MD), standardized mean difference (SMD) or risk ratio (RR) with 95% confidence intervals on an intention-to-treat basis for all relevant outcome measures.
MAIN RESULTS
We included 21 studies involving a total of 6384 participants in the quantitative analyses. Risk of bias is very low to moderate. All studies reported appropriate methods of randomization and blinding. Most studies reported appropriate methods of allocation concealment. Four studies, three with methylphenidate and one with modafinil, had a primary aim of improving apathy. In these studies, all participants had clinically significant apathy at baseline. Methylphenidate may improve apathy compared to placebo. This finding was present when apathy was assessed using the apathy evaluation scale (AES), which was used by all three studies investigating methylphenidate: MD -4.99, 95% CI -9.55 to -0.43, n = 145, 3 studies, low quality of evidence, but not when assessed with the neuropsychiatric inventory (NPI)-apathy subscale, which was used by two of the three studies investigating methylphenidate: MD -0.08, 95% CI -3.85 to 3.69, n = 85, 2 studies, low quality of evidence. As well as having potential benefits for apathy, methylphenidate probably also slightly improves cognition (MD 1.98, 95% CI 1.06 to 2.91, n = 145, 3 studies, moderate quality of evidence), and probably improves instrumental activities of daily living (MD 2.30, 95% CI 0.74 to 3.86, P = 0.004, n = 60, 1 study, moderate quality of evidence), compared to placebo. There may be no difference between methylphenidate and placebo in the risk of developing an adverse event: RR 1.28, 95% CI 0.67 to 2.42, n = 145, 3 studies, low quality of evidence. There was insufficient evidence from one very small study of modafinil to determine the effect of modafinil on apathy assessed with the FrSBe-apathy subscale: MD 0.27, 95% CI -3.51 to 4.05, n = 22, 1 study, low quality of evidence. In all other included studies, apathy was a secondary outcome and participants were not selected on the basis of clinically significant apathy at baseline. We considered the evidence on apathy from these studies to be indirect and associated with publication bias. There was low or very low quality of evidence on cholinesterase inhibitors (ChEIs) (six studies), ChEI discontinuation (one study), antipsychotics (two studies), antipsychotic discontinuation (one study), antidepressants (two studies), mibampator (one study), valproate (three studies) and semagacestat (one study).
AUTHORS' CONCLUSIONS
Methylphenidate may demonstrate a benefit for apathy and may have slight benefits for cognition and functional performance in people with AD, but this finding is associated with low-quality evidence. Our meta-analysis is limited by the small number of studies within each drug class, risk of bias, publication bias, imprecision and inconsistency between studies. Additional studies should be encouraged targeting people with AD with clinically significant apathy which investigate apathy as a primary outcome measure, and which have a longer duration and a larger sample size. This could increase the quality of evidence for methylphenidate, and may confirm whether or not it is an effective pharmacotherapy for apathy in AD.
Topics: Alanine; Alzheimer Disease; Antidepressive Agents; Apathy; Azepines; Benzhydryl Compounds; Biphenyl Compounds; Central Nervous System Stimulants; Cholinesterase Inhibitors; Humans; Methylphenidate; Modafinil; Randomized Controlled Trials as Topic; Sulfonamides; Valproic Acid
PubMed: 29727467
DOI: 10.1002/14651858.CD012197.pub2 -
Cureus Jul 2021Narcolepsy is characterized by excessive daytime sleepiness (EDS) and cataplexy. Histamine neurons play an important role in enhancing wakefulness. The objective of our... (Review)
Review
Narcolepsy is characterized by excessive daytime sleepiness (EDS) and cataplexy. Histamine neurons play an important role in enhancing wakefulness. The objective of our study was to evaluate the efficacy of pitolisant, a histamine 3 (H3)-receptor antagonist/inverse agonist, in patients with a high burden of narcolepsy symptoms. We conducted an advanced PubMed search strategy with inclusion and exclusion criteria. The outcome included the Epworth Sleepiness Scale (ESS) and adverse effects frequency. Our primary outcome included the mean ESS score at the endpoint and showed that pitolisant was superior to the placebo, but not non-inferior to modafinil. Adverse effects were less common and shorter in duration in the pitolisant group compared to the modafinil-treated patients. Pitolisant was efficacious in reducing excessive daytime sleepiness and cataplexy compared with placebo, and it was well-tolerated in patients with severe narcolepsy symptoms as compared with modafinil.
PubMed: 34345566
DOI: 10.7759/cureus.16095