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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 -
EJNMMI Research May 2023The dopamine transporter (DaT) PET ligand [F]FE-PE2I is used to aid the diagnosis of Parkinson's disease. After encountering four patients with a history of daily...
BACKGROUND
The dopamine transporter (DaT) PET ligand [F]FE-PE2I is used to aid the diagnosis of Parkinson's disease. After encountering four patients with a history of daily sertraline use, who all showed atypical findings on [F]FE-PE2I PET, we suspected that the selective serotonin reuptake inhibitor (SSRI), sertraline, might interfere with the results and lead to globally reduced striatal [F]FE-PE2I binding due to sertraline's high affinity for DaT.
METHODS
We rescanned the four patients with [F]FE-PE2I PET after a 5-day sertraline pause. Sertraline plasma concentration was estimated based on body weight and dose, and specific binding ratios (SBR) in caudate nucleus, known to be more preserved in Parkinson's, were used to estimate the effect on tracer binding. Comparison was made to a patient with [F]FE-PE2I PET before and after a 7-day Modafinil pause.
RESULTS
We found a significant effect of sertraline on caudate nucleus SBR (p = 0.029). The effect showed a linear dose-dependent relationship that corresponds to a reduction in SBR by 0.32 or 0.44 for a 75 kg male or a 65 kg female, respectively, taking a daily dose of 50 mg sertraline.
CONCLUSION
Sertraline is one of the most commonly used antidepressants and in contrast to other SSRI's, sertraline show high affinity for DaT. We recommend that sertraline treatment is taken into account when patients are undergoing [F]FE-PE2I PET especially in patients showing apparent globally reduced PE2I binding. If tolerable, pausing of the sertraline treatment should be considered, especially for doses above 50 mg/day.
PubMed: 37221321
DOI: 10.1186/s13550-023-01000-6 -
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 -
Sleep Medicine Reviews Jun 2023Idiopathic hypersomnia is a central hypersomnolence disorder of unknown origin characterized by excessive daytime sleepiness despite normal or long sleep time, and... (Review)
Review
Idiopathic hypersomnia is a central hypersomnolence disorder of unknown origin characterized by excessive daytime sleepiness despite normal or long sleep time, and frequent severe sleep inertia. Management strategies have been largely derived from expert consensus, due to a lack of disease-specific assessments and reliance on case series and rare randomized controlled studies. Guidelines recommend treatment with off-label medications. Modafinil, which was approved for idiopathic hypersomnia until 2011 in Europe, is the most commonly used treatment and improved sleepiness in two recent randomized placebo-controlled trials. In 2021, low-sodium oxybate (LXB) was approved in the United States for idiopathic hypersomnia. In a placebo-controlled, double-blind, randomized withdrawal study, LXB reduced daytime sleepiness and sleep inertia, and improved daily functioning. Here, treatment options are reviewed considering the authors' professional experience, current guidelines, and the latest research developments. The choice of pharmacotherapy should be guided by symptom profile, age, comorbidities (eg, depressive symptoms, cardiovascular problems), and concomitant medications (eg, oral contraceptives). Nonpharmacologic approaches have a role in management. An instrument (idiopathic hypersomnia severity scale) has been validated in idiopathic hypersomnia specifically, opening a path to better assessment of symptoms, impact, and response to treatment. Continued research on idiopathic hypersomnia is needed to support treatment algorithms.
Topics: Humans; Idiopathic Hypersomnia; Expert Testimony; Disorders of Excessive Somnolence; Modafinil; Sleep; Sodium Oxybate; Narcolepsy; Randomized Controlled Trials as Topic
PubMed: 36921459
DOI: 10.1016/j.smrv.2023.101766 -
Sleep Sep 2023Idiopathic hypersomnia (IH) is a chronic disorder characterized by excessive daytime sleepiness unexplained by another disorder or drug/medication use. Although the... (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVES
Idiopathic hypersomnia (IH) is a chronic disorder characterized by excessive daytime sleepiness unexplained by another disorder or drug/medication use. Although the orexin system plays a role in sleep-wake regulation, orexin A levels in the cerebrospinal fluid are normal in people with IH. This phase 1b, randomized, placebo-controlled, crossover study aimed to investigate the safety, pharmacokinetics, and pharmacodynamics of danavorexton, a small-molecule orexin-2 receptor agonist, in adults with IH.
METHODS
Adults with IH aged 18-75 years were randomized to one of two treatment sequences of single intravenous infusions of danavorexton 112 mg and placebo. Pharmacodynamic endpoints included the maintenance of wakefulness test (MWT), the Karolinska Sleepiness Scale (KSS), and the psychomotor vigilance task (PVT). Adverse events were monitored throughout the study period.
RESULTS
Of 28 randomized participants, 12 (44.4%) had a treatment-emergent adverse event (TEAE) and 10 (37.0%) had a TEAE considered related to study drug, most of which were mild or moderate. Four participants (18.2%) had urinary TEAEs while receiving danavorexton, all of which were mild in severity. There were no deaths or TEAEs leading to discontinuation. Improvements in MWT, KSS, and PVT scores were observed with danavorexton compared to placebo. Following drug administration, a mean sleep latency of 40 min (maximum value) was observed during the MWT within 2 h of danavorexton infusion in most participants.
CONCLUSIONS
A single infusion of danavorexton improves subjective and objective excessive daytime sleepiness in people with IH with no serious TEAEs, indicating orexin-2 receptor agonists are promising treatments for IH. Clinical Trial: Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT04091438.
Topics: Humans; Adult; Idiopathic Hypersomnia; Modafinil; Orexins; Cross-Over Studies; Benzhydryl Compounds; Disorders of Excessive Somnolence; Wakefulness
PubMed: 36883238
DOI: 10.1093/sleep/zsad049 -
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 -
Psychopharmacology Bulletin Feb 2023Literature on ADHD has taken long strides recently as heaps of new data are pouring in through countless papers. Here, authors try to outline changing paradigms in ADHD... (Review)
Review
OBJECTIVES
Literature on ADHD has taken long strides recently as heaps of new data are pouring in through countless papers. Here, authors try to outline changing paradigms in ADHD practice. DSM-5 changes regarding the typology and diagnostic criteria are highlighted. Overview of co-morbidities, associations, developmental trajectories, and syndromic continuity across lifespan is outlined. Recent insights into aetiology and diagnostic tools are briefly discussed. New medications in the pipeline are also described.
METHODS
EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systemic Reviews were searched for all relevant updates in ADHD literature as of June, 2022.
RESULTS
DSM-5 brought about changes to the diagnostic criteria of ADHD. These included replacing types with presentations, pushing age to 12, and, incorporating adult diagnostic criteria. In the same vein, DSM-5 allows now for diagnosing concurrent ADHD and ASD. Associations of ADHD to allergy, obesity, sleep disorders, and, epilepsy have been demonstrated in recent literature. Neurocircuity underlying ADHD has been extended beyond frontal-striatal to include CTC as well as DMN accounting for ADHD heterogeneity. NEBA was FDA-approved to differentiate ADHD from hyperkinetic ID. Atypical antipsychotics use to address behavioural facets in ADHD is on the rise with no solid evidence-base. α-2 agonists are FDA-approved as monotherapy or adjunctive to stimulants. Pharmacogenetic testing is readily available for ADHD. Different formulations of stimulants abound on the market widening clinicians' repertoire. Stimulant-related exacerbation of anxiety and tics were challenged in recent studies. Drugs for ADHD in the pipeline include-dasotraline, armodafinil, tipepidine, edivoxetine, metadoxine, and memantine.
CONCLUSIONS
Literature on ADHD keeps expanding towards advancing our understanding of the complex and heterogeneous intricacies of this commonplace neurodevelopmental disorder and hence informing better decisions on how best to manage its diverse cognitive, behavioural, social and medical facets.
Topics: Adult; Humans; Child; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Antipsychotic Agents; Anxiety; Anxiety Disorders
PubMed: 36873919
DOI: No ID Found -
Sleep May 2023Obstructive sleep apnea (OSA) is a highly prevalent condition characterized by episodes of partial or complete breath cessation during sleep that induces sleep...
Obstructive sleep apnea (OSA) is a highly prevalent condition characterized by episodes of partial or complete breath cessation during sleep that induces sleep fragmentation (SF). One of the frequent manifestations of OSA is the presence of excessive daytime sleepiness (EDS) associated with cognitive deficits. Solriamfetol (SOL) and modafinil (MOD) are wake-promoting agents commonly prescribed to improve wakefulness in OSA patients with EDS. This study aimed to assess the effects of SOL and MOD in a murine model of OSA characterized by periodic SF. Male C57Bl/6J mice were exposed to either control sleep (SC) or SF (mimicking OSA) during the light period (06:00 h to 18:00 h) for 4 weeks, which consistently induces sustained excessive sleepiness during the dark phase. Both groups were then randomly assigned to receive once-daily intraperitoneal injections of SOL (200 mg/kg), MOD (200 mg/kg), or vehicle for 1 week while continuing exposures to SF or SC. Sleep/wake activity and sleep propensity were assessed during the dark phase. Novel Object Recognition test, Elevated-Plus Maze Test, and Forced Swim Test were performed before and after treatment. SOL or MOD decreased sleep propensity in SF, but only SOL induced improvements in explicit memory, while MOD exhibited increased anxiety behaviors. Chronic SF, a major hallmark of OSA, induces EDS in young adult mice that is mitigated by both SOL and MOD. SOL, but not MOD, significantly improves SF-induced cognitive deficits. Increased anxiety behaviors are apparent in MOD-treated mice. Further studies aiming to elucidate the beneficial cognitive effects of SOL are warranted.
Topics: Male; Animals; Mice; Sleep Deprivation; Sleep; Sleep Apnea, Obstructive; Modafinil; Disorders of Excessive Somnolence; Mice, Inbred C57BL
PubMed: 36866452
DOI: 10.1093/sleep/zsad057