[Wakefulness-promoting agents for severe fatigue: to use or not to use?] / Medicatie tegen ernstige aanhoudende vermoeidheid.

About 20% of adults experience excessive daytime sleepiness or severe fatigue. Causes include somatic conditions, psychiatric disorders, and medication or drug use. Treatment depends on the underlying cause. If sleepiness persists despite optimal treatment of the underlying condition, exclusion of other causes, and behavioral interventions, wakefulness-promoting agents may be considered. However, no established pharmacological strategy exists for symptomatic treatment. Modafinil and stimulants like methylphenidate may offer some benefit based on experiences with narcolepsy or idiopathic hypersomnia. Studies in specific patient groups (e.g., multiple sclerosis, Parkinson's disease, traumatic brain injury, cancer-related fatigue) show variable results. The use of wakefulness-promoting agents is discouraged for addressing unexplained fatigue, as seen in the context of chronic fatigue syndrome.

Modafinil, an atypical CNS stimulant?

Modafinil is a central nervous system stimulant approved for the treatment of narcolepsy and sleep disorders. Due to its wide range of biochemical actions, modafinil has been explored for other potential therapeutic uses. Indeed, it has shown promise as a therapy for cognitive disfunction resulting from neurologic disorders like ADHD, and as a smart drug in non-medical settings. The mechanism(s) of actions underlying the therapeutic efficacy of this agent remains largely elusive. Modafinil is known to inhibit the dopamine transporter, thus decreasing dopamine reuptake following neuronal release, an effect shared by addictive psychostimulants. However, modafinil is unique in that only a few cases of dependence on this drug have been reported, as compared to other psychostimulants. Moreover, modafinil has been tested, with some success, as a potential therapeutic agent to combat psychostimulant and other substance use disorders. Modafinil has additional, but less understood, actions on other neurotransmitter systems (GABA, glutamate, serotonin, norepinephrine, etc.). These interactions, together with its ability to activate selected brain regions, are likely one of the keys to understand its unique pharmacology and therapeutic activity as a CNS stimulant. In this chapter, we outline the pharmacokinetics and pharmacodynamics of modafinil that suggest it has an "atypical" CNS stimulant profile. We also highlight the current approved and off label uses of modafinil, including its beneficial effects as a treatment for sleep disorders, cognitive functions, and substance use disorders.

Modafinil Therapy and Mental Status Following Aneurysmal Subarachnoid Hemorrhage: Comprehensive Stroke Center Analysis.

BACKGROUND: Disorders of consciousness impair early recovery after aneurysmal subarachnoid hemorrhage (aSAH). Modafinil, a wakefulness-promoting agent, is efficacious for treating fatigue in stroke survivors, but data pertaining to its use in the acute setting are scarce. This study sought to assess the effects of modafinil use on mental status after aSAH. METHODS: Modafinil timing and dosage, neurological examination, intubation status, and physical and occupational therapy participation were documented. Repeated-measures paired tests were used for a before-after analysis of modafinil recipients. Propensity score matching (1:1 nearest neighbor) for modafinil and no-modafinil cohorts was used to compare outcomes. RESULTS: Modafinil (100-200 mg/day) was administered to 21% (88/422) of aSAH patients for a median (IQR) duration of 10.5 (4-16) days and initiated 14 (7-17) days after aSAH. Improvement in mentation (alertness, orientation, or Glasgow Coma Scale score) was documented in 87.5% (77/88) of modafinil recipients within 72 hours and 86.4% (76/88) at discharge. Of 37 intubated patients, 10 (27%) were extubated within 72 hours after modafinil initiation. Physical and occupational therapy teams noted increased alertness or participation in 47 of 56 modafinil patients (83.9%). After propensity score matching for baseline covariates, the modafinil cohort had a greater mean (SD) change in Glasgow Coma Scale score than the no-modafinil cohort at discharge (2.2 [4.0] vs. -0.2 [6.32], P = 0.003). CONCLUSIONS: A temporal relationship with improvement in mental status was noted for most patients administered modafinil after aSAH. These findings, a favorable adverse-effect profile, and implications for goals-of-care decisions favor a low threshold for modafinil initiation in aSAH patients in the acute-care setting.

Contingency management plus acceptance and commitment therapy for initial cocaine abstinence: Results of a sequential multiple assignment randomized trial (SMART).

BACKGROUND: This study tested an adaptive intervention for optimizing abstinence outcomes over phases of treatment for cocaine use disorder using a SMART design. Phase 1 assessed whether 4 weeks of contingency management (CM) improved response with the addition of Acceptance and Commitment Therapy (ACT). Phase 2 assessed pharmacological augmentation with modafinil (MOD) vs. placebo (PLA) for individuals not achieving abstinence during Phase 1. METHOD: For Phase 1 of treatment, participants (N=118) were randomly allocated to ACT+CM or Drug Counseling (DC+CM), the comparison condition. At week 4, treatment response was defined as the submission of six consecutive cocaine-negative urine drug screens (UDS). Phase 1 non-responders were re-randomized to MOD or PLA as adjunct to their initial treatment. Phase 1 responders continued receiving their initial treatment. Primary outcomes included response rate and proportion of cocaine-negative UDS for Phase 1 and 2. Analyses used Bayesian inference with 80% pre-specified as the posterior probability (PP) threshold constituting moderate evidence that an effect exists. RESULTS: Phase 1 response was higher in the ACT+CM group (24.5%) compared to the DC+CM group (17.5%; PP = 84.5%). In Phase 2, the proportion of cocaine-negative UDS among Phase 1 responders did not differ by initial treatment (PP = 61.8%) but remained higher overall compared to Phase 1 non-responders (PPs > 99%). No evidence of an effect favoring augmentation with MOD was observed. DISCUSSION: Adding ACT to CM increased abstinence initiation. Initial responders were more likely to remain abstinent compared to initial non-responders, for whom modafinil was not an effective pharmacotherapy augmentation strategy.

Idiopathic hypersomnia with a video recording of a spontaneous sleep attack: A case report.

RATIONALE: Although patients with central disorders of hypersomnolence (CDH) exhibit characteristic symptoms of hypersomnia frequently, it takes 5 to 15 years from the onset for its diagnosis due to the lack of symptom recognition. Here, we present a case of idiopathic hypersomnia (IH), a CDH, wherein early diagnosis was aided by a video footage of a spontaneous sleep attack. PATIENT CONCERNS: A 21-year-old man lost consciousness while driving and experienced an accident. He had complained of excessive daytime sleepiness (EDS) over half a year. During his hospitalization for close monitoring of the loss of consciousness, an in-room surveillance camera captured a 14-minutes long spontaneous sleep attack, during which he experienced general muscle weakness and loss of consciousness without warnings or convulsions leading to a fall from the bed. There were no abnormalities in vital signs. DIAGNOSES: There was no significant cataplexy and less than 2 sleep-onset rapid eye movements (SOREM) in 2 sleep latency tests, with a mean sleep latency of 2.1 and 4.6 minutes. Other sleep deprivation syndromes were excluded from differential diagnosis and finally, a diagnosis of IH was confirmed according to the criteria of the Third Edition of the International Classification of Sleep Disorders. During the course of the disease, attention-deficit/hyperactive disorder (ADHD) and a gaming disorder also diagnosed. INTERVENTIONS: Pharmacological treatment with modafinil was administered for IH and methylphenidate for ADHD. Cognitive behavioral therapy was performed for the gaming disorder. OUTCOMES: The EDS improved, and sleep attacks were no longer observed. The disruption of daily life caused by the gaming disorder was also reduced. LESSONS: Video recordings of sleep attacks are beneficial for identifying the cause of loss of consciousness. Home video recordings may be helpful in the early diagnosis of IH.

Narcolepsy Severity Scale-2 and Idiopathic Hypersomnia Severity Scale to better quantify symptoms severity and consequences in Narcolepsy type 2.

STUDY OBJECTIVES: Narcolepsy type 2 (NT2) is an understudied central disorder of hypersomnolence sharing some similarities with narcolepsy type 1 and idiopathic hypersomnia (IH). We aimed: (1) to assess systematically the symptoms in patients with NT2, with self-reported questionnaires: Epworth Sleepiness Scale (ESS), Narcolepsy Severity Scale (NSS), IH Severity Scale (IHSS), and (2) to evaluate the responsiveness of these scales to treatment. METHODS: One hundred and nine patients with NT2 (31.4 ±â€…12.2 years old, 47 untreated) diagnosed according to ICSD-3 were selected in a Reference Center for Narcolepsy. They all completed the ESS, subgroups completed the modified NSS (NSS-2, without cataplexy items) (n = 95) and IHSS (n = 76). Some patients completed the scales twice (before/during treatment): 42 ESS, 26 NSS-2, and 30 IHSS. RESULTS: Based on NSS-2, all untreated patients had sleepiness, 58% disrupted nocturnal sleep, 40% hallucinations, and 28% sleep paralysis. On IHSS, 76% reported a prolonged nocturnal sleep, and 83% sleep inertia. In the independent sample, ESS and NSS-2 scores were lower in treated patients, with same trend for IHSS scores. After treatment, ESS, NSS-2, and IHSS total scores were lower, with a mean difference of 3.7 ±â€…4.1, 5.3 ±â€…6.7, and 4.1 ±â€…6.2, respectively. The minimum clinically important difference between untreated and treated patients were 2.1 for ESS, 3.3 for NSS-2, and 3.1 for IHSS. After treatment, 61.9% of patients decreased their ESS > 2 points, 61.5% their NSS-2 > 3 points, and 53.3% their IHSS > 3 points. CONCLUSIONS: NSS-2 and IHSS correctly quantified symptoms' severity and consequences in NT2, with good performances to objectify response to medications. These tools are useful for monitoring and optimizing NT2 management, and for use in clinical trials.

Headache improves with armodafinil.

This case report recounts the details of a patient diagnosed with narcolepsy and cataplexy whose headaches improved once treatment with armodafinil began. The clinical significance of this report lies in the fact that armodafinil is known to cause headaches, at least initially. But perhaps through a reduced need for caffeine and/or a regulation of sleep/wake, armodafinil may reduce headache frequency and severity. CITATION: Barone DA. Headache improves with armodafinil. J Clin Sleep Med. 2024;20(3):469-470.

COMPARATIVE ANALYSIS OF EFFECTIVENESS OF OBESITY TREATMENT IN PRIMARY CARE USING PATIENT-ORIENTED APPROACH WITH MOTIVATIONAL COUNSELING FOR LIFESTYLE CORRECTION AND ITS COMBINATION WITH ARMODAFINIL THERAPY IN PATIENTS WITH CONCOMITANT SHIFT WORK SLEEP DISORDER.

OBJECTIVE: Aim: Conduct a comparative analysis of effectiveness of obesity treatment in primary care using patient-oriented approach with motivational counseling for lifestyle correction and its combination with armodafinil therapy in patients with concomitant shift work sleep disorder. PATIENTS AND METHODS: Materials and Methods: 75 patients with obesity were studied, 38 patients had shift work disorder. Patients were divided into 2 groups: I (37 patients with obesity treated with motivational counseling) and II (38 patients with obesity and shift work disorder treated additionally with armodafinil 150 mg daily). The examination was at baseline, after 1st, 3th and 6th months. Statistical analysis was provided. RESULTS: Results: After 1 month of treatment, there were improvement of eating behavior, level of anxiety and depression, prognosis of diabetes development. At 3rd month, more pronounced changes were observed in 2nd group: 10% body weight loss, changes in eating behavior, sleep quality, anxiety level (p<0.05). After 6 months, examined indicators in both groups normalized, but dynamics in 2nd group was more significant; armodafinil-treated group had significantly better results in body weight loss, BMI, WC, HC, ConI, AVI, BPs, HOMA index, serotonin, leptin, levels of anxiety and depression, eating behavior, daytime dysfunction, level of sleepiness, quality of life and risk of developing diabetes. CONCLUSION: Conclusions: The use of armofafinil in addition to patientoriented motivational counseling in lifestyle correction ("5 As" and "5R") in patients with obesity connected with shift work disorder and excessive daytime sleepiness allows to reduce body weight by more than 16,52%, in contrast to isolated use of the same technique of motivational counseling in obese patients without sleep disorder (only 5,51%).

Recovery Mimicking “Ideal” CPAP Adherence Does Not Improve Wakefulness or Cognition in Chronic Murine Models of OSA: Effect of Wake-Promoting Agents

Introduction: Obstructive sleep apnea (OSA) is a chronic condition characterized by intermittent hypoxia (IH) and sleep fragmentation (SF). OSA can induce excessive daytime sleepiness (EDS) and is associated with impaired cognition and anxiety. Solriamfetol (SOL) and modafinil (MOD) are widely used wake-promoting agents in OSA patients with EDS. Methods: Male C57Bl/6J mice were exposed to SF along with sleep controls (SC) or to IH and room air (RA) controls during the light (inactive) phase for 4 and 16 weeks, respectively. Both IH and SF exposures were then discontinued to mimic “ideal” continuous positive airway pressure (CPAP) adherence. All groups were then randomly assigned to receive once daily intraperitoneal injections of SOL, MOD, or vehicle (VEH) for 6 days. Sleep/wake activity was assessed along with tests of explicit memory, anxiety and depression were performed before and after treatments. Results: IH and SF exposures increased sleep percentage in the dark phase and reduced wake bouts lengths (i.e., EDS), and induced cognitive deficits and impulsivity in mice. Both SOL and MOD treatments effectively mitigated EDS when combined with recovery, while recovery alone did not improve EDS over the 6-day period. Furthermore, improvements explicit memory emerged only after SOL. Conclusion: Chronic IH and SF induce EDS in young adult mice that is not ameliorated by recovery except when combined with either SOL or MOD. SOL, but not MOD, significantly improves IH-induced cognitive deficits. Thus, SOL emerges as a viable adjuvant medication for residual EDS in OSA along with its positive impact on cognition. (AU)

Consciousness Recovery in Traumatic Brain Injury: A Systematic Review Comparing Modafinil and Amantadine.

OBJECTIVES: Acute traumatic brain injury is one of the most common causes of death and disability. Reduction in the level of consciousness is a significant complication that can impact morbidity. Glasgow Coma Scale (GCS) is the most widely used method of assessing the level of consciousness. Neurostimulants such as amantadine and modafinil are common pharmacologic agents that increase GCS in patients with brain trauma. This study aimed to compare the effectiveness of these 2 drugs. METHODS: This systematic review obtained articles from Google Scholar, PubMed, Scopus, Embase, and MEDLINE databases. Extensive searches were conducted separately by 4 individuals in 3 stages. Ultimately, 16 clinical trials, cohort studies, case reports, and case series articles were obtained after reading the title, abstract, and full text and considering the exclusion criteria. The data of the final article were entered into the analysis table. This study was registered with PROSPERO (registration number CRD42022334409) and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Amantadine seems to be associated with a higher overall response rate. In contrast, modafinil is associated with the most remarkable change in GCS score during treatment. However, the number of clinical trials with high quality and sample size has not been satisfactory to compare the effectiveness of these 2 drugs and their potential side effects. CONCLUSIONS: The authors recommend additional double-blind clinical trials are needed to be conducted with a larger sample size, comparing amantadine with modafinil to delineate the efficacy and adverse effects, both short and long term.

Pitolisant-supported bridging during drug holidays to deal with tolerance to modafinil in patients with narcolepsy.

STUDY OBJECTIVES: Modafinil is a common treatment for excessive daytime sleepiness (EDS) in narcolepsy. The long-term use of modafinil can lead to tolerance with the loss of efficacy and the continuous increase of its dose. Pharmacological strategies to deal with the tolerance to modafinil are lacking. We investigated the efficacy and safety of pitolisant-supported bridging during drug holidays in patients with tolerance to modafinil. METHODS: Narcolepsy patients on monotherapy with modafinil who developed symptoms of tolerance were eligible. The following alternating therapy regimen was established: Monday to Friday patients continued on modafinil whereas Saturday and Sunday they switched to pitolisant to "bridge" the EDS symptoms. Patients were assessed at baseline and after three months with the Epworth Sleepiness Scale (ESS) and the Ullanlinna Narcolepsy Scale (UNS). Health-related quality of life (HrQol) was evaluated by EuroQol5D. Adverse events were documented in the patients' diaries. RESULTS: 41 patients aged 30.9 ± 5.6 years were included. After three months of the alternating therapy regimen, the symptoms of tolerance decreased and the modafinil dose could be reduced by 41% (p < 0.01) resulting in better safety. The EDS improved on ESS (baseline: 18.2 ± 4.2, follow-up: 12.6 ± 4.0, p < 0.0001) and UNS (baseline: 25.8 ± 7.9, follow-up: 18.9 ± 5.9, p < 0.0001). The HrQol increased significantly. CONCLUSION: Patients with tolerance to modafinil could benefit from pitolisant-supported bridging during drug holidays. This alternating pharmacological strategy proved to be safe and helped to reduce EDS and to decrease the modafinil dose. Further randomized controlled studies are required to evaluate the different strategies to deal with the tolerance to modafinil. CLINICAL TRIAL REGISTRATION NUMBER: Clinical Trials.gov Identifier NCT05321355.

Recovery Mimicking "Ideal" CPAP Adherence Does Not Improve Wakefulness or Cognition in Chronic Murine Models of OSA: Effect of Wake-Promoting Agents.

INTRODUCTION: Obstructive sleep apnea (OSA) is a chronic condition characterized by intermittent hypoxia (IH) and sleep fragmentation (SF). OSA can induce excessive daytime sleepiness (EDS) and is associated with impaired cognition and anxiety. Solriamfetol (SOL) and modafinil (MOD) are widely used wake-promoting agents in OSA patients with EDS. METHODS: Male C57Bl/6J mice were exposed to SF along with sleep controls (SC) or to IH and room air (RA) controls during the light (inactive) phase for 4 and 16 weeks, respectively. Both IH and SF exposures were then discontinued to mimic "ideal" continuous positive airway pressure (CPAP) adherence. All groups were then randomly assigned to receive once daily intraperitoneal injections of SOL, MOD, or vehicle (VEH) for 6 days. Sleep/wake activity was assessed along with tests of explicit memory, anxiety and depression were performed before and after treatments. RESULTS: IH and SF exposures increased sleep percentage in the dark phase and reduced wake bouts lengths (i.e., EDS), and induced cognitive deficits and impulsivity in mice. Both SOL and MOD treatments effectively mitigated EDS when combined with recovery, while recovery alone did not improve EDS over the 6-day period. Furthermore, improvements explicit memory emerged only after SOL. CONCLUSION: Chronic IH and SF induce EDS in young adult mice that is not ameliorated by recovery except when combined with either SOL or MOD. SOL, but not MOD, significantly improves IH-induced cognitive deficits. Thus, SOL emerges as a viable adjuvant medication for residual EDS in OSA along with its positive impact on cognition.

Cognitive Rehabilitation for Patients with Schizophrenia: A Narrative Review of Moderating Factors, Strategies, and Outcomes.

OBJECTIVE: Antipsychotic drugs constitute the basis of schizophrenia therapy; however, available pharmaceutical agents lack efficacy for treating the cognitive deficits caused by the illness. The aim of the present work is to present current data regarding cognitive rehabilitation of schizophrenia, providing information and guidance to health professionals. METHOD: A literature search was conducted in the PubMed and Google Scholar Databases from inception up to 1/9/2022. Relevant articles were explored for factors affecting cognitive function, including genetics, psychopathology, time in the course of the illness, and drug therapy. Characteristics and outcome of cognitive rehabilitation programs are briefly presented. RESULTS: A total of 562 relevant articles were retrieved, 39 of which were selected for the review. Factors contributing to a favorable outcome are young age, early phase of disease, symptomatic control of hostility and conceptual disorganization, lack of negative symptoms, management of drug side effects, and cognitive and cortical reserve. Some evidence for a procognitive effect seems to exist for atypical antipsychotics, clozapine, aripiprazole, memantine, modafinil, d-serine, and cycloserine. The Val/Val polymorphism of the COMT gene seems to be associated with worse outcome. Specific remediation strategies include programs such as Cognitive Enhancement Therapy (CET), Cognitive Adaptation Training (CAT), and RehaCom Cognitive Therapy Software, among others, all employing a range of techniques, from paper-and-pencil to computer-assisted, bottom-up, or top-down approaches, and varying neurocognitive targets. CONCLUSION: Cognitive symptoms, closely related to functional impairment, still remain a therapeutic challenge. Cognitive rehabilitation strategies are as yet the only treatment modality offering cognitive improvement to patients who struggle to recover.

Are There Prevalent Sex Differences in Psychostimulant Use Disorder? A Focus on the Potential Therapeutic Efficacy of Atypical Dopamine Uptake Inhibitors.

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.

High-dose armodafinil in treatment-refractory bipolar depression.

BACKGROUND: Bipolar depression is a serious neuropsychiatric disorder associated with a high risk of morbidity and suicidality. Standard antidepressants approved for treating major depressive disorder fail to exert efficacy in bipolar depression. Although 5 agents have been developed for the treatment of bipolar depression, treatment resistance is still observed in some patients, and requires off-label pharmacotherapy. Modafinil and armodafinil have been reported to improve treatment-resistant bipolar depression, but with inconsistent results. METHODS: We present a case of a 65-year-old woman with severe bipolar depression who failed to respond to electroconvulsive therapy and IV ketamine but later responded to high-dose armodafanil. RESULTS: The patient responded to high-dose armodafinil (gradually titrated to 1,000 mg/d) and achieved remission with good tolerability for 5 years. Recently, she contracted COVID-19 and developed muscular weakness. After a lengthy workup, we became concerned for myopathy as an adverse effect from armodafinil. The patient's dose of armodafinil was significantly reduced and she subsequently became very depressed and functionally disabled before improving again when armodafinil 1,000 mg/d was reinstated. CONCLUSIONS: We propose that some of the negative results seen in research of armodafinil for bipolar depression may be due to the use of low doses (100 to 200 mg/d), and higher doses may be needed for adequate response in treatment-resistant bipolar depression.

[Psychostimulants: An Overview].

Treatment of narcolepsy is based on the need to regulate life rhythms. Psychostimulants such as modafinil, methylphenidate-immediate release, and pemoline are used to treat hypersomnia. A psychosocial approach is considered the mainstay of treatment for attention-deficit/hyperactivity disorder (ADHD), and medication is used to treat moderate or severe ADHD symptoms. Two of the four drugs approved in Japan for ADHD therapy (osmotic-release oral system methylphenidate and lisdexamfetamine dimesylate) are psychostimulants, which are administered via the ADHD proper distribution management system.

[Use of psychoactive substances as a treatment for psychosis]. / Uso de sustancias psicoactivas como tratamiento de la psicosis.

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.

TITLE: Uso de sustancias psicoactivas como tratamiento de la psicosis.Introducción. Los trastornos psicóticos se consideran problemas crónicos de salud mental. Aunque se ha demostrado que estos trastornos pueden presentarse con sintomatologías muy heterogéneas, el tratamiento farmacológico se basa en el uso de antipsicóticos típicos y atípicos, cuyo mecanismo de acción principal es el bloqueo dopaminérgico, limitando su efecto a la mejora de los síntomas positivos, sin mejorar el resto de la sintomatología y presentando una gran cantidad de efectos adversos graves. Por este motivo se están estudiando nuevas dianas terapéuticas distintas al sistema dopaminérgico. El objetivo principal de esta revisión es comprobar si estas sustancias psicoactivas utilizadas en la práctica clínica podrían aportar beneficios adicionales como tratamiento complementario para personas con trastornos psicóticos. Desarrollo. Para esta revisión sistemática se realizó una búsqueda bibliográfica en las bases de datos PsycINFO, Medline, Psicodoc, PubMed y Google Scholar. Se incluyeron 28 artículos en la revisión. Entre los principales resultados encontramos que el cannabidiol es más efectivo para mejorar los síntomas positivos y la psicopatología; el modafinilo, para los síntomas cognitivos, el funcionamiento motor y emocional y la calidad de vida; y la ketamina, para los síntomas negativos. Además, todas las sustancias presentaron un buen perfil de tolerabilidad y seguridad, especialmente en comparación con los antipsicóticos. Conclusión. Con los resultados obtenidos, se abre la posibilidad de tener una guía de actuación para los clínicos/profesionales de la salud sobre el uso del cannabidiol, el modafinilo y la ketamina como tratamiento adyuvante para pacientes con cuadros psicóticos.

Solriamfetol enhances wakefulness and improves cognition and anxiety in a murine model of OSA.

BACKGROUND: Obstructive sleep apnea (OSA) is a chronic condition characterized by intermittent hypoxia (IH). Excessive daytime sleepiness (EDS) is a common consequence of OSA and is associated with cognitive deficits and anxiety. Modafinil (MOD) and Solriamfetol (SOL) are potent wake-promoting agents clinically used to improve wakefulness in OSA patients with EDS. METHODS: Male C57Bl/6J mice were exposed to either IH or room air (RA) controls during the light phase for 16 weeks. Both groups were then randomly assigned to receive once-daily intraperitoneal injections of SOL (200 mg/kg), MOD (200 mg/kg) or vehicle (VEH) for 9 days while continuing IH exposures. Sleep/wake activity was assessed during the dark (active) phase. Novel object recognition (NOR), elevated-plus maze test (EPMT), and forced swim test (FST) were performed before and after drug treatment. RESULTS: IH exposure increased dark phase sleep percentage and reduced wake bouts lengths and induced cognitive deficits and anxiogenic effects. Both SOL and MOD treatments decreased sleep propensity under IH conditions, but only SOL promoted improvements in NOR performance (explicit memory) and reduced anxiety-like behaviors. CONCLUSION: Chronic IH, a hallmark feature of OSA, induces EDS in young adult mice that is ameliorated by both SOL and MOD. SOL, but not MOD, significantly improves IH-induced cognitive deficits and promotes anxiolytic effects. Thus, SOL could potentially benefit OSA patients beyond EDS management.