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Journal of Sleep Research Feb 2023Sleep restriction therapy (SRT) is an effective stand-alone behavioural intervention for insomnia disorder. However, its daytime side effects, particularly sleepiness,... (Clinical Trial)
Clinical Trial
Armodafinil to reduce the sleepiness related side-effects of sleep restriction therapy being used to treat insomnia disorder: An open label clinical trial pilot study compared with historical controls.
Sleep restriction therapy (SRT) is an effective stand-alone behavioural intervention for insomnia disorder. However, its daytime side effects, particularly sleepiness, may be troubling for patients and/or may be a necessary part of the patient's treatment journey. This pilot trial aims to explore the potential benefit of armodafinil, a wakefulness promoter. Patients were treated with SRT with open label adjunctive armodafinil (150 mg/day). Thirty-three patients from previous studies that have undergone exactly the same SRT intervention acted as controls. The primary outcome measure was the insomnia severity index (ISI), and secondary outcomes were the Epworth sleepiness scale, sleep restriction adherence scale (SRAS), and safety from baseline through to 12 weeks. We recruited 25 patients into the trial. Data for the primary end point (ISI at 12 weeks) was available for 20 of the participants. The baseline insomnia severity index was 20.2 (SD 3.3) and decreased to 9.1 (SE 1.1), with no change, to 10.2 and 11.2 at weeks 6 and 12 respectively (all p > 0.05 compared with baseline). The insomnia severity index values for armodafinil patients were statistically inferior to historical controls at the primary time point of 12 weeks (11.2 vs. 6.7, p < 0.01). Sleep restriction therapy plus armodafinil treatment was associated with frequent minor side effects but was generally safe and acceptable to patients. Sleep restriction therapy was associated with a robust clinical response in the insomnia severity index values for insomnia patients. Based upon historical control data, armodafinil does not appear to have beneficial adjunctive effects in addition to sleep restriction therapy alone.
Topics: Humans; Modafinil; Pilot Projects; Sleep Initiation and Maintenance Disorders; Sleepiness; Treatment Outcome; Wakefulness
PubMed: 36003019
DOI: 10.1111/jsr.13699 -
Current Addiction Reports 2022This review summarizes recent clinical trial research on pharmacological treatments for substance use disorders, with a specific focus on agents with potential abuse... (Review)
Review
PURPOSE OF REVIEW
This review summarizes recent clinical trial research on pharmacological treatments for substance use disorders, with a specific focus on agents with potential abuse liability.
RECENT FINDINGS
Pharmacological treatments for substance use disorders may include gabapentinoids, baclofen, modafinil, ketamine, cannabinoids, gamma-hydroxybutyrate, and psychedelics. Gabapentinoids may decrease negative subjective effects of withdrawal in alcohol and cannabis use disorders. Cannabinoids similarly appear to decrease use and withdrawal symptoms in cannabis use disorder, while research shows stimulant medications may reduce cravings and increase abstinence in cocaine use disorder. Ketamine and psychedelics may help treat multiple substance use disorders. Ketamine may reduce withdrawal symptoms, promote abstinence, and diminish cravings in alcohol and cocaine use disorders and psychedelics may promote remission, decrease use, and reduce cravings in alcohol and opioid use disorders.
SUMMARY
Regardless of current regulatory approval statuses and potentials for abuse, multiple agents should not be dismissed prematurely as possible treatments for substance use disorders. However, further clinical research is needed before effective implementation can begin in practice.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40429-022-00432-9.
PubMed: 35990796
DOI: 10.1007/s40429-022-00432-9 -
Psychiatry Research Oct 2022Novelty seeking is a tendency to approach new situations, putatively driven by the brain's catecholaminergic system. It is traditionally measured via self-report, but a... (Randomized Controlled Trial)
Randomized Controlled Trial
Novelty seeking is a tendency to approach new situations, putatively driven by the brain's catecholaminergic system. It is traditionally measured via self-report, but a laboratory-based paradigm, the human Behavioral Pattern Monitor (hBPM), quantifies behavior in a novel environment and has utility in cross-species studies of neuropsychiatric disorders. Our primary aim assessed whether self-reported novelty-seeking traits were associated with novelty-seeking behavior in the hBPM. An existing sample of 106 volunteers were categorized as high vs. low novelty seekers using the Temperament and Character Inventory (TCI). Subjects had been randomized to one dose of amphetamine (10 or 20 mg) or modafinil (200 or 400 mg), allowing us to explore whether a pharmacological catecholamine challenge further enhanced novelty-seeking behavior. High TCI novelty-seekers had more hBPM motor activity and novel object interactions. The exploratory analyses, although limited by low power, suggested that amphetamine and modafinil did not markedly moderate novelty-seeking traits. The hBPM demonstrates construct validity as a lab-based measure of novelty seeking and thus useful in translational studies of neuropsychiatric conditions and treatment options. Further research may illuminate whether a biological predisposition towards higher catecholaminergic activity, combined with the novelty-seeking trait, may increase propensity for risky and addictive behaviors.
Topics: Character; Exploratory Behavior; Humans; Modafinil; Temperament
PubMed: 35964417
DOI: 10.1016/j.psychres.2022.114776 -
Cureus Aug 2022[This corrects the article DOI: 10.7759/cureus.27287.].
[This corrects the article DOI: 10.7759/cureus.27287.].
PubMed: 38348022
DOI: 10.7759/cureus.c69 -
Cureus Jun 2022Introductionː Postoperative cognitive dysfunction has long-term consequences of increased mortality, loss of autonomy, and prolonged hospitalization. We sought to...
Introductionː Postoperative cognitive dysfunction has long-term consequences of increased mortality, loss of autonomy, and prolonged hospitalization. We sought to determine whether exposing patients to modafinil may attenuate or prevent this devastating syndrome from affecting the elderly postoperatively. Methodsː Adults aged 65 and older and American Society of Anesthesiologists (ASA) I-III physical status scheduled for elective noncardiac/non-neurosurgical surgery were included. Subjects were tested with the Trail Making Test (TMT) and Rey Auditory Visual Learning Test (RAVLT) preoperatively as well as in the immediate postoperative period, at 1 week, and at 3 months. After baseline testing, patients were randomized into three groups: 0) placebo pre and post-procedure; 1) modafinil only pre-procedure and placebo post-procedure; and 2) modafinil pre and post-procedure. A nonsurgical control group was also utilized. Resultsː Seventy-six subjects completed the trial 3 months post-surgery. The baseline RAVLT obtained was analyzed with 2-way ANOVA with repeated measures and showed improvement in learning in all groups (p = 0.03). At 1-week post-surgery, Group 0 subjects demonstrated no learning improvement in the RAVLT. However, there was a significant improvement in learning in both groups that received modafinil (p<0.01), and in the nonsurgical controls (p<0.01). This learning benefit normalized at 3 months. Conclusionː In this prospective, double-blind, placebo-controlled trial, we found that patients who received modafinil showed improvement in the RAVLT at 1 week. However, this learning benefit normalized at 3 months. Further study should examine dose effect, timing, and route of administration to determine if the effect can be enhanced and if in fact, wakefulness is improved post-surgically.
PubMed: 35891830
DOI: 10.7759/cureus.26204 -
Metabolites Jun 2022Armodafinil, the R enantiomer of modafinil, was approved in 2007 by the US Food and Drug Administration as a wake-promoting agent for excessive sleepiness treatment. Due...
Armodafinil, the R enantiomer of modafinil, was approved in 2007 by the US Food and Drug Administration as a wake-promoting agent for excessive sleepiness treatment. Due to its abuse by students and athletes, there is a need of its quantification. Quantitative analysis by liquid chromatography-mass spectrometry, however, though very common and sensitive, frequently cannot be performed without isotopically labeled standards which usually have to be specially synthesized. Here we reported our investigation on the preparation of deuterated standard of armodafinil based on the simple and inexpensive hydrogen-deuterium exchange reaction at the carbon centers. The obtained results clearly indicate the possibility of introduction of three deuterons into the armodafinil molecule. The introduced deuterons do not undergo back exchange under neutral and acidic conditions. Moreover, the deuterated and non-deuterated armodafinil isotopologues revealed co-elution during the chromatographic analysis. The ability to control the degree of deuteration using different reaction conditions was determined. The proposed method of deuterated armodafinil standard preparation is rapid, cost-efficient and may be successfully used in its quantitative analysis by LC-MS.
PubMed: 35888702
DOI: 10.3390/metabo12070578 -
Biomolecules Jun 2022Dopamine (DA), the most abundant human brain catecholaminergic neurotransmitter, modulates key behavioral and neurological processes in young and senescent brains,...
Dopamine (DA), the most abundant human brain catecholaminergic neurotransmitter, modulates key behavioral and neurological processes in young and senescent brains, including motricity, sleep, attention, emotion, learning and memory, and social and reward-seeking behaviors. The DA transporter (DAT) regulates transsynaptic DA levels, influencing all these processes. Compounds targeting DAT (e.g., cocaine and amphetamines) were historically used to shape mood and cognition, but these substances typically lead to severe negative side effects (tolerance, abuse, addiction, and dependence). DA/DAT signaling dysfunctions are associated with neuropsychiatric and progressive brain disorders, including Parkinson's and Alzheimer diseases, drug addiction and dementia, resulting in devastating personal and familial concerns and high socioeconomic costs worldwide. The development of low-side-effect, new/selective medicaments with reduced abuse-liability and which ameliorate DA/DAT-related dysfunctions is therefore crucial in the fields of medicine and healthcare. Using the rat as experimental animal model, the present work describes the synthesis and pharmacological profile of ()-MK-26, a new modafinil analogue with markedly improved potency and selectivity for DAT over parent drug. Ex vivo electrophysiology revealed significantly augmented hippocampal long-term synaptic potentiation upon acute, intraperitoneally delivered ()-MK-26 treatment, whereas in vivo experiments in the hole-board test showed only lesser effects on reference memory performance in aged rats. However, in effort-related FR5/chow and PROG/chow feeding choice experiments, ()-MK-26 treatment reversed the depression-like behavior induced by the dopamine-depleting drug tetrabenazine (TBZ) and increased the selection of high-effort alternatives. Moreover, in in vivo microdialysis experiments, ()-MK-26 significantly increased extracellular DA levels in the prefrontal cortex and in nucleus accumbens core and shell. These studies highlight ()-MK-26 as a potent enhancer of transsynaptic DA and promoter of synaptic plasticity, with predominant beneficial effects on effort-related behaviors, thus proposing therapeutic potentials for ()-MK-26 in the treatment of low-effort exertion and motivational dysfunctions characteristic of depression and aging-related disorders.
Topics: Animals; Dopamine; Dopamine Plasma Membrane Transport Proteins; Hippocampus; Humans; Motivation; Neuronal Plasticity; Rats
PubMed: 35883437
DOI: 10.3390/biom12070881 -
SAGE Open Medical Case Reports 2022Kleine-Levin syndrome (KLS) is an extremely rare relapsing-remitting neuropsychiatric condition characterized by recurrent incidents of major hypersomnolence along with...
Kleine-Levin syndrome (KLS) is an extremely rare relapsing-remitting neuropsychiatric condition characterized by recurrent incidents of major hypersomnolence along with hyperphagia, hypersexual behavior, and mood or cognitive disturbances alternating with asymptomatic periods. Here, we present a case of a young male chiefly presenting with recurring episodes of acute onset behavioral changes. The patient's episodes were characterized by repetitive incidents of prolonged sleep for more than 20 h, followed by social withdrawal and apathy. He was diagnosed with KLS because of the periodic patterns of hypersomnolence accompanied by other cognitive and mood disturbances and lacked characteristics of central hypersomnolence disorders or atypical depression. There are varying success rates among medications such as lithium, stimulants such as modafinil, antiepileptics such as carbamazepine and valproate. Similarly, the use of antidepressants such as tricyclic agents and selective serotonin reuptake inhibitors has largely been negative. Our case report addresses a patient with KLS who was successfully treated with 20 mg of Escitalopram.
PubMed: 35847426
DOI: 10.1177/2050313X221110985 -
Health Psychology Research 2022Narcolepsy is a debilitating sleep disorder that presents with excessive daytime sleepiness (EDS) and cataplexy, which is a sudden paralysis of muscle tone triggered by... (Review)
Review
Narcolepsy is a debilitating sleep disorder that presents with excessive daytime sleepiness (EDS) and cataplexy, which is a sudden paralysis of muscle tone triggered by strong emotions such as laughing. It is also associated with many other disorders, including psychiatric disorders, neurologic illnesses, and medication side effects. Common causes of delayed and incorrect diagnoses of these conditions include lack of physician familiarity with narcolepsy symptoms and comorbidities which mask narcolepsy signs and symptoms. Current pharmacologic therapies include Modafinil and Armodafinil for EDS and sodium oxybate for cataplexy. This review discusses the epidemiology, pathophysiology, risk factors, presentation, treatment of narcolepsy, and the role of a novel drug, Pitolisant, in the treatment of EDS in adults with narcolepsy. Pitolisant is a histamine-3 receptor (H3R), competitive antagonist, and inverse agonist, acting through the histamine system to regulate wakefulness. It is a novel drug approved in August 2019 by the FDA, is not classified as a controlled substance, and is approved for use in Europe and the United States to treat EDS and cataplexy in narcolepsy. Recent phase II and III trials have shown that Pitolisant helps reduce the ESS score and cataplexy. In summary, based on comparative studies, recent evidence has shown that Pitolisant is non-inferior to Modafinil in the treatment of EDS but superior to Modafinil in reducing cataplexy.
PubMed: 35774905
DOI: 10.52965/001c.34222 -
Neuropsychiatric Disease and Treatment 2022The acute phase of Coronavirus disease-19 (COVID-19) is well known. However, there is now an increasing number of patients suffering from the post-acute sequelae of...
BACKGROUND
The acute phase of Coronavirus disease-19 (COVID-19) is well known. However, there is now an increasing number of patients suffering from the post-acute sequelae of COVID-19 (PASC Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms and that last for at least 2 months and cannot be explained by an alternative diagnosis), including neuropsychiatric symptoms. The purpose of this report is to describe the sociodemographic, diagnostic and treatment characteristics of patients evaluated in an outpatient psychiatric setting for PASC.
METHODS
A retrospective review of 30 individuals with documented COVID-19 illness treated at a university hospital-based Post-COVID-19 Recovery Program were referred to an outpatient psychiatric department for consultation and treatment from December 2020 to July 2021. All individuals complained of neuropsychiatric symptoms including anxiety, depression, fatigue and cognitive problems. Data on sociodemographic characteristics, psychiatric diagnosis, prominent psychological themes and treatment prescribed were described and, where applicable, analyzed with SPSS software.
RESULTS
The study population consisted of patients between 25 and 82 years old, with a predominance of women between 46 and 60 years. Approximately half of the patient population had a primary diagnosis of major depressive disorder, often combined with prominent anxiety. Over two-thirds of the patient population reported a combination of depression, fatigue and cognitive complaints, predominantly memory and slowed processing speed. Prominent stressors and psychological themes included social and occupational decline, isolation, lack of empathy and understanding from family, friends and employers, and apprehension about future ability to return to their baseline level of function. Treatments recommended included individual and group psychotherapy, medication and cognitive rehabilitation. Modafinil and antidepressants, often in combination, were the most commonly used medications, intended to target the pervasive fatigue, depressive, and anxiety these individuals were facing.
CONCLUSION
Clinical experience from this patient population underscored the significant medical, emotional, neurocognitive and functional sequelae of PASC. Management of these individuals requires a collaborative approach with the availability of psychotherapeutic interventions, pharmacologic treatment, neurocognitive assessment and remediation to address these symptoms.
PubMed: 35761861
DOI: 10.2147/NDT.S357262