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Drug and Alcohol Dependence Mar 2024This study tested an adaptive intervention for optimizing abstinence outcomes over phases of treatment for cocaine use disorder using a SMART design. Phase 1 assessed... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Humans; Acceptance and Commitment Therapy; Bayes Theorem; Cocaine-Related Disorders; Treatment Outcome; Cocaine; Modafinil; Polyesters
PubMed: 38309089
DOI: 10.1016/j.drugalcdep.2023.111078 -
Frontiers in Physiology 2023Literature suggests pilots experience fatigue differently. So-called fatigue-resistant or -vulnerable individuals might also respond differently to countermeasures or...
Literature suggests pilots experience fatigue differently. So-called fatigue-resistant or -vulnerable individuals might also respond differently to countermeasures or stimulants. This study, which is part of a larger randomized controlled clinical trial, aims to investigate the effect of caffeine and modafinil on fatigue-resistant and -vulnerable pilots. This study included 32 healthy employees of the Royal Netherlands Air Force, who completed three test days, separated by at least 7 days. After a regular work day, the subjects were randomly administered either 300 mg caffeine, 200 mg modafinil or placebo at midnight. Hereafter the subjects performed the psychomotor vigilance test (PVT), vigilance and tracking test (VigTrack) and Stanford sleepiness scale (SSS) six times until 8 a.m. the next day. Subjects were ranked on the average number of lapses on the PVT during the placebo night and divided into three groups: fatigue-vulnerable (F), -intermediate (FINT) and -resistant (F), with 11, 10 and 11 subjects in each group, respectively. Area under the curve (AUC) of the PVT, VigTrack and SSS during the test nights were calculated, which were used in univariate factorial analysis of variance (ANOVA). Tukey's HSD tests were used to differentiate between the groups. A significant effect of treatment was found in the ANOVA of both PVT parameters, VigTrack mean reaction time and SSS. There was a statistically significant effect of fatigue group on all PVT parameters and VigTrack mean percentage omissions, where F and F scored better than F. There was a significant interaction effect between treatment and fatigue group for PVT number of lapses. This is congruent for the AUC analyses in which for all parameters (except for the SSS) the performance of the F group was consistently worse than that of the F and F groups. This study demonstrates that the performance of individuals with different fatigue tolerances are differently affected by simulants after a limited period of sleep deprivation. The classification of fatigue tolerance through PVT lapses when sleep deprived seems to be able to predict this.
PubMed: 38260091
DOI: 10.3389/fphys.2023.1303758 -
International Journal of Molecular... Jan 2024Children with fetal alcohol spectrum disorders (FASDs) demonstrate deficits in social functioning that contribute to early withdrawal from school and delinquency, as...
Children with fetal alcohol spectrum disorders (FASDs) demonstrate deficits in social functioning that contribute to early withdrawal from school and delinquency, as well as the development of anxiety and depression. Dopamine is involved in reward, motivation, and social behavior. Thus, we evaluated whether neonatal ethanol exposure (in an animal model of FASDs) has an impact on social recognition memory using the three-chamber social novelty discrimination test during early and middle adolescence in male and female rats, and whether the modafinil analog, the novel atypical dopamine reuptake inhibitor CE-123, can modify this effect. Our study shows that male and female rats neonatally exposed to ethanol exhibited sex- and age-dependent deficits in social novelty discrimination in early (male) and middle (female) adolescence. These deficits were specific to the social domain and not simply due to more general deficits in learning and memory because these animals did not exhibit changes in short-term recognition memory in the novel object recognition task. Furthermore, early-adolescent male rats that were neonatally exposed to ethanol did not show changes in the anxiety index but demonstrated an increase in locomotor activity. Chronic treatment with CE-123, however, prevented the appearance of these social deficits. In the hippocampus of adolescent rats, CE-123 increased BDNF and decreased its signal transduction TrkB receptor expression level in ethanol-exposed animals during development, suggesting an increase in neuroplasticity. Thus, selective dopamine reuptake inhibitors, such as CE-123, represent interesting drug candidates for the treatment of deficits in social behavior in adolescent individuals with FASDs.
Topics: Humans; Adolescent; Child; Pregnancy; Female; Male; Animals; Rats; Social Interaction; Ethanol; Fetal Alcohol Spectrum Disorders; Dopamine Uptake Inhibitors; Dopamine; Benzhydryl Compounds
PubMed: 38256113
DOI: 10.3390/ijms25021041 -
Drug and Alcohol Dependence Feb 2024Identifying co-occurring mental disorders and elevated risk is vital for optimization of healthcare processes. In this study, we will use DeepBiomarker2, an updated...
Prediction of adverse events risk in patients with comorbid post-traumatic stress disorder and alcohol use disorder using electronic medical records by deep learning models.
BACKGROUND
Identifying co-occurring mental disorders and elevated risk is vital for optimization of healthcare processes. In this study, we will use DeepBiomarker2, an updated version of our deep learning model to predict the adverse events among patients with comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD), a high-risk population.
METHODS
We analyzed electronic medical records of 5565 patients from University of Pittsburgh Medical Center to predict adverse events (opioid use disorder, suicide related events, depression, and death) within 3 months at any encounter after the diagnosis of PTSD+AUD by using DeepBiomarker2. We integrated multimodal information including: lab tests, medications, co-morbidities, individual and neighborhood level social determinants of health (SDoH), psychotherapy and veteran data.
RESULTS
DeepBiomarker2 achieved an area under the receiver operator curve (AUROC) of 0.94 on the prediction of adverse events among those PTSD+AUD patients. Medications such as vilazodone, dronabinol, tenofovir, suvorexant, modafinil, and lamivudine showed potential for risk reduction. SDoH parameters such as cognitive behavioral therapy and trauma focused psychotherapy lowered risk while active veteran status, income segregation, limited access to parks and greenery, low Gini index, limited English-speaking capacity, and younger patients increased risk.
CONCLUSIONS
Our improved version of DeepBiomarker2 demonstrated its capability of predicting multiple adverse event risk with high accuracy and identifying potential risk and beneficial factors.
Topics: Humans; Stress Disorders, Post-Traumatic; Alcoholism; Electronic Health Records; Deep Learning; Comorbidity
PubMed: 38217979
DOI: 10.1016/j.drugalcdep.2023.111066 -
Sleep May 2024Narcolepsy type 2 (NT2) is an understudied central disorder of hypersomnolence sharing some similarities with narcolepsy type 1 and idiopathic hypersomnia (IH). We...
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 ± 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 ± 4.1, 5.3 ± 6.7, and 4.1 ± 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.
Topics: Humans; Narcolepsy; Male; Female; Adult; Severity of Illness Index; Idiopathic Hypersomnia; Surveys and Questionnaires; Disorders of Excessive Somnolence; Hallucinations; Middle Aged; Modafinil; Young Adult; Sleep Paralysis; Self Report; Wakefulness-Promoting Agents
PubMed: 38197577
DOI: 10.1093/sleep/zsad323 -
Clinical Gastroenterology and... Jan 2024Fatigue is highly prevalent in patients with IBD, affecting 72% of patients with active inflammatory bowel disease (IBD) and 47% in remission, and is associated with...
Fatigue is highly prevalent in patients with IBD, affecting 72% of patients with active inflammatory bowel disease (IBD) and 47% in remission, and is associated with poor quality of life and significantly wider costs. However, understanding the mechanisms of IBD fatigue remains limited, as reflected in a lack of effective treatments..
PubMed: 38191015
DOI: 10.1016/j.cgh.2023.12.030 -
Neurology India 2023There is scarce literature on functional neuroimaging data in Kleine-Levin syndrome. The current case report presents the electrical and metabolic status of cortical...
There is scarce literature on functional neuroimaging data in Kleine-Levin syndrome. The current case report presents the electrical and metabolic status of cortical activity utilizing functional near-infrared spectroscopy (fNIRS) and quantitative electroencephalography (qEEG) before and after treatment of symptomatic phase of illness with modafinil.
Topics: Humans; Kleine-Levin Syndrome; Spectroscopy, Near-Infrared; Electroencephalography; Modafinil
PubMed: 38174469
DOI: 10.4103/0028-3886.391382 -
Acta Psychiatrica Scandinavica Dec 2023In recent years, safety concerns about modafinil exposure during pregnancy have emerged. In particular, increased risks for major congenital anomalies (MCA) and impaired...
Effects of maternal modafinil treatment on fetal development and neonatal growth parameters - a multicenter case series of the European Network of Teratology Information Services (ENTIS).
OBJECTIVE
In recent years, safety concerns about modafinil exposure during pregnancy have emerged. In particular, increased risks for major congenital anomalies (MCA) and impaired fetal growth were reported, although study results were conflicting. Our investigation aims to examine previously reported safety signals.
METHOD
Multicenter case series based on data from 18 Teratology Information Services from 12 countries. Modafinil exposed pregnancies with an estimated date of birth before August 2019 were included in this study. For prospectively ascertained pregnancies, cumulative incidences of pregnancy outcomes, rate of nonchromosomal MCA in first trimester exposed pregnancies and percentiles of neonatal/infant weight and head circumference (HC) were calculated. Potential dose-dependent effects on fetal growth were explored by linear regression models. Retrospectively ascertained cases were screened for pattern of MCA and other adverse events.
RESULTS
One hundred and seventy-five prospectively ascertained cases were included, of which 173 were exposed at least during the first trimester. Cumulative incidences for live birth, spontaneous abortion and elective termination of pregnancy were 76.9% (95% CI, 68.0%-84.8%), 9.3% (95% CI, 5.0%-16.9%), and 13.9% (95% CI, 8.1%-23.1%), respectively. Nonchromosomal MCA was present in 3/150 live births, corresponding to an MCA rate of 2.0% (95%CI, 0.6%-6.1%), none were reported in pregnancy losses. Compared to reference standards, birth weight (BW) tended to be lower and neonatal HC to be smaller in exposed newborns (data available for 144 and 73 of 153 live births, respectively). In nonadjusted linear regression models, each 100 mg increase of average dosage per pregnancy day was associated with a decrease in standard deviation score (SDS) of -0.28 SDS (95% CI, -0.45 to -0.10) for BW and of -0.28 SDS (95% CI, -0.56 to 0.01) for HC. Screening of 22 retrospectively reported cases did not reveal any specific pattern of MCA or other adverse outcomes.
CONCLUSION
The results do not indicate an increased risk of MCA after in utero exposure to modafinil, but a tendency toward lower BW and reduced neonatal HC. However, these findings should be regarded as preliminary. Until further studies allow for a definite conclusion, modafinil should not be used during pregnancy.
PubMed: 38110225
DOI: 10.1111/acps.13643 -
Clinical Pharmacology and Therapeutics Feb 2024
PubMed: 38108195
DOI: 10.1002/cpt.3142 -
Pediatric Research Apr 2024The aim of this scoping review is to examine the extent and depth of the literature on effects of central nervous system (CNS) stimulant medications on physical function... (Review)
Review
The aim of this scoping review is to examine the extent and depth of the literature on effects of central nervous system (CNS) stimulant medications on physical function in children with cerebral palsy (CP). A systematic search for relevant peer-reviewed studies was conducted of PubMed, CINAHL, Cochrane, SPORTDiscus, Embase, & Scopus (January 2002 & August 2022). We included studies that examined the effects of CNS stimulants on physical function in children with CP. Four studies met our selection criteria. All studies explored the effect of Modafinil on physical function outcomes. Three studies of the four included studies reported positive effects of Modafinil on spasticity, motor performance, and gait, whereas one study reported no significant effects of Modafinil. Our findings suggest that there is very low-quality evidence that suggests that Modafinil may enhance physical improvements in body structure and function, including reduction in spasticity and improvements in gait parameters. IMPACT: Central nervous system stimulants were examined for efficacy on physical function and spasticity in children with cerebral palsy. The evidence on the effects of central nervous system stimulants on physical function in children with CP is limited and inconsistent.
Topics: Child; Humans; Central Nervous System Stimulants; Cerebral Palsy; Gait; Modafinil; Muscle Spasticity; Treatment Outcome
PubMed: 38071277
DOI: 10.1038/s41390-023-02933-3