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Benzodiazepine (BDZ) addiction is a widespread and multifaceted phenomenon. For many patients, especially females, the concomitant use of other drugs also increases their risk of QTc prolongation, possibly leading to complications such as seizures and even sudden death. However, the relationship between BDZ use and QTc prolongation is currently unclear. The present study aims to examine patterns of polysubstance use among a sample of Italian adults with BDZ dependence in relation with their QTc prolongation risk. We used Latent Class Analysis (LCA) on data collected from 251 inpatients of the Addiction Medicine Unit in Verona to group patients into three classes according to their substance use and their QTc prolongation risk. Results showed no significant relationship between QTc prolongation and BDZ use in any of the classes considered. We conclude that BDZs, even if used long-term and at high dosages, can be considered safe in terms of cardiovascular complications for patients.
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Síndrome de QT Prolongado , Adulto , Femenino , Humanos , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/epidemiología , Benzodiazepinas/efectos adversos , Análisis de Clases Latentes , Electrocardiografía , Factores de RiesgoRESUMEN
BACKGROUND: Empirical evidence has shown that virtual reality (VR) scenarios can increase the effects of relaxation techniques, reducing anxiety by enabling people to experience emotional conditions in more vivid settings. OBJECTIVE: This pilot randomized controlled study aims to investigate whether the progressive muscle relaxation technique (PMRT) associated with a personalized scenario in VR promotes psychological well-being and facilitates the recall of relaxing images more than the standard complementary intervention that involves the integration of PMRT and guided imagery (GI). METHODS: On the basis of a longitudinal, between-subject design, 72 university students were randomly exposed to one of two experimental conditions: (1) standard complementary procedure (PMRT and GI exposure) and (2) experimental procedure (PMRT and personalized VR exposure). Individuals were assessed by a therapist before and after 7 training sessions based on measures investigating anxiety, depression, quality of life, coping strategies, sense of presence, engagement, and side effects related to VR exposure. Heart rate data were also collected. RESULTS: Differences in changes between the 2 groups after the in vivo PMRT session conducted by the psychotherapist (T1) were statistically significant for state anxiety (F1,67=30.56; P<.001) and heart rate (F1,67=4.87; P=.01). Individuals in the VR group obtained lower scores both before (t67=-2.63; P=.01; Cohen d=0.91) and after (t67=-7.23; P<.001; Cohen d=2.45) the relaxation session when it was self-administered by participants (T2). A significant reduction in perceived state anxiety at T1 and T2 was observed for both groups (P<.001). After the VR experience, individuals reported feeling higher engagement in the experience than what was mentioned by participants in the GI group (F1,67=2.85; P=.03; ηp2=0.15), and they experienced the environment as more realistic (F1,67=4.38; P=.003; ηp2=0.21). No differences between groups regarding sense of presence were found (F1,67=1.99; P=.11; ηp2=0.11). Individuals exposed before to the VR scenario (T1) referred to perceiving the scenario recalled in-imagination at T2 as more realistic than what those in the GI group experienced (F1,67=3.21; P=.02; ηp2=0.12). The VR group had lower trait anxiety levels than the GI group after the relaxation session during session 7 (T2; t67=-2.43; P=.02). CONCLUSIONS: Personalized relaxing VR scenarios can contribute to improving relaxation and decreasing anxiety when integrated with PMRT as a complementary relaxation method. TRIAL REGISTRATION: ClinicalTrials.gov NCT05478941; https://classic.clinicaltrials.gov/ct2/show/NCT05478941. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/44183.
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Entrenamiento Autogénico , Imágenes en Psicoterapia , Humanos , Proyectos Piloto , Calidad de Vida , Terapia por RelajaciónRESUMEN
Methadone is a chiral synthetic opioid primarily used to treat heroin and prescription-opioid addiction: the (R)-enantiomer (Levomethadone) activates the µ-opioid receptor more potently than the (S)-enantiomer, which is a more potent blocker of the hERG potassium channels, resulting in QTc prolongation. The purpose of this retrospective study was to assess the effect of methadone on the QTc interval and to investigate the benefits of Levomethadone. The electrocardiograms of 165 patients taking methadone at various dosages and for different periods of time were examined: the QTc value was manually measured and then adjusted using Bazett's formula. Data analysis revealed a linear association between the dosage of methadone and QTc length; no correlation was found between the QTc value and gender, age, or duration of therapy. In total, 14% of the sample (23 patients) showed a prolongation of the QTc interval (>470 ms in males and >480 ms in females); 10 of the 23 patients with QTc elongation underwent a change of therapy from Methadone to Levomethadone-in 90% of these patients, a normalization in the QTc length was established. This study confirmed the role of methadone, specifically its dosage, in QTc prolongation and the efficiency of Levomethadone as an adequate therapeutic substitute in these circumstances. This study validates the importance of careful electrocardiographic monitoring in methadone-treated patients.
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BACKGROUND: Virtual reality (VR) is an innovative tool that can facilitate exposure to either stressful or relaxing stimuli and enables individuals who have difficulties visualizing scenes to be involved in a more realistic sensorimotor experience. It also facilitates multisensory stimulation, a sense of presence, and achievement of relaxation. VR scenarios representing visual and auditory elements of natural relaxing environments can facilitate the learning of relaxation techniques such as the progressive muscle relaxation technique (PMRT). A complementary standardized technique deployed to reduce anxiety symptoms is the integration of PMRT and guided imagery (GI). Exposure to a pleasant imaginary environment helps the establishment of an association between a relaxing scenario and the relaxation technique, consequently promoting relaxation. Empirical evidence has shown that VR scenarios can increase the effects of relaxation techniques by enabling people to experience emotional conditions in more vivid settings. OBJECTIVE: The main aim of this pilot study protocol is to investigate the impact on state anxiety of PMRT, associated with a personalized relaxing scenario in VR, and the role of VR scenarios in facilitating the recall of relaxing images and a sense of presence. A secondary aim is to understand if relaxing sessions administered via Zoom are more effective for managing anxiety and stress than a procedural setting based on audio-track guidance. METHODS: Based on a longitudinal, between-subject design, 108 university students will be randomly exposed to one of three experimental conditions: (1) PMRT via Zoom and GI exposure, (2) PMRT via Zoom and personalized VR exposure, and (3) PMRT based on audio-track guidance and personalized VR exposure. Individuals are assessed before and after 7 training sessions based on self-report questionnaires investigating anxiety, depression, quality of life, coping strategies, sense of presence, engagement, and side effects related to VR exposure. Heart rate data are also detected by an Mi Band 2 sensor. RESULTS: The experimental procedure is ongoing. In this paper, preliminary data from a sample of 40 participants will be illustrated. The experimental phase is expected to conclude in May 2023, and the final results of the research will be presented in June 2023. CONCLUSIONS: The results of this study will help shape the experimental design to apply it on a subsequent randomized controlled trial, also considering clinical samples. This work is expected to measure whether VR is a more engaging and helpful technique in promoting relaxation and decreasing anxiety levels than GI, by making the visualization process easier and by helping people to face more realistic sensory experiences. Assessing the efficacy of the PMRT in alternative delivery modes may extend its applications, especially in situations where the standard procedure is more challenging to be administered. To our knowledge, no equivalent study has been published so far on this matter. TRIAL REGISTRATION: ClinicalTrials.gov NCT05478941; https://clinicaltrials.gov/ct2/show/NCT05478941. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44183.
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One of the core features of hoarding is a significant resistance to discarding objects, which is fueled by dysfunctional beliefs and unwarranted negative emotions that hoarders tend to feel when disposing of their possessions. To our knowledge, longitudinal studies investigating the psychological effects that people who hoard experience after separating from their valuable possessions have yet to be conducted. Our study's principal aim was to explore psychological processes that individuals with high hoarding features (n = 53; 49.1%) and individuals with low hoarding features (n = 55; 50.9%) experienced when they had to separate from a valuable possession. To do this, we evaluated participants' thoughts and feelings at several time points after they had to leave a valuable object at the University laboratory (evaluations were specifically conducted at baseline, during the week, and at the end of the week). To investigate hoarding and anxiety, as well as depressive, obsessive-compulsive, and emotional processes-related features, a mixed-method approach was employed involving self-report questionnaires, ad hoc surveys, and a daily self-monitoring schedule. Our findings showed that compared to participants with low hoarding features, participants with high hoarding traits: 1) scored higher for anxiety sensitivity, distress tolerance, and emotional dysregulation; 2) reported having more negative emotions when leaving their object; 3) had more intrusive object-related beliefs; and 4) experienced a higher frequency of negative emotions as well as a higher level of distress during the week. Both groups experienced more negative emotions in the first part of the week, which decreased as the time at which participants could receive their object back drew closer. Finally, dysfunctional beliefs about leaving a personal object (Saving Cognitions Inventory), sensitivity to anxiety (Anxiety Sensitivity Index-3), and distress tolerance (Distress Tolerance Scale) contributed to the level of discomfort that participants with higher hoarding scores reported when they had to leave their possession. These results highlight the relevance of emotional processes in the hoarding disorder framework as well as underscore the importance of assessing and treating them in clinical settings.
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Trastorno de Acumulación , Acaparamiento , Humanos , Emociones/fisiología , Ansiedad/psicología , Trastornos de Ansiedad/psicología , Cognición , Acaparamiento/psicologíaRESUMEN
Zolpidem is indicated in cases of severe insomnia in adults and, as for BDZs, its assumption should be limited to short periods under close medical supervision. Since several drugs cause corrected QT interval (QTc) elongation, the authors investigated whether high daily doses of Zolpidem could cause QTc elongation. The study was conducted in the Addiction Medicine Unit of the G.B. Rossi University Hospital in Verona. The data were collected from hospitalizations carried out between January 2015 and February 2020 and refer to a total of 74 patients, 38 males and 36 females, who were treated for detoxification from high doses of Zolpidem with the "Verona Detox Approach With Flumazenil." One patient out of 74 had QTc elongation (479 ms). The patient was male and took a daily dose of 50 mg of Zolpidem; he did not take concomitant therapies that could cause QTc lengthening. He had no electrolyte alterations, no contemporary or previous intake of barbiturates, heroin, cocaine, THC, alcohol, NMDA or nicotine which could cause an elongation of the QTc interval. The present study highlights the low risk of QTc elongation due to high dosages of Zolpidem; however, if, on one hand, we can affirm that Zolpidem is a safe drug, on the other, the widespread use of high dosages of this drug for prolonged periods of time is problematic and worrying.
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Nicotine addiction is a widespread, worldwide epidemic, causing six million deaths per year. A large variety of treatments for smoking cessation are currently available, including Cytisine, which is a promising drug due to its low cost and high safety levels. Notwithstanding the important amount of research on tobacco addiction treatments, smoking remains one of the most difficult substance use disorders to treat, probably also due to the fact that pharmacological treatment often overlooks other maintaining factors in this addiction, such as sensory impact and cue reactivity. To address this gap in both treatment protocols and scientific literature, we propose a study protocol in which we will compare the effects of combining Cytisine with Nirdosh, a herbal tobacco substitute, to Cytisine only in two groups of patients (C + N and C) who will also undergo exposure to four different virtual reality settings that will assess the importance of environmental cues. We will further assess mood and craving in the two samples, and include a control group taken from the general population. We expect the C + N group to report a more positive mood and a lower sensitivity to tobacco-related environmental cues.
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Benzodiazepine (BDZ) abuse, especially concerning high doses of BDZs, is an impairing substance use disorder (SUD) that is often difficult to treat. Craving and cue reactivity (CR) are two important phenomena that have a prominent role in maintaining addiction and triggering relapses in BDZ abuse; nevertheless, they have rarely been addressed in scientific literature. The present study aims to fill these gaps by implementing a highly innovative virtual reality (VR) design to assess the impact of substance-related environmental cues on BDZ craving, as well as their influence on patients' affective states. Therefore, on one hand, this research will contribute to the assessment of VR feasibility in the study of these phenomena, and, on the other, it will help disentangle the role that CR and craving have on mood and attention, which are equally important factors to consider when treating SUDs. We will recruit a healthy control group and a patient group comprising people seeking treatment for BDZ detoxification. The experimental design will consist of the presentation of three VR scenarios, one neutral, one BDZ-related but without BDZ cues, and another with BDZ cues. The craving will be measured through a virtual analog scale (VAS); the Profile of Mood States (POMS) and Alcohol Attention Scale (AAS) questionnaires in a modified version will also be administered. We will additionally control for VR-induced feelings of sickness by administering the Simulator Sickness Questionnaire (SSQ), and the Presence Questionnaire (PQ) will be used to investigate participants' sense of presence in virtual environments. We expect patients to exhibit higher levels of craving, and that the craving will be higher after exposure to a cue-related virtual environment as compared to a neutral scenario.
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Vaccination against COVID-19 is crucial in the attempt of containing the virus' spread, but facing a viral pathogen with such a high prevalence means that vaccination strategies are facing an unprecedented situation. People that use illicit drugs may have elevated risk of adverse outcomes from COVID-19 given their high prevalence of underlying medical conditions, including respiratory and pulmonary disease, chronic liver disease, cardiovascular and cerebrovascular conditions, diabetes, and compromised immune systems. Despite a widespread distribution on the Italian territory, a large presence of health personnel and a long-standing experience in vaccinations, addiction clinics have yet to be involved in the vaccination campaign against COVID-19. The aim of this study was to investigate the beliefs of drug users attending some Italian addiction clinics, in order to envisage any vaccine administration strategies involving the services themselves. A questionnaire used for the Italian general population to investigate the relative importance of some factors in influencing the propensity to vaccinate against COVID-19, was administrated to drug users in a multicenter survey. The majority of respondents expressed general confidence in vaccines and a good willingness to undergo vaccination. Given strong peer networks, high coverage of treatment and harm reduction interventions, Italian public addiction clinics could play a strategic role in administering the vaccine in this hard-to-reach population, usefully aiding the global campaign against the virus.
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In recent years, many studies have focused on resting-state brain activity, and especially on functional connectivity (FC), an approach that typically describes the statistical interdependence of activity in distant brain regions through specific networks. Our aim was to study the neurophysiological correlates of emotion dysregulation. Therefore, we expected that both the Default Mode Network (DMN), and the Ventral Attention Network (VAN) would have been involved. Indeed, the latter plays a role in the automatic orienting of attention towards biologically salient stimuli and includes key regions for emotion control and modulation. Starting from a community sample of 422 female students, we selected 25 women with high traits of emotion dysregulation (HD group) and 25 with low traits (LD group). They underwent a 64-channel EEG recording during a five-minute resting state with eyes open. Seed-based FC was computed on the EEG Alpha band (8-13 Hz) as a control band, and on EEG Gamma power (30-50 Hz) as the relevant measure. The power within each network and inter-network connectivity (Inter-NC) was also calculated. Analysis of the EEG Gamma band revealed, in the HD group, higher levels of Inter-NC between the VAN and all other resting-state networks as compared with the LD group, while no differences emerged in the Alpha band. Concerning correlations, Alpha power in the VAN was negatively correlated in the HD group with affective lability (ALS-18 questionnaire), both for total score (ρ = -0.52, p FDR < 0.01) and the Depression/Elation subscale) ρ = -0.45, p FDR < 0.05). Consistent with this, in the Gamma band, a positive correlation was found between VAN spectral power and the Depression/Elation subscale of ALS-18, again in the HD group only (ρ = 0.47, p FDR < 0.05). In conclusion, both resting state FC and network power in the VAN were found to be related to high emotion dysregulation, even in our non-clinical sample with high traits. Emotion dysregulation was characterized, in the EEG gamma band, by a VAN strongly connected to all other networks, a result that points, in women prone to emotion dysregulation, to a strong automatic orienting of attention towards their internal state, bodily sensations, and emotionally intense related thoughts.
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Films, compared with emotional static pictures, represent true-to-life dynamic stimuli that are both ecological and effective in inducing an emotional response given the involvement of multimodal stimulation (i.e., visual and auditory systems). We hypothesized that a direct comparison between the two methods would have shown greater efficacy of movies, compared to standardized slides, in eliciting emotions at both subjective and neurophysiological levels. To this end, we compared these two methods of emotional stimulation in a group of 40 young adults (20 females). Electroencephalographic (EEG) Alpha rhythm (8-12 Hz) was recorded from 64 scalp sites while participants watched (in counterbalanced order across participants) two separate blocks of 45 slides and 45 clips. Each block included three groups of 15 validated stimuli classified as Erotic, Neutral and Fear content. Greater self-perceived arousal was found after the presentation of Fear and Erotic video clips compared with the same slide categories. sLORETA analysis showed a different lateralization pattern: slides induced decreased Alpha power (greater activation) in the left secondary visual area (Brodmann Area, BA, 18) to Erotic and Fear compared with the Neutral stimuli. Instead, video clips elicited reduced Alpha in the homologous right secondary visual area (BA 18) again to both Erotic and Fear contents compared with Neutral ones. Comparison of emotional stimuli showed smaller Alpha power to Erotic than to Fear stimuli in the left precuneus/posterior cingulate cortex (BA 7/31) for the slide condition, and in the left superior parietal lobule (BA 7) for the clip condition. This result matched the parallel analysis of the overlapped Mu rhythm (corresponding to the upper Alpha band) and can be interpreted as Mu/Alpha EEG suppression elicited by greater motor action tendency to Erotic (approach motivation) compared to Fear (withdrawal motivation) stimuli. Correlation analysis found lower Alpha in the left middle temporal gyrus (BA 21) associated with greater pleasantness to Erotic slides (r 38 = -0.62, p = 0.009), whereas lower Alpha in the right supramarginal/angular gyrus (BA 40/39) was associated with greater pleasantness to Neutral clips (r 38 = -0.69, p = 0.012). Results point to stronger emotion elicitation of movies vs. slides, but also to a specific involvement of the two hemispheres during emotional processing of slides vs. video clips, with a shift from the left to the right associative visual areas.
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Cytisine is considered to be the oldest medication for smoking cessation and has been used for this purpose in some Eastern/Central European and Central Asian countries for over 50 years. Several sources points towards cytisine's efficacy and effectiveness; it's well tolerated when taken at the recommended dose, and adverse events reported in trials are typically non-serious and self-limiting gastrointestinal and sleep disturbances. We report a suspect case of urticaria during treatment for smoking cessation with cytisine in a woman of 48 years treated for smoking at the Unit of Addiction Medicine, Department of Internal Medicine, Hospital Trust of Verona, Italy. The therapeutic protocol of cytisine that was used is of the "inductive" type; it consists in gradually increasing the daily capsules taken, with a parallel reduction in the number of cigarettes smoked until complete cessation between the fifth and ninth day of therapy (quit day) The number of capsules taken is then gradually reduced. She was treated for the firsts three days with betamethasone 1 mg/die, on the advice of her general practitioner, and suspended Cytisine. A week later the patient showed signs of recovery.
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Cese del Hábito de Fumar , Urticaria , Alcaloides , Azocinas , Cápsulas , Femenino , Humanos , Quinolizinas , Urticaria/inducido químicamente , Vareniclina/uso terapéuticoRESUMEN
Cognitive behavioral therapy (CBT) is the most successful protocol in gambling disorder (GD) treatment. However, it presents some weaknesses, especially concerning relapse prevention (RP). RP is one of the most important therapeutic steps, aiming at managing cravings and to avoid future relapse increasing perceived self-efficacy. Encouraging results come from the blending of psychotherapy and virtual reality (VR), containing gambling cues. The goal of Alter Game (approved by the Ethical Commission, Prot. No. 69346) is verifying the efficacy of an innovative psychological treatment for GD based on the integration of traditional CBT therapy and an immersive VR cue exposure therapy using a serious virtual game, which is a game designed for purposes other than entertainment. RP in virtual cue-exposure therapy allows pathological gamblers to manage the urge to gamble and to avoid relapse by becoming aware of which internal and external triggers are related to craving. We hypothesize that the integrated intervention will be more effective than simple CBT with regard to self-efficacy, craving, and gambling-related distortions. Four virtual ecological environments were developed, and a virtual app, Exludo, interfaced with a computerized multiparametric acquisition system for biofeedback, was created. A sample of about 60 patients aged between 18 and 65 with GD referring to the Addiction Medicine Unit of Verona (Rossi Hospital) will be recruited. Patients will be randomly assigned to the CBT group (16 CBT sessions) or the CBT + VR group (8 CBT sessions + 8 VR cue-exposure therapy sessions). The MCMI-III, the BIS-11, and the SOGS will be used to evaluate inclusion and exclusion criteria, while the Gambling Related Cognitions Scale and the Multidimensional Gambling Self-Efficacy Scale will be used to verify changes as a function of the treatment. Craving will be evaluated through VAS, and psychophysiological variables will be assessed through biofeedback. A pre-test/post-test experimental design with a 1-month follow-up will be conducted. This study will examine an innovative psychotherapeutic protocol for GD treatment, and it will help in identifying new virtual tools to increase the efficacy of traditional therapeutic approaches that could also be applied to treat other addictions.
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Benzodiazepines (BZDs) represent one of the most widely used groups of pharmaceuticals, but if used for long periods of time they are associated with dependence and an increased risk of harmful effects. High-dose (HD) BZD dependence is a specific substance use disorder associated with a poor quality of life. It is especially important to pinpoint differences in HD BZD addict subgroups in order to tailor treatment to the individual's specific needs, also considering possible comorbidities with other substance use disorders. We conducted a study to evaluate HD BZD dependence (converted doses to diazepam equivalents, mg) in an Italian sample of 1,354 participants. We also investigated if and to which extent participants co-used other substances (alcohol, tobacco, cannabis/cannabinoids, cocaine, and heroin). We then performed latent class analysis (LCA) to identify the use patterns of these substances, finding three classes: participants in Class 1 (4.3% of the sample) had the highest probability of also using cocaine and alcohol (Polysubstance BZD users); Class 2 comprised subjects with the highest probability of being former heroin, cocaine, THC, and alcohol users (Former polysubstance BZD users); Class 3 represented mono-dependence BZD users (78.5% of the sample) and was the most prevalent among women, while young men were most prevalent in Class 1. The present study underlines different characteristics in HD BZD users both concerning other addictions and sex, and also highlights the need for a stricter control of BZD use, ranging from prescriptions to sales.
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In the last years, only few studies in literature have focused on the use and abuse of benzodiazepines (BZDs) in sport. Benzodiazepine-related problems include misuse, addiction, driving impairments, and morbidity and mortality related to overdose and withdrawal. Two clinical cases regarding elite endurance athletes evidenced that they had started to use BZDs to counteract insomnia, to recover faster from training sessions and to manage muscle pain. One of the important points that emerged from their stories was that their sports doctors did not recognize the drugs' addictive properties, and did not intervene to gradually reduce the dosage. Experts have previously provided recommendations for BZD therapy management in clinical practice. In this article, we would like to address sports medicine physicians specifically and provide guidelines to help them manage situations involving BZD prescription, the recognition of addiction, and intervention strategies.
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ABSTRACT: Substance use disorders (SUDs) are characterized by a recurrent and maladaptive use of drugs and/or alcohol. Cognitive behavioral therapies (CBTs) comprise different types of interventions: traditional CBT and the more recent "third wave" behavior therapies, such as acceptance and commitment therapy (ACT), dialectical behavior therapy (DBT), mindfulness-based cognitive therapy (MBCT), and schema therapy (ST). We searched English-language articles published between 2014 and present. This review includes randomized controlled trials (RCTs), quasi-RCTs, pilot studies, and reviews of CBTs for SUDs available on PubMed. Results seem to indicate that CBT and MBCT are effective interventions for SUDs; however, the studies showed a high degree of heterogeneity, so no exhaustive conclusions could be outlined at this time. ACT and DBT in SUD management are limited to few studies and results are therefore inconclusive.
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Terapia Cognitivo-Conductual , Evaluación de Resultado en la Atención de Salud , Trastornos Relacionados con Sustancias/terapia , HumanosRESUMEN
Young adults exhibit greater sensitivity than adults to nicotine reinforcement, and Attention Deficit Hyperactivity Disorder (ADHD) increases the risk for early-onset smoking. We investigated the correlation between ADHD Self-Report Scale (ASRS) scores and smoking, evaluated the prevalence of ADHD symptomatology (not diagnoses) in smokers and non-smokers and its comorbidity with benzodiazepine and gambling addictions. A total of 389 young adults from 14 schools in Northern Italy fill out a survey and the Adult ADHD Self-Report Scale (ASRS). A total of 15.2% of subjects tested positive at the ASRS, which correlated with smoking; moreover, smokers had twice the probability of testing positive at the ASRS. ADHD symptomatology, especially when comorbid with tobacco abuse, is an important condition to monitor because early nicotine exposure could be a gateway for other addictive behaviors.