The Effect of Methylphenidate on Cognition in Patients with Comorbid Attention Deficit/Hyperactivity Disorder and Amphetamine Use Disorder: An Exploratory Single-Blinded within-Subject Study.

INTRODUCTION: Attention deficit/hyperactivity disorder (ADHD) with co-occurring substance use disorder (SUD) is associated with poor treatment outcomes. Two randomized controlled trials, utilizing robust doses of stimulants, demonstrated a significant effect on treatment outcomes in patients with ADHD/SUD. This study aimed to investigate differences in executive functioning and explore the dose-dependent effect of OROS-methylphenidate (MPH) in patients with comorbid ADHD and amphetamine use disorder (ADHD+AMPH) and patients with ADHD only. METHODS: Three groups (ADHD+AMPH, ADHD only, and healthy controls) were assessed repeatedly with a neuropsychological test battery. An exploratory within-subject single-blinded design was employed where the ADHD only group received a maximum dose of 72 mg OROS-MPH, the ADHD+AMPH group a maximum dose of 180 mg, whereas the healthy subjects did not receive any study medication. Both ADHD groups received the same dose titration up to 72 mg OROS-MPH. RESULTS: The ADHD+AMPH group demonstrated a significantly poorer motor inhibition and spatial working memory and reported more severe ADHD symptoms compared to the ADHD only group. 180 mg OROS-MPH was associated with a significant improvement in executive functioning in the dual diagnosis group. However, the exploratory study design and recruitment issues do not allow for any conclusion to be drawn regarding the effect of 180 mg OROS-MPH. CONCLUSION: Patients with ADHD+AMPH present with more severe neurocognitive deficits compared to ADHD only. The effect of 180 mg OROS-MPH on cognition in patients with ADHD+AMPH was inconclusive. Future studies should consider recruitment issues and high drop-out rates in this study population.

Impulsive choice in individuals with comorbid amphetamine use disorder and attention deficit-hyperactivity disorder.

BACKGROUND: Amphetamine use disorder (AMPH) and attention deficit-hyperactivity disorder (ADHD) often co-occur and are associated with poor treatment outcomes. Elevated impulsivity is a core feature in both disorders. Little is known however about the specific neurocognitive profile regarding different facets of impulsivity, and specifically impulsive choice, in comorbid populations. METHODS: Three groups (ADHD + AMPH, ADHD only and healthy controls (HC)) were assessed with self-reported impulsivity and cognitive tasks of impulsive choice, operationalized as delay aversion (DA) and reflection impulsivity. RESULTS: Twenty-nine participants with comorbid ADHD + AMPH, 25 participants with ADHD only and 116 HC completed screening, including self-rating scales, and cognitive testing. 20, 16 and 114 participants completed computerized cognitive tasks in the ADHD + AMPH group, ADHD group and HC group, respectively. The ADHD + AMPH group reported significantly higher motor, attentional and non-planning impulsiveness, and showed a significantly higher degree of impulsive choice, compared to both groups. There were no differences in task-related impulsiveness between ADHD only and HC. CONCLUSIONS: The current findings suggest that individuals with ADHD + AMPH have overall elevated levels of impulsivity compared to individuals with ADHD only. In addition, that ADHD + AMPH is specifically associated with impairments in task-related impulsive choice, which was not found in ADHD only compared to HC. The neurocognitive profile in this specific patient group may represent a need for more systematic screening within healthcare settings in order to develop effective and targeted treatment for comorbid patients. TRIAL REGISTRATION: EudraCT, 2012-004298-20.

The clinical course of comorbid substance use disorder and attention deficit/hyperactivity disorder: protocol and clinical characteristics of the INCAS study.

BACKGROUND: Substance use disorders (SUD) often co-occur with attention deficit hyperactivity disorder (ADHD). Although the short-term effects of some specific interventions have been investigated in randomized clinical trials, little is known about the long-term clinical course of treatment-seeking SUD patients with comorbid ADHD. AIMS: This paper presents the protocol and baseline clinical characteristics of the International Naturalistic Cohort Study of ADHD and SUD (INCAS) designed and conducted by the International Collaboration on ADHD and Substance Abuse (ICASA) foundation. The overall aim of INCAS is to investigate the treatment modalities provided to treatment-seeking SUD patients with comorbid ADHD, and to describe the clinical course and identify predictors for treatment outcomes. This ongoing study employs a multicentre observational prospective cohort design. Treatment-seeking adult SUD patients with comorbid ADHD are recruited, at 12 study sites in nine different countries. During the follow-up period of nine months, data is collected through patient files, interviews, and self-rating scales, targeting a broad range of cognitive and clinical symptom domains, at baseline, four weeks, three months and nine months. RESULTS: A clinically representative sample of 578 patients (137 females, 441 males) was enrolled during the recruitment period (June 2017-May 2021). At baseline, the sample had a mean age (SD) of 36.7 years (11.0); 47.5% were inpatients and 52.5% outpatients; The most prevalent SUDs were with alcohol 54.2%, stimulants 43.6%, cannabis 33.1%, and opioids 14.5%. Patients reported previous treatments for SUD in 71.1% and for ADHD in 56.9%. Other comorbid mental disorders were present in 61.4% of the sample: major depression 31.5%, post-traumatic stress disorder 12.1%, borderline personality disorder 10.2%. CONCLUSIONS: The first baseline results of this international cohort study speak to its feasibility. Data show that many SUD patients with comorbid ADHD had never received treatment for their ADHD prior to enrolment in the study. Future reports on this study will identify the course and potential predictors for successful pharmaceutical and psychological treatment outcomes. TRIAL REGISTRATION: ISRCTN15998989 20/12/2019.

Self-rated impulsivity in healthy individuals, substance use disorder and ADHD: psychometric properties of the Swedish Barratt impulsiveness scale.

BACKGROUND: Impulsivity is associated with several psychiatric disorders, including substance use disorders (SUD) and attention deficit hyperactivity disorder (ADHD). A widely used questionnaire to assess impulsivity is the Barratt Impulsiveness Scale (BIS), and the aim of the current study was to evaluate the psychometric properties of the Swedish version of the BIS (swe-BIS). METHODS: The original BIS was translated to Swedish and back-translated by an authorized translator. The swe-BIS was administered to healthy controls (n = 113), patients with alcohol use disorder (n = 97), amphetamine use disorder (n = 37) and attention deficit hyperactive disorder (ADHD; n = 26). A subset of subjects (n = 62) completed the swe-BIS twice within 1 week. Psychometric evaluation of the swe-BIS included assessment of different indices of reliability (internal consistency, test-retest and agreement) and validity (response processess, divergent and convergent). Confirmatory factor analyses (CFA) were performed to assess several indices of model fit in five different models based on previously suggested subscales. RESULTS: Cronbach's alpha for all swe-BIS items in the full sample was 0.89, ranging from 0.78-0.87 within the different subgroups. The Pearson test-retest correlation for total score was 0.78 (p < 0.001), with greater test-retest correlations within compared to across different subscales. The Bland-Altman plot indicated high level of agreement between test and retest. The healthy individuals had lower swe-BIS score compared to the patients (t(267.3) = - 8.6; p < 0.001), and the swe-BIS total score was also significantly different between each of the four participant groups (p < 0.01 for all group comparisons). Furthermore, swe-BIS had greater correlations with impulsivity related scales compared to non-impulsivity related scales. The CFA analyses indicated that while no suggested model showed an optimal fit, the best model fit indices was found for the 3-factor model. CONCLUSIONS: The swe-BIS was found to have good to excellent psychometric properties with respect to the assessed indices of reliability and validity, supporting use of the scale in clinical research in both healthy individuals and patients with SUD and ADHD.

The International Collaboration on ADHD and Substance Abuse (ICASA): Mission, Results, and Future Activities.

BACKGROUND: The International Collaboration on ADHD and Substance Abuse (ICASA) is a network of 28 centers from 16 countries initiated to investigate the link between attention deficit-hyperactivity disorder (ADHD) and substance use disorder (SUD). In this article, we present the mission, the results of finished studies, and the current and future research projects of ICASA. METHODS: During the past 10 years, 3 cross-sectional studies were conducted: two International ADHD in Substance use disorders Prevalence (IASP-1 and IASP-2) studies, directed at the screening, diagnosis, and the prevalence of adult ADHD in treatment-seeking patients with SUD, and the Continuous performance test for ADHD in SUD Patients (CASP) study, testing a novel continuous performance test in SUD patients with and without adult ADHD. Recently, the prospective International Naturalistic Cohort Study of ADHD and Substance Use Disorders (INCAS) was initiated, directed at treatment provision and treatment outcome in SUD patients with adult ADHD. RESULTS: The IASP studies have shown that approximately 1 in 6 adult treatment-seeking SUD patients also have ADHD. In addition, those SUD patients with adult ADHD compared to SUD patients without ADHD report more childhood trauma exposure, slower infant development, greater problems controlling their temperament, and lower educational attainment. Comorbid patients also reported more risk-taking behavior, and a higher rate of other psychiatric disorders compared to SUD patients without ADHD. Screening, diagnosis, and treatment of this patient group are possible even before abstinence has been achieved. The results of the CASP study are reported separately in this special issue. CONCLUSIONS: The ICASA research to date has demonstrated a high prevalence of comorbid ADHD and SUD, associated with elevated rates of additional comorbidities and risk factors for adverse outcomes. More research is needed to find the best way to treat these patients, which is the main topic of the ongoing INCAS study.

Working Memory Training in Alcohol Use Disorder: A Randomized Controlled Trial.

BACKGROUND: Alcohol use disorder (AUD) is associated with cognitive deficits such as impaired executive functions, which are hypothesized to contribute to the progression of the disease and worsen treatment outcome. Training of working memory (WM) to improve cognitive functions and thereby reduce alcohol use has been proposed as a novel treatment strategy. METHODS: Patients with AUD (n = 50) who were recruited to an outpatient addiction clinic were randomized to receive 5 weeks of active WM training or control training. Participants had weekly follow-up visits, and all cognitive training sessions were done online at home. Primary outcomes were WM function and change in self-reported heavy drinking. Secondary outcomes were craving, other drinking outcomes, and performance on a range of neuropsychological tasks from the Cambridge Neuropsychological Test Automated Battery. RESULTS: The active training group demonstrated a significantly greater improvement in verbal WM compared with the control group. No statistically significant effect of training was found on the primary drinking outcome, but a trend was observed indicating that WM training reduces the number of drinks per drinking occasion. WM training had no statistically significant effect on any of the other neuropsychological tasks. CONCLUSIONS: Cognitive training can improve WM function in individuals with AUD, suggesting that such interventions are feasible to administer in this patient population. The results do not support an effect of WM training on heavy drinking or transfer effects to other cognitive domains. Future studies should evaluate WM training as an adjunct to evidence-based treatments for AUD to assess potential synergistic effects.