Psychosis with use of amphetamine drugs, methylphenidate and atomoxetine in adolescent and adults.

BACKGROUND: Use of psychostimulants and relative drugs has increased worldwide in treatment of attention-deficit hyperactivity disorder (ADHD) in adolescents and adults. Recent studies suggest a potential association between use of psychostimulants and psychotic symptoms. The risk may not be the same between different psychostimulants. OBJECTIVE: To assess whether amphetamine or atomoxetine use is associated with a higher risk of reporting symptoms of psychosis than methylphenidate use in adolescents and adults, particularly in patients with ADHD. METHODS: Using VigiBase, the WHO's pharmacovigilance database, disproportionality of psychotic symptoms reporting was assessed among adverse drug reactions related to methylphenidate, atomoxetine and amphetamines, from January 2004 to December 2018, in patients aged 13-25 years. The association between psychotic symptoms and psychostimulants was estimated through the calculation of reporting OR (ROR). FINDINGS: Among 13 863 reports with at least one drug of interest, we found 221 cases of psychosis with methylphenidate use, 115 with atomoxetine use and 169 with a prescription of an amphetamine drug. Compared with methylphenidate use, amphetamine use was associated with an increased risk of reporting psychotic symptoms (ROR 1.61 (95% CI 1.26 to 2.06)]. When we restricted the analysis to ADHD indication, we found a close estimate (ROR 1.94 (95% CI 1.43 to 2.64)). No association was found for atomoxetine. CONCLUSION: Our study suggests that amphetamine use is associated with a higher reporting of psychotic symptoms, compared with methylphenidate use. CLINICAL IMPLICATIONS: The prescription of psychostimulants should consider this potential adverse effect when assessing the benefit-risk balance.

Modeling methamphetamine use disorder in mammals: Sex differences in behavioral, biochemical, and transcriptional consequences.

Methamphetamine (METH) is the most commonly misused amphetamine-type stimulant throughout the globe. METH is very rewarding, and its misuse can lead to a diagnosis of METH use disorder (MUD). Although METH use is observed in both sexes, there are, however, reported differences in the clinical manifestations of METH use and its consequences. These observations indicate the need for more research on the long-term sex-dependent consequences of METH taking in both preclinical and clinical settings. In effect, sex is a biological variable that can impact conclusions drawn from various basic and clinical studies. Thus, the present chapter provides a succinct review of the current state of the research on METH and its sex-associated consequences. In addition to behavioral and cognitive aspects of METH use, we discuss METH-induced changes in neurotransmitter systems and structures in the brain. Thus, the book chapter serves to highlight the significance of sex as a critical element that needs to be considered during discussions of novel therapeutic approaches to MUD.

The pharmacology and neurotoxicology of synthetic cathinones.

The synthetic cathinones are man-made compounds derived from the naturally occurring drug cathinone, which is found in the khat plant. The drugs in this pharmacological class that will be the focus of this chapter include mephedrone, MDPV, methcathinone and methylone. These drugs are colloquially known as "bath salts". This misnomer suggests that these drugs are used for health improvement or that they have legitimate medical uses. The synthetic cathinones are dangerous drugs with powerful pharmacological effects that include high abuse potential, hyperthermia and hyperlocomotion. These drugs also share many of the pharmacological effects of the amphetamine class of drugs including methamphetamine, amphetamine and MDMA and therefore have high potential to cause damage to the central nervous system. The synthetic cathinones are frequently taken in combination with other psychoactive drugs such as alcohol, marijuana and the amphetamine-like stimulants, creating a situation where heightened pharmacological and neurotoxicological effects are likely to occur. Despite the structural features shared by the synthetic cathinones and amphetamine-like stimulants, including their actions at monoamine transporters and receptors, the effects of the synthetic cathinones do not always match those of the amphetamines. In particular, the synthetic cathinones are far less neurotoxic than their amphetamine counterparts, they produce a weaker hyperthermia, and they cause less glial activation. This chapter will briefly review the pharmacology and neurotoxicology of selected synthetic cathinones with the aim of delineating key areas of agreement and disagreement in the literature particularly as it relates to neurotoxicological outcomes.

Suicide, Stimulants, and Selective Serotonin Reuptake Inhibitors: A Retrospective Chart Review.

Background: Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) may increase the risk of suicide among children and youth, although the association between suicide risk and the combination of SSRIs with other medication such as stimulants in this population remains unclear. This study explored whether the combination of SSRIs with stimulants influenced suicide risk. Methods: A retrospective cohort study was conducted at a single children's hospital campus-based ambulatory psychiatric clinic between September 1, 2017, and September 30, 2020. Subjects were 6-21 years of age and prescribed either stimulants or stimulants and SSRIs only. The primary outcome was suicidal thoughts and behaviors (STB), defined by documented suicidal thoughts, plans, or behaviors. Firth logistic regression evaluated associations between medication class and STB. Results: Among 349 patients, the prevalence of STB was 5.7% (n = 20). In unadjusted model, patients prescribed SSRIs and stimulants had a 2.9-fold increase of STB compared to patients prescribed stimulants only, along with increasing age, male sex, and the diagnoses of anxiety and/or depression. In the final model adjusted for each of these factors, the observed association of medication regiment with STB was attenuated (odds ratio [OR]: 1.3, confidence interval [CI]: 0.3-4.9, p = 0.7). The magnitude of the adjusted association between depressive diagnosis and STB was notable (OR: 3.6, CI: 1.0-12.6, p = 0.049). Conclusions: Among patients followed in a children's hospital-based ambulatory psychiatric clinic, a combination medication regimen of SSRIs and stimulants after adjusting for genetic sex, age, anxiety diagnosis, and depression diagnosis, the observed association between STB and combination stimulant and SSRI treatment was attenuated. This finding suggests that other factors, including depression, may have contributed to the association between SSRI treatment and STB. Larger, prospective studies of the relationship between combination pharmacotherapy and suicide risk are warranted to guide clinical/pharmacological decision making and to better clarify these relationships.

The Impact of Methylphenidate on Pubertal Maturation and Bone Age in ADHD Children and Adolescents: Results from the ADHD Drugs Use Chronic Effects (ADDUCE) Project.

OBJECTIVE: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age. METHOD: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age. RESULTS: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable. CONCLUSION: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth.

Methylphenidate and Sleep Difficulties in Children and Adolescents With ADHD: Results From the 2-Year Naturalistic Pharmacovigilance ADDUCE Study.

OBJECTIVE: Short-term RCTs have demonstrated that MPH-treatment significantly reduces ADHD-symptoms, but is also associated with adverse events, including sleep problems. However, data on long-term effects of MPH on sleep remain limited. METHODS: We performed a 2-year naturalistic prospective pharmacovigilance multicentre study. Participants were recruited into three groups: ADHD patients intending to start MPH-treatment (MPH-group), those not intending to use ADHD-medication (no-MPH-group), and a non-ADHD control-group. Sleep problems were assessed with the Children's-Sleep-Habits-Questionnaire (CSHQ). RESULTS: 1,410 participants were enrolled. Baseline mean CSHQ-total-sleep-scores could be considered clinically significant for the MPH-group and the no-MPH-group, but not for controls. The only group to show a significant increase in any aspect of sleep from baseline to 24-months was the control-group. Comparing the MPH- to the no-MPH-group no differences in total-sleep-score changes were found. CONCLUSION: Our findings support that sleep-problems are common in ADHD, but don't suggest significant negative long-term effects of MPH on sleep.

ADHD medications use and risk of mortality and unintentional injuries: a population-based cohort study.

We assessed the association between the use of medications for attention-deficit/hyperactivity disorder (ADHD) and the risk of all-cause mortality and unintentional injuries leading to emergency department (ED) or hospital admission in individuals aged ≤24 years with ADHD. We conducted a population-based retrospective cohort study between 2000 and 2021 using Quebec health administrative data. Individuals were followed from the first ADHD diagnosis or ADHD medication claim until turning 25, death, or study end. Exposure was defined as mutually exclusive episodes of ADHD medication use and/or coverage under the public provincial drug plan (PDP): 1) covered and not treated with ADHD medication; 2) covered and treated with ADHD medication; and 3) not covered under the PDP. The risk of all-cause mortality and unintentional injuries associated with exposure episodes was estimated using multivariable survival analyses. The cohort included n = 217 192 individuals aged 1-24 years with a male to female ratio of close to 2:1. Compared to non-medication use, episodes of ADHD medication use, overall, were associated with reduced all-cause mortality (adjusted hazard ratio, aHR 0.61, 95% CI 0.48-0.76) and unintentional injury leading to ED (0.75, 0.74-0.77) or hospitalisation (0.71, 0.68-0.75). Episodes of stimulants were associated with a lower risk of all-cause mortality and reduced risk of unintentional injuries, while episodes with non-stimulants and with both stimulants and non-stimulants concomitantly were associated with reduced risk of unintentional injuries, but not of all-cause mortality. Although residual confounding cannot be excluded, stimulants may have a protective effect in terms of risk of all-cause mortality and both stimulants and non-stimulants for ADHD may reduce the risk of unintentional injuries. The findings of the current study should inform clinical decision making on the choice of starting a pharmacological treatment for ADHD, when a balance needs to be struck between expected benefits and possible risks.

Neuronal activation of nucleus accumbens by local methamphetamine administration induces cognitive impairment through microglial inflammation in mice.

More than half of methamphetamine (METH) users present with cognitive impairment, making it difficult for them to reintegrate into society. However, the mechanisms of METH-induced cognitive impairment remain unclear. METH causes neuronal hyperactivation in the nucleus accumbens (NAc) by aberrantly releasing dopamine, which triggers dependence. In this study, to clarify the involvement of hyperactivation of NAc in METH-induced cognitive impairment, mice were locally microinjected with METH into NAc (mice with METH (NAc)) and investigated their cognitive phenotype. Mice with METH (NAc) exhibited cognitive dysfunction in behavioral analyses and decreased long-term potentiation in the hippocampus, with NAc activation confirmed by expression of FosB, a neuronal activity marker. In the hippocampus of mice with METH (NAc), activated microglia, but not astroglia, and upregulated microglia-related genes, Il1b and C1qa were observed. Finally, administration of minocycline, a tetracycline antibiotic with suppressive effect on microglial activation, to mice with METH (NAc) ameliorated cognitive impairment and synaptic dysfunction by suppressing the increased expression of Il1b and C1qa in the hippocampus. In conclusion, activation of NAc by injection of METH into NAc elicited cognitive impairment by facilitating immune activation in mice. This study suggests that immunological intervention could be a therapeutic strategy for addiction-related cognitive disturbances.

Assessment of lisdexamfetamine on executive function in rats: A translational cognitive research.

Executive function, including working memory, attention and inhibitory control, is crucial for decision making, thinking and planning. Lisdexamfetamine, the prodrug of d-amphetamine, has been approved for treating attention-deficit hyperactivity disorder and binge eating disorder, but whether it improves executive function under non-disease condition, as well as the underlying pharmacokinetic and neurochemical properties, remains unclear. Here, using trial unique non-matching to location task and five-choice serial reaction time task of rats, we found lisdexamfetamine (p.o) enhanced spatial working memory and sustained attention under various cognitive load conditions, while d-amphetamine (i.p) only improved these cognitive performances under certain high cognitive load condition. Additionally, lisdexamfetamine evoked less impulsivity than d-amphetamine, indicating lower adverse effect on inhibitory control. In vivo pharmacokinetics showed lisdexamfetamine produced a relative stable and lasting release of amphetamine base both in plasma and in brain tissue, whereas d-amphetamine injection elicited rapid increase and dramatical decrease in amphetamine base levels. Microdialysis revealed lisdexamfetamine caused lasting release of dopamine within the medial prefrontal cortex (mPFC), whereas d-amphetamine produced rapid increase followed by decline to dopamine level. Moreover, lisdexamfetamine elicited more obvious efflux of noradrenaline than that of d-amphetamine. The distinct neurochemical profiles may be partly attributed to the different action of two drugs to membranous catecholamine transporters level within mPFC, detecting by Western Blotting. Taken together, due to its certain pharmacokinetic and catecholamine releasing profiles, lisdexamfetamine produced better pharmacological action to improving executive function. Our finding provided valuable evidence on the ideal pharmacokinetic and neurochemical characteristics of amphetamine-type psychostimulants in cognition enhancement.

Drivers and Barriers to Tolerable and Effective Treatment for ADHD: The Importance of Treatment Perseverance and Duration of Effect.

OBJECTIVE: To examine treatment outcomes for classes of ADHD drugs in conjunction with physicians' prescribing rationales and the utility of treatment perseverance in treatment effectiveness. METHODS: A retrospective non-interventional study using physician-provided chart data for treated adolescent and adult ADHD patients in the United States (April-June 2019). Multivariable analyses compared the effectiveness and tolerability of drug classes. RESULTS: Among the 1,232 ADHD patients included in this study, 37.7% experienced one, 11.8% two, and 6.7% three treatment changes post their first prescribed regimen. These changes were mostly attributed to lack of rapid onset and duration of effect. Achieving best response correlated with the number of previous treatments for adolescents, but not adults. Maintaining full response correlated with the length of current treatment for adolescents and adults. CONCLUSION: Physicians' prescribing rationales targeted duration of effect and tolerability. ER monotherapy demonstrated potential advantages over other regimens. Treatment perseverance is integral to effective ADHD management.

Stimulant Drugs and Stimulant Use Disorder.

The authors aim to summarize several key points of stimulant drugs and stimulant use disorder, including their indications, short-term and long-term adverse effects, current treatment strategies, and association with opioid medications. The global prevalence of stimulant use has seen annual increase in the last decade. Multiple studies have shown that stimulant use and stimulant use disorder are associated with a range of individual and public health issues. Stimulant misuse has led to a significant increase of overdose deaths in the United States.

Effect of Risk Mitigation Guidance opioid and stimulant dispensations on mortality and acute care visits during dual public health emergencies: retrospective cohort study.

OBJECTIVE: To determine the effect of opioid and stimulant Risk Mitigation Guidance (RMG) dispensations on mortality and acute care visits during the dual public health emergencies of overdose and covid-19. DESIGN: Population based retrospective cohort study. SETTING: British Columbia, Canada. PARTICIPANTS: 5882 people with opioid or stimulant use disorder who received RMG prescriptions for opioids (n=5356) and/or stimulants (n=1061) (535 received both) from 27 March 2020 to 31 August 2021. MAIN OUTCOME MEASURES: All cause and overdose specific mortality and acute care visits in the week after RMG opioid or stimulant dispensation. RMG recipients were matched 1:1 with controls through use of high dimensional propensity score matching. Marginal structural models, executed on weekly time steps, were used to measure the effect of dispensations on outcomes. RESULTS: RMG opioid dispensations of one day or more were associated with reduced all cause mortality (adjusted hazard ratio 0.39, 95% confidence interval 0.25 to 0.60) and overdose related mortality (0.45, 0.27 to 0.75) in the subsequent week. Dispensations of RMG stimulants (≥1 days) were not significantly associated with reduced all cause mortality (adjusted hazard ratio 0.50, 0.20 to 1.23) or overdose related mortality (0.53, 0.18 to 1.56). The protective effect of RMG opioid dispensations increased with the number of days the medications were dispensed in a given week. People who received four or more days of RMG opioid dispensations had reduced all cause mortality (adjusted hazard ratio 0.09, 0.04 to 0.21) and overdose related mortality (0.11, 0.04 to 0.32) compared with the control group. Opioid RMG dispensations did not significantly modify the odds of all cause or overdose related acute care visits. Dispensations of RMG stimulants were associated with a significant decrease in the odds of acute care visits for any cause but did not affect the odds of overdose related acute care visits. CONCLUSIONS: RMG opioid dispensations were associated with reduced overdose related and all cause mortality among a sample of people with opioid use disorder. Pharmaceutical alternatives to the illegal drug supply are promising interventions to reduce mortality in people with opioid use disorder.

Protocol of a monocentric, double-blind, randomized, superiority, controlled trial evaluating the effect of in-prison OROS-methylphenidate vs. placebo treatment in detained people with attention-deficit hyperactivity disorder (BATIR).

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is characterized by difficulty paying attention, poor impulse control, and hyperactive behavior. It is associated with several adverse health and social outcomes and leads to an increased risk of criminality and recidivism. Worldwide, ADHD is thus highly prevalent in prisons. However, ADHD treatment has been neglected in such environments. Stimulant medications such as osmotic-release oral system methylphenidate (OROS-MPH) are first-line treatments in the general population, but they are under-prescribed in prisons due to concerns about abuse, even though such claims are not empirically supported. This project aims to compare the efficacy of a 3-month in-prison OROS-MPH vs. placebo treatment on the severity of core ADHD symptoms and relevant in- and post-prison outcomes. METHODS: This study is a phase III, double-blinded, randomized, superiority, controlled trial of OROS-MPH vs. placebo. After randomization, the participants will receive 3 months of treatment with OROS-MPH or placebo (1:1 ratio) while incarcerated. Upon release, all participants will be offered the treatment (OROS-MPH) for 1 year but will remain blinded to their initial study group. The study will be conducted at the Division of Prison Health, Geneva, Switzerland, among incarcerated men (n = 150). Measures will include (1) investigator-rated ADHD symptoms, (2) acute events collected by the medical and prison teams, (3) assessment of the risk of recidivism, (4) medication side effects, (5) medication adherence, (6) study retention, (7) health care/prison costs, and (8) 1-year recidivism. Analyses will include bivariable and multivariable modeling (e.g., regression models, mixed-effects models, survival analyses) and an economic evaluation (cost-benefit analysis). DISCUSSION: We expect that early identification and treatment of ADHD in prison will be an important public health opportunity and a cost-effective approach that is likely to reduce the vulnerability of incarcerated individuals and promote pathways out of criminal involvement. The study will also promote standards of care for people with ADHD in prison and provide recommendations for continuity of care after release. TRIAL REGISTRATION: ClinicalTrials.gov NCT05842330 . Registered on June 5, 2023. Kofam.ch SNCTP000005388. Registered on July 17, 2023.

Is age of onset and duration of stimulant therapy for ADHD associated with cocaine, methamphetamine, and prescription stimulant misuse?

BACKGROUND: To assess whether age of onset and duration of stimulant therapy for attention-deficit/hyperactivity disorder (ADHD) are associated with cocaine, methamphetamine, and prescription stimulant misuse during adolescence. METHODS: Nationally representative samples of US 10th and 12th grade students (N = 150,395) from the Monitoring the Future study were surveyed via self-administered questionnaires from 16 annual surveys (2005-2020). RESULTS: An estimated 8.2% of youth received stimulant therapy for ADHD during their lifetime (n = 10,937). More than one in 10 of all youth reported past-year prescription stimulant misuse (10.4%)-past-year cocaine (4.4%) and methamphetamine (2.0%) use were less prevalent. Youth who initiated early stimulant therapy for ADHD (≤9 years old) and for long duration (≥6 years) did not have significantly increased adjusted odds of cocaine or methamphetamine use relative to population controls (ie, non-ADHD and unmedicated ADHD youth). Youth who initiated late stimulant therapy for ADHD (≥10 years old) and for short duration (<1 year) had significantly higher odds of past-year cocaine or prescription stimulant misuse in adolescence than those initiating early stimulant therapy for ADHD (≤9 years old) and for long duration (≥6 years). Youth who initiated late stimulant therapy for ADHD (≥10 years) for short duration (<1 year) had significantly higher odds of past-year cocaine, methamphetamine, and prescription stimulant misuse versus population controls during adolescence. No differences in past-year cocaine, methamphetamine, and prescription stimulant misuse were found between individuals who only used non-stimulant therapy for ADHD relative to youth who initiated early stimulant therapy (≤9 years old) and for long duration (≥6 years). CONCLUSIONS: An inverse relationship was found between years of stimulant therapy and illicit and prescription stimulant misuse. Adolescents with later initiation and/or shorter duration of stimulant treatment for ADHD should be monitored for potential illicit and prescription stimulant misuse.

Translating the nuanced risk for substance use among adolescents treated for attention-deficit/hyperactivity disorder (ADHD) into clinical practice: a commentary on McCabe et al. (2023).

In their recent examination of the Monitoring the Future (MTF) data, McCabe et al. (Journal of Child Psychology and Psychiatry, 2023) address the complex, longstanding, and clinically valuable questions of whether and how stimulant medication treatment for adolescents with ADHD relates to their risk for substance use. Here, we expand on the authors' interpretations of their nuanced findings of increased risk for illicit stimulant use and non-prescribed stimulant medication use for youth with later age of medication treatment initiation and shorter treatment duration. We particularly focus on highlighting tangible clinical implications, and we recommend ways future research can build on the authors' findings to further clarify this important issue.

Could psychostimulant drug use among university students be related to ADHD symptoms? A preliminary study.

We aimed to explore if psychostimulant use among student could be linked to attention deficit-hyperactivity disorder (ADHD) symptoms using a self-administered questionnaire sent by email to French students in 2021. Participants were asked about their psychostimulant use and the presence of ADHD symptoms using the Wender Utah Rating Scale and the Adult Self-Report Scale. Among the 4431 respondents, the prevalence of psychostimulant use was concerning and significantly associated with ADHD symptoms. This association could be related to undiagnosed ADHD or to psychobehavioral impairments induced by psychostimulant use underlining the need of ADHD screening and targeted prevention measures.

Treatment with psychostimulants and atomoxetine in people with psychotic disorders: reassessing the risk of clinical deterioration in a real-world setting.

BACKGROUND: Although attention-deficit hyperactivity disorder (ADHD) is often comorbid with schizophrenia spectrum and other psychotic disorders (SZSPD), concerns about an increased risk of psychotic events have limited its treatment with either psychostimulants or atomoxetine. AIMS: To examine whether the risk of hospital admission for psychosis in people with SZSPD was increased during the year following the introduction of such medications compared with the year before. METHOD: This was a retrospective cohort study using Quebec (Canada) administrative health registries, including all Quebec residents with a public prescription drug insurance plan and a diagnosis of psychotic disorder, defined by relevant ICD-9 or ICD-10 codes, who initiated either methylphenidate, amphetamines or atomoxetine, between January 2010 and December 2016, in combination with antipsychotic medication. The primary outcome was time to hospital admission for psychosis within 1 year of initiation. State sequence analysis was also used to visualise admission trajectories for psychosis in the year following initiation of these medications, compared with the previous year. RESULTS: Out of 2219 individuals, 1589 (71.6%) initiated methylphenidate, 339 (15.3%) amphetamines and 291 (13.1%) atomoxetine during the study period. After adjustment, the risk of hospital admission for psychosis was decreased during the 12 months following the introduction of these medications when used in combination with antipsychotics (adjusted HR = 0.36, 95% CI 0.24-0.54; P < 0.0001). CONCLUSIONS: These findings suggest that, in a real-world setting, when used concurrently with antipsychotic medication, methylphenidate, amphetamines and atomoxetine may be safer than generally believed in individuals with psychotic disorders.

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.