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Exploring longitudinal course and treatment-baseline severity interactions in secondary outcomes of smoking cessation treatment in individuals with attention-deficit hyperactivity disorder.

ABSTRACT: BACKGROUND:A double blind, placebo-controlled randomized trial (NCT00253747) evaluating osmotic-release oral system methylphenidate (OROS-MPH) for smoking-cessation revealed a significant interaction effect in which participants with higher baseline ADHD severity had better abstinence outcomes with OROS-MPH while participants with lower baseline ADHD severity had worse outcomes. OBJECTIVES:This current report examines secondary outcomes that might bear on the mechanism for this differential treatment effect. METHODS:Longitudinal analyses were conducted to evaluate the effect of OROS-MPH on three secondary outcomes (ADHD symptom severity, nicotine craving, and withdrawal) in the total sample (N = 255, 56% Male), and in the high (N = 134) and low (N = 121) baseline ADHD severity groups. RESULTS:OROS-MPH significantly improved ADHD symptoms and nicotine withdrawal symptoms in the total sample, and exploratory analyses showed that in both higher and lower baseline severity groups, OROS-MPH statistically significantly improved these two outcomes. No effect on craving overall was detected, though exploratory analyses showed statistically significantly decreased craving in the high ADHD severity participants on OROS-MPH. No treatment by ADHD baseline severity interaction was detected for the outcomes. CONCLUSIONS:Methylphenidate improved secondary outcomes during smoking cessation independent of baseline ADHD severity, with no evident treatment-baseline severity interaction. Our results suggest divergent responses to smoking cessation treatment in the higher and lower severity groups cannot be explained by concordant divergence in craving, withdrawal and ADHD symptom severity, and alternative hypotheses may need to be identified.

SUBMITTER: Luo SX

PROVIDER: S-EPMC6060016 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Exploring longitudinal course and treatment-baseline severity interactions in secondary outcomes of smoking cessation treatment in individuals with attention-deficit hyperactivity disorder.

Luo Sean X SX Wall Melanie M Covey Lirio L Hu Mei-Chen MC Scodes Jennifer M JM Levin Frances R FR Nunes Edward V EV Winhusen Theresa T

The American journal of drug and alcohol abuse 20180125 6

<h4>Background</h4>A double blind, placebo-controlled randomized trial (NCT00253747) evaluating osmotic-release oral system methylphenidate (OROS-MPH) for smoking-cessation revealed a significant interaction effect in which participants with higher baseline ADHD severity had better abstinence outcomes with OROS-MPH while participants with lower baseline ADHD severity had worse outcomes.<h4>Objectives</h4>This current report examines secondary outcomes that might bear on the mechanism for this di ...[more]

PMID: 29370538

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Project description:OBJECTIVE:To determine whether treatment of attention-deficit/hyperactivity disorder (ADHD) with osmotic-release oral system (OROS) methylphenidate promotes abstinence from smoking among smokers with ADHD who have greater severity of ADHD symptoms at baseline or greater improvement in ADHD during treatment. METHOD:This is a secondary analysis of data from a randomized, double-blind, 11-week trial conducted between December 2005 and January 2008 at 6 clinical sites; the original trial was sponsored by the National Drug Abuse Clinical Trials Network. Adult cigarette smokers (aged 18-55 years) who met DSM-IV criteria for ADHD were randomly assigned to OROS methylphenidate (72 mg/d) (n = 127) or matching placebo (n = 128). All participants received nicotine patches (21 mg/d) and weekly individual smoking cessation counseling. Logistic regression was used to model prolonged abstinence from smoking (ascertained by self-report and breath carbon monoxide testing) as a function of treatment, baseline ADHD Rating Scale-IV (ADHD-RS) score, change in ADHD-RS score during treatment, and their interactions. RESULTS:Treatment interacted with both ADHD-RS score at baseline (P = .01) and change in ADHD-RS score during treatment (P = .008). Among patients with higher ADHD-RS scores (> 36) at baseline and the most improvement in ADHD during treatment (ADHD-RS change score ? 24), 70.0% of those who took OROS methylphenidate achieved abstinence from smoking compared to 36.8% of those who took placebo (P = .02). In contrast, among patients with the lowest ADHD-RS baseline scores (? 30), 30.3% of those who took OROS methylphenidate achieved abstinence from smoking compared to 60.7% of those who took placebo (P = .02). CONCLUSIONS:OROS methylphenidate, in combination with nicotine patch, may be an effective treatment for nicotine dependence among smokers with more severe ADHD and more robust response of ADHD symptoms to medication. OROS methylphenidate may be counterproductive among smokers with lower severity of ADHD. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT00253747.

Project description:ImportanceSignificant concern exists over treating youths with attention-deficit/hyperactivity disorder (ADHD) with antipsychotic medications, yet little is known about the factors associated with antipsychotic treatment.ObjectivesTo describe the percentage of youths who fill antipsychotic prescriptions in the year following a new diagnosis of ADHD and characterize the clinical and demographic factors associated with antipsychotic initiation.Design, setting, and participantsA retrospective longitudinal cohort analysis of antipsychotic treatment was performed in 187 563 youths, aged 3 to 24 years, with a new diagnosis of ADHD (without recent diagnosis of any US Food and Drug Administration [FDA]-indicated conditions for antipsychotic treatment). The sample was derived from the 2010 to 2015 MarketScan Commercial Database, with the analysis completed between November 1, 2018, and May 30, 2019.Main outcomes and measuresThe percentage of youths prescribed an antipsychotic in the first year following a new diagnosis of ADHD. Among those prescribed antipsychotic medications, the percentage who received a diagnosis of conduct disorder, oppositional defiant disorder, or a disorder for which 1 or more antipsychotic medication has received an indication for use in youths from the FDA (schizophrenia, bipolar disorder, and Tourette disorder) and the percentage that filled an antipsychotic prescription before filling a stimulant prescription (methylphenidate or amphetamine derivative).ResultsOf the 187 563 youths included in the study, 114 305 (60.9%) were male with a mean (SD) age of 13.74 (5.61) years. In the year following a new ADHD diagnosis, 4869 youths (2.6%; 95% CI, 2.5%-2.7%) with ADHD were prescribed an antipsychotic. Youths treated with antipsychotics with ADHD were more likely than their peers who were not receiving an antipsychotic to have recently received diagnoses of self-harm and/or suicidal ideation (adjusted odds ratio [aOR], 7.5; 95% CI, 5.9-9.6), oppositional defiant disorder (aOR, 4.4; 95% CI, 3.9-4.9), and substance use disorder (aOR, 4.0; 95% CI, 3.6-4.5). The youths who received antipsychotics were also more likely to have received inpatient treatment (aOR, 7.9; 95% CI, 6.7-9.3). During the year following the new ADHD diagnosis, 52.7% (95% CI, 51.3%-54.1%) of youths treated with antipsychotics received a diagnosis for which antipsychotics have either an FDA or evidence-supported indication for their use. Among youths who initiated antipsychotic medications, 47.9% (95% CI, 46.5%-49.3%) did not receive a stimulant prescription between their ADHD diagnosis and antipsychotic initiation. Antipsychotic prescribing was proportionally highest for preschool-aged children (4.3%) and associated with neurodevelopmental disorders (aOR, 3.9; 95% CI, 1.3-11.2) and recent inpatient mental health treatment (aOR, 8.9; 95% CI, 1.7-45.8).Conclusions and relevanceApproximately half of youths with a new ADHD diagnosis may have an evidence-supported indication for an antipsychotic medication. Less than half of these youths received a stimulant; the evidence-supported first line treatment for ADHD, before the antipsychotic was initiated. Use of antipsychotic prescribing appears to be associated with high levels of psychiatric comorbidity.

Project description:Attention-deficit/hyperactivity disorder has been identified to involve the impairment of large-scale functional networks within grey matter, and recent studies have suggested that white matter, which also encodes neural activity, can manifest intrinsic functional organization similar to that of grey matter. However, the alterations in white matter functional networks in attention-deficit/hyperactivity disorder remain unknown. We recruited a total of 99 children, including 66 drug-naive patients and 33 typically developing controls aged from 6 to 14, to characterize the alterations in functional networks within white matter in drug-naive children with attention-deficit/hyperactivity disorder. Using clustering analysis, resting-state functional MRI data in the white matter were parsed into different networks. Intrinsic activity within each network and connectivity between networks and the associations between network activity strength and clinical symptoms were assessed. We identified eight distinct white matter functional networks: the default mode network, the somatomotor network, the dorsal attention network, the ventral attention network, the visual network, the deep frontoparietal network, the deep frontal network and the inferior corticospinal-posterior cerebellum network. The default mode, somatomotor, dorsal attention and ventral attention networks showed lower spontaneous neural activity in patients. In particular, the default mode network and the somatomotor network largely showed higher connectivity with other networks, which correlated with more severe hyperactive behaviour, while the dorsal and ventral attention networks mainly had lower connectivity with other networks, which correlated with poor attention performance. In conclusion, there are two distinct patterns of white matter functional networks in children with attention-deficit/hyperactivity disorder, with one being the hyperactivity-related hot networks including default mode network and somatomotor network and the other being inattention-related cold networks including dorsal attention and ventral attention network. These results extended upon our understanding of brain functional networks in attention-deficit/hyperactivity disorder from the perspective of white matter dysfunction.

Dataset Information

Exploring longitudinal course and treatment-baseline severity interactions in secondary outcomes of smoking cessation treatment in individuals with attention-deficit hyperactivity disorder.

Publications

Exploring longitudinal course and treatment-baseline severity interactions in secondary outcomes of smoking cessation treatment in individuals with attention-deficit hyperactivity disorder.

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