Atomoxetine treatment of adults with ADHD and comorbid alcohol use disorders

Wilens, Timothy E.; Adler, Lenard A.; Weiss, Margaret; Michelson, David; Ramsey, Janet L.; Moore, Rodney J.; Renard, Didier; Brady, Kathleen T.; Trzepacz, Paula T.; Schuh, Leslie M.; Ahrbecker, Lisa; Levine, Louise R.

doi:10.1016/j.drugalcdep.2008.02.009

Cited by 151 publications

(134 citation statements)

References 56 publications

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“…Therefore, there may be significant overlap between the CBT treatment for SUD and a proven CBT treatment for ADHD. Furthermore, the fact that the three positive ADHD medication trials in subjects with SUD did not include a psychosocial treatment 5,6,10 and that all the studies that did include a psychosocial treatment have been negative [7][8][9] supports the possibility that the CBT may have had an impact on ADHD.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, all three studies that included patients in outpatient SUD treatment attributed the reduction in ADHD symptoms in the placebo group to the CBT psychosocial intervention, [7][8][9] and the only studies to find a difference between medication and placebo did not allow concurrent SUD treatment. 5,6,10 However, it is not known if these findings apply to adolescents enrolled in substance treatment, and the impact of ADHD treatment on both ADHD and SUD in this population is not known. These are the research gaps that this 12-week, double-blind, randomized, controlled trial of atomoxetine seeks to address.…”

Section: Introductionmentioning

confidence: 99%

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Randomized, Controlled Trial of Atomoxetine for Attention-Deficit/Hyperactivity Disorder in Adolescents With Substance Use Disorder

Thurstone

Riggs

Salomonsen‐Sautel

et al. 2010

Journal of the American Academy of Child & Adolescent Psych

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Objective-To evaluate the effect of atomoxetine hydrochloride versus placebo on attentiondeficit/hyperactivity disorder (ADHD) and substance use disorder (SUD) in adolescents receiving motivational interviewing / cognitive behavioral therapy (MI/CBT) for SUD.Method-This single-site, randomized, controlled trial was conducted between December 2005 and February 2008. Seventy adolescents (13-19 years) with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) ADHD, a DSM-IV ADHD checklist score greater than or equal to 22, and at least one non-tobacco SUD were recruited from the community. All subjects received 12 weeks of atomoxetine hydrochloride + MI/CBT versus placebo + MI/CBT. The main outcome measure for ADHD was self-report DSM-IV ADHD checklist score. For SUD, the main outcome was self-report number of days used non-tobacco substances in the past 28 days using the Timeline Followback interview.Results-Change in ADHD scores did not differ between atomoxetine + MI/CBT and placebo + MI/CBT (F4,191 = 1.23, p = 0.2975). Change in days used non-nicotine substances in the last 28 days did not differ between groups (F3,100 = 2.06, p = 0.1103).Conclusions-There was no significant difference between the atomoxetine + MI/CBT and placebo + MI/CBT groups in ADHD or substance use change. The MI/CBT and/or a placebo effect may have contributed to a large treatment response in the placebo group.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Randomized, Controlled Trial of Atomoxetine for Attention-Deficit/Hyperactivity Disorder in Adolescents With Substance Use Disorder

Thurstone

Riggs

Salomonsen‐Sautel

et al. 2010

Journal of the American Academy of Child & Adolescent Psych

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“…Atomoxetine was shown to reduce cumulative heavy drinking days in the treatment of psychiatric patients with comorbid alcohol use disorders (Wilens et al, 2008). Interestingly, GIRK2 knockout mice show reduced ethanol-induced conditioned taste aversion and conditioned place preference and are less sensitive than wild-type mice to some of the acute effects of ethanol, including anxiolysis, habituated locomotor stimulation, and acute handlinginduced convulsions (Hill et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Atomoxetine was shown to reduce cumulative heavy drinking days in the treatment of psychiatric patients with comorbid alcohol use disorders (Wilens et al, 2008). Therefore, we also examined the effects of atomoxetine on GIRK channel activation induced by ethanol.…”

Section: Table 1 Inhibitory Effects Of Atomoxetine and Reboxetine Onmentioning

confidence: 99%

“…Their clinical efficacy is hypothesized to be linked mainly with potent inhibition of presynaptic norepinephrine transporters (Wong et al, 2000;Hajós et al, 2004;Simpson and Plosker, 2004). Furthermore, recent studies have suggested that the drugs are potentially useful for the treatment of several other psychiatric conditions, including anxiety disorders, eating disorders, substance use disorders, and narcolepsy (Kadhe et al, 2003;Hajós et al, 2004;Szerman et al, 2005;McElroy et al, 2007;Geller et al, 2007;Wilens et al, 2008). However, the molecular mechanisms underlying the various effects of NRIs have not yet been sufficiently clarified.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of G-Protein-Activated Inwardly Rectifying K+ Channels by the Selective Norepinephrine Reuptake Inhibitors Atomoxetine and Reboxetine

Kobayashi

Washiyama

Ikeda

2010

Neuropsychopharmacol

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Atomoxetine and reboxetine are commonly used as selective norepinephrine reuptake inhibitors (NRIs) for the treatment of attentiondeficit/hyperactivity disorder and depression, respectively. Furthermore, recent studies have suggested that NRIs may be useful for the treatment of several other psychiatric disorders. However, the molecular mechanisms underlying the various effects of NRIs have not yet been sufficiently clarified. G-protein-activated inwardly rectifying K + (GIRK or Kir3) channels have an important function in regulating neuronal excitability and heart rate, and GIRK channel modulation has been suggested to be a potential treatment for several neuropsychiatric disorders and cardiac arrhythmias. In this study, we investigated the effects of atomoxetine and reboxetine on GIRK channels using the Xenopus oocyte expression assay. In oocytes injected with mRNA for GIRK1/GIRK2, GIRK2, or GIRK1/GIRK4 subunits, extracellular application of atomoxetine or reboxetine reversibly reduced GIRK currents. The inhibitory effects were concentrationdependent, but voltage-independent, and time-independent during each voltage pulse. However, Kir1.1 and Kir2.1 channels were insensitive to atomoxetine and reboxetine. Atomoxetine and reboxetine also inhibited GIRK currents induced by activation of cloned A 1 adenosine receptors or by intracellularly applied GTPgS, a nonhydrolyzable GTP analogue. Furthermore, the GIRK currents induced by ethanol were concentration-dependently inhibited by extracellularly applied atomoxetine but not by intracellularly applied atomoxetine. The present results suggest that atomoxetine and reboxetine inhibit brain-and cardiac-type GIRK channels, revealing a novel characteristic of clinically used NRIs. GIRK channel inhibition may contribute to some of the therapeutic effects of NRIs and adverse side effects related to nervous system and heart function.

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Alcohol Use Disorders

Sher¹

2010

The Corsini Encyclopedia of Psychology

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This guideline is one of three pieces of NICE guidance addressing alcohol-use disorders. The present guideline addresses the management of alcohol dependence and harmful alcohol use in people 10 years and older including: assessment, pharmacological interventions, psychological and psychosocial interventions, and settings of assisted withdrawal and rehabilitation. The two other NICE guidelines address: 1) The prevention of alcohol-use disorders in people 10 years and older, which is public health guidance on the price of alcohol, advertising and availability of alcohol, how best to detect alcohol misuse both in and outside primary care and brief interventions to manage alcohol misuse in these settings (NICE, 2010a), and 2) The assessment and clinical management in people 10 years and older of acute alcohol withdrawal, including delirium tremens, liver damage, acute and chronic pancreatitis and the management of Wernicke's encephalopathy (NICE, 2010b). This guideline will sometimes use the term alcohol misuse, which will encompass both people with alcohol dependence and harmful alcohol use. The guideline recommendations have been developed by a multidisciplinary team of healthcare professionals, lay member, service user and carer representatives, and guideline methodologists, after careful consideration of the best available evidence. It is intended that the guideline will be useful to clinicians and service commissioners in providing and planning high-quality care for people who misuse alcohol while also emphasising the importance of the experience of care for them and their carers. Although the evidence base is expanding, there are also a number of gaps in the literature. The guideline makes a number of research recommendations specifically to address gaps in the evidence base. In the meantime, it is hoped that the guideline will assist clinicians, people who misuse alcohol and their carers by identifying the merits of particular treatment approaches where the evidence from research and clinical experience exists. National guideline 1.1.1What are clinical practice guidelines? Clinical practice guidelines are 'systematically developed statements that assist clinicians and patients in making decisions about appropriate treatment for specific conditions' (Mann, 1996). They are derived from the best available research evidence, using predetermined and systematic methods to identify and evaluate the evidence relating to the specific condition in question. Where evidence is lacking, the guidelines incorporate statements and recommendations based upon the consensus statements developed by the Guideline Development Group (GDG). Clinical guidelines are intended to improve the process and outcomes of healthcare in a number of different ways. They can:

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Atomoxetine treatment of adults with ADHD and comorbid alcohol use disorders

Cited by 151 publications

References 56 publications

Randomized, Controlled Trial of Atomoxetine for Attention-Deficit/Hyperactivity Disorder in Adolescents With Substance Use Disorder

Randomized, Controlled Trial of Atomoxetine for Attention-Deficit/Hyperactivity Disorder in Adolescents With Substance Use Disorder

Inhibition of G-Protein-Activated Inwardly Rectifying K+ Channels by the Selective Norepinephrine Reuptake Inhibitors Atomoxetine and Reboxetine

Alcohol Use Disorders

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