Correlates of alcohol use in adults with ADHD and comorbid alcohol use disorders: exploratory analysis of a placebo-controlled trial of atomoxetine.
BACKGROUND
Attention-deficit/hyperactivity disorder (ADHD) and substance use disorder are often comorbid in adults. The effects of ADHD treatment on comorbid alcohol use disorder have not been extensively studied.


OBJECTIVE
To assess correlates of ADHD and alcohol use outcomes in ADHD with comorbid alcohol use disorders, via a post-hoc exploratory subgroup analysis of a previously conducted, randomized, double-blind, placebo-controlled study of recently abstinent adults.


METHODS
Adults who had ADHD and alcohol use disorders and were abstinent for 4-30 days were randomized to daily atomoxetine 25-100 mg (mean final dose = 89.9 mg) or placebo for 12 weeks. Changes in ADHD symptoms from baseline to endpoint were assessed using the ADHD Investigator Symptom Rating Scale (AISRS) total score, alcohol use by the timeline followback method, and alcohol cravings by the Obsessive Compulsive Drinking Scale.


RESULTS
Of 147 subjects receiving atomoxetine (n = 72) or placebo (n = 75) in the primary study, 80 (54%) completed 12 weeks (n = 32 atomoxetine; n = 48 placebo). Improvements in ADHD symptoms on the AISRS correlated significantly with decreases in alcohol cravings (Pearson's r = 0.28; 95% confidence interval [CI] = 0.11-0.43; p = 0.002), and the correlation was most notable with atomoxetine (r = 0.29; CI [0.04 - 0.51]; p = 0.023) rather than with placebo (r = 0.24; CI [0.00-0.46]; p = 0.055). On-treatment drinking levels correlated with AISRS scores (r = 0.12; CI [0.05 -0.19]; p = 0.001). Relapse to alcohol abuse significantly correlated with worse ADHD symptoms on 15 of 18 items of the AISRS in the placebo group (p < 0.05 for each).


CONCLUSIONS
No baseline predictor (other than degree of sobriety) of alcohol use or ADHD outcomes emerged. ADHD symptom improvements correlated significantly with reductions in alcohol cravings, and relapse to alcohol abuse correlated significantly with worsening of most ADHD symptoms in the placebo group, but not in the atomoxetine group. This post-hoc subgroup analysis is of a hypothesis-generating nature, and the generalizability of the findings may be limited by exclusion of adults with common ADHD comorbidities from the base study. Further, prospective clinical trials in larger and more heterogeneous patient populations are warranted to confirm or reject these preliminary associations. TRIAL REGISTRATION (BASE STUDY): ClinicalTrials.gov identifier: NCT00190957.
Massachusetts General Hospital, Boston, MA 02114, USA. twilens@partners.org
Timothy E
TE
Wilens
Lenard A
LA
Adler
Yoko
Y
Tanaka
Feng
F
Xiao
Deborah N
DN
D'Souza
Stephen W
SW
Gutkin
Himanshu P
HP
Upadhyaya
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects*; D020751:Alcohol-Induced Disorders / Q000150:complications / Q000188:drug therapy*; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000188:drug therapy*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000819:agonists; D004311:Double-Blind Method; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D011437:Propylamines / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors
D018759:Adrenergic Uptake Inhibitors; D002492:Central Nervous System Depressants; D011437:Propylamines; D000431:Ethanol; D000069445:Atomoxetine Hydrochloride