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Review
, 226 (2), 189-200

A Review of the Abuse Potential Assessment of Atomoxetine: A Nonstimulant Medication for Attention-Deficit/Hyperactivity Disorder

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Review

A Review of the Abuse Potential Assessment of Atomoxetine: A Nonstimulant Medication for Attention-Deficit/Hyperactivity Disorder

Himanshu P Upadhyaya et al. Psychopharmacology (Berl).

Abstract

Rationale: Treatment of attention-deficit/hyperactivity disorder (ADHD) has for many years relied on psychostimulants, particularly various formulations of amphetamines and methylphenidate. These are central nervous system stimulants and are scheduled because of their abuse potential. Atomoxetine (atomoxetine hydrochloride; Strattera®) was approved in 2002 for treatment of ADHD, and was the first nonstimulant medication approved for this disorder. It was classified as an unscheduled medication indicating a low potential for abuse. However, the abuse potential of atomoxetine has not been reviewed.

Objectives: In this article, we review the evidence regarding abuse potential of atomoxetine, a selective inhibitor of the presynaptic norepinephrine transporter, which is unscheduled/unrestricted in all countries where it is approved.

Methods: Results from receptor binding, in vitro electrophysiology, in vivo microdialysis, preclinical behavioral, and human laboratory studies have been reviewed.

Results: Atomoxetine has no appreciable affinity for, or action at, central receptors through which drugs of abuse typically act, i.e., dopamine transporters, GABA(A) receptors, and opioid μ receptors. In behavioral experiments in rodents, atomoxetine does not increase locomotor activity, and in drug discrimination studies, its profile is similar to that of drugs without abuse potential. Atomoxetine does not serve as a reinforcer in monkey self-administration studies, and human laboratory studies suggest that atomoxetine does not induce subjective effects indicative of abuse.

Conclusion: Neurochemical, preclinical, and early clinical studies predicted and supported a lack of abuse potential of atomoxetine, which is consistent with the clinical trial and postmarketing spontaneous event data in the past 10 years.

Figures

Fig. 1
Fig. 1
Atomoxetine does not affect a GABA-ergic IPSPs or b the resting membrane potential of ventrobasal thalamic neurons in rat brain slices. Data points reflect percentage of control in a and mean ± SD in b. *Significant difference from control at p ≤ 0.05. Abbreviations: AUC = area under the curve; GABA = γ-aminobutyric acid (GABA); IPSP = inhibitory postsynaptic potential (IPSP); SD = standard deviation
Fig. 2
Fig. 2
Effects of placebo, desipramine (100 and 200 mg), methylphenidate (90 mg), phentermine (60 mg), and atomoxetine (45, 90, and 180 mg) on the Drug Rating Questionnaire item “How much do you like the effects you are feeling now?” Six-hour maximum scores (Jasinski et al. 2008). Abbreviations: ATX = atomoxetine; DMI = desipramine; MPH = methylphenidate; PHN = phentermine; SE = standard error of the mean. Letters above the bars represent statistical significance: p < 0.05 vs. a placebo, b DMI 100 mg, c DMI 200 mg, d MPH 90 mg, e PHN 60 mg, f ATX 45 mg, g ATX 90 mg, h ATX 180 mg

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