Children with oppositional defiant disorder (ODD) and a concurrent Axis I diagnosis are often prescribed drug therapy for attention deficit hyperactivity disorder (ADHD) to manage disruptive behavior. However, ODD symptoms tend to be poorly controlled, raising questions about the effectiveness of drug therapy in children with the condition. Safety and long term consequences of pharmacological agents for ODD are important factors clinicians must consider before initiating treatment. The purpose of this literature review is to examine the pharmacodynamics and efficacy of drug therapy used for ODD in school-age children and adolescents. Additionally, awareness of poor behavior patterns and recognition of symptoms associated with ODD in children among health care providers was explored. A literature review exploring ODD and drug therapy for ODD and related behavioral disorders was conducted from various online databases. Results from 15 reviewed studies suggest that pharmacologic therapy is typically prescribed for ODD symptoms when a comorbid condition such as ADHD, a mood disorder, or an anxiety disorder is present. Drug therapy for ADHD has demonstrated effective behavioral outcomes in reducing ODD symptom severity in children and tolerable side effects when used for short-term therapy. Studies have demonstrated success and better control of ODD symptoms with a focused drug therapy regimen. Overall, the benefits of drug therapy can potentially outweigh the risks of adverse effects, and improve the quality of life in children with ODD. In conclusion, uncovering the reasons for poorly controlled ODD in children can be of clinical significance to health care providers and can support decision making when considering drug therapy for children with this condition.

Attention-deficit/hyperactivity disorder (ADHD) is highly comorbid with substance use disorders, particularly cocaine. Preclinical studies using the well-validated Spontaneously Hypertensive Rat (SHR) model of ADHD suggest that adolescent treatment with the stimulant methylphenidate increases cocaine abuse risk in adulthood, highlighting the need to identify alternative medications for teenagers with ADHD. Experiments 1-4 tested the hypothesis that atomoxetine, a non-stimulant that improves prefrontal cortex functioning in adolescent SHR, would not increase cocaine abuse risk. The speed to acquire cocaine self-administration, the efficacy and motivating influence of cocaine reinforcement, and reactivity to cocaine cues in adulthood following discontinuation of adolescent atomoxetine treatment were examined in male SHR and two genetic control strains: inbred Wistar-Kyoto (WKY) and outbred Wistar (WIS). Because atomoxetine is not always as clinically efficacious as methylphenidate, Experiments 5-9 tested the hypothesis that an alternative stimulant, d-amphetamine, would improve cognitive performance in adolescent SHR during a strategy set-shifting task and not increase cocaine abuse risk in adult SHR after adolescent d-amphetamine was discontinued. Across experiments, adult SHR acquired cocaine self-administration faster than control strains and also were more sensitive to cocaine’s reinforcing and motivating influence and more reactive to cocaine cues. As hypothesized, adolescent atomoxetine did not increase any measure of cocaine abuse risk in adult SHR and modestly reduced SHR’s reactivity to cocaine cues. In WKY control, however, adolescent atomoxetine accelerated acquisition of cocaine self-administration. d-Amphetamine improved set-shifting deficits in adolescent SHR, demonstrating pro-cognitive effects as hypothesized. When self-administration was acquired, cocaine intake was lower in adult SHR that received adolescent d-amphetamine compared to vehicle-treated SHR, consistent with the hypothesis. Adolescent d-amphetamine slowed acquisition and reduced the efficacy and motivating influence of cocaine reinforcement in WIS control, but accelerated acquisition in WKY control. Collectively, these results highlight the heuristic value of SHR in evaluating comorbid ADHD and cocaine abuse risk, and suggest that atomoxetine and d-amphetamine may be safer medications than methylphenidate for teenagers with ADHD. However, findings in control strains emphasize the need for accurate ADHD diagnosis, as the long-term consequences of treatment could be favorable (d-amphetamine in WIS) or unfavorable (atomoxetine and d-amphetamine in WKY) in misdiagnosed individuals.

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