Genetics studies support the theory that attention deficit hyperactivity disorder (ADHD) is a heterogeneous disorder and is dependent on several interacting genes. The most prominent theory is that there is a modification of the genes that control the dopamine transporter (DAT) and that certain genetic aberrations of the DAT genotype are associated with a higher risk for ADHD and substance abuse. Medications that inhibit the DAT-and therefore increase the available dopamine at the synapse-ameliorate the symptoms of ADHD. Also of note, there is also a role for norepinephrine (NE) in improving attention and alertness as well as focusing. Conveniently, dopamine is metabolized to NE by the enzyme dopamine beta-hydroxylase. And so, with an increase in available dopamine, there is also an increase in available NE. The medications that increase available dopamine are the traditional psychostimulants such as methylphenidate and amphetamine. However, these medications, in addition to targeting the dopamine receptors in the cerebral prefrontal cortex, also target receptors in the nucleus accumbens-the pleasure center of the brain. In those individuals who are genetically predisposed to substance use disorder (SUD), overstimulation of this area causes euphoria and ultimately a physical craving to continue this stimulation, causing, initially, misuse of the medication and, ultimately, the development of addiction. There is strong consensus that the rates of ADHD in substance abuse treatment samples are 2-3 times the rate found in the general population, and thus, the use of psychostimulants should be avoided. In 2002, the Food and Drug Administration approved the first nonpsychostimulant, atomoxetine (Strattera), as an alternative to controlled substances. Until now, this medication was the only one in its pharmacologic class-although there are other medications whose mechanism of action is to increase dopamine and/or NE and are used to treat ADHD such as bupropion, venlafaxine, desipramine, clonidine, and guanfacine. Currently, Supernus Pharmaceuticals has received approval from the Food and Drug Administration for a new medication in this class-viloxazine (Qelbree)-a once-a-day, nonstimulant medication, as an extended-release formulation for the treatment of ADHD in children 6-17 years old. It comes in once-daily tablets of 100, 150, or 200 mg and has the added advantage of not being a controlled substance, making it harder to abuse and more effortless to renew prescriptions. We probably will begin to see the medication prescribed off-label to adults with a history of SUDs as a first-line treatment option.
Viloxazine was first used in the United Kingdom during the 1970s to treat depression. It was not approved in the United States at that time, although it was allowed for the treatment of cataplexy and narcolepsy with an orphan designation. In 2002, it was discontinued because of business reasons.
Several warnings and precautions have been identified that clinicians should be aware. For instance, higher rates of suicidal thoughts and behaviors were reported than in patients treated with placebo during clinical studies. There were also noted higher rates of insomnia and irritability, and although a causal link between the emergence of these symptoms and the emergence of suicidal impulses has not been established, there is a concern that these and other symptoms such as depressed mood, anxiety, agitation, akathisia, mania, hypomania, panic attacks, impulsive behavior, and aggression may represent precursors to emerging suicidal ideation or behavior. And so, patients being treated with Qelbree should be observed for the emergence of such symptoms.
Other concerns include increases in heart rate and diastolic blood pressure, activation of mania or hypomania, somnolence, and fatigue. If the patient has a diagnosis of bipolar disorder, noradrenergic drugs such as Qelbree may induce a manic or mixed episode. In addition, on the basis of findings from animal reproduction studies, Qelbree may cause maternal harm when used during pregnancy and should be discontinued when pregnancy is recognized unless the benefits of therapy outweigh the potential risk to the mother. Studies are insufficient to determine a drug-associated risk of major birth defects, miscarriage, or adverse maternal outcomes. There are also no data on the presence of the drug in human milk, the effects on the breastfed infant, or the effects on milk production.
Be mindful that, often, an SUD may be misinterpreted as ADHD-for example, presence of impulsive traits as well as risk-taking and disruptive behaviors. If both an SUD and ADHD have been diagnosed, treatment for both disorders should occur concomitantly using psychotherapy and nonstimulants. If psychostimulants are used, extended-release formulations should be considered, and the patient should be intensively monitored for misuse. In addition, because ADHD is a risk factor for cigarette smoking and SUD, teenagers and young adults with ADHD should be queried for both potential problems. Treating ADHD helps protect against the onset of cigarette smoking, SUDs, and SUD-related criminality.
Qelbree may be a satisfactory first-line treatment for adults with ADHD and who also experience an addiction use disorder. However, in summary, the nurse should pay close attention to any changes, especially sudden changes in mood, behavior, thoughts, or feelings or if the patient develops suicidal thoughts or actions. Such management is important when Qelbree treatment is started or when the dose is changed.